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Bosnian J. of Basic Medical Sciences     Open Access   (SJR: 0.441, CiteScore: 1)
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Bosnian Journal of Basic Medical Sciences
Journal Prestige (SJR): 0.441
Citation Impact (citeScore): 1
Number of Followers: 0  

  This is an Open Access Journal Open Access journal
ISSN (Print) 1512-8601 - ISSN (Online) 1840-4812
Published by FBIH Assoc of Basic Medical Sciences Homepage  [1 journal]
  • Evaluation of cerebrospinal fluid neurofilament light chain levels in
           multiple sclerosis and non-demyelinating diseases of the central nervous
           system: clinical and biochemical perspective

    • Authors: Burak Arslan, Gökçe Ayhan Arslan, Aslı Tuncer, Rana Karabudak, Aylin Sepici Dinçel
      Abstract: The neurofilament light chain (NfL) is a promising biomarker in the diagnosis, prognosis, and treatment response evaluation of neurological diseases. The aims of this study were to compare the cerebrospinal fluid (CSF) NfL levels in multiple sclerosis (MS) and certain non-demyelinating diseases of the central nervous system (NDCNS); to determine the relationship between clinical and radiological features and CSF NfL levels in patients with MS; and to compare the enzyme-linked immunosorbent assay (ELISA) and single molecule array (SIMOA) methods for NfL measurement using paired CSF and serum samples. We retrospectively analyzed the clinical data and performed NfL measurements in CSF and serum samples of newly diagnosed and treatment-naive patients with CNS diseases evaluated between 1 January 2019 and 1 January 2020. Eligible patients were divided into three groups: MS (n=23), differential diagnosis of MS (n=19), and NDCNS (n=42). First, we compared the CSF NfL levels among the three groups using the previously validated CSF ELISA assay. Next, we evaluated the relationship between CSF NfL levels and the clinical and radiological findings in MS group. Finally, we compared CSF and serum samples from patients of the MS groups (paired serum and CSF samples, n=19) using two different methods (ELISA and SIMOA). The CSF NfL level was the highest in the NDCNS group (1169.64 [535.92-5120.11] pg/mL, p=0.025). There was a strong positive correlation between the number of T2 lesions and CSF NfL level (r=0.786, p<0.001) in the MS group. There was excellent consistency between ELISA and SIMOA for CSF samples, but not for serum samples. Our results indicated that CSF NfL levels may also be used in the management of NDCNS and that SIMOA is the most reliable method for serum NfL determination.
      PubDate: 2022-04-30
      DOI: 10.17305/bjbms.2021.7326
      Issue No: Vol. 22, No. 2 (2022)
  • ROS responsive polyethylenimine-based fluorinated polymers for enhanced
           transfection efficiency and lower cytotoxicity

    • Authors: Peng Hua, Donglin Yang, Ruie Chen, Peiqi Qiu, Meiwan Chen
      Abstract: Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF12.5%, TKPF25% and TKPF50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Such gene vectors exhibited the following features: (1) fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions; (2) The fluorophilic effect mediated efficient cellular uptake and endosomal escape; (3) ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. Notably, TKPFs also exhibited great serum resistance in gene delivery and TKPF50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrates that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.
      PubDate: 2022-04-30
      DOI: 10.17305/bjbms.2021.6704
      Issue No: Vol. 22, No. 2 (2022)
  • LKB1 suppression promotes cardiomyocyte regeneration via LKB1-AMPK-YAP

    • Authors: Shuang Qu, Qiao Liao, Cheng Yu, Yue Chen, Han Luo, Xuewei Xia, Duofen He, Zaicheng Xu, Pedro A. Jose, Zhuxin Li, Wei Eric Wang, Qing Rex Lyu, Chunyu Zeng
      Abstract: The regenerative potential of cardiomyocytes in adult mammals is limited. Previous studies reported that cardiomyocyte proliferation is suppressed by AMP-activated protein kinase (AMPK). The role of liver kinase B1 (LKB1), as the major upstream kinase for AMPK, on cardiomyocyte proliferation is unclear. In this study, we found that the LKB1 levels rapidly increased after birth. With loss- and gain-of-function study, our data demonstrated that LKB1 levels negatively correlate with cardiomyocyte proliferation. We next identified Yes-associated protein (YAP) as the downstream effector of LKB1 using high-throughput RNA sequencing. Our results also demonstrated that AMPK plays an essential role in Lkb1 knockdown-induced cardiomyocyte proliferation. Importantly, deactivated AMPK abolished the LKB1-mediated regulation of YAP nuclear translocation and cardiomyocyte proliferation. Thus, our findings suggested the role of LKB1-AMPK-YAP axis during cardiomyocyte proliferation, which could be used as a potential target for inducing cardiac regeneration after injury.
      PubDate: 2022-04-29
      DOI: 10.17305/bjbms.2021.7225
      Issue No: Vol. 22, No. 2 (2022)
  • Role and Significance of c-KIT Receptor Tyrosine Kinase in Cancer: A

    • Authors: Emana Sheikh, Tony Tran, Semir Vranic, Arkene Levy, R. Daniel Bonfil
      Abstract: c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.
      PubDate: 2022-04-27
      DOI: 10.17305/bjbms.2021.7399
      Issue No: Vol. 22, No. 2 (2022)
  • Genetic risk factors in melanoma etiopathogenesis and the role of genetic
           counseling: A concise review

    • Authors: Semir Vranic, Nikola Serman, Mislav Glibo, Ljiljana Serman, Zrinka Bukvic Mokos
      Abstract: Melanoma is a highly aggressive cancer originating from melanocytes. Its etiopathogenesis is strongly related to genetic, epigenetic, and environmental factors. Melanomas encountered in clinical practice are predominantly sporadic, whereas hereditary melanomas account for approximately 10% of the cases. Hereditary melanomas mainly develop due to mutations in the CDKN2A gene, which encodes two tumor suppressor proteins involved in the cell cycle regulation. CDKN2A, along with CDK4, TERT, and POT1 genes, is a high-risk gene for melanoma. Among the genes that carry a moderate risk are MC1R and MITF, whose protein products are involved in melanin synthesis. The environment also contributes to the development of melanoma. Patients at risk of melanoma should be offered genetic counseling to discuss genetic testing options and the importance of skin UV protection, avoidance of sun exposure, and regular preventive dermatological examinations. Although cancer screening cannot prevent the development of the disease, it allows for early diagnosis when the survival rate is the highest.
      PubDate: 2022-04-21
      DOI: 10.17305/bjbms.2021.7378
      Issue No: Vol. 22, No. 2 (2022)
  • First-line treatment of patients with HER2-positive metastatic gastric and
           gastroesophageal carcinoma

    • Authors: Selin Aktürk Esen, Yakup Ergun, Cihan Erol, Rukiye Arikan, Muhammed Muhiddin Er, Muhammed Mustafa Atci, Atakan Topçu, Gökhan Uçar, Baran Akagündüz, Musa Bariş Aykan, Miraç Özen, Naziyet Köse Baytemur, Melike Özçelik, Elif Şahin , Denizcan Güven , Serkan Menekşe, Naziye Ak, Fatih Teker, Engin Kut, Teoman Şakalar, Özkan Alan, Turgut Kaçan , Nazim Serdar Turhal, Saadettin Kiliçkap, Sema Türker , Mehmet Ali Nahit Şendur, Osman Köstek, Mustafa Karaağaç , Abdullah Sakin , Haci Mehmet Türk, Dilek Çağlayan , Şener Cihan, Yusuf Açikgöz , Doğan Uncu
      Abstract: Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, FOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.
      PubDate: 2022-04-17
      DOI: 10.17305/bjbms.2021.7069
      Issue No: Vol. 22, No. 2 (2022)
  • Acceptance, effects, and tolerability in the vaccination process against
           SARS-CoV-2 virus among cancer patients in Bosnia and Herzegovina: a
           single-center cross-sectional study

    • Authors: Timur Ceric, Emir Sokolović, Anes Pašić, Emina Borovac-Gurda, Velda Smajlbegović, Berisa Hasanbegović, Emina Bičakčić Filipović, Elma Kapisazović, Selma Sokolović, Semir Bešlija
      Abstract: The SARS-CoV-2 pandemic has been the main public health issue since the end of 2019. The vaccination campaign in Bosnia and Herzegovina started in April 2021, with several vaccines available. Our study aimed to evaluate the acceptance, effects, and tolerability of vaccines against SARS-COV 2 virus among cancer patients. We conducted a cross-sectional, observational study between 22 October and 30 November 2021, at the Clinic of Oncology, Clinical Center University of Sarajevo. Patients were enrolled during their regular visit to the Clinic of Oncology by agreeing to complete an individual paper questionnaire. The study included 1063 patients with malignant diseases, of whom 681 (64.1%) were adequately vaccinated patients. In the study population, 76.9% of patients reported that they did not experience any side effects due to vaccination, while only 0.5% had side effects, causing a delay in their treatment. Among adequately vaccinated patients, there were 40 patients (3.8%) who were infected with SARS-CoV-2 after the second or booster dose of the vaccine. Five patients (0.5%) were hospitalized due to COVID-19 after being adequately vaccinated. The findings of our study suggest that cancer patients have a higher acceptance of vaccines against SARS-CoV-2 than the general population in Bosnia and Herzegovina. Vaccination side effects are tolerable and do not cause major delays in specific cancer treatment. The protective effects of SARS-CoV-2 vaccines in the cancer patients presented in our study are comparable to available results of similar studies, which included the general population.
      PubDate: 2022-04-08
      DOI: 10.17305/bjbms.2021.7134
      Issue No: Vol. 22, No. 2 (2022)
  • Strategies and safety considerations of booster vaccination in COVID-19

    • Authors: Hanyan Meng, Jianhua Mao, Qing Ye
      Abstract: First-generation SARS-CoV-2 vaccines have played a significant role in controlling the COVID-19 pandemic, preventing severe diseases, and reducing mortality. However, the continuous emergence of SARS-CoV-2 variants, the persistence of breakthrough infections, and the seemingly rapid decline in the protective efficacy of SARS-CoV-2 vaccines have presented additional challenges for the next phase. There is an urgent need to confirm the necessity of further booster vaccination and combination vaccine approaches. This paper summarizes the latest literature on SARS-CoV-2 variants and vaccine effectiveness and concludes that it is essential to implement booster immunization strategies. Priority should be given to high-risk groups, the elderly, and immunocompromised people. In addition, heterologous vaccination has a longer duration of effect and a broader spectrum than homologous vaccination, making it more conducive to managing the immune escape of SARS-CoV-2 variants.
      PubDate: 2022-04-03
      DOI: 10.17305/bjbms.2021.7082
      Issue No: Vol. 22, No. 2 (2022)
  • Exploring autophagy related prognostic genes of Alzheimer's disease
           based on pathway crosstalk analysis

    • Authors: Fang Qian, Wei Kong, Shuaiqun Wang
      Abstract: Recent studies have shown that different signaling pathways are involved in the pathogenesis of Alzheimer's disease (AD), with complex molecular connections existing between these pathways. Autophagy is crucial for the degradation and production of pathogenic proteins in AD, and it shows link with other AD-related pathways. However, current methods for identifying potential therapeutic targets for AD are primarily based on single-gene analysis or a single signal pathway, both of which are somewhat limited. Finding other methods is necessary for providing novel underlying AD therapeutic targets. Therefore, given the central role of autophagy in AD and its interplay with its pathways, we aimed to identify prognostic genes related to autophagy within and between these pathways based on pathway crosstalk analysis. The method of pathway analysis based on global influence (PAGI) was applied to find the feature mRNAs involved in the crosstalk between autophagy and other AD-related pathways. Subsequently, the weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression module of feature mRNAs and differential lncRNAs. Finally, based on 2 autophagy-related crosstalk genes (CD40 and SMAD7), we constructed a prognosis model by multivariate Cox regression, which could predict the overall survival of AD patients with medium-to-high accuracy. In conclusion, we provided an effective method for extracting autophagy-related significant genes based on pathway crosstalk in AD. We found the biomarkers valuable to the AD prognosis, which may also play an essential role in the development and treatment of AD.
      PubDate: 2022-04-02
      DOI: 10.17305/bjbms.2021.7019
      Issue No: Vol. 22, No. 2 (2022)
  • Astrocytes and human artificial blood-brain barrier models

    • Authors: Tanja Zidarič, Lidija Gradišnik, Tomaž Velnar
      Abstract: The blood-brain barrier (BBB) functions as a highly selective border of endothelial cells, protecting the central nervous system from potentially harmful substances by selectively controlling the entry of cells and molecules, including components of the immune system. To study the BBB properties, find suitable therapies, and identify new drug targets, there is a need to develop representative in vitro BBB models. In this article, we describe the astrocyte roles in the BBB functioning and human in vitro BBB models.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6943
      Issue No: Vol. 22, No. 2 (2022)
  • Call for emergency action to limit global temperature increases, restore
           biodiversity, and protect health

    • Authors: Lukoye Atwoli, Abdullah H. Baqui, Thomas Benfield, Raffaella Bosurgi, Fiona Godlee, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Carlos Augusto Monteiro, Ian Norman, Kirsten Patrick, Nigel Praities, Marcel Olde Rikkert, Eric J. Rubin, Peush Sahni, Richard Smith, Nicholas J Talley, Sue Turale, Damián Vázquez
      Pages: 153 - 155
      Abstract: The UN General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (COP26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature, and protect health. Read more in  PDF.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6411
      Issue No: Vol. 22, No. 2 (2022)
  • Role of dynamic contrast enhanced magnetic resonance imaging in the
           diagnosis and management of vascular lesions of the head and neck

    • Authors: Raluca Petea-Balea, Manuela Lenghel , Horatiu Rotar, Cristian Dinu, Simion Bran, Florin Onisor, Rares Roman, Simona Senila, Csaba Csutak, Anca Ciurea
      Pages: 156 - 163
      Abstract: Vascular anomalies comprise a wide and heterogeneous group of lesions that may be found in all parts of the body, with most of the cases of vascular malformations involving the head and neck region. Ultrasound (US) is the reliable first-line imaging technique to assess flow parameters. However, in some cases, US fails to depict the real extent of the lesions. On the other hand, magnetic resonance imaging (MRI) allows the evaluation of the full extension and anatomic relationship of the vascular anomalies with the neighboring structures and provides hemodynamic characterization using dynamic contrast enhanced MRI (DCE-MRI), avoiding unnecessary invasive catheter-based procedures. DCE-MRI angiography can make a distinction between low and high flow vascular anomalies and it is useful for selecting adequate therapy and appreciating prognosis. The aim of this paper is to review the role of DCE -MRI in the evaluation of flow characteristics and lesion extent in vascular anomalies of the head and neck region.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6019
      Issue No: Vol. 22, No. 2 (2022)
  • Poorly differentiated clusters and tumor budding are important prognostic
           factors in colorectal carcinomas

    • Authors: Aura Jurescu, Alis Dema, Adrian Văduva, Adelina Gheju, Octavia Vița, Robert Barna, Codruța Lăzureanu, Marioara Cornianu, Sorina Tăban, Ciprian Duță, Stelian Pantea
      Pages: 164 - 177
      Abstract: The aim of our study was to assess the prognostic value of the two new grading systems based on the quantification of tumor budding - TB (GBd) and poorly differentiated clusters - PDCs (PDCs-G) in colorectal carcinomas (CRC). We performed a retrospective study on 71 CRC patients who underwent surgery at the Emergency County Hospital, Timișoara. CRC cases were classified based on haematoxylin-eosin slides, using the conventional grading system, GBd and PDCs-G, respectively. We used two-tier and three-tier grading schemes for each system. Subsequently,  we evaluated  associations with other prognostic factors in CRC. Based on the three-tier GBd (GBd-3t)  most cases (34/69, 49.27%) were classified as G3Bd-3t, while based on the conventional grading system, the majority of the cases (55/69, 79.71%) were considered G2. On the other hand, based on the three-tier PDCs-G system (PDCs-G-3t), most cases (31/69, 44.93%) were PDCs-G2-3t. We also noted a more significant association of GBd-3t with other prognostic parameters analyzed, as compared to the conventional grading system. Nodal status, tumor stage, and lymphovascular invasion were strongly correlated with GBd-3t (p=0.0001). Furthermore, we noted that PDCs-G-3t correlated more significantly than the conventional grading system with nodal status (p<0.0001), tumor stage (p=0.0003), lymphovascular invasion (p<0.0001), perineural invasion (p=0.005) and the tumor border configuration (p<0.0001). High GBd and PDCs-G grades correlate directly with other negative prognostic factors in CRC.Thus, these new parameters/classification methods could be used as additional tools for risk stratification in patients with CRC.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6110
      Issue No: Vol. 22, No. 2 (2022)
  • Inflammatory cells in the ascending aortic aneurysm in patients with type
           2 diabetes versus patients with hypertension

    • Authors: Aleksandra Milutinović, Ruda Zorc-Pleskovič
      Pages: 178 - 184
      Abstract: Aortic aneurysms occur relatively frequently in the ascending thoracic aorta, but are rarely seen in patients with type 2 diabetes. Our aim was to evaluate inflammatory cell infiltration in the ascending aortic aneurysm wall in patients with diabetes without arterial hypertension (DM2 group, N=6) versus hypertensive non-diabetic patients (AH group, N=34). For histologic analysis, the sections were stained with hematoxylin-eosin and Movat pentachrome. The immunohistochemical staining was used to analyze the infiltration of pro-inflammatory (CD68) and anti-inflammatory macrophages (CD163), T helper (CD4) and T killer cells (CD8), and B (CD79a) and plasma cells (CD138) in all three layers of aneurysms of both groups. The statistical significance of the differences between groups was evaluated by ANOVA and the Welch test. In comparison to the AH group, the DM2 group developed less severe infiltration of pro-inflammatory macrophages (P=0.004) and B cells (P=0.025) in the tunica intima, and tunica media (P=0.049, P=0.007, respectively), and fewer plasma cells in the tunica media (P=0.024) and tunica adventitia (P=0.017). We found no significant differences in the number of T helper, T killer cells, and anti-inflammatory macrophages and in the amount of collagen and elastic fibers, ground substance, and smooth muscle cells in all three layers of the vessel wall. Except in tunica adventitia of DM2 group, there were more collagen fibers overall (P=0.025).  Thus, we conclude that the histological structure of the aneurysm in diabetics without hypertension is almost the same as in hypertensive patients without diabetes. Diabetics had significantly less inflammatory infiltration in all three layers of the vessel wall, and more collagen fibers in tunica adventitia.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6488
      Issue No: Vol. 22, No. 2 (2022)
  • Quercetin ameliorates testosterone secretion disorder by inhibiting
           endoplasmic reticulum stress through the miR-1306-5p/HSD17B7 axis in
           diabetic rats

    • Authors: Di Wang, Yan Li, Qian-qian Zhai, Yun-feng Zhu, Bei-yan Liu, Yun Xu
      Pages: 191 - 204
      Abstract: Testicular damage and testosterone secretion disorder are associated with diabetes mellitus. Quercetin,  a common flavonoid, has antioxidant, anti-cancer,  and blood sugar lowering effects. Therefore, this study aims to investigate the effect of quercetin on the reproductive system of male rats with diabetes in vivo and in vitro and elucidate its mechanism. Streptozotocin (STZ)  induction was used to establish a diabetes model in forty male Sprague Dawley (SD) rats, which were subsequently administered with 20 or 50 mg/kg of quercetin. Leydig cells of rat testes were treated by high glucose (HG) followed by 5 or 10 μM quercetin. Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose,and inhibited oxidative stress. RT-qPCR and Western blotting revealed that quercetin alleviated STZ-induced testicular damage and promoted testosterone synthesis. Both doses of quercetin reduced ROS and MDA levels, and increased SOD level in HG-treated cells. Both, in vivo and in vitro results confirmed that a high dose of quercetin was more effective. MiR-1306-5p was upregulated in testicular tissue of diabetic rats and HG-treated cells. 17β-hydroxysteroid dehydrogenase (HSD17B7) was a target of miR-1306-5p and HSD17B7 was downregulated in STZ-induced rat tissues and HG-treated cells. HSD17B7 overexpression reversed the increase of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (Grp78) protein levels as well as eIF2α phosphorylation level and promotion of cell apoptosis caused by miR-1306-5p overexpression. Moreover, overexpression of HSD17B7 activated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis in HG-treated cells. In conclusion, quercetin inhibits ER stress and improves testosterone secretion disorder through the miR-1306-5p/HSD17B7 axis in diabetic rats.

      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6299
      Issue No: Vol. 22, No. 2 (2022)
  • CircFOXM1 promotes the proliferation, migration, invasion, and
           glutaminolysis of glioblastoma by regulating the miR-577/E2F5 axis

    • Authors: Xuhui Fan, Meng Liu, Li Fei, Zhihui Huang, Yufeng Yan
      Pages: 205 - 216
      Abstract: Circular RNA (circRNA) is a key regulator of tumor progression. However, the role of circFOXM1 in glioblastoma (GBM) progression is unclear. The aim of this study was to investigate the role of circFOXM1 in GBM progression. The expression levels of circFOXM1, miR-577, and E2F transcription factor 5 (E2F5) were examined by real-time quantitative polymerase chain reaction. Cell counting kit 8 assay, EdU staining, and transwell assay were used to detect cell proliferation, migration, and invasion. The levels of glutamine, glutamate, and α-ketoglutarate were determined to evaluate the glutaminolysis ability of cells. Protein expression was tested by Western blot analysis. Dual-luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation assay were employed to verify the interaction between miR-577 and circFOXM1 or E2F5. Mice xenograft model for GBM was constructed to perform in vivo experiments. Our results showed that circFOXM1 was highly expressed in GBM tumor tissues and cells. Silencing of cir FOXM1 inhibited GBM cell proliferation, migration, invasion, glutaminolysis, as well as tumor growth. MiR-577 could be sponged by circFOXM1, and its inhibitor could reverse the suppressive effect of circFOXM1 downregulation on GBM progression. E2F5 was a target of miR-577, and the effect of its knockdown on GBM progression was consistent with that of circFOXM1 silencing. CircFOXM1 positively regulated E2F5 expression, while miR-577 negatively regulated E2F5 expression. In conclusion, our data confirmed that circFOXM1 could serve as a sponge of miR-577 to enhance the progression of GBM by targeting E2F5, which revealed that circFOXM1 might be a biomarker for GBM treatment.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6028
      Issue No: Vol. 22, No. 2 (2022)
  • The long-term outcome and risk factors for precursor B cell acute
           lymphoblastic leukemia without specific fusion genes in Chinese children:
           experiences from multiple centers

    • Authors: Pinli Zou, Min Zhou, Jinquan Wen, Xin Liao, Yali Shen, Haiyan Liu, Lin Song, Jianwen Xiao
      Pages: 238 - 246
      Abstract: Specific fusion genes play important roles as risk factors for strategic treatment in pediatric B-cell acute lymphoblastic leukemia (B-ALL), and the risk factors in patients without common fusion genes have not been well demonstrated. We collected and analyzed clinical and laboratory findings, treatment responses and outcomes in B-ALL patients without specific fusion genes. Whole-exome sequencing (WES) and/or RNA sequencing (RNAseq) data from bone marrow relapsed patients were also analyzed. 283 patients were enrolled in the study. Traditional elements and treatment responses at different time points (TPs) were evaluated to classify risk groups and adjust the treatment strategy. Treatment-related mortality was found in 11 (3.89%) patients, 49 (17.31%) patients relapsed, and the ten-year prospective event-free survival (pEFS) was 78.2±2.5%. Univariate analysis revealed that significant differences were not found in the pEFS of traditional risk factors, including sex, age, WBC count or chromosome status; good responses of BM smears at TP1 and minimal residual disease (MRD) levels at TP2 and TP3 were strongly associated with prolonged pEFS. Compared with the IR or the HR group, patients in the SR group presented with longer pEFS and a lower relapse rate. Multivariable analysis of outcomes and hazard ratios revealed that a positive MRD level was a key risk factor. WES or RNAseq was performed for BM relapse patients, and adverse and unreported genetic abnormalities were discovered. Favorable outcomes were acquired in the cohort. The study results showed that traditional risk factors and poor prednisone response were overcome by modified chemotherapy, and a positive MRD level was a key risk factor in these patients. NGS is needed to discover more risk-related molecular abnormalities.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.5879
      Issue No: Vol. 22, No. 2 (2022)
  • Altered molecular pathways and prognostic markers in active systemic
           juvenile idiopathic arthritis: integrated bioinformatic analysis

    • Authors: Yi Ren, Hannah Labinsky, Andriko Palmowski, Henrik Bäcker, Michael Müller, Arne Kienzle
      Pages: 247 - 260
      Abstract: Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and extra-articular symptoms. While recent advances have unraveled a range of risk factors, the pathomechanisms involved in SJIA and potential prognostic markers for treatment success remain partly unknown. In this study, we included 70 active SJIA and 55 healthy control patients from the National Center for Biotechnology Information to analyze for differentially expressed genes (DEGs) using R. Functional enrichment analysis, protein-protein interaction (PPI), and gene module construction were performed for DEGs and hub gene set. We additionally examined immune system cell composition with CIBERSORT and predicted prognostic markers and potential treatment drugs for SJIA. In total, 94 upregulated and 24 downregulated DEGs were identified. Two specific modules of interest and eight hub genes (ARG1, DEFA4, HP, MMP8, MMP9, MPO, OLFM4, PGLYRP1) were screened out. Functional enrichment analysis suggested that complex neutrophil-related functions play a decisive role in the disease pathogenesis. CIBERSORT indicated neutrophils, M0 macrophages, CD8+ T cells, and naïve B cells to be relevant drivers of disease progression. Additionally, we identified TPM2 and GZMB as potential prognostic markers for treatment response to canakinumab. Moreover, sulindac sulfide, (-)-catechin, and phenanthridinone were identified as promising treatment agents. This study provides a new insight into molecular and cellular pathogenesis of active SJIA and highlights potential targets for further research.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6016
      Issue No: Vol. 22, No. 2 (2022)
  • Construction and validation of a preterm birth risk assessment model using
           fuzzy analytic hierarchy process

    • Authors: Stavroula Barbounaki, Antigoni Sarantaki
      Pages: 291 - 299
      Abstract: Preterm births account for almost 1 million deaths globally. The objective of this study is to develop and evaluate a model that assists clinicians in assessing the risk of preterm birth, using fuzzy multicriteria analysis. The model allows experts to incorporate their intuition and judgment into the decision-making process and takes into consideration six (6) risk dimensions reflecting the socio-economic, behavioural and medical profile of pregnant women, thus adopting a holistic approach to risk assessment. Each risk dimension is further analysed and measured in terms of risk factors associated with it. Data was collected from a selected group of 35 experts, each one with more than 20 years of obstetric experience. The model criteria were selected after a thorough literature analysis, so as to ensure a holistic approach to risk assessment. The criteria were reviewed by the experts and the model structure was finalised. The fuzzy analytic hierarchy method was applied to calculate the relative importance of each criterion and subsequent use of the model in assessing and ranking pregnant women by their preterm risk. The proposed model utilises fuzzy logic and multicriteria analysis. It addresses the multifactorial nature of decision making when assessing the preterm birth risk. It also incorporates the obstetricians’ intuitive judgement during risk assessment and it can be used to classify cases based upon their risk level. Additionally, it can be applied to evaluate the risk of individual cases in a personalised manner. The proposed model is compared and validated for its predictive value against judgments made by experts. 
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6431
      Issue No: Vol. 22, No. 2 (2022)
  • Selection of optimal therapeutic modality for early-stage extranodal
           natural killer/T-cell lymphoma patients under the guidance of
           single-nucleotide polymorphism signature

    • Authors: Zhe-Sheng Chen, Dong-Hua Yang
      Pages: 300 - 301
      Abstract: The therapeutic modalities of early-stage and advanced extranodal natural killer/T-cell lymphoma (NKTCL) patients are completely different. The former is mainly radiotherapy with or without chemotherapy, while the latter relies on chemotherapy-based systemic treatment. According to Ann Arbor staging system, approximately 70% of the NKTCL patients are classified as early-stage cases who are promising to be cured.Considering NKTCL is sensitive to radiation but may be resistant to chemotherapy, the radiotherapy is considered to be the most important treatment for some early-stage patients with a satisfactory local control rate and could be used alone. However, systemic recurrence after radiotherapy in a portion of NKTCL patients seriously affects their long-term survival, and the first-line treatment combined with radiotherapy and chemotherapy is considered necessary. Therefore, the use of radiotherapy alone in early-stage NKTCL is still a controversial issue. Read more in PDF.
      PubDate: 2022-04-01
      DOI: 10.17305/bjbms.2021.6419
      Issue No: Vol. 22, No. 2 (2022)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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