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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 401 - 253 of 253 Journals sorted by number of followers
Pharmazeutische Zeitung     Full-text available via subscription   (Followers: 11)
Pharmazeutische Industrie     Full-text available via subscription   (Followers: 9)
Pharmaceutical Fronts     Open Access   (Followers: 8)
Advanced Herbal Medicine     Open Access   (Followers: 8)
Pharmaceutical Journal     Free   (Followers: 8)
Drug Metabolism and Pharmacokinetics     Hybrid Journal   (Followers: 6)
Molekul     Open Access   (Followers: 5)
Advances in Pharmacology and Pharmacy     Open Access   (Followers: 5)
AAPS Open     Open Access   (Followers: 5)
Journal of Drug Research in Ayurvedic Sciences     Open Access   (Followers: 4)
Journal of Drug Delivery Science and Technology     Hybrid Journal   (Followers: 3)
Advances in Traditional Medicine     Hybrid Journal   (Followers: 3)
ACS Pharmacology & Translational Science     Hybrid Journal   (Followers: 3)
Canadian Journal of Pain     Open Access   (Followers: 3)
PharmaNutrition     Hybrid Journal   (Followers: 3)
Journal of Pharmacological Sciences     Open Access   (Followers: 3)
Journal of Herbal Science     Full-text available via subscription   (Followers: 3)
Archives of Pharmacy and Pharmaceutical Sciences     Open Access   (Followers: 2)
Advances in Pharmacoepidemiology & Drug Safety     Open Access   (Followers: 2)
Indian Journal of Drugs in Dermatology     Open Access   (Followers: 2)
European Journal of Medicinal Plants     Open Access   (Followers: 2)
Journal of Education and Science     Open Access   (Followers: 2)
Asian Journal of Pharmaceutical Research and Health Care     Open Access   (Followers: 2)
Journal of Herbal Medicine     Hybrid Journal   (Followers: 2)
Current Issues in Pharmacy and Medical Sciences     Open Access   (Followers: 2)
Drug Safety - Case Reports     Open Access   (Followers: 2)
Current Research in Drug Discovery     Open Access   (Followers: 2)
International Journal of Immunopathology and Pharmacology     Open Access   (Followers: 2)
British Journal of Pharmacy (BJPharm)     Open Access   (Followers: 2)
Journal of Pharmaceutical Sciences and Pharmacology     Full-text available via subscription   (Followers: 2)
Psychiatry and Clinical Psychopharmacology     Open Access   (Followers: 1)
Herbal Medicines Journal     Open Access   (Followers: 1)
Journal of Applied Pharmaceutical Research     Open Access   (Followers: 1)
Integrative Medicine International     Open Access   (Followers: 1)
Drugs : Real World Outcomes     Hybrid Journal   (Followers: 1)
Safety and Risk of Pharmacotherapy     Open Access   (Followers: 1)
Regulatory Mechanisms in Biosystems     Open Access   (Followers: 1)
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 1)
Separation Science plus (SSC plus)     Hybrid Journal   (Followers: 1)
Open Pharmacoeconomics & Health Economics Journal     Open Access   (Followers: 1)
Ethiopian Pharmaceutical Journal     Full-text available via subscription   (Followers: 1)
Journal of the American College of Clinical Pharmacy : JACCP     Hybrid Journal   (Followers: 1)
Advanced Therapeutics     Hybrid Journal   (Followers: 1)
Pharmactuel     Open Access   (Followers: 1)
East and Central African Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
Journal of Metabolomics & Systems Biology     Open Access   (Followers: 1)
Journal of Pharmaceutical Technology, Research and Management     Open Access   (Followers: 1)
Farmakoèkonomika : Modern Pharmacoeconomic and Pharmacoepidemiology     Open Access   (Followers: 1)
Farmasains : Jurnal Ilmiah Ilmu Kefarmasian     Open Access   (Followers: 1)
Current Research in Pharmacology and Drug Discovery     Open Access   (Followers: 1)
Expert Review of Precision Medicine and Drug Development     Hybrid Journal   (Followers: 1)
OpenNano     Open Access   (Followers: 1)
Emerging Trends in Drugs, Addictions, and Health     Open Access   (Followers: 1)
Journal of Biopharmaceutics Sciences     Open Access   (Followers: 1)
Pediatric Pharmacology     Open Access   (Followers: 1)
Journal of Medicinal Plants for Economic Development     Open Access   (Followers: 1)
Journal of Pharmaceutical Health Care and Sciences     Open Access   (Followers: 1)
Chinese Herbal Medicines     Full-text available via subscription   (Followers: 1)
Pharmakon : Arzneimittel in Wissenschaft und Praxis     Full-text available via subscription   (Followers: 1)
Medicines     Open Access   (Followers: 1)
Future Journal of Pharmaceutical Sciences     Open Access   (Followers: 1)
Pharmacy & Pharmacology     Open Access   (Followers: 1)
Sustainable Chemistry and Pharmacy     Full-text available via subscription   (Followers: 1)
Pharmacological Research - Modern Chinese Medicine     Open Access  
Clinical Complementary Medicine and Pharmacology     Open Access  
Exploratory Research in Clinical and Social Pharmacy     Open Access  
Indonesian Journal of Pharmaceutical Education     Open Access  
Future Drug Discovery     Open Access  
IUPHAR/BPS Guide to Pharmacology CITE     Open Access  
Journal of Applied Pharmaceutical Sciences and Research     Open Access  
Cephalalgia Reports     Open Access  
Pharmacon : Jurnal Farmasi Indonesia     Open Access  
Pharmacia     Open Access  
Research Results in Pharmacology     Open Access  
Journal of Toxins     Open Access  
Journal of Pharmaceutics & Pharmacology     Open Access  
Natural Product Communications     Open Access  
PharmaTutor     Open Access  
International Journal of Pharmaceutical Sciences and Developmental Research     Open Access  
Toxicological Research     Hybrid Journal  
Current Medical Science     Hybrid Journal  
EUREKA : Health Sciences     Open Access  
Iraqi Journal of Pharmacy     Open Access  
Revista Colombiana de Ciencias Químico-Farmacéuticas     Open Access  
Medicine in Drug Discovery     Open Access  
Frontiers in Medical Technology     Open Access  
International Journal of Medical and Pharmaceutical Case Reports     Open Access  
Asian Journal of Research in Medical and Pharmaceutical Sciences     Open Access  
Journal of Pharmaceutical Health Services Research     Hybrid Journal  
AboutOpen     Open Access  
Current Protocols in Pharmacology     Hybrid Journal  
Medical Cannabis and Cannabinoids     Open Access  
Ukrainian Biopharmaceutical Journal     Open Access  
Pharmaceutical Journal of Sri Lanka     Open Access  
Isan Journal of Pharmaceutical Sciences (IJPS)     Open Access  
Ciencia e Investigación     Open Access  
Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community)     Open Access  
Toxicon : X     Open Access  
International Journal of Pharmaceutics: X     Open Access  
Jurnal Farmasi dan Ilmu Kefarmasian Indonesia     Open Access  
Open Pharmacology Journal     Open Access  
ExRNA     Open Access  
International Journal of Pharmaceutics & Pharmacology     Open Access  
Antibody Therapeutics     Open Access  
Journal of Faculty of Pharmacy of Ankara University     Open Access  
Iraqi Journal of Pharmaceutical Sciences     Open Access  
Journal of Medicinal Botany     Open Access  
Journal of Medicinal Herbs and Ethnomedicine     Open Access  
International Journal of Pharmacokinetics     Hybrid Journal  
Neuropsychopharmacology Reports     Open Access  
Reviews on Clinical Pharmacology and Drug Therapy     Full-text available via subscription  
SynOpen     Open Access  
Matrix Science Pharma     Open Access  
Contract Pharma     Full-text available via subscription  
Journal of Cellular Neuroscience and Oxidative Stress     Open Access  
Istanbul Journal of Pharmacy     Open Access  
Acta Pharmaceutica Indonesia     Open Access  
Indonesian Journal of Pharmacy     Open Access  
EMC - Cosmetologia Medica e Medicina degli Inestetismi Cutanei     Full-text available via subscription  
High-Throughput     Open Access  
Scientia Pharmaceutica     Open Access  
Trends in Peptide and Protein Sciences     Open Access  
Acta Physiologica Hungarica     Full-text available via subscription  
Jurnal Farmasi Sains dan Praktis     Open Access  
Jurnal Kefarmasian Indonesia     Open Access  
Pharmaceutical Historian     Open Access  
Planta Medica International Open     Open Access  
Archives of Razi Institute     Open Access  
Journal of Pharmaceutical Research     Open Access  
EJNMMI Radiopharmacy and Chemistry     Open Access  
FarmaJournal     Open Access  
Journal of Negative and No Positive Results     Open Access  
Pharmaciana     Open Access  
Folia Medica Indonesiana     Open Access  
Актуальні питання фармацевтичної та медичної науки та практики     Open Access  
International Journal of Pharmacology, Phytochemistry and Ethnomedicine     Open Access  
Фармацевтичний часопис     Open Access  
Ciência Equatorial     Open Access  
Iranian Journal of Pharmaceutical Research     Open Access  
Research & Reviews : A Journal of Drug Design & Discovery     Full-text available via subscription  
Asian Journal of Medical and Pharmaceutical Researches     Open Access  
Research & Reviews : A Journal of Pharmacognosy     Full-text available via subscription  
Ars Pharmaceutica     Open Access  
Pharmacognosy Communications     Partially Free  
Egyptian Pharmaceutical Journal     Open Access  
Pharmacological Reports     Hybrid Journal  
PZ Prisma : Materialien zur Fort- und Weiterbildung     Full-text available via subscription  
Chinese Journal of Pharmaceutical Analysis     Full-text available via subscription  
Journal of Nanopharmaceutics and Drug Delivery     Full-text available via subscription  
Journal of Hydrogels     Full-text available via subscription  
Manufacturing Chemist     Full-text available via subscription  
Pharmaceutica Analytica Acta     Open Access  
Journal of Pharmacovigilance     Open Access  
Current Pharmacology Reports     Hybrid Journal  
Nigerian Journal of Natural Products and Medicine     Full-text available via subscription  
International Journal of Herbs and Pharmacological Research     Open Access  
Bangladesh Journal of Physiology and Pharmacology     Open Access  
Research Journal of Pharmacognosy     Open Access  

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Similar Journals
Journal Cover
International Journal of Immunopathology and Pharmacology
Journal Prestige (SJR): 0.471
Citation Impact (citeScore): 2
Number of Followers: 2  

  This is an Open Access Journal Open Access journal
ISSN (Print) 0394-6320 - ISSN (Online) 2058-7384
Published by Sage Publications Homepage  [1175 journals]
  • Epidemiological and clinical characteristics of vaccinated COVID-19
           patients: A meta-analysis and systematic review

    • Authors: Wen Tian, Xingxiang Ren, Mei Han, Yuanyuan Zhang, Xu Gao, Zhihai Chen, Wei Zhang
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objective: With the global epidemic of coronavirus disease 2019 (COVID-19), vaccination rates are increasing globally. This study evaluated the relevant clinical manifestations of vaccinated COVID-19 patients. Methods: We searched carefully in 11 databases such as PubMed, Embase, Scopus, Cochrane Library, Web of Science, Ovid, China National Knowledge Infrastructure Database, Wan Fang Data, Sinomed, VIP Database, and Reading Showing Database up to 26 March 2022. To search for articles that have described the characteristics of vaccinated patients including epidemiological and clinical symptoms. Statistical analysis of the extracted data using STATA 14.0. Results: A total of 58 articles and 263,708 laboratory-confirmed COVID-19 patients were included. Most of the patients in the vaccinated group had more asymptomatic infection and fewer severe illnesses. There were significant differences in ethnicity, and strain infected with COVID-19, and comorbidities (hyperlipidemia, diabetes, obesity, kidney disease, immunocompromised, cardiovascular disease, and tumor) and symptoms (fever, cough, gastrointestinal symptoms, neurological symptoms, and dysgeusia/anosmia) between vaccinated group and unvaccinated group. Oxygen support, use of steroid, days in hospital, hospital treatment, ICU treatment, death, and poor prognosis were also significantly different. Conclusion: Compared with the vaccinated group, patients in the unvaccinated group had a more severe clinical manifestations. Vaccines are also protective for infected people.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-11-22T12:50:46Z
      DOI: 10.1177/03946320221141802
      Issue No: Vol. 36 (2022)
  • Integrated analysis of the genomic and transcriptional profile of gliomas
           with isocitrate dehydrogenase-1 and tumor protein 53 mutations

    • Authors: Han-Qing Liu, Wei-Xin Li, Ya-Wen An, Tao Wu, Guang-Yu Jiang, Yu Dong, Wei-Xin Chen, Jian-Chun Wang, Cheng Wang, Shuo Song
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Background: The gene mutation of isocitrate dehydrogenase-1 (IDH1) is commonly found in LGG and some GBM patients and usually carries tumor protein 53 (TP53) mutations. However, the underlying mechanisms on both mutations of glioma patients in IDH1 and TP53 are still unclear. Aim: To find the potential target markers in GBM and LGG patients with IDH1 and TP53 mutation.Method: A total of 1122 glioma patients from The Cancer Genome Atlas were enrolled and divided as wild-type (without IDH1 and TP53 mutations) or both mutant (both IDH1 and TP53 mutations). The data of clinicopathological characteristics, mRNA, mutations, and copy number alteration were analyzed. Results: IDH1 and TP53 mutations, not gene expression, affect the survival probability of GBM and LGG patients, which might be related to neuron function, immune function, tumor invasion, and metastasis. The effects of the selected gene (EMILIN3, SAA1, VSTM2A, HAMP, IFT80, and CHIC2) on glioma patients could be regulated by IDH1 and TP53 mutations and had a higher survival possibility in these patients. Conclusions: The selected genes in GBM and LGG patients with IDH1 and TP53 mutations could be a potential prognosis marker in the future.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-11-15T09:57:05Z
      DOI: 10.1177/03946320221139262
      Issue No: Vol. 36 (2022)
  • PM2.5 activated NLRP3 inflammasome and IL-1β release in MH-S cells by
           facilitating autophagy via activating Wnt5a

    • Authors: Guanli Yuan, Yinfeng Liu, Zheng Wang, Xiaotong Wang, Zhuoxiao Han, Xixin Yan, Aihong Meng
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Particulate matter 2.5 (PM2.5)-induced pulmonary inflammation is an important issue worldwide. NLRP3 inflammasome activation has been found to be involved in pulmonary inflammation development. However, whether PM2.5 induces pulmonary inflammation by activating the NLRP3 inflammasome has not yet been fully elucidated. This study researched whether PM2.5 induces the NLRP3 inflammasomes activation to trigger pulmonary inflammation.Mice and MH-S cells were exposed to PM2.5, BOX5, and Rapamycin. Hematoxylin and eosin staining was performed on the lung tissues of mice. M1 macrophage marker CD80 expression in the lung tissues of mice and LC3B expression in MH-S cells was detected by immunofluorescence. IL-1β level in the lavage fluid and MH-S cells were detected by enzyme-linked immunosorbent assay. Protein expression was detected by Western blot. Autophagy assay in MH-S cells was performed by LC3B-GFP punctae experiment.PM2.5 exposure induced the lung injury of mice and increased NLRP3, P62, Wnt5a, LC3BII/I, and CD80 expression and IL-1β release in the lung tissues. PM2.5 treatment increased NLRP3, pro-caspase-1, cleaved caspase-1, Pro-IL-1β, Pro-IL-18, P62, LC3BII/I, and Wnt5a expression, IL-1β release, and LC3B-GFP punctae in MH-S cells. However, BOX5 treatment counteracted this effect of PM2.5 on lung tissues of mice and MH-S cells. Rapamycin reversed the effect of BOX5 on PM2.5-induced lung tissues of mice and MH-S cells.PM2.5 activated the NLRP3 inflammasome and IL-1β release in MH-S cells by facilitating the autophagy via activating Wnt5a. The findings of this study provided a new clue for the treatment of pulmonary inflammation caused by PM2.5.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-11-08T10:31:16Z
      DOI: 10.1177/03946320221137464
      Issue No: Vol. 36 (2022)
  • Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic
           fatty liver disease associated with insulin resistance in diabetic rats
           via regulation of PI3K/AKT/FoxO1 pathway

    • Authors: Esraa SA Ahmed, Hebatallah E Mohamed, Mostafa A Farrag
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectiveNon-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM.MethodsA diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30 mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination.ResultsLut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified via the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells’ insulin sensitivity.ConclusionLut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-11-02T01:46:24Z
      DOI: 10.1177/03946320221137435
      Issue No: Vol. 36 (2022)
  • Niloticin binds to MD-2 to promote anti-inflammatory pathway activation in
           macrophage cells

    • Authors: Guirong Chen, Chang Liu, Mingbo Zhang, Xiaobo Wang, Yubin Xu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesNiloticin is an active compound isolated from Cortex phellodendri with uncharacterized anti-inflammatory activity. We assessed the drug potential of niloticin and examined its ability to target myeloid differentiation protein 2 (MD-2) to ascertain the mechanism for its anti-inflammatory activity.MethodsThe Traditional Chinese Medicine Systems Pharmacology Database was used to evaluate niloticin. Bio-layer interferometry and molecular docking technologies were used to explore how niloticin targets MD-2, which mediates a series of toll-like receptor 4 (TLR4)-dependent inflammatory responses. The cytokines involved in the lipopolysaccharide (LPS)-TLR4/MD-2-NF-κB pathway were evaluated using ELISA, RT-qPCR, and western blotting.ResultsNiloticin could bind to MD-2 and had no evident effects on cell viability. Niloticin treatment significantly decreased the levels of NO, IL-6, TNF-α, and IL-1β induced by LPS (p < 0.01). IL-1β, IL-6, iNOS, TNF-α, and COX-2 mRNA expression levels were decreased by niloticin (all p < 0.01). Compared with that in the control group, the increase in TLR4, p65, MyD88, p-p65, and iNOS expression levels induced by LPS were suppressed by niloticin (all p < 0.01).ConclusionOur results suggest that niloticin has therapeutic potential and binds to MD-2. Niloticin binding to MD-2 antagonized the effects of LPS binding to the TLR4/MD-2 complex, resulting in the inhibition of the LPS-TLR4/MD-2-NF-κB signaling pathway.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-31T11:30:29Z
      DOI: 10.1177/03946320221133017
      Issue No: Vol. 36 (2022)
  • Licochalcone A inhibits IgE-mediated allergic reaction through
           PLC/ERK/STAT3 pathway

    • Authors: Jin Shu, Xu Cui, Xin Liu, Wenxing Yu, Weisong Zhang, Xiaojing Huo, Chao Lu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Licochalcone (LicA) is a flavonoid commonly derived from the licorice plant that is reported to have a variety of pharmacological activities. However, few studies have focused on its anti-allergic properties. IgE-mediated passive and systemic anaphylaxis mice models were used to assess the in vivo anti-allergic effect of LicA and its underlying mechanism, while degranulation, cytokines, and chemokines released from laboratory of allergic disease (LAD2) cells were used to assess its in vitro anti-allergic effect. We used western blot analysis to explore the downstream signaling pathway of its anti-allergic effect. We found that in the mouse model, LicA attenuated IgE-mediated paw inflammation, recovered the allergy-induced drop in body temperature, and reduced the concentrations of tumor necrosis factor-alpha and monocyte chemo-attractant protein-1 in mouse serum in a dose-dependent manner. LicA inhibited the allergic reaction via inhibition of IgE-mediated LAD2 cell activation through the PLC/ERK/STAT3 pathway.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-20T11:40:12Z
      DOI: 10.1177/03946320221135462
      Issue No: Vol. 36 (2022)
  • Influence of nitric oxide signaling mechanisms in cancer

    • Authors: R Ramírez-Patiño, G Avalos-Navarro, LE Figuera, JJ Varela-Hernández, LA Bautista-Herrera, JF Muñoz-Valle, MP Gallegos-Arreola
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Nitric oxide (NO) is a molecule with multiple biological functions that is involved in various pathophysiological processes such as neurotransmission and blood vessel relaxation as well as the endocrine system, immune system, growth factors, and cancer. However, in the carcinogenesis process, it has a dual behavior; at low doses, NO regulates homeostatic functions, while at high concentrations, it promotes tissue damage or acts as an agent for immune defense against microorganisms. Thus, its participation in the carcinogenic process is controversial. Cancer is a multifactorial disease that presents complex behavior. A better understanding of the molecular mechanisms associated with the initiation, promotion, and progression of neoplastic processes is required. Some hypotheses have been proposed regarding the influence of NO in activating oncogenic pathways that trigger carcinogenic processes, because NO might regulate some signaling pathways thought to promote cancer development and more aggressive tumor growth. Additionally, NO inhibits apoptosis of tumor cells, together with the deregulation of proteins that are involved in tissue homeostasis, promoting spreading to other organs and initiating metastatic processes. This paper describes the signaling pathways that are associated with cancer, and how the concentration of NO can serve a beneficial or pathological function in the initiation and promotion of neoplastic events.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-19T09:59:22Z
      DOI: 10.1177/03946320221135454
      Issue No: Vol. 36 (2022)
  • Blood phenotype O and indirect bilirubin are associated with lower, early
           COVID-19—related mortality: A retrospective study

    • Authors: Alaa Efat, Sabry Shoeib, Ali ElKholy, Osama Saied Hussein Aboelela, Doaa Elshamy
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesTo evaluate the ABO blood type and indirect bilirubin to predict early mortality in adults with severe COVID-19.MethodsThis retrospective observational study was conducted on 268 adult patients with laboratory-confirmed COVID-19 who had attended the intensive care unit (ICU), Quena general hospital and Luxor International Hospital, and other hospitals or centers for the treatment of COVID-19, during the period from January 2021 till December 2021.Results Relation between mortality and ABO group were highly significant, as we found non-O blood group with more risk of early mortality and intensive care unit admission ICU. There were significant differences between dead and alive cases as regards platelets, white blood cells WBCs (neutrophil, lymphocyte), albumin, liver enzymes aspartate transeferase (AST), alanine transferase (ALT), total direct and indirect bilirubin, creatinine, and urea.Conclusion There was a highly significant relation between dead cases and ABO blood group as between the O and non-O groups; also, group O was associated with less severe manifestations and or ventilation and less mortality in patients with severe COVID-19 infection. Direct bilirubin>0.5 was found to be the best predictor for mortality in cases with COVID-19 so indirect bilirubin may be considered a good protector against complications of the infection.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-12T05:38:04Z
      DOI: 10.1177/03946320221133952
      Issue No: Vol. 36 (2022)
  • Analysis of TRIM27 prognosis value and immune infiltrates in
           hepatocellular carcinoma

    • Authors: Haichuan Wang, Yu Zhang, Li Yan, Qiang Lv, Jie Lu, Bei Yun
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Up-regulation of tripartite motif-containing 27 (TRIM27) in varieties of tumors found that TRIM27 advanced tumor metastasis and invasion. Nevertheless, the relation of TRIM27 and immune infiltration in hepatocellular carcinoma (HCC) and the prognostic value of TRIM27 expression is unknown. We assessed TRIM27 association with immune infiltrates and the prognostic value of TRIM27 in HCC. From the Cancer Genome Atlas, we obtained TRIM27 transcriptional expression profiles of HCC and normal tissues. Using the Human Protein Atlas to evaluate the expression TRIM27, protein-protein interaction (PPI) networks were produced using the STRING database. Functional enrichment analysis was performed by using the clusterProfiler package. The tumor immune estimation resource was used to determine the relation of TRIM27 expression and immune infiltrates. We found that the expression of TRIM27 was up-regulated in HCC tissues compared with adjacent normal tissues. High TRIM27 expression correlated with high pathologic stage and high TNM stage. The receiver operating characteristic curve of TRIM27 area was 0.946. Kaplan–Meier analyses showed poor prognosis in HCC patients with high expression of TRIM27. Correlation analysis suggested that the expression of TRIM27 was related to immune infiltrates and tumor purity. This study indicated in HCC up-regulated the expression of TRIM27 is correlated to poor survival and immune infiltration. TRIM27 is an underlying target of immune therapy and is an underlying biomarker for poor prognosis in HCC.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-11T07:58:23Z
      DOI: 10.1177/03946320221132986
      Issue No: Vol. 36 (2022)
  • Seroprevalence of SARS-CoV-2 antibodies in vaccinated healthcare workers
           in Marrakech (Morocco)

    • Authors: Taoufik Ben Houmich, Abdelali Tali, Fayrouz Debbagh, Asma Lamrani Hanchi, Nabila Soraa
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionThe SARS-CoV-2 pandemic has had a considerable impact, causing millions of deaths worldwide, including many healthcare workers (HCWs). The pharmaceutical industry has been working diligently since the start of the pandemic to develop various vaccines to fight the spread of the virus and protect the population.ObjectiveTo study the seroprevalence of neutralizing anti-SARS-CoV-2 antibodies in vaccinated HCWs at the Mohamed VI University Hospital in Marrakech and to determine the parameters that can influence immune response.MethodsA cross-sectional study of 138 HCWs was performed between October and December 2021 by measuring IgG antibodies directed against the spike antigen of SARS-CoV-2 using an Abbott Architect® SARS-CoV-2 IgG II assay.ResultsThe mean age was 31.42 years, the sex ratio was 2.94 women to each man, and the overall prevalence was 97%. We found 39.5% of the participants had experienced COVID-19 infections pre-vaccination, which decreased to 26.8% after vaccination. Neutralizing antibody titers were dependent on the type of vaccine: they were higher with the Pfizer-BioNTech vaccine, the number of doses (p < .001), and post-vaccine COVID-19 form. The post-vaccine COVID-19 infection rates were lower with the Sinopharm vaccine.ConclusionHeterologous vaccination with non-mRNA and mRNA vaccines and the consideration of post-vaccination COVID-19 infection as a booster could help optimize vaccine results while reducing potential side effects.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-10T06:09:06Z
      DOI: 10.1177/03946320221133697
      Issue No: Vol. 36 (2022)
  • Omicron variant of SARS-CoV-2 infection elicits cross-protective immunity
           in people who received boosters or infected with variant strains

    • Authors: Selia Chowdhury, Md. Shahraj Chowdhury, Nurjahan Shipa Chowdhury, Samia Chowdhury, Shajeda Chowdhury
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionThe B.1.1.529 (Omicron) variant of SARS-CoV-2 is the most antigenically unique SARS-CoV-2 variant of concern to date, which is currently widespread across the world. Omicron variant and its sublineages contain a plethora of mutations than other variants of concern, which increases their transmissibility and virulence. Concerns regarding potential immunological evasion have been reignited by emerging subvariants of the Omicron variant. Determining the effectiveness of Omicron-induced immunity and whether it is cross-protective against other variants is a crucial aspect of the research. MethodA systematic search of relevant articles until September 25, 2022, from databases such as PubMed, Scopus, Google Scholar, and ScienceDirect was done independently by two authors. A total of 11 articles discussing about immunological evasion of different Omicron subvariants were included in the study. ResultsNumerous studies have demonstrated that Omicron variant causes a restricted immune response after infection. Omicron infection boosts preexisting vaccine-induced immunity, but it may not be enough to establish widespread, cross-neutralizing humoral immunity in unvaccinated people. ConclusionDue to co-circulation and the emergence of novel SARS-CoV-2 variants, findings highlight the importance of booster vaccinations for immune protection. More studies should focus on the efficacy of Omicron-induced immunity, its cross-protective properties against other variants, and development of a universal vaccine.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-10T05:58:12Z
      DOI: 10.1177/03946320221133001
      Issue No: Vol. 36 (2022)
  • The protective mechanism of salidroside modulating miR-199a-5p/TNFAIP8L2
           on lipopolysaccharide-induced MLE-12 cells

    • Authors: Yang Tan, Yong-fan Zou, Huang-bo Zhang, Xu Liu, Chuan-yun Qian, Ming-Wei Liu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesSalidroside is used for treating inflammation-based diseases; however, its molecular mechanism is unclear. In this study, we determined the protective role of salidroside on the endotoxin-induced damage caused to the mouse alveolar epithelial type II (MLE-12) cells and its underlying mechanism.MethodsAn in vitro model for acute lung injury was constructed by inducing the MLE-12 cells using lipopolysaccharide (lipopolysaccharides, 1 mg/L). Then, The MTT assay was conducted to assess the survival rate of the MLE-12 cells in the different groups. After the treatment, apoptosis of MLE-12 cells was determined, and the mRNA and protein expression of miR-199a-5p, HMGB1, NF-kB65, TNFAIP8L2, p-IkB-α, and TLR4 was estimated by Western Blotting and RT-PCR. ELISA was also used to measure the concentration of inflammatory cytokine molecules IL-1β, IL-6, TNF-α, and IL-18 in the cell-free supernatant. Lastly, cell morphology was examined using the AO/EB technique.ResultsWe showed that salidroside reduced the protein and gene expression of HMGB1, NF-kB65, miR-199a-5p, p-IkB-α, and TLR4, whereas it increased the gene and protein expression of TNFAIP8L2. Furthermore, it decreased the concentrations of cytokine molecules like IL-1β, IL-6, TNF-α, and IL-18 in the cell-free supernatant. MLE-12 also showed a lower apoptosis rate, higher survival rate, and better cell morphology.ConclusionSalidroside significantly inhibited the LPS-induced MLE-12 cell damage. Our results suggest that this could be by reducing miR-199a-5p and enhancing TNFAIP8L2 expression.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-10T05:45:45Z
      DOI: 10.1177/03946320221132712
      Issue No: Vol. 36 (2022)
  • Syk promotes phagocytosis by inducing reactive oxygen species generation
           and suppressing SOCS1 in macrophage-mediated inflammatory responses

    • Authors: Young-Su Yi, Han Gyung Kim, Ji Hye Kim, Woo Seok Yang, Eunji Kim, Jae Gwang Park, Nur Aziz, Narayanan Parameswaran, Jae Youl Cho
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectiveInflammation, a vital innate immune response against infection and injury, is mediated by macrophages. Spleen tyrosine kinase (Syk) regulates inflammatory responses in macrophages; however, its role and underlying mechanisms are uncertain.Materials and MethodsIn this study, overexpression and knockout (KO) cell preparations, phagocytosis analysis, confocal microscopy, reactive oxygen species (ROS) determination, mRNA analysis, and immunoprecipitation/western blotting analyses were used to investigate the role of Syk in phagocytosis and its underlying mechanisms in macrophages during inflammatory responses.ResultsSyk inhibition by Syk KO, Syk-specific small interfering RNA (siSyk), and a selective Syk inhibitor (piceatannol) significantly reduced the phagocytic activity of RAW264.7 cells. Syk inhibition also decreased cytochrome c generation by inhibiting ROS-generating enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and ROS scavenging suppressed the phagocytic activity of RAW264.7 cells. LPS induced the tyrosine nitration (N-Tyr) of suppressor of cytokine signaling 1 (SOCS1) through Syk-induced ROS generation in RAW264.7 cells. On the other hand, ROS scavenging suppressed the N-Tyr of SOCS1 and phagocytosis. Moreover, SOCS1 overexpression decreased phagocytic activity, and SOCS1 inhibition increased the phagocytic activity of RAW264.7 cells.ConclusionThese results suggest that Syk plays a critical role in the phagocytic activity of macrophages by inducing ROS generation and suppressing SOCS1 through SOCS1 nitration during inflammatory responses.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-08T01:24:14Z
      DOI: 10.1177/03946320221133018
      Issue No: Vol. 36 (2022)
  • COVID-19 diversity: A case of multisystem inflammatory syndrome in
           children masquerading as juvenile systemic lupus erythematosus

    • Authors: Ali Sobh, Madiha abdalla, Ashraf M Abdelrahman, Doaa Mosad Mosa
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some systemic lupus erythematosus (SLE) manifestations intermingled with Kawasaki disease features. These emerging presentations were dubbed under the umbrella term ‘multisystem inflammatory syndrome in children (MIS-C)’. A one and half-year-old girl, admitted to Mansoura University Children’s Hospital (MUCH) with fever, bad general condition, vomiting, widespread maculopapular, vasculitic rash, hands and feet oedema, oral ulceration, arthralgia and lymphadenopathy. Moreover, bicytopenia, positive antinuclear, anti–double-stranded DNA antibodies and low C3 qualified her as a case of juvenile SLE. Despite the child received the initial therapy of immunosuppressive medication, her general condition deteriorated with fever persistence and rash exacerbation. At that time, the skin of her hands and feet started to peel. Thus, an expanded study for other alternatives was obligatory; SARS-CoV-2 infection testing revealed positive IgG serology, and retesting for lupus autoantibodies turned negative. HRCT chest showed bilateral basal consolidation with ground-glass appearance. Furthermore, Echo exhibited coronary artery dilation with thrombus inside. This evolution raised the concern for COVID-related MIS-C syndrome. This report provides a model of COVID-19 heterogeneity with protean immune-related manifestations. This case has a unique presentation that necessities its description, in order to provide a nidus for future studies in this new entity.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-07T05:35:33Z
      DOI: 10.1177/03946320221131981
      Issue No: Vol. 36 (2022)
  • Network pharmacology and bioinformatics analyses identify the intersection
           genes and mechanism of Huang Bai for recurrent aphthous stomatitis

    • Authors: Lulu Tang, ling Huang, yingtao Lai
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Recurrent aphthous stomatitis (RAS) are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. However, there is still no effective treatment method for RAS without side effects. Traditionally, Cortex Phellodendri known as “Huang Bai” was used to treat RAS for antibacterial and anti-inflammatory properties in China. Network pharmacology methods and bioinformatics analysis were utilized to search and fish incorporating target. Network analysis and silico validation were used to discover the pharmacological mechanisms of “Huang Bai” for the treatment of RAS. A total of 25 active ingredients in HB, 200 drug targets, and 578 differentially expressed genes (DEGs) between Recurrent aphthous stomatitis and normal samples were obtained. The Gene Ontology enrichment analysis revealed that the immune response was the most significantly enriched term within the DEGs. The KEGG pathway analysis identified 60 significant pathways, most of which involved in the inhibition of inflammation and regulation of immunological response. The functions are dependent on a multi-pathway, particularly the TNF signaling pathway and the HIF-1 signaling pathway. We identified six hub genes in the PPI network, most of which were validated as highly expressed in oral ulcers by DiseaseMeth databases. In addition, molecular docking displayed that the primary molecule combined well with the key targets. “Huang Bai” contains potential anti-RAS active compounds. This study reflects the multi-component multi-target multi-pathway action characteristics of “Huang Bai.” Our study provides potential biomarkers or treatment targets for further research.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-10-01T08:47:20Z
      DOI: 10.1177/03946320221129134
      Issue No: Vol. 36 (2022)
  • The mechanism of radiotherapy for lung adenocarcinoma in promoting protein
           SIRT6-mediated deacetylation of RBBP8 to enhance the sensitivity of
           targeted therapy

    • Authors: Jiying Wang, Zhaoying Sheng, Zhiyi Dong, Qiongya Wu, Yong Cai
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundLung cancer has the fastest increase in morbidity and mortality, and is one of the most threatening malignant tumors to human health and life. Both radiotherapy and targeted therapy are typical treatments after lung cancer surgery. Radiotherapy is a means of locally killing cancer lesions, and it plays an important role in the entire management of lung cancer. Gefitinib is one of the most commonly used targeted therapy drugs in the treatment of lung cancer. The purpose of this project is to explore the mechanism by which deacetylation of RBBP8 mediated by radiotherapy-promoting protein SIRT6 in lung adenocarcinoma enhances the sensitivity of targeted therapy.MethodsIn both the cell experiments and the animal experiments, the samples were divided into five groups: Model group, RT group, CT group, RT+CT group, and RT+CT+inhibitor group. The CCK8 method was used to detect the viability of each group of cells. The flow cytometry experiment was used to analyze the apoptotic characteristics of each group of cells. The scratch test was used to detect the migration ability of each group of cells. Transwell invasion test was used to determine the invasion ability of each group of cells. The lung tumor tissues of each group of mice were collected to analyze the tumor size, volume, and metastasis characteristics. The TUNEL experiment was used to detect the apoptosis characteristics of the cells in the lung cancer tissues of each group mice. Immunohistochemistry experiments were used to analyze the distribution and relative expression characteristics of protein SIRT6 in mouse lung cancer tissues. The colorimetric experiments were used to detect the activity of Caspase 3 and Caspase 8 in each group. Western blot method was used to detect the expression of SIRT6, RBBP8, and MYC in each group.ResultsIn each experiment, the results of the experiment have mutually proven consistency, and there is no contradiction. In addition to the Model group, the other 4 groups used different treatment methods. The better the curative effect, the lower the cell viability of cancer cells and the higher the apoptotic ratio. This is reflected in the CCK8 test, flow cytometry analysis, cell scratch test, Transwell cell migration test, and TUNEL detection. At the same time, colorimetric detection and Western blot analysis also analyzed the levels of SIRT6, RBBP8 and other cancer-related proteins in each group at the molecular level, implying the importance of SIRT6 protein in the treatment process.ConclusionOur project has proved that radiotherapy can promote the protein SIRT6 to deacetylate RBBP8 proteins, and ultimately enhance targeted therapy drug sensitivity.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-09-29T08:21:55Z
      DOI: 10.1177/03946320221130727
      Issue No: Vol. 36 (2022)
  • Multiple sites of thrombosis without thrombocytopenia after a second dose
           of Pfizer-BioNTech COVID-19 vaccine

    • Authors: Roberto Scendoni, Cristina Petrelli, Mauro Giustozzi, Francesco O Logullo
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      In the current international scientific panorama, rare cases of venous thrombotic complications following mRNA vaccine administration have been reported, consisting mainly of cerebral sinus thromboses and acute venous thromboembolism. The present paper describes the case of a 75-year-old woman in good health who developed cerebral venous thrombosis, deep venous thrombosis, and bilateral pulmonary emboli after receiving a second dose of Pfizer-BioNTech COVID-19 vaccine. A series of laboratory tests performed during hospitalization yielded interesting results, allowing us to exclude thrombophilic risk factors and to certify the absence of thrombocytopenia in the patient. Although COVID-19 vaccination is the most important tool in stopping the pandemic, pharmacovigilance is crucial for detecting potential multisystem thrombotic events, even for mRNA vaccines.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-09-20T04:54:27Z
      DOI: 10.1177/03946320221128534
      Issue No: Vol. 36 (2022)
  • The Yin and Yang dualistic features of autophagy in thermal burn wound

    • Authors: Alexandra Ripszky Totan, Maria Greabu, Iulia-Ioana Stanescu-Spinu, Marina Imre, Tudor-Claudiu Spinu, Daniela Miricescu, Radu Ilinca, Elena Claudia Coculescu, Silviu Constantin Badoiu, Bogdan-Ioan Coculescu, Crenguta Albu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Burn healing should be regarded as a dynamic process consisting of two main, interrelated phases: (a) the inflammatory phase when neutrophils and monocytes infiltrate the injury site, through localized vasodilation and fluid extravasation, and (b) the proliferative-remodeling phase, which represents a key event in wound healing. In the skin, both canonical autophagy (induced by starvation, oxidative stress, and environmental aggressions) and non-canonical or selective autophagy have evolved to play a discrete, but, essential, “housekeeping” role, for homeostasis, immune tolerance, and survival. Experimental data supporting the pro-survival roles of autophagy, highlighting its Yang, luminous and positive feature of this complex but insufficient explored molecular pathway, have been reported. Autophagic cell death describes an “excessive” degradation of important cellular components that are necessary for normal cell function. This deadly molecular mechanism brings to light the darker, concealed, Yin feature of autophagy. Autophagy seems to perform dual, conflicting roles in the angiogenesis context, revealing once again, its Yin–Yang features. Autophagy with its Yin–Yang features remains the shadow player, able to decide quietly whether the cell survives or dies.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-09-19T02:57:48Z
      DOI: 10.1177/03946320221125090
      Issue No: Vol. 36 (2022)
  • Coexpression of lymphocyte-activation gene 3 and programmed death ligand-1
           in tumor infiltrating immune cells predicts worse outcome in renal cell

    • Authors: Chan Ho Lee, Soo Jin Jung, Won Ik Seo, Jae Il Chung, Dae Sim Lee, Dae Hoon Jeong, Youkyoung Jeon, Inhak Choi
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesLymphocyte-activation gene 3 (LAG-3) represents a potential immune checkpoint target for cancer treatment. We investigated LAG-3 expression and its prognostic value in patients with surgically treated clear cell renal cell carcinoma (RCC) and correlated LAG-3 expression with programmed cell death ligand 1(PD-L1).MethodsWe evaluated LAG-3 and PD-L1 expression using immunohistochemistry on tissue microarrays incorporating 134 primary excision specimens of clear cell RCC (ccRCC). The patients were analyzed as two groups: the whole cohort and those with metastatic RCC (mRCC). The cancer genome atlas (TCGA) data analysis of LAG-3 was done through UALCAN web servers.ResultsUsing the UALCAN cancer transcriptional data analysis, we found that LAG-3 was overexpressed in ccRCC. LAG-3 expression was significantly correlated with PD-L1 expression in the whole cohort and in the mRCC group (all, p < 0.05). Both LAG-3⁺ RCC and PD-L1⁺ RCC presented with a higher TNM stage and higher Fuhrman nuclear grade (all, p < 0.05). PD-L1⁺/LAG-3⁺ RCC and PD-L1⁻/LAG-3⁺ RCC showed poorer cancer-specific survival (CSS) than PD-L1⁻/LAG-3⁻ RCC (all, p = 0.01). Similarly, PD-L1⁺/LAG-3⁺ mRCC and PD-L1⁻/LAG-3⁺ mRCC showed poorer CSS than PD-L1⁻/LAG-3⁻ mRCC (all, p < 0.05). Multivariate analysis showed that PD-L1⁺/LAG-3⁺ mRCC (hazard ratio: 3.19; 95% CI: 0.77–13.67; p = 0.033) was a predictor of poor CSS.ConclusionBoth LAG-3⁺ and PD-L1⁺ RCC have adverse pathological features, and their coexpression predicts worse clinical outcomes. Our findings suggest LAG-3 blockade in combination with programmed cell death 1/PD-L1 blockade as a potential therapeutic approach for RCC.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-09-09T05:41:14Z
      DOI: 10.1177/03946320221125588
      Issue No: Vol. 36 (2022)
  • Various phenotypes of LRBA gene with compound heterozygous variation: A
           case series report of pediatric cytopenia patients

    • Authors: Jiafeng Yao, Hao Gu, Wenjun Mou, Zhenping Chen, Jie Ma, Honghao Ma, Nan Li, Rui Zhang, Tianyou Wang, Jin Jiang, Runhui Wu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objective:LPS-responsive beige-like anchor (LRBA) deficiency is one of the most common monogenic disorders causing common variable immunodeficiency (CVID) and CVID-like disorders. However, the clinical spectrum of compound heterozygous (CHZ) LRBA variation should be extended. In this study, we presented five cases of compound heterozygous LRBA with various refractory cytopenias.Materials and Methods:Retrospective analysis of the clinical manifestations, management, and outcomes of five cases (from five pedigrees) with LRBA gene CHZ variants which initially manifested as single/multilineage immune cytopenias was performed. Results: 1. Gene variations: All five patients inherited the compound heterozygous LRBA variations from their parents which were thought to be pathogenic. BEACH, DUF4704, and LamG were the main affected domains of LRBA gene in this case series. 2. Immune dysregulation of clinic: (1) Hypogammaglobulinemia were recorded in four patients, and the proportion of Treg was decreased in two patients. Only one patient had been with increased TCRαβ+CD4/CD8 double-negative T cells (DNT). (2) Lymphoproliferative manifestations were seen in three patients. (3) All five patients were complained with cytopenia, although they showed different clinical manifestations. None of the parents was asymptomatic. (4) Other immune disorders: P5 also had relapsed infections and autoimmune endocrinopathy. 3. Management and outcomes: P1 and P5 responded well to immunomodulatory therapy and P3 was effectively treated with hemophagocytic lymphohistiocytosis (HLH) first-line regimen chemotherapy. P4 showed no responses to steroids and IVIG. However, TPO-R agonist was effective.Conclusion:Unlike homozygous mutations, compound heterozygous LRBA variation should always be kept in mind for the various phenotypes and different treatment responses.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-09-08T04:35:54Z
      DOI: 10.1177/03946320221125591
      Issue No: Vol. 36 (2022)
  • Erratum

    • Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.

      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-09-08T02:26:44Z
      DOI: 10.1177/03946320221121036
      Issue No: Vol. 36 (2022)
  • A new indicator: The diagnostic value of CD8+T/B lymphocyte ratio in
           sepsis progression

    • Authors: Yizhi Peng, Xiaofan Wang, Sheng Yin, Min Wang
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectiveTo reveal the value of single lymphocyte subpopulation and their ratios in the progression of sepsis.MethodsFrom January 2019 to March 2021, 39 sepsis patients, 16 septic shock patients, and 50 healthy volunteers were recruited in the Second Xiangya Hospital for this cross-sectional study. The absolute quantitation of CD4+T, CD8+T, B lymphocytes, and NK cells in peripheral blood were determined by flow cytometry. SPSS Software was used to analyze the results.ResultsOn the whole, the numbers of lymphocytes in the sepsis group and in the septic shock group were lower than that in the healthy control group. Surprisingly, the percentage of CD8+T lymphocytes in the septic shock group was slightly higher than that in the sepsis group. The percentage of B lymphocytes in the sepsis group was higher than that in the healthy control group. The AUC of CD8+T/B was 0.724, with the sensitivity and specificity being 75.00% and 71.79%, respectively.ConclusionThe immune expression pattern of patients with sepsis was not a simple decrease in the number of lymphocytes. The change in the ratios of lymphocyte subpopulation might be more meaningful along the development and progression of sepsis. The ratio of CD8+T/B could be used to diagnose the progression of sepsis and reduce the misdiagnosis rate to a certain extent.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-08-28T12:53:58Z
      DOI: 10.1177/03946320221123164
      Issue No: Vol. 36 (2022)
  • Coexistence of anti-topoisomerase I and anticentromere antibodies in a
           patient with systemic sclerosis. Efficacy of treatment combining rituximab
           and nintedanib. A case report

    • Authors: Lydia Montolio-Chiva, Diego Carmona-Talavera, Jose M López-Ortega, Ana V Orenes-Vera, Eduardo Flores-Fernández, Juan J Alegre-Sancho
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      In the diagnostic of systemic sclerosis (SSc), both anti-centromere (ACA) and anti-topoisomerase I (ATA) antibodies are considered mutually exclusive, though their coexistence has been also reported in some patients. Notably, nintedanib has been approved for the treatment of interstitial lung disease associated to SSc. Herein, we present the clinical case of a 41-year-old woman with SSc who shows an immunological seroconversion (from ACA positivity to a coexistence of ACA and ATA antibodies) together with changes in her clinical phenotype. Besides, the patient responds positively to the treatment of her lung involvement with a combination of immunomodulators and antifibrotic agents.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-08-19T02:30:33Z
      DOI: 10.1177/03946320221115310
      Issue No: Vol. 36 (2022)
  • Small cell lung cancer with relapsing polychondritis: A report of one case
           and the review of literature

    • Authors: Yuan Liu, Ning Wang, Jian Xu, Ying Bi, Xue Han, Meng Dai, Chunfang Liu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      The present study reports the clinical data of a patient with small cell lung cancer who developed relapsing polychondritis. We report a case of a 57-year-old female presented with cough, expectoration, and fever. A Computed Tomography (CT) scan performed at the hospital revealed diffuse thickening of bronchial walls in both lungs. Bronchoscopy revealed that the tracheal mucosa was thickened, narrowed, and collapsed, and the bronchoscope could pass through. The bronchial mucosa on both sides was thickened and edematous, the surface was rough, each bronchus was narrow, and the intervertebral ridges were widened. Needle biopsy: considering small cell carcinoma in combination with immunohistochemical results. Her symptom was not improved after anti-infective therapy. The left auricle was red and swollen, the auricle collapsed, and the left eye had subconjunctival hemorrhage during her hospitalization without obvious cause. After multidisciplinary consultation, pulmonary small cell lung cancer cT0N2Mx rumen lymph node metastasis and RP were considered. Treatment: Prednisone, orally for RP. Chemotherapy combined with radiotherapy was given for small cell lung cancer. The chemotherapy regimen was carboplatin combined with etoposide. The patient has already been followed for 1 year after receiving chemoradiotherapy; the condition of the patient is stable at present. Based on the case of our patient, for cases of RP with symptoms such as auricle chondritis, ocular inflammatory disease, and nasal chondritis, we should pay great attention to whether the case is caused by lung cancer with relapsing polychondritis. Because of the rarity of the disease, the clinician should improve the recognition of the disease in order to strive for early diagnosis and therapy.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-08-14T12:27:59Z
      DOI: 10.1177/03946320221120962
      Issue No: Vol. 36 (2022)
  • Biomarkers of inflammation and left ventricular remodelling in psoriasis
           patients treated with infliximab

    • Authors: Helga Midtbø, Ester Kringeland, Eva Gerdts, Per Magne Ueland, Klaus Meyer, Anja Linde, Arve Ulvik, Roland Jonsson, Kåre Steinar Tveit
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objective: Psoriasis is an immune mediated disorder associated with T cell activation and cardiovascular disease (CVD). We explored the association of inflammation with left ventricular (LV) remodelling in psoriasis patients receiving treatment with the tumour necrosis factor-α (TNF-α) blocker infliximab. Methods: Psoriasis patients (n = 47, age 47 ± 14 years, 66% men) and 99 control subjects without psoriasis (age 47 ± 11 years, 72% men) were examined by echocardiography in a cross-sectional study. LV remodelling was assessed by LV mass index for height in the allometric power of 2.7. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), neopterin, kynurenine:tryptophan ratio (KTR) and the pyridoxic acid ratio (PAr) index were measured. Results: Serum concentration of neopterin (p = .007) was higher in psoriasis patients, while the other inflammatory biomarkers had similar levels. LV mass index was lower in patients than controls (35.6 ± 9.6 g/m2.7 vs. 40.3 ± 9.8 g/m2.7, p = .008). In the total study population, serum SAA (β = 0.18, p = .02), KTR (β = 0.20, p = .02) and the PAr index (β = 0.26, p = .002) were all associated with higher LV mass index independent of age, sex, body mass index, hypertension, smoking, renal function and psoriasis. Also in psoriasis patients, higher SAA level (β = 0.34, p = .02), KTR (β = 0.32, p = .02) and the PAr index (β = 0.29, p = .05) were associated with higher LV mass index independent of body mass index, hypertension and diabetes. Conclusion: Higher levels of the inflammatory biomarkers SAA, KTR and the PAr index were associated with greater LV mass index in psoriasis patients, indicating a role of chronic inflammation in LV remodelling evident even during treatment with TNF-α blockers.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-08-13T02:17:34Z
      DOI: 10.1177/03946320221111131
      Issue No: Vol. 36 (2022)
  • Identification of heterogeneous subsets of aortic
           interleukin-17A-expressing CD4+ T cells in atherosclerotic mice

    • Authors: Guizhen Lin, Lei Zhang, Zheng Yan, Wei Jiang, Beibei Wu, Dongsheng Li, Xiaofang Xiong
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives: T helper 17 (Th17) cells are involved in the inflammatory response of atherosclerosis. However, their heterogeneity in the atherosclerotic aorta remains elusive. This study was designed to identify aortic Th17 subsets. Methods: The surface markers and transcription factors of aortic interleukin-17A (IL-17A)-expressing T cells were determined by flow cytometry in an ApoE-deficient mouse atherosclerotic model. Viable aortic IL-17A-expressing T cell subsets were isolated by flow cytometry on the basis of surface markers, followed by characterizing their transcription factors by either flow cytometry or real-time RT-PCR. The effect of aortic IL-17A-expressing T cell subsets on aortic endothelial cells was determined in vitro. Results: C-X-C Motif Chemokine Receptor 3 (CXCR3), interleukin-17 receptor E (IL-17RE), CD200, and C-C Motif Chemokine Receptor 4 (CCR4) marked three subsets of aortic IL-17A-expressing T cells: CXCR3+IL-17RElowCD200+CCR4- T cells expressing T-box protein expressed in T cells (T-bet) and interferon-gamma (IFN-γ), CXCR3+IL-17RElowCD200+CCR4+ T cells expressing T-bet but fewer IFN-γ, and CXCR3−IL-17REhighCD200+CCR4+ T cells expressing very low T-bet and no IFN-γ. Based on these markers, viable aortic Th17 cells, Th17.1 cells, and transitional Th17.1 cells were identified. Both Th17.1 cells and transitional Th17.1 cells were more proliferative than Th17 cells. Compared with Th17 cells, Th17.1 cells plus transitional Th17.1 cells induced higher expression of C-X-C motif chemokine ligand 1 (CXCL1), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine 5 (CXCL5), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in aortic endothelial cells. Conclusion: IL-17A-expressing CD4+ T cells were heterogeneous in atherosclerotic aortas.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-08-06T06:31:21Z
      DOI: 10.1177/03946320221117933
      Issue No: Vol. 36 (2022)
  • Progesterone-induced blocking factor 1 and cytokine profile of follicular
           fluid of infertile women qualified to in vitro fertilization: The
           influence on fetus development and pregnancy outcome

    • Authors: Rafał Adamczak, Natalia Ukleja-Sokołowska, Kinga Lis, Zbigniew Bartuzi, Mariusz Dubiel
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Introduction: Progesterone is essential for both the initiation and the maintenance of pregnancy. The immunological effects of progesterone are mediated by the progesterone-induced blocking factor (PIBF), which is an immunomodulatory factor with anti-abortive properties. The aim of the research was to establish the cytokine profile and PIBF1 concentration in follicular fluid (FF) of patients undergoing in vitro fertilization (IVF).Methods: Seventy-eight patients who qualified for IVF underwent a detailed medical interview, including the course of fertility treatment and physical, gynecological, and cytological examinations. The concentration of PIBF1, IL-18, IL-2, IL-4, IL-6, IL-10, interferon-γ (IFN-γ), IL-1α, IL-1β, IL-5, IL-8, and IL-15 in FF during ovarian puncture was measured using commercially available ELISA kits.Results: IL-1 beta concentration was lower in the FF of patients with successful IVF. IL-8 concentration in FF correlated with the number of cumulus-oocyte complexes (COC-1), metaphase II (MII), and top-quality embryos. PIBF1 concentration had a positive correlation with the number of MII and top-quality embryos. IL-2 and IL-6 concentrations were positively correlated with the number of COC-1 and MII. An important parameter in assessing the chances of successful IVF is the number of top-quality embryos achieved.Conclusion: Higher PIBF1 concentration in FF may indicate a greater possibility of successful IVF due to the higher number of top-quality embryos. IL-1 beta concentration was found to be lower in the FF of patients with successful IVF. Therefore, PIBF1 and IL-1 beta in FF could be candidates for a marker of successful IVF.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-07-21T10:33:58Z
      DOI: 10.1177/03946320221111134
      Issue No: Vol. 36 (2022)
  • COVID-19: Clinical laboratory diagnosis and monitoring of novel
           coronavirus infected patients using molecular, serological and biochemical
           markers: A review

    • Authors: Ghulam Rasool, Muhammad Riaz, Mazhar Abbas, Hina Fatima, Muhammad Mustafa Qamar, Farzana Zafar, Zahed Mahmood
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      COVID-19, a novel coronavirus disease, has provoked a variety of health and safety concerns, and socioeconomic challenges around the globe. The laboratory diagnosis of SARS-CoV-2 was quickly established utilizing nucleic acid amplification techniques (NAAT) after the disease causing virus has been identified, and its genetic sequence has been determined. In addition to NAAT, serological tests based on antibodies testing against SARS-CoV-2 were introduced for diagnostic and epidemiologic studies. Other biochemical investigations include monitoring of peripheral blood cells count, platelets/lymphocyte ratio, coagulation profile, cardiac, and inflammatory markers such as cytokines storm are also crucial in combating COVID-19 pandemic. Further, accurate and reliable laboratory results for SARS-CoV-2 play very important role in the initiation of early treatment and timely management of COVID-19 patients, provide support in clinical decision-making process to control infection, and detection of asymptomatic cases. The Task Force on Coronavirus-19 constituted by International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has recognized informational framework for epidemiology, pathogenesis, and recommended the PCR-based analysis, serological and biochemical assays for analysis, monitoring, and management of disease. This literature review provides an overview of the currently used diagnostic techniques in clinical laboratories for the diagnosis, treatment monitoring, and management of COVID-19 patients. We concluded that each assays differ in their performance characteristics and the utilization of multiple techniques is necessary for the accurate diagnosis and management of SARS-CoV-2 infection.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-07-16T02:25:42Z
      DOI: 10.1177/03946320221115316
      Issue No: Vol. 36 (2022)
  • MUC1 expressing tumor growth was retarded after human mucin 1 (MUC1)
           plasmid DNA immunization

    • Authors: Hye-Youn Son, Hwan-Kyu Jeong, Vasso Apostolopoulos, Chul-Woo Kim
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionNaked DNA is one of the attractive tools for vaccination studies. We studied naked DNA vaccination against the human tumor antigen, mucin, which is encoded by the MUC1 gene.MethodsWe constructed the pcDNA3.0-MUC1 (pcDNA-MUC1) plasmid expressing an underglycosylated MUC1 protein. BALB/c mice were immunized intradermally thrice at 2-weeks intervals with pcDNA-MUC1. Two weeks after the last immunization, tumor challenge experiments were performed using either the CT26 or TA3HA tumor cell lines, both of which transduce human MUC1.ResultsImmune cell population monitoring from pcDNA-MUC1-immunized animals indicated that immune cell activation was induced by MUC1-specific immunization. Using intracellular fluorescence activated cell sorting and enzyme-linked immunosorbent spot assay, we reported that interferon-γ secreting CD8+ T cells were mainly involved in MUC1-specific immunization. In all mice immunized with MUC1 DNA, tumor growth inhibition was observed, whereas control mice developed tumors (p < 0.001).ConclusionOur results suggest that intradermal immunization with MUC1 DNA induces MUC1-specific CD8+ T cell infiltration into tumors, elicits tumor-specific Th1-type immune response, and inhibits tumor growth.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-07-15T06:16:11Z
      DOI: 10.1177/03946320221112358
      Issue No: Vol. 36 (2022)
  • Identification of potential biomarkers and immune infiltration
           characteristics in severe asthma

    • Authors: Yuanyuan Jiang, Shuanglinzi Deng, Xinyue Hu, Lisha Luo, Yingyu Zhang, Daimo Zhang, Xiaozhao Li, Juntao Feng
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives: We hope to identify key molecules that can be used as markers of asthma severity and investigate their correlation with immune cell infiltration in severe asthma. Methods: An asthma dataset was downloaded from the Gene Expression Omnibus database and then processed by R software to obtain differentially expressed genes (DEGs). First, multiple enrichment platforms were applied to analyze crucial biological processes and pathways and protein–protein interaction networks related to the DEGs. We next combined least absolute shrinkage and selection operator logistic regression and the support vector machine-recursive feature elimination algorithms to screen diagnostic markers of severe asthma. Then, a local cohort consisting of 40 asthmatic subjects (24 with moderate asthma and 16 with severe asthma) was used for biomarker validation. Finally, infiltration of immune cells in asthma bronchoalveolar lavage fluid and their correlation with the screened markers was evaluated by CIBERSORT. Results: A total of 97 DEGs were identified in this study. Most of these genes are enriched in T cell activation and immune response in the asthma biological process. CC-chemokine receptor 7 (CCR7) and natural killer cell protein 7(NKG7) were identified as markers of severe asthma. The highest area under the ROC curve (AUC) was from a new indicator combining CCR7 and NKG7 (AUC = 0.851, adj. p < 0.05). Resting and activated memory CD4 T cells, activated NK cells, and CD8 T cells were found to be significantly higher in the severe asthma group (adj. p < 0.01). CCR7 and NKG7 were significantly correlated with these infiltrated cells that showed differences between the two groups. In addition, CCR7 was found to be significantly positively correlated with eosinophils (r = 0.38, adj. p < 0.05) infiltrated in bronchoalveolar lavage fluid. Conclusion: CCR7 and NKG7 might be used as potential markers for asthma severity, and their expression may be associated with differences in immune cell infiltration in the moderate and severe asthma groups.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-07-12T12:51:21Z
      DOI: 10.1177/03946320221114194
      Issue No: Vol. 36 (2022)
  • Evaluation of the wound healing effect of neomycin-silver nano-composite
           gel in rats

    • Authors: Ahmed Hossni El Banna, Fady Sayed Youssef, Hisham Youssef Elzorba, Ahmed M. Soliman, Gehad Genidy Mohamed, Sameh Hamed Ismail, Mohamed Refaat Mousa, Hossny Awad Elbanna, Afaf Sayed Osman
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives: Both nano silver and neomycin have wound healing properties. Silver nanoparticles have been used as main compounds for therapeutic drug delivery systems against various ailments. The present study aimed to prepare a neomycin silver nano-composite gel easily, rapidly, and cheaply method to improve wound healing. Methods: Forty-five Wistar rats (150–200 g) divided into nine groups: wound untreated, wound fusidic acid treated, wound neomycin treated, three groups with wound and neomycin silver nano-composite gel at 1:1, 1:2, and 1:3 concentrations, respectively, and three groups wound treated silver nano gel at the previous concentrations, respectively. Percentages of wound healing and histopathological examination of the wound area were assessed in all groups. Results: Atomic force microscopy (AFM) and transmission electron microscopy (TEM) images demonstrated the spherical shape of neomycin silver nano-composite gel without aggregation but homogenous dispersion in a gel matrix. Dynamic light scattering (DLS) showed a 4 nm size of nano silver, which agrees with AFM image data analysis but not with TEM image due to the good coating of the gel matrix to silver nanoparticles. Dynamic light scattering Zeta potential was −21 mV, illustrating the high bioactivity of the neomycin silver nano-composite. The groups receiving neomycin silver nano-composite gel showed a significantly higher and dose dependent wound healing compared to other treatment groups. Conclusion: The present work confirmed the potential wound healing activity of neomycin silver nano-composite gel compared to either alone.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-07-11T05:07:41Z
      DOI: 10.1177/03946320221113486
      Issue No: Vol. 36 (2022)
  • Purpurin suppresses atopic dermatitis via TNF-α/IFN-γ-induced
           inflammation in HaCaT cells

    • Authors: Jae-Hoon Oh, Seung-Ho Kim, Ok-Kyoung Kwon, Jung-Hee Kim, Sei-Ryang Oh, Sang-Bae Han, Ji-Won Park, Kyung-Seop Ahn
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectiveWe investigated whether purpurin inhibits various pathways of inflammation leading to atopic dermatitis.Introduction1,2,4-Trihydroxyanthraquinone, commonly called purpurin, is an anthraquinone that is a naturally occurring red/yellow dye. Purpurin is a highly antioxidative anthraquinone and previous studies have reported antibacterial, anti-tumor, and anti-oxidation activities in cells and animals. However, the skin inflammatory inhibition activity mechanism study of purpurin has not been elucidated in vitro.MethodsIn this study, we investigated the anti-inflammatory activity of purpurin in HaCaT (human keratinocyte) cell lines stimulated with a mixture of tumor necrosis factor-alpha (TNF-α)/Interferon-gamma (IFN-γ). The inhibitory effect of Purpurin on cytokines (IL-6, IL-8, and IL-1β) and chemokine (TARC, MDC, and RANTES) was confirmed by ELISA and RT-qPCR. We investigated each signaling pathway and the action of inhibitors through western blots.ResultsThe expression levels of cytokines and chemokines were dose-dependently suppressed by purpurin treatment in TNF-α/IFN-γ-induced HaCaT cells from ELISA and real-time PCR. Purpurin also inhibited protein kinase B (AKT), mitogen-activated protein kinase (MAPKs), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) activation in TNF-α/IFN-γ-stimulated HaCaT cells. Additionally, there was a synergistic effect when purpurin and inhibitor were applied together, and inflammation was dramatically reduced.ConclusionTherefore, these results demonstrate that purpurin exhibits anti-inflammatory and anti-atopic dermatitis activity in HaCaT cells.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-07-07T05:49:32Z
      DOI: 10.1177/03946320221111135
      Issue No: Vol. 36 (2022)
  • A network pharmacology approach to explore and validate the potential
           targets of ginsenoside on osteoporosis

    • Authors: Ling Guo, Qingliu Zhen, Xiaoyue Zhen, Zhaoyang Cui, Chao Jiang, Qiang Zhang, Kun Gao, Deheng Luan, Xuanchen Zhou
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Background: Osteoporosis (OP) is determined as a chronic systemic bone disorder to increase the susceptibility to fracture. Ginsenosides have been found the anti-osteoporotic activity of in vivo and in vitro. However, its mechanism remains unknown.Methods: The potential mechanism of ginsenosides in anti-osteoporotic activity was identified by using network phamacology analysis. The active compounds of ginsenosides and their targets associated to OP were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Drug Bank, Pharmmapper, and Cytoscape. The Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis target genes were performed in String, Phenopedia, DisGeNET database, and Metascape software. The protein to protein interaction were created by String database and Cytoscape software. The molecular docking was used to investigate the interactions between active coumpounds and potential targets by utilizing SwissDock tool, UCSF Chimera, and Pymol software. Results: A total of eight important active ingredients and 17 potential targets related to OP treatment were subjected to analyze. GO analysis showed the anti-osteoporosis targets of ginsenoside mainly play a role in the response to steroid hormone. KEGG enrichment analysis indicated that ginsenoside treats OP by osteoblast differentiation signal pathway. Lastly, the molecular docking outcomes indicated that ginsenoside rh2 had a good binding ability with four target proteins IL1B, TNF, IFNG, and NFKBIA. Conclusion: IL1B, TNF, IFNG, and NFKBIA are the most important targets and osteoblast differentiation is the most valuable signaling pathways in ginsenoside for the treatment of OP, which might be beneficial to elucidate the mechanism concerned to the action of ginsenoside and might supply a better understanding of its anti-OP effects.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-07-06T05:00:02Z
      DOI: 10.1177/03946320221107239
      Issue No: Vol. 36 (2022)
  • Preventative effects of antioxidants on changes in sebocytes, outer root
           sheath cells, and Cutibacterium acnes-pretreated mice by particulate
           matter: No significant difference among antioxidants

    • Authors: Mi Hee Kwack, Dae-Lyong Ha, Weon Ju Lee
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesParticulate matter (PM) is an air pollutant that can damage human skin; antioxidants have shown some efficacy in alleviating PM-induced skin inflammation. We investigated the antioxidant effects of punicalagin, epigallocatechin-3-gallate (EGCG), and resveratrol on PM-induced changes in cultured human sebocytes, outer root sheath (ORS) cells, and Cutibacterium acnes-pretreated mice.MethodsSebocytes and ORS cells were cultured with 100 μg/mL PM10 and 5 μM punicalagin, 1 μM EGCG, or 1 μM resveratrol for 24 h. In C. acnes-pretreated mice, inflammatory nodules were treated with 100 μg/mL PM10 and 5 μM punicalagin, 1 μM EGCG, or 1 μM resveratrol. Cell viability was measured using an MTT assay. Antioxidant effects were analyzed according to RNA expression, using real-time PCR, as well as reactive oxygen species (ROS) and sebum measurements.ResultsAntioxidants inhibited the upregulation of inflammatory cytokines, matrix metalloproteinase, aryl hydrocarbon receptor, and NF-kB as well as the production of ROS induced by PM10 in cultured sebocytes and ORS cells. The preventative effects of punicalagin and EGCG on biomarker expression in cultured sebocytes and ORS cells were slightly greater than those of resveratrol, though the difference was not significant. In C. acnes-pretreated mice, the antioxidants inhibited inflammatory cytokine and matrix metalloproteinase expression as well as sebum production.ConclusionsAntioxidants effectively reduced the expression of inflammatory biomarkers and sebum production in cultured sebocytes, ORS cells, and C. acnes-pretreated mice.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-07-02T05:56:37Z
      DOI: 10.1177/03946320221112433
      Issue No: Vol. 36 (2022)
  • Mucin 5AC expression is common but unrelated to tumor progression in
           pancreatic adenocarcinoma

    • Authors: Sebastian Dwertmann Rico, Franziska Büscheck, David Dum, Andreas M Luebke, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Doris Höflmayer, Daniel Perez, Jakob R Izbicki, Michael Neipp, Hamid Mofid, Thies Daniels, Christoph Isbert, Christoph Fraune, Katharina Möller, Anne Menz, Christian Bernreuther, Patrick Lebok, Till Clauditz, Guido Sauter, Ria Uhlig, Waldemar Wilczak, Ronald Simon, Stefan Steurer, Eike Burandt, Andreas Marx, Till Krech
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Introduction: Mucin 5AC (MUC5AC) belongs to the family of secreted gel-forming mucins. It is physiologically expressed in some normal mucin producing epithelial cells but also in pancreatic, ovarian, and colon cancer cells. The role of MUC5AC expression in cancer is not fully understood. This study was designed to explore the role of MUC5AC for pancreatic cancer progression, its association to microsatellite instability, and its diagnostic utility. Methods: Mucin 5AC expression was studied immunohistochemically in a tissue microarray (TMA) from 532 pancreatic cancers, 61 cancers of the ampulla Vateri, six acinar cell carcinomas and 12 large sections of pancreatitis. Results: Mucin 5AC staining was interpretable in 476 of 599 (79%) arrayed cancers. Staining was completely absent in normal pancreas and pancreatitis, but frequent in pancreatic cancer. Membranous and cytoplasmic MUC5AC expression was most common in pancreatic adenocarcinomas (71% of 423), followed by carcinomas of the ampulla Vateri (43% of 47), and absent in six acinar cell carcinomas. Mucin 5AC expression was unrelated to tumor phenotype (tumor stage, tumor grade, lymph node, and distant metastasis), and microsatellite instability in ductal adenocarcinomas and carcinomas of the ampulla Vateri. Conclusion: Our study indicates that MUC5AC is an excellent biomarker for pancreatic cancer diagnosis, especially to support the sometimes-difficult diagnosis on small biopsies. Mucin 5AC expression is unrelated to pancreatic cancer aggressiveness.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-06-29T01:25:51Z
      DOI: 10.1177/03946320221106504
      Issue No: Vol. 36 (2022)
  • Formononetin regulates endothelial nitric oxide synthase to protect
           vascular endothelium in deep vein thrombosis rats

    • Authors: Zhongxiao Zhou, Haimeng Zhou, Xin Zou, Xiaowei Wang, Mengjun Yan
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectiveFormononetin is a bioactive isoflavone that has numerous medicinal benefits. We explored the feasibility and its mechanism of formononetin on treating acute deep vein thrombosis (DVT) in rats.Materials and methodsInferior vena cava (IVC) stenosis was performed to establish the DVT rat model. First, different doses of formononetin were used to observe the feasibility of formononetin on treating DVT. In sham and DVT groups, rats were orally treated with vehicle. In the remaining groups, formononetin (10 mg/kg, 20 mg/kg, and 40 mg/kg) was orally treated once a day for 7 days at 24 h after IVC. After 7 days, the levels of thrombosis and inflammation related factors in plasma were measured. The expression of endothelial nitric oxide synthase (eNOS) was analyzed by western blot and immunofluorescence. Molecular docking was used to evaluate the interaction between the formononetin and eNOS. Further, the NOS inhibitor (L-NAME) was used to explore the mechanism of formononetin for DVT.ResultAfter treatment with formononetin, the average weights of thrombosis were decreased, and the levels of thrombosis and inflammation related factors were also significantly decreased. Additionally, phosphorylation of eNOS was increased with the formononetin administration. There is a good activity of formononetin to eNOS (total score = −6.8). However, the effects of 40 mg/kg formononetin were concealed by the NOS inhibitor (L-NAME).ConclusionFormononetin reduces vascular endothelium injury induced by DVT through increasing eNOS in rats, which provides a potential drug for treatment of venous thrombosis.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-06-22T05:49:07Z
      DOI: 10.1177/03946320221111117
      Issue No: Vol. 36 (2022)
  • LINC01088 regulates the miR-95/LATS2 pathway through the ceRNA mechanism
           to inhibit the growth, invasion and migration of gastric cancer cells

    • Authors: Zhuan Wen, Yong Li, Bibo Tan, Zihao Chen, Qun Zhao, Ming Tan, Yijie Zhao, Yuxiang Xia, Liqiao FanΔ
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Background: In gastric cancer, a malignant condition with a dismal prognosis, long non-coding RNAs (LncRNAs) play a significant regulatory role. They often compete with microRNAs through the ceRNA mechanism to affect the expression of target mRNA. However, the specific clinical value and mechanism of action of LncRNA in gastric cancer are still unclear. Methods: This study detected the expression and clinical value of LINC01088 in gastric cancer tissues. Furthermore, the biological functions of LINC01088 and the regulation mechanism of the miR-95/LATS2 pathway were explored.Results: LINC01088 and LATS2 mRNA expression decreased, and miR-95 increased in gastric cancer tissues. LINC01088 has an excellent positive correlation with LATS2 mRNA, which may be a ceRNA pair; LINC01088 has binding sites with miR-95. Gene interference tests on gastric cancer cell lines revealed that LINC01088 could prevent gastric cancer cells from proliferating, invading, and migrating. The function of LINC01088 is achieved by regulating the miR-95/LATS2 pathway through the ceRNA mechanism.Conclusion: The results of this study show that LINC01088 expression is significantly reduced in gastric cancer tissues and cell lines. LINC01088 inhibits gastric cancer cells’ proliferation, invasion, and migration by regulating the miR-95/LATS2 pathway via the ceRNA mechanism.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-06-21T10:36:44Z
      DOI: 10.1177/03946320221108271
      Issue No: Vol. 36 (2022)
  • Activation of STAT6 by intranasal allergens correlated with the
           development of eosinophilic chronic rhinosinusitis in a mouse model

    • Authors: Hongqi Wei, Longjiang Xu, Peng Sun, Hongyu Xing, Zhengwen Zhu, Jisheng Liu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease characterized by prominent eosinophilic infiltration along with a T-helper-2 (Th2) response. It has been well documented that signal transducer and activator of transcription 6 (STAT6) is a nuclear transcription factor that mediates Th2-type immunity and is implicatory of STAT1 and STAT3 in the pathogenesis of allergic airway diseases. However, little is known about the association between STATs and ECRS. Here, we explored the relationship between STAT1, STAT3, and/or STAT6 and eosinophilic inflammation accompanied by Th2-type immunity in a mouse model of ECRS. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was first established. The mucosal histological alterations were determined using hematoxylin and eosin staining. The number of eosinophils in peripheral blood was measured using a blood cell analyzer. The cytokine (IL-4, IL-5, IL17 A and IFN-γ) expression levels in the sinonasal mucosa and total and OVA-specific IgE from serum were measured using ELISA. Then, the protein levels of STAT1, STAT3, STAT6, phosphorylated STAT1 (p-STAT1), p-STAT3, p-STAT6, T-box expressed in T-cells (T-bet), GATA binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor γ (RORγt) in the sinonasal mucosa were examined by immunohistochemical staining or Western blotting. Local administration of OVA combined with SEB (OVA + SEB) induced multiple polyp-like lesions, accompanied by prominent eosinophilic infiltration in the sinonasal mucosa. The OVA- and OVA+SEB-treated groups showed significantly higher eosinophil counts from peripheral blood and total and OVA-specific IgE levels from serum than those in the PBS- and SEB-treated groups. The levels of p-STAT6 were markedly increased by OVA + SEB exposure, as well as GATA-3, IL-4, and IL-5, but did not affect STAT6, p-STAT1, p-STAT3, T-bet, RORγt, IFN-γ, or IL-17A. Furthermore, an eosinophil count in the sinonasal mucosa showed a positive correlation with the level of p-STAT6 in the ECRS mouse model. Signal transducer and activator of transcription 6 signaling could be activated in the OVA+SEB-induced ECRS model and might be a crucial signal transducer in the development of Th2-skewed ECRS.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-06-21T09:03:29Z
      DOI: 10.1177/03946320221109529
      Issue No: Vol. 36 (2022)
  • A novel 8-genome instability-associated lncRNAs signature predicting
           prognosis and drug sensitivity in gastric cancer

    • Authors: Changhong Yi, Xiulan Zhang, Xia Chen, Birun Huang, Jing Song, Minghui Ma, Xiaolu Yuan, Chaohao Zhang
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundGenome instability lncRNA (GILnc) is prevalently related with gastric cancer (GC) pathophysiology. However, the study on the relationship GILnc and prognosis and drug sensitivity of GC remains scarce.MethodWe extracted expression data of 375 GC patients from TCGA cohort and 205 GC patients from GSE26942 cohort. Then, lncRNA was separated from expression data, and systematically characterized the 8 marker lncRNAs using the LASSO method. Next, we constructed a GILnc model (GILnc score) to quantify the GILnc index of each GC patient. Finally, we analyzed the relationship between GILnc score and clinical traits including survival outcomes, TP53, and drug sensitivity of GC.ResultsBased on a computational frame, 205 GILncs in GC has been identified. Then, a 8 GILncs was successfully established to predict overall survival in GC patients based on LASSO analysis, divided GC samples into high GILnc score and low GILnc score groups with significantly different outcome and was validated in multiple independent patient cohorts. Furthermore, GILnc model is better than the prediction performance of two recently published lncRNA signatures, and the high GILnc score group was more sensitive to mitomycin. Besides, the GILnc score has greater prognostic significance than TP53 mutation status alone and is capable of identifying intermediate subtype group existing with partial TP53 functionality in TP53 wild-type patients. Finally, GILnc signature as verified in GSE26942.ConclusionWe applied bioinformatics approaches to suggest that a 8 GILnc signature could serve as prognostic biomarkers, and provide a novel direction to explore the pathogenesis of GC.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-06-13T09:46:12Z
      DOI: 10.1177/03946320221103195
      Issue No: Vol. 36 (2022)
  • LINC00680 modulates docetaxel resistance in breast cancer via the
           miR-320b/CDKL5 axis

    • Authors: Jia Li, Jing Ke, Cheng-lin Qin, Xun Zhu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Introduction: Increasing evidence has indicated that LINC00680 represents an oncogenic factor in cancer; however, the mechanism by which LINC00680 contributes to breast cancer (BC) remains unknown. Methods: A dual-luciferase reporter assay was used to explore the relationship between LINC00680, miR-320b, and cyclin-dependent kinase 5 (CDKL5). A CCK-8 assay and transwell assay were utilized to evaluate the proliferation and invasion in docetaxel-resistant BC cells, respectively. Results: LINC00680 and CDKL5 protein levels were both upregulated when induced by different concentrations of docetaxel. LINC00680 knockdown decreased the expression level of drug resistance-related genes, proliferation, and invasion of BC cells. Bioinformatics prediction and dual-luciferase assays revealed that miR-320b targeted the 3′-unstranslated regions (UTR) of both LINC00680 and CDKL5, suggesting that the modulation of LINC00680 on CDKL5 occurred via sequestering miR-320b. Conclusion: Overall, this study highlights the important role of LINC00680 in docetaxel resistance through the miR-320b/CDKL5 pathway and provides a novel therapeutic strategy for BC drug resistance.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-06-06T11:45:24Z
      DOI: 10.1177/03946320221105608
      Issue No: Vol. 36 (2022)
  • A monoclonal antibody against basic fibroblast growth factor attenuates
           cisplatin resistance in lung cancer by suppressing the
           epithelial-mesenchymal transition

    • Authors: Penghui Hu, Kaman So, Hongjie Chen, Qimou Lin, Meng Xu, Yiguang Lin
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives: To investigate the underlying mechanisms of how the basic fibroblast growth factor monoclonal antibody (bFGFmAb) attenuates cisplatin (DDP) resistance in lung cancer using A549 cells and cisplatin-resistant A549 cells (A549/DDP). Methods: Cancer cell proliferation, cell viability, and 50% inhibitory concentration (IC50) of cisplatin were assessed. Transwell assays were utilized to evaluate the invasion activity of tumor cells in response to treatment. Epithelial-to-mesenchymal transition markers and drug resistance proteins were analysed using Western blots. Results: We demonstrate that the bFGFmAb inhibits the proliferation and invasion of both A549 and A549/DDP cells. The bFGFmAb increases cisplatin sensitivity of both A549 and A549/DDP cells as evidenced by an increase in the IC50 of cisplatin in A549 and A549/DDP cells. Furthermore, bFGFmAb significantly increases the expression of E-cadherin, whilst decreasing the expression of N-cadherin and bFGF in both cell lines, thereby showing inhibition of epithelial-to-mesenchymal transition. In addition, we demonstrate that bFGFmAb significantly reduces the expression of the lung resistance protein. Conclusions: Our data suggests that the humanized bFGFmAb is a promising agent to attenuate cisplatin resistance in NSCLC. The underlying mechanism for this effect of bFGFmAb may be associated with the inhibition of epithelial-to-mesenchymal transition and reduced expression of lung resistance protein.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-06-02T02:00:00Z
      DOI: 10.1177/03946320221105134
      Issue No: Vol. 36 (2022)
  • Laboratory biomarker predictors for disease progression and outcome among
           Egyptian COVID-19 patients

    • Authors: Lamiaa A Fathalla, Lamyaa M Kamal, Omina Salaheldin, Mahmoud A Khalil, Mahmoud M Kamel, Hagar H Fahim, Youssef AS Abdel-Moneim, Jawaher A Abdulhakim, Ahmed S Abdel-Moneim, Yomna M El-Meligui
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in more than five hundred million infected cases worldwide. The current study aimed to screen the correlation of different laboratory findings with disease severity and clinical outcomes of coronavirus disease (COVID-19) among Egyptian patients to obtain prognostic indicators of disease severity and outcome.A total of 112 laboratory-confirmed COVID-19 patients were examined. According to the severity of the disease, these patients were divided into three main groups: mild, moderate and severe cases. In addition, clinical characteristics and laboratory findings, including Hb, platelet count, white blood cell count, lymphocyte percentage, neutrophil percentage, neutrophil lymphocyte ratio (NLR), D-dimer, highly sensitive C-reactive protein (HS-CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine, were measured.The presence of hypertension and/or diabetes was found to be a significant risk factor for disease severity and poor outcome. Increased respiratory rate, levels of SpO2, HS-CRP, D-dimer, NLR, ALT, LDH, lymphopenia and neutrophilia, as well as changes in chest computed tomography (CT), were associated with increased disease severity and fatal consequences. Highly sensitive C-reactive protein, D-dimer, NLR and LDH constituted excellent predictors for both disease severity and death.Laboratory biomarkers, such as HS-CRP, D-dimer, NLR and LDH, are excellent predictors for both disease severity and death. They can predict mortality in patients at the time of admission secondary to SARS-CoV-2 infection and can help physicians identify high-risk patients before clinical deterioration.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-27T04:50:09Z
      DOI: 10.1177/03946320221096207
      Issue No: Vol. 36 (2022)
  • Inflammasome assembly is required for intracellular formation of
           β2-microglobulin amyloid fibrils, leading to IL-1β secretion

    • Authors: Naoe Kaneko, Wakako Mori, Mie Kurata, Toshihiro Yamamoto, Tamotsu Zako, Junya Masumoto
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionDialysis-related amyloidosis (DRA) caused by β2-microgloblin (B2M) fibrils is a serious complication for patients with kidney failure on long-term dialysis. Deposition of B2M amyloid fibrils is thought to be due not only to serum extracellular B2M but also to infiltrating inflammatory cells, which may have an important role in B2M amyloid deposition in osteoarticular tissues in patients with DRA. Here, we asked whether B2M amyloid fibrils activate the inflammasome and contribute to formation and deposition of amyloid fibrils in cells.MethodsAmyloid formation was confirmed by a thioflavin T (ThT) spectroscopic assay and scanning electron microscopy (SEM). Activation of inflammasomes was assessed by detecting interleukin (IL)-1β in culture supernatants from human embryonic kidney (HEK) 293T cells ectopically expressing inflammasome components. IL-1β secretion was measured by enzyme-linked immunosorbent assay. Expression and co-localization were analyzed by immunohistochemistry and dual immunofluorescence microscopy.ResultsB2M amyloid fibrils interacted directly with NLRP3/Pyrin and to activate the NLRP3/Pyrin inflammasomes, resulting in IL-1β secretion. When HEK293T cells were transfected with inflammasome components NLRP3 or Pyrin, along with ASC, pro-caspase-1, pro-IL-1β, and B2M, ThT fluorescence intensity increased. This was accompanied by IL-1β secretion, which increased in line with the amount of transfected B2M. In this case, morphological glowing of amyloid fibrils was observed by SEM. In the absence of ASC, there was no increase in ThT fluorescence intensity or IL-1β secretion, or any morphological glowing of amyloid fibrils. NLRP3 or Pyrin and B2M were co-localized in a “speck” in HEK293T cells, and co-expressed in infiltrated monocytes/macrophages in the osteoarticular synovial tissues in a patient with DRA.ConclusionTaken together, these data suggest that inflammasome assembly is required for the subsequent triggering of intracellular formation of B2M amyloid fibrils, which may contribute to osteoarticular deposition of B2M amyloid fibrils and inflammation in patients with DRA.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-26T07:10:33Z
      DOI: 10.1177/03946320221104554
      Issue No: Vol. 36 (2022)
  • Procollagen C-protease enhancer protein is a prognostic factor for glioma
           and promotes glioma development by regulating multiple tumor-related
           pathways and immune microenvironment

    • Authors: Zijun Zhao, Jiahui Zhao, Zairan Wang, Yue Wu, Zhanzhan Zhang, Zihan Song, Jihao Miao, Boheng Liu, Shiyang Zhang, Boyu Sun, Zongmao Zhao
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesGlioma is a common type of brain tumor with high incidence and mortality rates. Procollagen C-protease enhancer protein (PCOLCE) has been shown to regulate tumor growth and metastasis in several cancers. However, the role of PCOLCE in glioma is unknown. This study aims to assess the association between PCOLCE and prognosis of glioma, and investigated the potential mechanisms.MethodsThe prognostic value of PCOLCE was determined using data from nine publicly available glioma cohorts. We also investigated the relationship between PCOLCE and glioma immune microenvironment and predicted response to immunotherapy based on the expression levels of PCOLCE. The potential roles of PCOLCE in glioma were also explored and validated in cell experiment.ResultsSurvival analysis suggested that high-PCOLCE expression was associated with poor prognosis in glioma. Upregulation of PCOLCE enhanced an immune suppressive microenvironment in glioma by regulating immunocyte infiltration and Cancer-Immunity Cycle. Cox and ROC analysis revealed that PCOLCE was a prognostic factor for glioma and could be used to predict survival of the patients. Patients with low-PCOLCE expression were more likely to respond to Immunotherapy with ICI (immune checkpoint inhibitor) and survive longer. Enrichment analysis showed that PCOLCE was associated with multiple tumor-related pathways. Finally, we demonstrated that the knockdown of PCOLCE inhibited glioma development by regulating cell cycle and promoting apoptosis in in vitro experiments.ConclusionPCOLCE promotes glioma progression by regulating multiple tumor-related pathways and immune microenvironment and can be used as a prognostic factor for glioma.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-24T08:21:57Z
      DOI: 10.1177/03946320221104548
      Issue No: Vol. 36 (2022)
  • Time-serial expression of toll-like receptor 4 signaling during
           polymicrobial sepsis in rats

    • Authors: En-Pei Lee, Mao-Jen Lin, Han-Ping Wu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Sepsis caused by aggressive infection is a severe clinical problem with an increasing incidence worldwide. Toll-like receptors and their common adapter myeloid differentiation factor 88 (MyD88) can activate immune responses by recognizing a foreign microbe’s product. This study aimed to identify the different time expression of TLR four signaling pathway in an experimental rodent model of polymicrobial sepsis. A randomized animal study was investigated in rats with septic peritonitis induced by cecal ligation and puncture (CLP). The expressions of MyD88-dependent pathway biomarkers, including MyD88, nuclear factor-κB (NF-κB), and serum tumor necrosis factor-α (TNF-α), were analyzed and compared to the sham controls at the different time points after CLP surgery. CLP-induced sepsis increased liver MyD88 mRNA expression and protein expression compared to the control groups at 2 h after surgery. The MyD88 mRNA and protein expressions in rats with CLP-induced sepsis marked increased at 4 and 6 h, and their NF-κB activities and serum TNF-α levels also increased at 4 h after CLP surgery (both p < .05). The different serial expression of MyD88-ependent pathway during sepsis may be used as biomarkers during sepsis. These results may provide further helpful information for using pro-inflammatory biomarkers of innate immunity such as MyD88 and TNF-α in clinical sepsis or related abdominal surgical emergency in the future.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-21T11:48:16Z
      DOI: 10.1177/03946320221090021
      Issue No: Vol. 36 (2022)
  • Elevated serum cholesterol levels are associated with proteinuria over
           0.5 g/day in premenopausal women with systemic lupus erythematosus

    • Authors: Haijun Liu, Qianhua Li, Xiuning Wei, Jianda Ma, KangXia Long, Xia Ouyang, Nemin Liu, Yongsheng Li, Liping He, Lie Dai, Xiaoyan Cai
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Background: Systemic lupus erythematosus (SLE) commonly occurs in premenopausal women and is associated with elevated estrogen levels. Patients with SLE may have abnormal serum triglyceride (TG) levels, and lipid reportedly promotes kidney damage in patients with nephrosis. Since estrogen regulates lipid levels, we investigated the serum lipid levels of premenopausal women with SLE and their relationship with proteinuria. Methods: This cross-sectional study included 123 premenopausal women with SLE (SLE group), who were classified into 24-h urine protein exceeding 0.5 g (24 h-UPRO> 0.5 g, n = 22) and 24 h-UPRO ≤ 0.5 g (n = 101) subgroups, and 100 similarly aged healthy women (control group). Clinical characteristics and biomarker levels were compared between these groups. The associated factors of proteinuria over 0.5 g/day were evaluated using multivariate logistic regression. A receiver operating characteristic (ROC) curve was plotted to assess the cholesterol (CH) cut-off associated with increased development of proteinuria over 0.5 g/day. Results: The SLE group had significantly higher serum TG levels than that of control group. 24 h-UPRO were significantly correlated with serum creatinine, CH, TG, and uric acid levels. Serum CH level was the greatest associated factor for proteinuria over 0.5 g/day. The area under the ROC curve was 0.843, with a CH cut-off of 4.58 mmol/L. Patients with serum CH above 4.58 mmol/L had a higher proportion of type IV LN, but with no statistical difference. Conclusions: In premenopausal SLE patients, serum TG levels were higher than in healthy women, and serum CH levels were the primary associated factor for proteinuria over 0.5 g/day. Proteinura over 0.5 g/day may occur in women with SLE with serum CH levels>4.58 mmol/L. CH levels may be useful for predicting proteinuria.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-20T11:32:07Z
      DOI: 10.1177/03946320221101287
      Issue No: Vol. 36 (2022)
  • Association of baseline parameters with year 0 and year 1 acute

    • Authors: Yu-Ping Chang, Yu-Mu Chen, Ya-Chun Chang, Shih-Feng Liu, Wen-Feng Fang, Tung-Ying Chao, Chao-Chien Wu, Huang-Chih Chang, Meng-Chih Lin, Yung-Che Chen
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesAcute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) can affect health status, hospitalization and readmission rates, and disease progression. This study aimed to identify independent markers associated with COPD AEs.MethodsThis study included male patients with COPD and collected data regarding their AEs and baseline clinical parameters.ResultsWe included 149 male patients. Among them, 58 were included in the year 0 high-AE group and 91 in the low-AE group. Multivariate analysis revealed that the high-AE group had higher white blood cell count, lower serum albumin level, and post-bronchodilator (BD) forced expiratory volume in one second (FEV1) (%) with a combined receiver operating characteristic curve (ROC) of 0.721 (p < 0.001). Additionally, 34 patients were included in the year 1 high-AE group and 70 in the low-AE group (p < 0.001). Multivariate analysis revealed that the high-AE group had higher platelet count, positive asthma history, and lower pre-BD FEV1 (%) with a combined ROC of 0.782 (p < 0.001).ConclusionIn male patients with COPD, baseline white blood cell count, albumin level, and post-BD FEV1 (%) were correlated with year 0 AE; on the other hand, baseline platelet count, positive asthma history, and pre-BD FEV1 (%) were associated with year 1 AE.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-20T10:34:30Z
      DOI: 10.1177/03946320221099073
      Issue No: Vol. 36 (2022)
  • Origin of M2 Mϕ and its macrophage polarization by TGF-β in a mice
           intervertebral injury model

    • Authors: Ayumu Kawakubo, Masayuki Miyagi, Yuji Yokozeki, Mitsufumi Nakawaki, Shotaro Takano, Masashi Satoh, Makoto Itakura, Gen Inoue, Masashi Takaso, Kentaro Uchida
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionStudies have identified the presence of M1 and M2 macrophages (Mϕ) in injured intervertebral discs (IVDs). However, the origin and polarization-regulatory factor of M2 Mϕ are not fully understood. TGF-β is a regulatory factor for M2 polarization in several tissues. Here, we investigated the source of M2 Mϕ and the role of TGF-β on M2 polarization using a mice disc-puncture injury model.MethodsTo investigate the origin of M2 macrophages, 30 GFP chimeric mice were created by bone marrow transplantation. IVDs were obtained from both groups on pre-puncture (control) and post-puncture days 1, 3, 7, and 14 and CD86 (M1 marker)- and CD206 (M2 marker)-positive cells evaluated by flow cytometry (n = 5 at each time point). To investigate the role of TGF-β on M2 polarization, TGF-β inhibitor (SB431542) was also injected on post-puncture days (PPD) 5 and 6 and CD206 expression was evaluated on day 7 by flow cytometry (n = 5) and real time PCR (n = 10).ResultsThe proportion of CD86+ Mϕ within the GFP+ population was significantly increased at PPD 1, 3, 7, and 14 compared to control. CD206-positive cells in GFP-populations were significantly increased on PPD 7 and 14. In addition, the percentage of CD206-positive cells was significantly higher in GFP-populations than in GFP+ populations. TGF-β inhibitor reduced CD206-positive cells and Cd206 expression at 7 days after puncture.ConclusionOur findings suggest that M2 Mϕ following IVD injury may originate from resident Mϕ. TGF-β is a key factor for M2 polarization of macrophages following IVD injury.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-20T06:28:22Z
      DOI: 10.1177/03946320221103792
      Issue No: Vol. 36 (2022)
  • COVID-19 and erythrocrine function: The roller coaster and danger

    • Authors: Hayder M Al-kuraishy, Ali I Al-Gareeb, Hope Onohuean, Gaber El-Saber Batiha
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Erythrocrine function refers to erythrocytes’ ability to synthesize and release active signaling molecules such as ATP and nitric oxide (NO). Erythrocyte NO regulates its deformability and increases its perfusion and circulation that prevent tissue hypoxia. Recently, there is a connotation between SARS-CoV-2 infection and erythrocrine function due to alteration in the release of NO and ATP from erythrocytes. SARS-CoV-2 binds erythrocyte band3 protein, which has a similar characteristic of ACE2, leading to alteration of erythrocyte physiology like oxygen transport with development of hypoxia. Similarly, SARS-CoV-2 infection activates erythrocyte protein kinase C alpha (PKC-α), causing significant changes in the erythrocyte functions. The erythrocytes can bind SARS-CoV-2 and its active particles with subsequent virus delivery to the liver and spleen macrophages. Thus, the erythrocytes act as elimination for SARS-CoV-2 in COVID-19. Moreover, the erythrocyte stored, release sphingosine-1 phosphate (S1P) improves endothelial and regulates lymphocyte functions. SARS-CoV-2 ORF8 protein binds the porphyrin part of hemoglobin heme at the β1 chain, causing hemolysis and dysfunctional hemoglobin to reduce oxygen-carrying capacity. In conclusion, SARS-CoV-2 infection and associated pro-inflammatory disorders lead to abnormal erythrocrine function with subsequent inflammatory complications and endothelial dysfunction due to deficiency of protective released molecules (NO, G1P, and ATP) from functional erythrocytes. In vitro, preclinical, and clinical studies are mandatory in this regard.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-20T04:31:56Z
      DOI: 10.1177/03946320221103151
      Issue No: Vol. 36 (2022)
  • Relationship between toll-like receptor expression in the distal facial
           nerve and facial nerve recovery after injury

    • Authors: Hye Kyu Min, In Hyeok Kim, Jae Min Lee, Junyang Jung, Hwa Sung Rim, Dae Woong Kang, Sang Hoon Kim, Seung Geun Yeo
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives: This study aimed to determine whether toll-like receptor expression patterns differ in the distal facial nerve during recovery after crushing and cutting injuries. Methods: Adult male Sprague-Dawley rats underwent crushing or cutting injury of the unilateral facial nerve. Their whisker movement and blink reflex were examined. Western blotting was performed with the normal nerve on the left side and the damaged nerve on the right side, four days, 14 days, and 3 months after injury. Results: The scores of whisker movements and blink reflex in the crushing group showed improvements, while the score of the cutting group was significantly lower at 14 days and 3 months (p < 0.05). Western blotting showed that TLRs 11 and 13 increased in the crushing group, and TLRs 1, 2, 3, 4, 5, 8, 10, 11, 12, and 13 increased in the cutting group after 14 days (p < 0.05). After 3 months, TLRs 10 and 11 increased in the crushing group, and TLRs 1, 4, 5, 8, 11, and 12 increased in the cutting group (p < 0.05). Conclusion: TLRs 1, 4, 5, 8, and 12 are related to nerve degeneration after facial nerve injury, and TLRs 10, 11, and 13 are related to recovery from facial palsy.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-19T04:11:18Z
      DOI: 10.1177/03946320221090007
      Issue No: Vol. 36 (2022)
  • Association between cytokine concentration kinetics and prolonged fever in
           febrile neutropenic children with bacteremia

    • Authors: Seong Koo Kim, Seung Beom Han, Jin Han Kang
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Introduction: Although prolonged fever in patients with neutropenic fever (NF) during empirical antibiotic therapy could be caused by dysregulated immune responses, its association with cytokine concentrations has rarely been investigated. This study determined the kinetics of cytokine concentrations in pediatric patients with NF and bacteremia and evaluated the impact of cytokine concentration kinetics on prolonged fever. Methods: Concentrations of 13 cytokines were measured on the initial day of NF (Day 1) and 3 days (Day 4) and 7 days (Day 8) later in 10 patients with NF with bacteremia, and their kinetics was determined. The results for each cytokine concentration on each sampling day were compared for patients with fever that lasted ⩾3 days and those with fever that lasted
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-16T11:40:25Z
      DOI: 10.1177/03946320221095015
      Issue No: Vol. 36 (2022)
  • Exploring the antihyperglycemic potential of tetrapeptides devised from
           AdMc1 via different receptor proteins inhibition using in silico

    • Authors: Ghulam Mustafa, Hafiza S Mahrosh, Muddassar Zafar, Syed A Attique, Rawaba Arif
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Introduction:Diabetes mellitus is a heterogenous group of chronic metabolic disorders that results due to deficiency in insulin secretion and signalling. Multiple factors held responsible for onset of diabetes due to defects in glucose metabolism and cellular signalling mechanism. Over the past few years, many plant derived bioactive compounds have been recorded with increased efficacy and fewer side-effects against variety of diseases.Methods:In the current study, molecular docking and molecular dynamics simulation approaches were employed to evaluate the tetrapeptides devised from AdMc1 protein of Momordica charantia. Due to unavailability of appropriate template for modelling of 3D structure of AdMc1 protein, I-TASSER server was employed for prediction of good quality tertiary structure. Predicted model was refined by GalaxyRefine Web and evaluated by Verify 3D, ERRAT and Ramachandran plot analysis. Next, a ready-to-dock library of fifty tetrapeptides as potent inhibitors was prepared and docked against aldose reductase (AR), protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, α-amylase and glycogen synthase kinase 3-beta as receptor proteins. Molecular dynamics (MD) simulation was performed on Schrodinger’s Desmond Module to check stability of the best docking complex.Results:Top five ligands were selected against each receptor protein based on their binding pattern and docking scores. Among selected ligands (i.e. VEID, TVEV, AYAY, EEIA, ITTV, TTIT, LPSM, RGIE, TTVE and EIAR) followed all parameters in drug scanning and ADMET screening tests. The MD simulations confirmed that the best selected peptide (i.e. VEID) docked with AR and PTP1B was structurally stable.Conclusion:In the light of overall results of all analyses employed in this study, the selected ligands could be further processed as potential hypoglycaemic drug candidates.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-15T03:57:19Z
      DOI: 10.1177/03946320221103120
      Issue No: Vol. 36 (2022)
  • Clinical and quality of life assessment in patients with latex allergy
           during COVID-19 pandemic: Possible protective role of continuous latex

    • Authors: Alessia Di Rienzo, Sara Urbani, David Longhino, Caterina Sarnari, Alessandro Buonomo, Angela Rizzi, Arianna Aruanno, Eleonora Nucera
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 ± 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A (p < 0.001), respiratory symptoms (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-15T02:56:48Z
      DOI: 10.1177/03946320221100367
      Issue No: Vol. 36 (2022)
  • IP-10 and complement activation as friend or foe in COVID-19

    • Authors: Saowalak Bunprakob, Pasin Hemachudha, Chanida Ruchisrisarod, Thirawat Supharatpariyakorn, Thiravat Hemachudha
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionThe Innate immune system senses danger signals of COVID-19 infection and produce an orchestration of cellular, complement and cytokines cascades. These led to the approach using immunosuppressive agents. It is intriguing whether certain biomarkers can aid the proper administration of such drugs.MethodsPlasma specimens of 58 COVID-19 patients with differing severity, from very mild illness (group A), mild (group B), moderate (group C), and severe/critical illness (group D) were assayed for cyto-chemokines and terminal complement complex (SC5b-9) during the course of diseases. None received anti-IL-6 therapy, there was no mortality in this cohort.ResultsIP-10 and RANTES levels were dominant cytokines. IP-10 levels increased significantly in all groups when compared between pre-nadir and nadir phases (group A, p =0.428; group B =0.034; group C =0.159; group D
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-05-09T08:35:01Z
      DOI: 10.1177/03946320221096202
      Issue No: Vol. 36 (2022)
  • Detection of exosomal miR-18a and miR-222 levels in Egyptian patients with
           hepatic cirrhosis and hepatocellular carcinoma

    • Authors: Eman A Elghoroury, Esmat E Abdelghaffar, Eman Awadallah, Solaf A Kamel, Dina Kandil, Eman M Hassan, Mirhane Hassan, Mahmoud M Kamel, Mohammed M Gomaa, Lamiaa A Fathalla
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundHepatocellular carcinoma (HCC) is known to be the second leading cause of cancer-related mortality worldwide. For improving the prognosis as well as reducing the rate of mortality, early diagnosis of HCC is a must.AimsThis study was conducted to assess the ability of the serum expression of exosomal miR-18a and miR-222 to differentiate and diagnose patients with HCC, patients with liver cirrhosis, and healthy controls.MethodsThis study included 51 patients with liver cirrhosis, 51 patients with HCC on top of hepatitis C virus (HCV) infection, and 50 healthy controls.ResultsmiR-18a and miR-222 were assessed using reverse transcription-polymerase chain reaction. MiR-18a and miR-222 levels were significantly higher in the liver cirrhosis and HCC groups than the control group (p ˂ 0.001). However, no statistically significant difference was found between patients with HCC and liver cirrhosis (p = 0.4 for miR-18a and p = 0.1 for miR-222). ROC curve analyses to evaluate the diagnostic performances of the two miRNAs as important noninvasive diagnostic markers revealed a best cutoff value of 2 for miR-18a to differentiate between liver cirrhosis, HCC, and healthy controls. And for mir-222, a cutoff value of 1.7 and 1.9 showed the highest specificity for discrimination between liver cirrhosis, HCC, and healthy controls, respectively. Moreover, logistic regression model revealed that miR-18a expression was independent predictive factor in HCC patients (p = 0.004), while miR-222 expression was independent predictive factor in liver cirrhosis patients (p < 0.001).ConclusionmiR-18a and miR-222 were significantly discriminative markers between patients with liver cirrhosis and HCC and healthy individuals. Therefore, they have a prognostic rather than a diagnostic value. Moreover, miR-18a and miR-222 could be useful in identifying liver injuries, including fibrosis and cirrhosis.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-25T02:25:06Z
      DOI: 10.1177/03946320221097832
      Issue No: Vol. 36 (2022)
  • Prevalence of transfusion-transmitted infections in multiple blood
           transfusion-dependent thalassemic patients in Asia: A systemic review

    • Authors: Muhammad Riaz, Mazhar Abbas, Ghulam Rasool, Ibrahim Salam Baig, Zahed Mahmood, Naveed Munir, Imtiaz Mahmood Tahir, Syed Muhammad Ali Shah, Muhammad Akram
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundThalassemia is a hereditary hemolytic anemia marked by a defect in synthesizing one or more globin chains in hemoglobin. In Pakistan, approximately 10,000 patients with thalassemia are primarily dependent on blood transfusions. The β-thalassemia patients require blood transfusions and iron chelation therapy. Patients who need blood transfusions are at an increased risk of contracting transfusion-transmitted infections (TTIs) such as hepatitis B and C viruses (HBV and HCV, respectively), as well as the human immunodeficiency virus (HIV).ObjectiveThis systemic review aims to assess the prevalence of TTIs in transfusion-dependent β-thalassemia patients in Asia.MethodsThe data for the systematic review were gathered from PubMed, Google Scholar, the Directory of Open Access Journals (DOAJ), and ScienceDirect using the following keywords: “prevalence, HBV, HCV, HIV, thalassemia, and transfusion-transmitted infections (TTIs)," and so on. This review includes the research articles that address the prevalence of viral infections in thalassemic patients following blood transfusion.ResultsA preliminary search of various databases identified 231 potential studies. 157 duplicate studies were eliminated, and the eligibility of 59 full-length articles was determined. Only 43 studies met the inclusion criteria. Among the 43 studies analyzed, 11 reported a high prevalence of HCV alone in thalassemic patients, while 21 reported a high prevalence of HCV and HBV infection in thalassemic patients. Eight studies reported the prevalence of all three TTIs examined, namely, HCV, HBV, and HIV, in patients with transfusion-dependent thalassemia.ConclusionPreventable transfusion-transmitted infections occur frequently, and robust national policies and hemovigilance are required to detect and mitigate the infection risk.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-22T04:37:45Z
      DOI: 10.1177/03946320221096909
      Issue No: Vol. 36 (2022)
  • Dose-dependent effects of oleuropein administration on regulatory T-cells
           in patients with rheumatoid arthritis: An in vitro approach

    • Authors: Zahra Yousefi, Zahra Mirsanei, Fatemeh S Bitaraf, Sepideh Mahdavi, Mehdi Mirzaii, Reza Jafari
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Introduction:Rheumatoid arthritis (RA) is an autoimmune disease that is identified with chronic inflammation and progressive destruction of the joints. The defective activity of regulatory T cells (Tregs) plays a crucial role in RA development. Oleuropein (OLEU) is the most common polyphenolic compound in olive leaf extracts with numerous pharmacological activities. In this study, the potential effects of OLEU in shifting CD4+ T cells toward Tregs are evaluated in patients with RA.Methods32 healthy controls (HC) and 45 RA patients were included in two groups. The immunoturbidometric technique was used to measure serum levels of c-reactive protein (CRP) and rheumatoid factor (RF). Isolated CD4+ T cells from peripheral blood mononuclear cells (PBMCs) of HC and RA patients were cultured with appropriate concentrations of OLEU. The cytotoxicity effects of OLEU were determined using the MTT assay at 24, 48, and 72 h. The percentage of CD4+CD25 + FoxP3 regulatory T lymphocytes (Tregs) and the expressions of IL-10 and TGF-β were evaluated by flow cytometry and immunoassay techniques after treatment of cells with different concentrations of OLEU for 24 h. The serum levels of RF and CRP in patients with RA were 11.8 ± 5.32 IU/ml and 6.36 ± 5.82 mg/l, respectively.ResultsOLEU had a dose-dependent effect on the CD4+ T cells via increasing the frequency of CD4+CD25 + FoxP3 Tregs (p = 0.0001). Moreover, it induced the production of IL-10 (p = 0.0001) and TGF-β (p < 0.01) in both HC and RA patients.ConclusionThe findings of this study suggest that OLEU may have immunomodulatory effects by inducing Tregs, and it might help in developing a novel nutrition strategy for management of autoimmune diseases such as RA.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-12T05:09:51Z
      DOI: 10.1177/03946320221086084
      Issue No: Vol. 36 (2022)
  • Bisphenol-A/Radiation mediated inflammatory response activates

    • Authors: Omayma AR Abo-Zaid, Fatma SM Moawed, Hend A Hassan, Enas M Moustafa
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundBisphenol (BPA) and ionizing radiation exposure (IR) are potent oxidants that cause free radical induction, leading to signaling pathway activation that alters cell growth. Due to the insufficient knowledge of the impact of BPA and IR on the lungs, the current study determined the impact of BPA and IR on the lung tissue of adult female Wistar rats.MethodsForty Wister female rats were used in this study and were randomly divided into four groups. The rats received BPA (150 mg/kg body weight/day for 6 weeks) and were exposed to IR at 2 Gy/week up to 12 Gy for 6 weeks.ResultsIt was found that BPA and IR possess a harmful effect on the lungs via induction of oxidative stress, confirmed by increasing levels of malondialdehyde (MDA), nitric oxide, myeloperoxidase (MPO), and lactate dehydrogenase (LDH). Exposure to BPA and IR activates inflammatory cytokines TNF-α, IL-6, IL-1β, growth factors such as TGF-β, and gastrin-releasing peptides. BPA/IR exposures induced phosphorylated expression p-ERK1/2 and p-MEK1/2 associated with triggering of the GPER/EGFR/KRAS signaling factors, resulting in matrix metalloproteinase-2 and 9 overexpression and the development of lung tumors. Our findings support the causal role of two deleterious environmental pollutants BPA and IR, via the cytotoxicity in the respiratory system in the form of severe lung damage resulting in cancerous cells.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-12T02:36:22Z
      DOI: 10.1177/03946320221092918
      Issue No: Vol. 36 (2022)
  • Immune system and atherosclerosis: Hostile or friendly relationship

    • Authors: Iman Razeghian-Jahromi, Ali Karimi Akhormeh, Mahboobeh Razmkhah, Mohammad Javad Zibaeenezhad
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Coronary artery disease has remained a major health challenge despite enormous progress in prevention, diagnosis, and treatment strategies. Formation of atherosclerotic plaque is a chronic process that is developmentally influenced by intrinsic and extrinsic determinants. Inflammation triggers atherosclerosis, and the fundamental element of inflammation is the immune system. The immune system involves in the atherosclerosis process by a variety of immune cells and a cocktail of mediators. It is believed that almost all main components of this system possess a profound contribution to the atherosclerosis. However, they play contradictory roles, either protective or progressive, in different stages of atherosclerosis progression. It is evident that monocytes are the first immune cells appeared in the atherosclerotic lesion. With the plaque growth, other types of the immune cells such as mast cells, and T lymphocytes are gradually involved. Each cell releases several cytokines which cause the recruitment of other immune cells to the lesion site. This is followed by affecting the expression of other cytokines as well as altering certain signaling pathways. All in all, a mix of intertwined interactions determine the final outcome in terms of mild or severe manifestations, either clinical or subclinical. Therefore, it is of utmost importance to precisely understand the kind and degree of contribution which is made by each immune component in order to stop the growing burden of cardiovascular morbidity and mortality. In this review, we present a comprehensive appraisal on the role of immune cells in the atherosclerosis initiation and development.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-12T01:03:05Z
      DOI: 10.1177/03946320221092188
      Issue No: Vol. 36 (2022)
  • Single nucleotide polymorphism rs 2070874 at Interleukin-4 is associated
           with increased risk of type 1 diabetes mellitus independently of human
           leukocyte antigens

    • Authors: Awad E Osman, Imad Brema, Alaa AlQurashi, Abdullah Al-Jurayyan, Benjamin Bradley, Muaawia A Hamza
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionType 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of insulin-producing pancreatic beta (β-) cells. Previous studies suggested an imbalance between and pro- and anti-inflammatory cytokines exacerbates T1DM development.ObjectivesWe aimed to test the hypothesis that patients with T1DM carry a higher frequency of regulatory genes associated with low levels of the anti-inflammatory cytokines interleukin-4 (IL-4), its receptor (IL-4R), and interleukin-10 (IL-10).MethodsAccordingly, we compared frequencies of five different single nucleotide polymorphisms (SNPs) in T1DM patients and healthy controls who had been typed for HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes.ResultsThe frequencies of rs2070874 (IL-4) alleles C and T differed between T1DM patients and controls (cp = 0.0065), as did their codominant (cp = 0.026) and recessive (cp = 0.015) models. Increased frequencies were observed in T1DM patients for HLA alleles: DRB1*03 (pc < 0.0013), DRB1*04 (cp = 0.0169), DQA1*03 (cp = 0.0222), DQA1*05 (cp < 0.0006), DQB1*02 (cp = 0.0005), and DQB1*06 (cp < 0.0005). And lower frequencies were observed for: DRB1*07 (cp = 0.0078), DRB1*11 (cp = 0.0013), DRB1*13 (cp < 0.0364), DRB1*15 (cp < 0.0013), DQA1*01 (cp < 0.0006), and DQA1*02 (cp = 0.0348). Certain DRB1: DQA1: DQB1 haplotypes showed greater frequencies, including, 03:05:02 (p < 0.0001) and 04:03:03 (p = 0.0017), whereas others showed lower frequencies, including, 07:02:02 (p = 0.0032), 11:05:03 (p = 0.0007), and 15:01:06 (p = 0.0002). Stratification for the above HLA haplotypes with rs2070874 C/C exhibited no significant differences between T1DM patients overall and controls. However, when stratified for the vulnerable HLA haplotype (03:05:02/04:03:03), young patients in whom T1DM began at ≤13 years had a higher frequency of the SNP (rs2070874 C/C); a gene associated with low IL-4 production (p < 0.024).ConclusionThis study suggests that possession of the rs2070874 C/C genotype, which is associated with low production of IL-4, increases the risk of T1DM in young individuals carrying vulnerable HLA alleles/haplotypes.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-11T05:16:17Z
      DOI: 10.1177/03946320221090330
      Issue No: Vol. 36 (2022)
  • Patients with treated autoimmune hepatitis and persistent suppression of
           plasmacytoid dendritic cells: A different point of view

    • Authors: Irene P dos Santos, Mayra T de Assunção, Renan M Mauch, Natascha Silva Sandy, Marcos Tadeu Nolasco da Silva, Maria Angela Bellomo-Brandão, Adriana Gut Lopes Riccetto
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives: Plasmacytoid dendritic cells (pDCs) have been shown to have a role in autoimmune diseases, but their role in Autoimmune Hepatitis (AIH) is not completely clear. In the present study, we assessed the frequency of pDCs in peripheral blood of AIH patients under long-term standard immunosuppressive therapy. Methods: This cross-sectional analysis enrolled 27 AIH patients and 27 healthy controls. We analyzed and compared their proportion of pDCs, CD4+, CD8+, γδ T cells, CD25+ regulatory T (Treg) cells, FoxP3+, Foxp3+CD39+ Treg cells, total B (CD19+) cells, and plasma cells (CD38+) in peripheral blood using flow cytometry immunophenotyping. Results: AIH patients had a lower percentage of pDCs (median frequencies of 0.2% vs. 0.4%; p = .002) and higher expression of CD8 T cells (32.5% vs 28.6%; p = 0.008) in peripheral blood, when compared to healthy controls. We did not find statistically significant differences between the groups regarding the other cell subtypes.Conclusion: Our data suggest a persistent suppression of pDCs in AIH patients, along with increased CD8 T cell activity, years after AIH diagnosis and despite of good clinical response to treatment, thus pointing to a role of pDCs in the AIH pathogenesis.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-11T04:07:56Z
      DOI: 10.1177/20587384211068667
      Issue No: Vol. 36 (2022)
  • Evodiamine suppresses the progression of non-small cell lung carcinoma via
           endoplasmic reticulum stress-mediated apoptosis pathway in vivo and in

    • Authors: Yuting Li, Yuming Wang, Xiaoqun Wang, Lulu Jin, Lu Yang, Jinli Zhu, Hongwu Wang, Fang Zheng, Huantian Cui, Xiaojiang Li, Yingjie Jia
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundEvodiamine (EVO) is one of the major components isolated from Evodia rutaecarpa (Juss.). Recent studies have shown that EVO has an anti-cancer effect. However, the pharmacological mechanism by which EVO impacts cancer is still poorly understood.ObjectivesThis study focused on asking the anti-cancer effect of EVO in human non-small cell lung carcinoma (NSCLC), and in particular to investigate whether EVO acts via modulating the endoplasmic reticulum stress (ERS)-mediated apoptosis pathway.Materials and MethodsA Lewis lung carcinoma (LLC) tumor-bearing mouse model was treated with low-dose EVO (5 mg/kg) and high-dose EVO (10 mg/kg) intraperitoneally for 14 d. The effects of EVO on tumor growth, apoptosis, and ERS were assessed. In addition, NSCLC A549 and LLC cells were treated with EVO in vitro. The effects of EVO on cell proliferation, apoptosis, and ERS were investigated. Finally, 4-phenylbutyric acid (4-PBA), an ERS inhibitor, was used to validate whether EVO induced apoptosis of NSCLC cells by modulating ERS.ResultsEVO treatment significantly inhibited tumor growth in LLC tumor-bearing mice. H&E staining indicated that EVO treatment reduced the number of tumor cells and the nucleo-plasmic ratio. Immunostaining showed that EVO treatment significantly decreased the expression of Ki-67. TUNEL staining revealed that EVO induced apoptosis in the tumor. Likewise, EVO treatment up-regulated the expression of apoptosis-related genes and proteins and increased activation of the ERS pathway in the tumor. Additionally, EVO inhibited cell proliferation and increased cell apoptotic rates in A549 and LLC cells. EVO also increased the expression levels of genes and proteins associated with ERS-mediated apoptosis pathway in vitro. The effects of EVO on apoptosis were abolished by 4-PBA treatment.ConclusionsOur study demonstrated that EVO suppresses the progression of NSCLC by modulating the ERS-mediated apoptosis pathway.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-07T09:28:19Z
      DOI: 10.1177/03946320221086079
      Issue No: Vol. 36 (2022)
  • Roles of C-reactive protein polymorphisms and life event changes on
           cognitive function in bipolar patients receiving valproate

    • Authors: Po See Chen, Li-Yi Tang, Hui Hua Chang
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionPatients with bipolar disorder (BD) exhibit an inflamed condition that is associated with metabolic disturbance and cognitive impairment. Whether inflammation, represented by C-reactive protein (CRP), is causally associated with BD and influences treatment outcome has not been established.MethodsWe examined whether CRP is a causal factor for the risk of BD in drug-naïve, depressed BD patients and investigated whether polymorphisms in CRP and life event changes influence cognitive function in BD patients receiving valproate (VPA) treatment.ResultsOur results showed that BD patients had significantly higher CRP levels and worse cognitive function than the controls, while the frequencies of CRP single nucleotide polymorphisms in BD patients and in controls were not different. In addition, the life event scale score was higher for BD patients than for controls. Furthermore, the genotypes of CRP polymorphisms and the interactions between polymorphisms of CRP and life event scale score had a significant influence on cognitive performance in BD patients after 12 weeks of VPA treatment.ConclusionOur study demonstrated the clinical utility of the application of functional genetics in clarifying the interactions among CRP, life event stress, and BD and suggested the important roles of CRP gene–environment interactions in developing treatment strategies for BD.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-04-04T02:57:39Z
      DOI: 10.1177/03946320221084835
      Issue No: Vol. 36 (2022)
  • Clinical and hematological characteristics of 300 COVID-19 patients in
           Erbil, Kurdistan Region, Iraq

    • Authors: Rundk Ahmad Hwaiz, Sahar Mohammed Zaki Abdullah, Salah Tofik Jalal Balaky, Katan Sabir Ali, Mohammed Yousif Merza, Shakhawan Assad Khailani, Nazar Pauls Shabila
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundCOVID-19 primarily presents as a respiratory tract infection, but studies indicate that it could be considered a systemic disease that can spread to affect multiple organ systems, including respiratory, cardiovascular, gastrointestinal, hematopoietic, neurological, and immune systems.ObjectiveTo describe and analyze the clinical and hematological characteristics of 300 hospitalized COVID-19 patients in Erbil, Kurdistan.MethodsThis retrospective study included 300 patients of any age admitted to hospital due to confirmed COVID-19 between September 2020 and February 2021. Cases were diagnosed by reverse transcriptase polymerase chain reaction assays of nasopharyngeal swab specimens.ResultsThe highest proportion of patients were aged 21–40 years. The most common symptoms among the patients were myalgia (66.7%), fatigue (62.3%), headache (50.7%), and chest pain (52.7%). Differences in hematological and biochemical parameters were observed between deceased and recovered patients. Only the mid-range absolute count percentage (MID%) was significantly higher in the recovered patients than in the deceased ones (6.41% vs. 4.48, p = 0.019). Death was significantly higher among older patients (>40 years) than younger ones (≤40 years) (6.8% vs. 1.3%, p = 0.015), diabetic than non-diabetic (10.8% vs. 3%, p = 0.047), and those having chronic diseases than those without chronic diseases (10.6% vs. 2.1%, p = 0.006).ConclusionsDifferent hematological and biochemical parameter findings were observed among the COVID-19 patients. Low MID%, older age, and presence of diabetes mellitus and chronic disease were significantly associated with death among COVID-19 patients.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-03-27T12:00:11Z
      DOI: 10.1177/03946320221085465
      Issue No: Vol. 36 (2022)
  • ETS variant transcription factor 6 enhances oxidized low-density
           lipoprotein-induced inflammatory response in atherosclerotic macrophages
           via activating NF-κB signaling

    • Authors: Xiaofang Xiong, Zheng Yan, Wei Jiang, Xuejun Jiang
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives: Macrophages play a critical role in atherosclerosis by contributing to plaque development, local inflammation, and thrombosis. Elucidation of the molecular cascades in atherosclerotic macrophages is important for preventing and treating atherosclerosis. This study aims to deepen the understanding of the mechanisms that regulate the function of aorta macrophage in atherosclerosis. Methods: In the current study, the expression and function of ETS variant transcription factor 6 (ETV6) in aorta macrophages in a mouse atherosclerosis model. Aorta macrophages were enriched by flow cytometry. ETV6 expression was analyzed by quantitative RT-PCR. The role of ETV6 in macrophage-mediated pro-inflammatory response was evaluated both in vitro and in vivo after ETV6 silencing. Results: A remarkable elevation of ETV6 in aorta macrophages of atherosclerotic mice was observed. In addition, in vitro analysis indicated that oxidized low-density lipoprotein (oxLDL) up-regulated ETV6 in macrophages via the NF-κB pathway. ETV6 silencing suppressed oxLDL-induced expression of IL-1β, IL-6, and TNF-α in macrophages in vitro. However, ETV6 silencing did not impact the uptake of either oxLDL or cholesterol by macrophages. Furthermore, ETV6 silencing suppressed oxLDL-induced activation of the NF-κB pathway in macrophages, as evidenced by less phosphorylation of IKKβ and NF-κB p65, more cytoplasmic IκBα, and lower nuclear NF-κB p65. Moreover, ETV6 silencing inhibited the production of IL-1β and TNF-α in aorta macrophages in vivo. Conclusion: ETV6 supports macrophage-mediated inflammation in atherosclerotic aortas. This is a novel mechanism regulating the pro-inflammatory activity of atherosclerotic macrophages.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-03-19T11:02:40Z
      DOI: 10.1177/20587384221076472
      Issue No: Vol. 36 (2022)
  • Salvianolic acid B attenuates the inflammatory response in atherosclerosis
           by regulating MAPKs/ NF-κB signaling pathways in LDLR-/- mice and
           RAW264.7 cells

    • Authors: Yifan Zhang, Xiaoteng Feng, Min Du, Jie Ding, Ping Liu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives: Salvianolic acid B (Sal B) is the main effective water-soluble component of Salvia miltiorrhiza. In this study, the anti-inflammatory effect of Sal B was explored in high-fat-diet (HFD)-induced LDLR-/- mice and oxidized low-density-lipoprotein (ox-LDL)-induced or lipopolysaccharide (LPS)-induced RAW264.7 cells. Methods: The LDLR-/- mice were randomly divided into four groups after 12 weeks of high-fat diet. Then, the mice were administrated with 0.9% saline or Sal B (25 mg/kg) or Atorvastatin (1.3 mg/kg) for 12 weeks. RAW 264.7 cells were induced with ox-LDL/LPS, or ox-LDL/LPS plus different concentrations of Sal B (1.25 μg/mL, 2.5 μg/mL, 5 μg/mL), or ox-LDL plus Sal B plus MAPKs activators. ELISA was used for detecting serum lipid profiles and inflammatory cytokines, RT-qPCR used for gene expression, Oil Red O used for plaque sizes, and immunofluorescence staining used for NF-κB p65 and TNF-α production. Inflammation-related proteins and MAPKs pathways were detected by Western Blot. Results: The results showed that Sal B decreased the levels of serum lipids (TC, TG, and LDL-C), attenuated inflammatory cytokines, and improved lipid accumulation in the aorta. Sal B also attenuated the elevation of inflammatory cytokines induced by ox-LDL or LPS in RAW264.7 cells, and the phosphorylation of MAPKs/NF-κB pathways in the aorta and RAW264.7 cells, resulting in a significant decrease in the contents of p-JNK, p-ERK 1/2, p-P38, p-IκB, and p-NF-κB p65. Conclusions: Sal B could exert anti-inflammatory effects on atherosclerosis via MAPKs/NF-κB signaling pathways in vivo and in vitro.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-03-12T01:10:39Z
      DOI: 10.1177/03946320221079468
      Issue No: Vol. 36 (2022)
  • Autoimmune hepatitis in Egyptian children: A single center experience

    • Authors: Engy Mogahed, Hanaa El-Karaksy, Heba Zaki, Hala Abdullatif
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Background and aimAutoimmune hepatitis (AIH) has variable clinical manifestations and should be considered in the diagnostic work-up of any patient with cryptogenic liver disease. The aim of the study was to determine the clinical, biochemical, histopathological characteristics and treatment outcome of AIH in Egyptian children.Patients and methodsThis observational study was conducted at the Pediatric Hepatology Unit at Cairo University Pediatric Hospital, Egypt. All children (
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-03-02T12:56:59Z
      DOI: 10.1177/20587384211073265
      Issue No: Vol. 36 (2022)
  • Immune response against toxoplasmosis—some recent updates RH: Toxoplasma
           gondii immune response

    • Authors: Madiha Sana, Muhammad Rashid, Imran Rashid, Haroon Akbar, Jorge E Gomez-Marin, Isabelle Dimier-Poisson
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      AimsCytokines, soluble mediators of immunity, are key factors of the innate and adaptive immune system. They are secreted from and interact with various types of immune cells to manipulate host body’s immune cell physiology for a counter-attack on the foreign body. A study was designed to explore the mechanism of Toxoplasma gondii (T. gondii) resistance from host immune response.Methods and resultsThe published data on aspect of host (murine and human) immune response against T. gondii was taken from Google scholar and PubMed. Most relevant literature was included in this study. The basic mechanism of immune response starts from the interactions of antigens with host immune cells to trigger the production of cytokines (pro-inflammatory and anti-inflammatory) which then act by forming a cytokinome (network of cytokine). Their secretory equilibrium is essential for endowing resistance to the host against infectious diseases, particularly toxoplasmosis. A narrow balance lying between Th1, Th2, and Th17 cytokines (as demonstrated until now) is essential for the development of resistance against T. gondii as well as for the survival of host. Excessive production of pro-inflammatory cytokines leads to tissue damage resulting in the production of anti-inflammatory cytokines which enhances the proliferation of Toxoplasma. Stress and other infectious diseases (human immunodeficiency virus (HIV)) that weaken the host immunity particularly the cellular component, make the host susceptible to toxoplasmosis especially in pregnant women.Conclusion The current review findings state that in vitro harvesting of IL12 from DCs, Np and MΦ upon exposure with T. gondii might be a source for therapeutic use in toxoplasmosis. Current review also suggests that therapeutic interventions leading to up-regulation/supplementation of SOCS-3, IL12, and IFNγ to the infected host could be a solution to sterile immunity against T. gondii infection. This would be of interest particularly in patients passing through immunosuppression owing to any reason like the ones receiving anti-cancer therapy, the ones undergoing immunosuppressive therapy for graft/transplantation, the ones suffering from immunodeficiency virus (HIV) or having AIDS. Another imortant suggestion is to launch the efforts for a vaccine based on GRA6Nt or other similar antigens of T. gondii as a probable tool to destroy tissue cysts.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-03-01T06:48:41Z
      DOI: 10.1177/03946320221078436
      Issue No: Vol. 36 (2022)
  • PD-L1 expression in breast invasive ductal carcinoma with incomplete
           pathological response to neoadjuvant chemotherapy

    • Authors: Ahmad Alhesa, Heyam Awad, Sarah Bloukh, Mahmoud Al-Balas, Mohammed El-Sadoni, Duaa Qattan, Bilal Azab, Tareq Saleh
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objectives:To investigate the expression of programmed death-ligand 1 (PD-L1) in breast cancer in association with incomplete pathological response (PR) to neoadjuvant chemotherapy (NAC).MethodsPD-L1 expression was evaluated using immunohistochemistry in post-operative, post-NAC samples of 60 patients (n = 60) diagnosed with breast invasive ductal carcinoma with incomplete PR to NAC, including 31 matched pre-NAC and post-NAC samples (n = 31). PD-L1 protein expression was assessed using three scoring approaches, including the tumor proportion score (TPS), the immune cell score (ICS), and the combined tumor and immune cell score (combined positive score, CPS) with a 1% cut-off.ResultsIn the post-operative, post-NAC samples (n = 60), positive expression rate of PD-L1 was observed in 18.3% (11/60) of cases by TPS, 31.7% (19/60) by ICS, and 25% (15/60) by CPS. In matched samples, positive expression rate of PD-L1 was observed in 19.3% (6/31) of patients by TPS, 51.6% (16/31) by ICS, and 19.3% (6/31) by CPS in pre-NAC specimens, while it was observed in 22.6% (7/31) of matched post-NAC samples by TPS, 22.6% (7/31) by ICS, and 19.3% (6/31) by CPS. In the matched samples, there was a significant decrease in PD-L1 immunoexpression using ICS in post-NAC specimens (McNemar’s, p = 0.020), while no significant differences were found using TPS and CPS between pre- and post-NAC samples (p = 1.000, p = 0.617; respectively). PD-L1 immunoexpression determined by TPS or CPS was only significantly associated with ER status (p = 0.022, p = 0.021; respectively), but not with other clinicopathological variables. We could not establish a correlation between PD-L1 expression and the overall survival rate (p> 0.05). There were no significant differences in the tumor infiltrating lymphocytes count between the paired pre- and post-NAC samples (t = 0.581, p = 0.563 or Wilcoxon’s Signed Rank test; z = -0.625, p = 0.529).ConclusionOur findings indicate that PD-L1 protein expression in infiltrating immune cells was significantly reduced in breast tumors that developed incomplete PR following the exposure to NAC.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-02-28T10:09:37Z
      DOI: 10.1177/03946320221078433
      Issue No: Vol. 36 (2022)
  • Changes in immune profile affect disease progression in hepatocellular

    • Authors: Farshid Fathi, Reza F Saidi, Hamid Reza Banafshe, Mohsen Arbabi, Majid Lotfinia, Hossein Motedayyen
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Objective: Hepatocellular carcinoma (HCC) as a chronic liver condition is largely associated with immune responses. Previous studies have revealed that different subsets of lymphocytes play fundamental roles in controlling or improving the development and outcome of solid tumors like HCC. Hence, this study aimed to investigate whether immune system changes were related to disease development in HCC patients. Methods: Peripheral blood mononuclear cells were isolated from 30 HCC patients and 30 healthy volunteers using Ficoll density centrifugation. The isolated cells were stained with different primary antibodies and percentages of different immune cells were determined by flow cytometry. Results: HCC patients indicated significant reductions in the numbers of CD4+ cells, Tbet+IFNγ+cells, and GATA+IL-4+cells in peripheral blood in comparison with healthy individuals (p < 0.05). There was no significant change in IL-17+RORγt+cells between patient and healthy groups. In contrast, Foxp3+CD127lowcell frequency was significantly higher in patients than healthy subjects (p < 0.0001). The numbers of Th1, Th2, and Th17 cells were significantly lower in HCC patients than healthy control (p < 0.0001), although the reduction in Th2 cell numbers was not statistically significant. On the contrary, Treg percentage showed a significant increase in patients compared to healthy subjects (p < 0.0001). Other data revealed that Th1, Th2, and Th17 cell frequencies were significantly higher in healthy individuals than patients with different TNM stages of HCC, with the exception of Th2 in patients with stage II HCC (p < 0.01–0.05). Treg percentage was significantly increased in patients with different TNM stages (p < 0.0001). Among all CD4+ T cells, the frequency of Th2 cell was significantly associated with TNM stages of HCC (p < 0.05). Conclusion: Our data provide further evidence to show that immune changes may participate in determining HCC progression and disease outcome. However, it should be mentioned that more investigations are needed to clarify our results and explain possible impacts of other immune cells on the pathogenesis of HCC.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-02-28T06:09:20Z
      DOI: 10.1177/03946320221078476
      Issue No: Vol. 36 (2022)
  • C1q/TNF-related protein-1: Potential biomarker for early diagnosis of
           autism spectrum disorder

    • Authors: Hamed Raeisy, Paria Bayati, Farshid Noorbakhsh, Mitra Hakim Shooshtari, Mehrdad Eftekhar Ardebili, Mehdi Shekarabi, Nazanin Mojtabavi
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionAutism spectrum disorders (ASDs) are neurodevelopmental diseases characterized by communication inabilities, social interaction impairment, repetitive behavior, as well as learning problems. Although the exact mechanism underlying this disease is still obscure, researchers believe that several factors play a significant role in its development and pathogenesis. Some authors have reported an association between adipokines family and autism. C1q/TNF-related protein-1 (CTRP1) is a member of the adipokines family, and we hypothesized that this adipokine might have an influential role in the pathogenesis of ASDs. Since there is no specific marker for screening the disease, we evaluated CTRP1 as a potential marker for achieving this purpose.MethodsBlood samples were collected from 82 (41 ASDs boys, 41 healthy boys as controls) children aged 5–7 years old. CTRP1 gene expression and CTRP1 serum level were measured by quantitative realtime-PCR and enzyme-linked immunosorbent assay methods, respectively.ResultsIt was found that CTRP1 is significantly elevated in autistic children in comparison to healthy controls, both at the gene expression level, as well as at the serum level; demonstrating a good diagnostic value with a good range of sensitivity and specificity for detecting ASDs.ConclusionCTRP1 expression is elevated in ASDs boys aged 5–7 years old, suggesting a role for this adipokine in ASDs pathophysiology. Also, receiver operating characteristic curve analyses revealed that this adipokine could be utilized as a diagnostic biomarker for differentiating ASDs patients from healthy individuals along with other recently proposed biomarkers.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-02-24T10:25:20Z
      DOI: 10.1177/03946320221079471
      Issue No: Vol. 36 (2022)
  • Is there any predictor for relapse after treatment withdrawal in
           autoimmune hepatitis patients in the real life'

    • Authors: Bilger Çavuş, Filiz Akyuz, Raim İliaz, Alp Atasoy, Umit Akyuz, Kadir Demir, Fatih Besisik, Sabahattin Kaymakoglu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Backgrounds and AimsIn autoimmune hepatitis, there are uncertainties about whether to discontinue the treatment, when the treatment should be discontinued, and the risks of relapse in the cases where remission is achieved with immunosuppressive therapy. In this study, patients with AIH, whose immunosuppressive treatments were discontinued, were evaluated for the rates of remission and the risk of relapse.Materials and MethodsA total of 119 patients, who were diagnosed with AIH based on the AIHG scoring systems between 1990 and 2015, were evaluated. Patients were receiving standard azathioprine and steroid therapy. The treatment was discontinued in patients, who had been receiving treatment for at least 2 years, who had no clinical complaints, and whose aminotransferases were normal and when an increase occurred in AST values more than two times the normal after the treatment was interrupted, the case was considered as a relapse.ResultsAmong the patients, 83%(n = 99) were women. When the patients were diagnosed with AIH, their mean age was 36 ± 16(8–79) years; 70.6%(n = 84) were type 1, 3.4%(n = 4) type 2, and 26%(n = 31) were autoantibody-negative AIH. At the time of discontinuation, liver biopsy was performed in 8 of the patients and minimal-mild abnormalities were detected. Patients whose treatment was discontinued received treatment for an average of 101 ± 75(range: 24–280, median: 68.5) months; and, they were followed up for an average of 19 (1–110) months during the period without medication. Relapse occurred in 67%(n = 12) of the patients with drug withdrawal. Relapse occurred within the first 12 months in 67% of these patients (n = 8) and developed with an acute hepatitis attack in 42%. None of the clinical, laboratory, and histological data were found to be effective on relapse.ConclusionIn patients with AIH, relapse occurs in two-thirds of patients within an average of 19 month after the discontinuation of the medication. Most relapses occur at the early period and they are accompanied by an acute hepatitis attack.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-02-16T09:43:54Z
      DOI: 10.1177/03946320221077860
      Issue No: Vol. 36 (2022)
  • Quercetin attenuates the proliferation, inflammation, and oxidative stress
           of high glucose-induced human mesangial cells by regulating the
           miR-485-5p/YAP1 pathway

    • Authors: Huan Wan, Yaping Wang, Qingyun Pan, Xia Chen, Sijun Chen, Xiaohui Li, Weiguo Yao
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundDiabetic nephropathy (DN) is a kidney damage caused by diabetes and the main cause of end-stage renal disease. However, the current treatment of DN has many limitations. Quercetin is a bioflavonoid compound with therapeutic benefits in metabolic diseases. This study aims to determine the therapeutic potentials and underlying mechanism of quercetin on DN.MethodsWe collected blood samples from DN patients and healthy controls and treated human mesangial cells (HMCs) with high glucose (HG) to establish an in vitro model of DN. Then we assessed the expression difference of miR-485-5p as well as YAP1 in serum of DN patients and healthy controls and between HG-induced HMCs and control cells. qRT-PCR and western blot were performed to assess miR-485-5p and YAP1 expression levels; CCK-8 and ELISAs were used to examine cell proliferation, inflammation, and oxidative stress. Dual luciferase reporter assay was implemented to detect the binding of miR-485-5p and YAP1 mRNA sequence.ResultsQuercetin suppressed proliferation, inflammation, and oxidative stress of HMCs induced by HG. As for mechanism, miR-485-5p directly bound to YAP1 and inhibited YAP1 expression. The downregulation of miR-485-5p and upregulation of YAP1 were also observed in the serum of DN patients. Quercetin modulated miR-485-5p/YAP1 axis to regulate HG-induced inflammation and oxidative stress.Conclusion:Quercetin inhibits the proliferation, inflammation, and oxidative stress of HMCs induced by HG through miR-485-5p/YAP1 axis, which might provide a novel treatment strategy for DN.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-02-07T03:01:26Z
      DOI: 10.1177/20587384211066440
      Issue No: Vol. 36 (2022)
  • The effect of valproic acid on SLC5A8 expression in gonad-intact and
           gonadectomized rat thymocytes

    • Authors: Milda Juknevičienė, Ingrida Balnytė, Angelija Valančiūtė, Jūratė Stanevičiūtė, Kęstutis Sužiedėlis, Donatas Stakišaitis
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundValproic acid (VPA) pharmacological mechanisms are related to the anti-inflammatory and anti-viral effects. VPA is a histone deacetylases inhibitor and serves a role in its immunomodulatory impacts. VPA has complex effects on immune cell’s mitochondrial metabolism. The SLC5A8 transporter of short fatty acids has an active role in regulating mitochondrial metabolism. The study aimed to investigate whether SLC5A8 expresses the sex-related difference and how SLC5A8 expression depends on gonadal hormones, VPA treatment, and NKCC1 expression in rat thymocytes.MethodsControl groups and VPA-treated gonad-intact and gonadectomized Wistar male and female rats were investigated (n = 6 in a group). The VPA 300 mg/kg/day in drinking water was given for 4 weeks. The SLC5A8 (Slc5a8 gene) and NKCC1 (Slc12a2 gene) RNA expressions were determined by the RT-PCR method.ResultsThe higher Slc5a8 expression was found in the gonad-intact males than respective females (p = 0.004). VPA treatment decreased the Slc5a8 expression in gonad-intact and castrated males (p = 0.02 and p = 0.03, respectively), and increased in gonad-intact female rats compared to their control (p = 0.03). No significant difference in the Slc5a8 expression between the ovariectomized female control and VPA-treated females was determined (p> 0.05). VPA treatment alters the correlation between Slc5a8 and Slc12a2 gene expression in thymocytes of gonad-intact rats.ConclusionVPA effect on the Slc5a8 expression in rat thymocytes is gender- and gonadal hormone-dependent.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-02-05T05:45:22Z
      DOI: 10.1177/20587384211051954
      Issue No: Vol. 36 (2022)
  • Comparative study of six SARS-CoV-2 serology assays: Diagnostic
           performance and antibody dynamics in a cohort of hospitalized patients for
           moderate to critical COVID-19

    • Authors: Sameh Chamkhi, Tarak Dhaouadi, Imen Sfar, Salma Mokni, Alia Jebri, Dhouha Mansouri, Salma Ghedira, Emna Ben Jemia, Samia Ben Boujemaa, Mohamed Houissa, Hichem Aouina, Taïeb Ben Abdallah, Yousr Gorgi
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      BackgroundTo overcome the COVID-19 pandemic, serology assays are needed to identify past and ongoing infections. In this context, we evaluated the diagnostic performance of 6 immunoassays on samples from hospitalized patients for moderate to critical COVID-19.Methods701 serum samples obtained from 443 COVID-19 patients (G1: 356 positive RT-PCR patients and G2: 87 negative RT-PCR cases) and 108 pre-pandemic sera from blood donors were tested with 6 commercial immunoassays: (1) Elecsys Anti-SARS-CoV-2, Roche (Nucleocapsid, N), (2) Elecsys Anti-SARS-CoV-2 S, Roche (Spike, S), (3) Vidas SARS-COV-2 IgM/IgG, BioMérieux (S), (4) SARS-CoV-2 IgG, Abbott (N), (5) Access SARS-CoV-2 IgG, Beckman Coulter (Receptor Binding Domain), and (6) Standard F COVID-19 IgM/IgG Combo FIA, SD Biosensor (N).ResultsGlobal sensitivities of the evaluated assays were as follows: (1) Roche anti-N = 74.5% [69.6–79.3], (2) Roche anti-S = 92.7% [84.7–100], (3) Vidas IgM = 74.9% [68.6–81.2], (4) Vidas IgG = 73.9% [67.6–80.1], (5) Abbott = 78.6% [63.4–93.8], (6) Beckman Coulter = 74.5% [62–86.9], (7) SD Biosensor IgM = 73.1% [61–85.1], and (8) SD Biosensor IgG = 76.9% [65.4–88.4]. Sensitivities increased gradually from week 1 to week 3 as follow: (1) Roche anti-N: 63.3%, 81% and 82.1%; (2) Vidas IgM: 68.2%, 83.2% and 85.9%; and (3) Vidas IgG: 66.7%, 79.1% and 86.6%. All immunoassays showed a specificity of 100%. Seropositivity was significantly associated with a higher frequency of critical COVID-19 (50.8% vs. 38.2%), p = 0.018, OR [95% CI] = 1.668 [1.09–2.553]. Inversely, death occurred more frequently in seronegative patients (28.7% vs. 13.6%), p=3.02 E-4, OR [95% CI] = 0.392 [0.233–0.658].ConclusionEvaluated serology assays exhibited good sensitivities and excellent specificities. Sensitivities increased gradually after symptoms onset. Even if seropositivity is more frequent in patients with critical COVID-19, it may predict a recovery outcome.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-02-03T05:20:31Z
      DOI: 10.1177/20587384211073232
      Issue No: Vol. 36 (2022)
  • Protective effect of baicalin against arsenic trioxide-induced acute
           hepatic injury in mice through JAK2/STAT3 signaling pathway

    • Authors: Qianqian He, Xiaoqi Sun, Muqing Zhang, Li Chu, Yang Zhao, Yongchao Wu, Jianping Zhang, Xue Han, Shengjiang Guan, Chao Ding
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Baicalin (BA) is a kind of flavonoid that is isolated from Scutellaria baicalensis Georgi, which has been verified to have hepatoprotective effects in some diseases. However, the role of BA in acute hepatic injury induced by arsenic trioxide (ATO) remains unclear. The aim of this study was to investigate the protective action of BA on acute hepatic injury induced by ATO and to probe its possible mechanism. Mice were pretreated with BA (50, 100 mg/kg) by gavage. After 7 h, ATO (7.5 mg/kg) was injected intraperitoneally to induce liver injury. After 7 days of treatment, serum and hepatic specimens were collected and assayed to evaluate the hepatoprotective effect of BA. Pathological sections and the liver function index indicated that ATO caused significant liver injury. The fluorescence of reactive oxygen species and oxidative stress indicators showed that ATO also increased oxidative stress. The inflammatory markers in ATO-induced mice also increased significantly. Staining of the terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic factor assay showed that apoptosis increased. However, with BA pretreatment, these changes were significantly weakened. In addition, BA treatment promoted the expression of proteins related to the JAK2/STAT3 signaling pathway. The results suggest that BA can ameliorate acute ATO-induced hepatic injury in mice, which is related to the inhibition of oxidative stress, thereby reducing inflammation and apoptosis. The mechanism of this protection is potentially related to the JAK2/STAT3 signaling pathway.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-28T11:27:51Z
      DOI: 10.1177/20587384211073397
      Issue No: Vol. 36 (2022)
  • Garcinia kola treatment exhibits immunomodulatory properties while not
           affecting type 1 diabetes development in an experimental mouse model

    • Authors: Marina Cetkovic-Cvrlje, Shana Rogan, Emily Barbaro
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectiveT cells orchestrate an inflammatory response that destroys pancreatic insulin-producing β cells during the development of autoimmune type 1 diabetes (T1D). Garcinia kola Heckel (GK) is a plant widely exploited in West African traditional medicine. Some of the therapeutic effects of GK nut’s extract (GKE) have been suggested to be due to its anti-inflammatory potential. Since GKE has never been investigated in a T1D experimental model, nor in the T cells’ context, we aimed to determine whether GKE exhibits antidiabetic properties and affects T cells by its anticipated anti-inflammatory action.MethodsThe effect of aqueous GKE (aGKE) ingestion, 100 mg/kg daily by drinking water over the period of 6 weeks, has been tested in a low-dose streptozotocin-induced (LDSTZ) mouse model of autoimmune T1D. T cells were studied in vitro and in vivo in mice treated by aGKE.ResultsThe results showed that aGKE treatment, which started a week before induction of disease, neither delayed the development of T1D, nor reduced glycemia severity. Interestingly, aGKE treatment did affect T cells and their function, significantly decreasing the frequency of helper (TH) and cytotoxic (TC) T cells, while elevating the levels of pro-inflammatory cytokines, TNF-α, IL-6, and IFN-γ, and suppressing IL-2.ConclusionIn conclusion, our results did not confirm the antidiabetic property of GKE, while suggesting its therapeutic exploration in TH2-dependent pathologies that benefit from an aggravated TH1 response, such as allergies.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-18T06:00:43Z
      DOI: 10.1177/20587384211069831
      Issue No: Vol. 36 (2022)
  • Rapamycin as a potent and selective inhibitor of vascular endothelial
           growth factor receptor in breast carcinoma

    • Authors: Muhammad Shahidan Muhammad Sakri, Tengku Ahmad Damitri Al-Astani Tengku Din, Hasnan Jaafar, Vinod Gopalan, Wan Faiziah Wan Abdul Rahman
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-15T11:53:49Z
      DOI: 10.1177/20587384211059673
      Issue No: Vol. 36 (2022)
  • Enriched CD45RA−CD62L+ central memory T and decreased CD3+CD56+ natural
           killer T lymphocyte subsets in the rectum of ulcerative colitis patients

    • Authors: Masaya Iwamuro, Takahide Takahashi, Natsuki Watanabe, Takehiro Tanaka, Toshihiro Inokuchi, Sakiko Hiraoka, Fumio Otsuka, Hiroyuki Okada
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesTo investigate the distinctive features of lymphocytes promoting inflammation in ulcerative colitis.MethodsWe performed flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and colorectal mucosa lymphocytes in ulcerative colitis patients (n = 13) and control patients (n = 5).ResultsCD62L+/CD3+CD4+ (35.7 ± 14.0% vs. 19.9 ± 6.4%) and CD62L+/CD3+CD4− cells (17.1 ± 17.4% vs. 2.4 ± 3.9%) were higher in the rectum of ulcerative colitis patients than in control patients. Subpopulation analysis revealed that CD45RA−CD62L+/CD3+CD4+, that is, central memory T cell fraction in CD4+ T cells, was significantly increased in the rectum of ulcerative colitis, compared to that in control patients (23.3 ± 10.5% vs. 8.2 ± 4.0%). Comparison of rectum and colon samples in ulcerative colitis patients indicated that CD56+/CD3+ was decreased in the rectum compared to that in the colon (11.3 ± 12.5% vs. 21.3 ± 16.5%). The ratio of CD56+/CD3+ was also decreased in the rectum of active ulcerative colitis patients compared to that in ulcerative colitis patients at the endoscopic remission stages (2.8 ± 1.7% vs. 18.5 ± 13.3%).ConclusionWe demonstrated that CD62L+ T lymphocytes, particularly the CD45RA−CD62L+ T cell subset that represents central memory T cells, were increased in the rectum of patients with ulcerative colitis. In addition, the CD56+/CD3+ subset (natural killer T cells) was decreased in the rectum compared to that of less inflamed colonic mucosa. These results suggest that the enrichment of central memory T lymphocytes and the reduction of natural killer T cells in the gut mucosa are involved in the pathogenesis of ulcerative colitis.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-13T02:37:28Z
      DOI: 10.1177/20587384211051982
      Issue No: Vol. 36 (2022)
  • Elevated number of IL-21+ TFH and CD86+CD38+ B cells in blood of renal
           transplant recipients with AMR under conventional immuno-suppression

    • Authors: Jing Liu, Tongyu Tang, Zhihui Qu, Li Wang, Rui Si, Haifeng Wang, Yanfang Jiang
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      The objective of this study is to detect the number of different subsets of TFH and B cells in renal transplant recipients (RTR) with antibody-mediated acute rejection (AMR), acute rejection (AR), chronic rejection (CR), or transplant stable (TS). The present study was a prospective study. The numbers of ICOS +, PD-1+ and IL-21+ TFH, CD86+, CD38+, CD27+, and IgD- B cells in 21 patients with end-stage renal disease (ESRD) and post-transplant times were measured by flow cytometry. The level of serum IL-21 was detected by ELISA. The numbers of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, CD4+CXCR5+IL-21+ TFH, CD19+CD86+, and CD19 +CD86+CD38+ B cells as well as the level of serum IL-21 in the AMR, AR, and CR groups at post-transplantation were significantly higher than those at pre-transplantation. In contrast, the number of circulating CD19+CD27+IgD B cells was significantly increased in the TS groups in respect to the other groups. Moreover, the numbers of circulating CD4+CXCR5+IL-21+ TFH cells, CD19+CD86+CD38+ B cells as well as the level of serum IL-21 were positive related to the level of serum Cr while showing negative correlated with the values of eGFR in the AMR groups at post-transplantation for 4 and 12 weeks. Circulating TFH cells may be a biomarker in RTR with AMR, which can promote the differentiation of B cells into plasma cells by activating B cells, thereby promoting disease progression.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-11T02:26:20Z
      DOI: 10.1177/20587384211048027
      Issue No: Vol. 36 (2022)
  • Linear IGA bullous dermatosis potentially triggered by vaccination

    • Authors: Alberto Corrà, Veronica Bonciolini, Lavinia Quintarelli, Alice Verdelli, Marzia Caproni
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Linear IgA bullous dermatosis (LABD) is a mucocutaneous autoimmune blistering disease affecting both adults and children. It is caused by IgA antibodies targeting multiple antigens along the basement membrane zone, leading to disruption of dermoepidermal junction and development of bullous lesions which often presents in characteristic arrangement. Although most LABD cases have been reported to be idiopathic, different triggers have been described, including several drugs and infection. However, the occurrence of vaccine-induced cases of LABD is not widely known and accepted due to the few reports available. We present two cases of LABD occurred following different triggers, rising the suspicion for a possible pathogenetic role of vaccines.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-10T10:21:13Z
      DOI: 10.1177/20587384211021218
      Issue No: Vol. 36 (2022)
  • Cardioprotective effects of alantolactone on isoproterenol-induced cardiac
           injury and cobalt chloride-induced cardiomyocyte injury

    • Authors: Miaomiao Liu, Panpan Liu, Bin Zheng, Yu Liu, Li Li, Xue Han, Yangshuang Liu, Li Chu
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      ObjectivesAlantolactone (AL) is a compound extracted from the roots of Inula Racemosa that has shown beneficial effects in cardiovascular disease. However, the cardioprotective mechanism of AL against hypoxic/ischemic (H/I) injury is still unclear. This research aimed to determine AL’s ability to protect the heart against isoproterenol (ISO)-induced MI injury in vivo and cobalt chloride (CoCl2) induced H/I injury in vitro.MethodsElectrocardiography (ECG), lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) assays in addition to histological analysis of the myocardium were used to investigate the effects of AL in vivo. Influences of AL on L-type Ca2+ current (ICa-L) in isolated rat myocytes were observed by the patch-clamp technique. Furthermore, cell viability, apoptosis, oxidative stress injury, mitochondrial membrane potential, and intracellular Ca2+ concentration were examined in vitro.ResultsThe results indicated that AL treatment ameliorated the morphological and ECG changes associated with MI, and decreased levels of LDH, CK, and cTnI. Furthermore, pretreatment with AL elevated antioxidant enzyme activity and suppressed ROS production. AL prevented H/I-induced apoptosis, mitochondria damage, and calcium overload while reducing ICa-L in a concentration and time dependent fashion. The 50% inhibiting concentration (IC50) and maximal inhibitory effect (Emax) of AL were 17.29 μmol/L and 57.73 ± 1.05%, respectively.ConclusionAL attenuated MI-related injury by reducing oxidative stress, apoptosis, calcium overload, and mitochondria damage. These cardioprotective effects may be related to the direct inhibition of ICa-L.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-06T08:28:03Z
      DOI: 10.1177/20587384211051993
      Issue No: Vol. 36 (2022)
  • MicroRNA-30 inhibits the growth of human ovarian cancer cells by
           suppressing RAB32 expression

    • Authors: Yan Zhang, Min Zhou, Kun Li
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      IntroductionMicroRNAs (miRs) exhibit the potential to act as therapeutic targets for the management of human cancers including ovarian cancer. The role of microRNA-30 (miR-30) via modulation of RAB32 expression has not been studied in ovarian cancer. Consistently, the present study was designed to characterize the molecular role of miR-30/RAB32 axis in human ovarian cancer.MethodsCell viability was determined by MTT assay. Expression analysis was carried out by qRT-PCR. Dual luciferase assay was used to confirm the interaction between miR-30 and RAB32. Scratch-heal and transwell chamber assays were used to monitor the cell migration and invasion. Western blotting and immunofluorescence assays were used to determine the protein expression.ResultsThe results revealed significant (p < 0.05) downregulation of miR-30 in human ovarian cancer cell lines. Overexpression of miR-30 in ovarian SK-OV-3 and A2780 cancer cells significantly (p < 0.05) inhibited their proliferation. Besides, ovarian cancer cells overexpressing miR-30 showed significantly (p < 0.05) lower migration and invasion. The miR-30 upregulation also altered the expression pattern of marker proteins of epithelial–mesenchymal transition in ovarian cancer cells. In silico analysis predicted RAB32 as the molecular target of miR-30 at post-transcriptional level. The silencing of RAB32 mimicked the tumor-suppressive effects of miR-30 overexpression in ovarian cancer cells. Nonetheless, overexpression of RAB32 could prevent the tumor-suppressive effects of miR-30 on SK-OV-3 and A2780 cancer cells.ConclusionTaken together, the results suggest the tumor-suppressive role of miR-30 and point towards the therapeutic utility of miR-30/RAB32 molecular axis in the management of ovarian cancer
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-06T05:10:13Z
      DOI: 10.1177/20587384211058642
      Issue No: Vol. 36 (2022)
  • Abnormal sperm morphology is associated with sensitization to inhaled

    • Authors: Rafał Adamczak, Natalia Ukleja-Sokołowska, Magdalena Pasińska, Joanna Zielińska, Mateusz Leśny, Mariusz Dubiel
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Background: Allergy is associated with the loss of tolerance of environmental antigens, combined with a pathological immune response. There were no studies up to date that would show whether the quality of semen decreases in people with allergic diseases. Material and methods: The research included men who reported to the Gynecological Outpatient Clinic due to reproductive difficulties, defined as the lack of pregnancy after one year of regular intercourse. Semen quality was assessed according to the World Health Organization (WHO) standard. All patients underwent skin prick tests with the most important inhalation allergens (such as hazel, silver birch, mugwort, rye, dog, cat, Dermatophagoides farinae, Dermatophagoides pteronyssinus, alder, Alternaria alternata, Cladosporium herbarum, and grass mix). The data was statistically analyzed. Results: Results of 52 patients aged 25–52 years (34.62 ± 4.96) were analyzed. The mean BMI (Body mass index) was 28.25 (+ −3.77). It was found that 38 men (73%) had increased body weight, and 14 men (26.9%) were obese (BMI> = 30). 13 patients were smokers (25%), and 24 patients (46%) had skin tests positive for at least one inhaled allergen. Sperm tail defects were statistically more significant in patients allergic to birch, rye, cat, alder, and grass. In patients allergic to Alternaria alternata, head defects were statistically more significant (p < .05). No association was found between allergy to house dust mites, mugwort, hazel, and dogs and the deterioration of semen. Conclusion: Allergy due to inhalation allergens had an influence on the quality of male semen. Further research is necessary to establish the immunological bases of this phenomenon.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-05T10:11:36Z
      DOI: 10.1177/20587384211066718
      Issue No: Vol. 36 (2022)
  • Research on the mechanisms of taraxerol for the treatment of gastric
           cancer effect based on network pharmacology

    • Authors: Bingjie Huo, Yanru Song, Bibo Tan, Jianbo Li, Jie Zhang, Fengbin Zhang, Liang Chang
      Abstract: International Journal of Immunopathology and Pharmacology, Volume 36, Issue , January-December 2022.
      Background: Modern pharmacological studies have shown that traditional Chinese medicine (TCM) Taraxacum mongolicum possesses anti-cancer activity. Taraxerol (TRX) is a pentacyclic triterpene isolated from T. mongolicum, which is widely used in clinical treatment, and its anti-cancer effects have been extensively studied. However, the effects and molecular mechanism of TRX in gastric cancer (GC) have not been fully explicated. Methods: We used public databases to derive information on potential targets of TRX and proteins related to GC. Also, STRING and R3.6.2 software were used to analyze the protein–protein interaction (PPI). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were done to explain the potential mechanism underlying the regulatory role of TRX in GC. The role of TRX in GC was verified by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, apoptosis analysis, Transwell assay, and wound healing assay, and the key signaling pathways were verified. Results: We identified 135 potential targets for the treatment of GC via network pharmacological analysis. GO and KEGG enrichment analysis showed that steroid hormone receptor activity and the PI3K/AKT signaling pathway were the biological processes and pathways with the highest degree of enrichment. Additionally, cellular experiments revealed that TRX inhibited the proliferation, migration, and invasion of GC cells as well as induced G1 phase arrest and apoptosis in GC cells. Conclusion: Here, we used multi-target and multi-pathway network pharmacological analysis to verify the anti-cancer activity of TRX in GC. Also, in vitro experimental data were used to derive the potential molecular mechanism.
      Citation: International Journal of Immunopathology and Pharmacology
      PubDate: 2022-01-05T05:33:58Z
      DOI: 10.1177/20587384211063962
      Issue No: Vol. 36 (2022)
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