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- Medicines, Vol. 11, Pages 14: Cytokine Storm in COVID-19: Insight into
Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal Medicines Authors: Qingyuan Yu, Xian Zhou, Rotina Kapini, Anthony Arsecularatne, Wenting Song, Chunguang Li, Yang Liu, Junguo Ren, Gerald Münch, Jianxun Liu, Dennis Chang First page: 14 Abstract: Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS. Citation: Medicines PubDate: 2024-07-18 DOI: 10.3390/medicines11070014 Issue No: Vol. 11, No. 7 (2024)
- Medicines, Vol. 11, Pages 15: Deciphering Mechanisms, Prevention
Strategies, Management Plans, Medications, and Research Techniques for Strokes in Systemic Lupus Erythematosus Authors: Ola A. Al-Ewaidat, Moawiah M. Naffaa First page: 15 Abstract: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic condition characterized by an unpredictable course and a wide spectrum of manifestations varying in severity. Individuals with SLE are at an increased risk of cerebrovascular events, particularly strokes. These strokes manifest with a diverse range of symptoms that cannot be solely attributed to conventional risk factors, underscoring their significance among the atypical risk factors in the context of SLE. This complexity complicates the identification of optimal management plans and the selection of medication combinations for individual patients. This susceptibility is further complicated by the nuances of neuropsychiatric SLE, which reveals a diverse array of neurological symptoms, particularly those associated with ischemic and hemorrhagic strokes. Given the broad range of clinical presentations and associated risks linking strokes to SLE, ongoing research and comprehensive care strategies are essential. These efforts are critical for improving patient outcomes by optimizing management strategies and discovering new medications. This review aims to elucidate the pathological connection between SLE and strokes by examining neurological manifestations, risk factors, mechanisms, prediction and prevention strategies, management plans, and available research tools and animal models. It seeks to explore this medical correlation and discover new medication options that can be tailored to individual SLE patients at risk of stroke. Citation: Medicines PubDate: 2024-07-31 DOI: 10.3390/medicines11070015 Issue No: Vol. 11, No. 7 (2024)
- Medicines, Vol. 11, Pages 16: Postoperative Nausea and Vomiting in the
Ambulatory Surgery Center: A Narrative Review Authors: Justin Bell, Adam Bindelglass, Jennifer Morrone, Sherwin Park, Ana Costa, Sergio Bergese First page: 16 Abstract: Postoperative nausea and vomiting (PONV) is a common complication of ambulatory surgery, leading to numerous deleterious effects such as decreased patient satisfaction, prolonged recovery unit stays, and rarely, more serious complications such as aspiration pneumonia or wound dehiscence. In this paper, we present a narrative review of the literature regarding common risk factors for PONV including patient factors, surgical factors, and anesthetic factors. We then will review anesthetic techniques and antiemetic drugs demonstrated to mitigate the risk of PONV. Finally, we discuss the potential economic benefits of PONV prophylaxis in the perioperative ambulatory setting. Citation: Medicines PubDate: 2024-08-09 DOI: 10.3390/medicines11070016 Issue No: Vol. 11, No. 7 (2024)
- Medicines, Vol. 11, Pages 12: Incidence and Outcomes of COVID-19 Vaccine
Hypersensitivity Reactions and Success of COVID-19 Vaccine Provocation Tests Post Previous COVID-19 Vaccine Hypersensitivity Authors: Adi Kurniawan, Sukamto Koesnoe, Evy Yunihastuti, Hamzah Shatri First page: 12 Abstract: Background: The COVID-19 pandemic has led to high mortality rates. There have been reports of hypersensitivity reactions with mild to severe symptoms. The COVID-19 vaccine provocation test is a vaccination protocol for individuals with a history of hypersensitivity. This study aims to determine the benefits of COVID-19 vaccine provocation tests in patients with a history of hypersensitivity reactions to COVID-19 vaccines and its influencing factors. Objective: To determine the incidence, severity, outcome of hypersensitivity reactions, and success of the COVID-19 vaccine provocation test. Methods: A retrospective cohort study was conducted, using subjects taken from medical record data at the RSCM who had received COVID-19 vaccination with a history of hypersensitivity. Data was taken from the COVID-19 vaccination records at the RSCM, BPJS Health Primary Care application. Results: From a total of 29,036 doses of the COVID-19 vaccine, 44 patients experienced hypersensitivity reactions. As many as 38.64% did not continue vaccination, 2.27% experienced mild hypersensitivity, and 59.44% were successfully vaccinated. Conclusions: People with a history of hypersensitivity reactions to COVID-19 vaccines can still receive subsequent COVID-19 vaccinations at healthcare facilities equipped with anaphylaxis kits and immunology allergists. Citation: Medicines PubDate: 2024-05-27 DOI: 10.3390/medicines11060012 Issue No: Vol. 11, No. 6 (2024)
- Medicines, Vol. 11, Pages 13: An Unusual Case of Immune Complex-Mediated
Membranoproliferative Glomerulonephritis as Renal Manifestation of Idiopathic Hypereosinophilic Syndrome: A Case Report and Literature Review Authors: Michael Cieza-Terrones, José C. De La De La Flor, Christian Requejo, Daniel Villa, Jacqueline Apaza, Pablo Rodríguez-Doyágüez, Rocío Zamora, Carmen Asato-Higa, David Rivera-Estrella, Antonio Carrasco-Yalán First page: 13 Abstract: Background: Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by abnormal and persistent peripheral blood hypereosinophilia (eosinophil count ≥ 1.5× 109/L and ≥10% eosinophils) with duration ≥ 6 months, associated organ damage, and/or dysfunction attributable to tissue eosinophilic infiltrate of unknown cause. IHES affects different organs such as the heart, lungs, nervous system, and skin, with renal involvement being rare in this condition. Case Presentation: We present a case of a young patient with IHES and immune complex-mediated membranoproliferative glomerulonephritis with nephrotic syndrome, as a rare renal manifestation. We discuss the clinical, analytical, and histopathologic renal and hematologic features, comparing them with other reported cases in the literature. Citation: Medicines PubDate: 2024-06-02 DOI: 10.3390/medicines11060013 Issue No: Vol. 11, No. 6 (2024)
- Medicines, Vol. 11, Pages 10: A Modern Approach to the Treatment of
Traumatic Brain Injury Authors: Marat Syzdykbayev, Maksut Kazymov, Marat Aubakirov, Aigul Kurmangazina, Ernar Kairkhanov, Rustem Kazangapov, Zhanna Bryzhakhina, Saule Imangazinova, Anton Sheinin First page: 10 Abstract: Background: Traumatic brain injury manifests itself in various forms, ranging from mild impairment of consciousness to severe coma and death. Traumatic brain injury remains one of the leading causes of morbidity and mortality. Currently, there is no therapy to reverse the effects associated with traumatic brain injury. New neuroprotective treatments for severe traumatic brain injury have not achieved significant clinical success. Methods: A literature review was performed to summarize the recent interdisciplinary findings on management of traumatic brain injury from both clinical and experimental perspective. Results: In the present review, we discuss the concepts of traditional and new approaches to treatment of traumatic brain injury. The recent development of different drug delivery approaches to the central nervous system is also discussed. Conclusions: The management of traumatic brain injury could be aimed either at the pathological mechanisms initiating the secondary brain injury or alleviating the symptoms accompanying the injury. In many cases, however, the treatment should be complex and include a variety of medical interventions and combination therapy. Citation: Medicines PubDate: 2024-04-30 DOI: 10.3390/medicines11050010 Issue No: Vol. 11, No. 5 (2024)
- Medicines, Vol. 11, Pages 11: Medicines—Aims and Scope Updates
Authors: Hiroshi Sakagami First page: 11 Abstract: The journal Medicines (ISSN 2305-6320) was launched in 2014 [...] Citation: Medicines PubDate: 2024-05-14 DOI: 10.3390/medicines11050011 Issue No: Vol. 11, No. 5 (2024)
- Medicines, Vol. 11, Pages 8: Improved Outcomes in Eosinophilic Esophagitis
with Higher Medication Possession Ratio Authors: Nathan T. Kolasinski, Eric A. Pasman, Cade M. Nylund, Patrick T. Reeves, Daniel I. Brooks, Katerina G. Lescouflair, Steve B. Min First page: 8 Abstract: Eosinophilic esophagitis (EoE) disease activity can be caused by treatment non-adherence. Medication possession ratio (MPR) is an established metric of medication adherence. A higher MPR correlates with better outcomes in several chronic diseases, but MPR has not been investigated with respect to EoE. A retrospective cohort study was performed using an established EoE registry for the years 2005 to 2020. Treatment periods were identified, MPRs were calculated, and medical records were assessed for histologic remission (<15 eos/hpf), dysphagia, food impaction, stricture occurrence, and esophageal dilation that corresponded to each treatment period. In total, 275 treatment periods were included for analysis. The MPR in the histologic remission treatment period group was 0.91 (IQR 0.63–1) vs. 0.63 (IQR 0.31–0.95) for the non-remission treatment period group (p < 0.001). The optimal MPR cut-point for histologic remission was 0.7 (Sen 0.66, Spec 0.62, AUC 0.63). With MPRs ≥ 0.7, there were significantly increased odds of histologic remission (odds ratio 3.05, 95% confidence interval 1.79–5.30) and significantly decreased odds of dysphagia (OR 0.27, 95% CI 0.15–0.45), food impaction (OR 0.26, 95% CI 0.11–0.55), stricture occurrence (OR 0.52 95% CI 0.29–0.92), and esophageal dilation (OR 0.29, 95% CI 0.15–0.54). Assessing MPR before repeating an esophagogastroduodenoscopy may decrease unnecessary procedures in the clinical management of eosinophilic esophagitis. Citation: Medicines PubDate: 2024-03-26 DOI: 10.3390/medicines11040008 Issue No: Vol. 11, No. 4 (2024)
- Medicines, Vol. 11, Pages 9: Human Leucocyte Antigen Genetics in
Idiosyncratic Drug-Induced Liver Injury with Evidence Based on the Roussel Uclaf Causality Assessment Method Authors: Rolf Teschke, Gaby Danan First page: 9 Abstract: The human leucocyte antigen (HLA) allele variability was studied in cohorts of patients with idiosyncratic drug-induced liver injury (iDILI). Some reports showed an association between HLA genetics and iDILI, proposing HLA alleles as a potential risk factor for the liver injury. However, the strength of such assumptions heavily depends on the quality of the iDILI diagnosis, calling for a thorough analysis. Using the PubMed database and Google Science, a total of 25 reports of case series or single cases were retrieved using the terms HLA genes and iDILI. It turned out that in 10/25 reports (40%), HLA genetics were determined in iDILI cases, for which no causality assessment method (CAM) was used or a non-validated tool was applied, meaning the findings were based on subjective opinion, providing disputable results and hence not scoring individual key elements. By contrast, in most iDILI reports (60%), the Roussel Uclaf Causality Assessment Method (RUCAM) was applied, which is the diagnostic algorithm preferred worldwide to assess causality in iDILI cases and represents a quantitative, objective tool that has been well validated by both internal and external DILI experts. The RUCAM provided evidence-based results concerning liver injury by 1 drug class (antituberculotics + antiretrovirals) and 19 different drugs, comprising 900 iDILI cases. Among the top-ranking drugs were amoxicillin–clavulanate (290 cases, HLA A*02:01 or HLA A*30:02), followed by flucloxacillin (255 cases, HLA B*57:01), trimethoprim–sulfamethoxazole (86 cases, HLA B*14:01 or HLA B*14:02), methimazole (40 cases, HLA C*03:02), carbamazepine (29 cases, HLA A*31:01), and nitrofurantoin (26 cases, HLA A*33:01). In conclusion, the HLA genetics in 900 idiosyncratic drug-induced liver injury cases with evidence based on the RUCAM are available for studying the mechanistic steps leading to the injury, including metabolic factors through cytochrome P450 isoforms and processes that activate the innate immune system to the adaptive immune system. Citation: Medicines PubDate: 2024-04-11 DOI: 10.3390/medicines11040009 Issue No: Vol. 11, No. 4 (2024)
- Medicines, Vol. 11, Pages 6: ADME Gene-Related Pharmacogenomic Labeling of
FDA-Approved Drugs: Comparison with Clinical Pharmacogenetics Implementation Consortium (CPIC) Evidence Levels Authors: Subrata Deb, Robert Hopefl, Anthony Allen Reeves, Dena Cvetkovic First page: 6 Abstract: Pharmacogenomics (PGx) can facilitate the transition to patient-specific drug regimens and thus improve their efficacy and reduce toxicity. The aim of this study was to evaluate the overlap of PGx classification for drug absorption, distribution, metabolism, and elimination (ADME)-related genes in the U.S. Food and Drug Administration (FDA) PGx labeling and in the Clinical Pharmacogenetics Implementation Consortium (CPIC) database. FDA-approved drugs and PGx labeling for ADME genes were identified in the CPIC database. Drugs were filtered by their association with ADME (pharmacokinetics)-related genes, PGx FDA labeling class, and CPIC evidence level. FDA PGx labeling was classified as either actionable, informative, testing recommended, or testing required, and varying CPIC evidence levels as either A, B, C, or D. From a total of 442 ADME and non-ADME gene–drug pairs in the CPIC database, 273, 55, and 48 pairs were excluded for lack of FDA labeling, mixed CPIC evidence level provisional classification, and non-ADME gene–drug pairs, respectively. The 66 ADME gene–drug pairs were classified into the following categories: 10 (15%) informative, 49 (74%) actionable, 6 (9%) testing recommended, and 1 (2%) testing required. CYP2D6 was the most prevalent gene among the FDA PGx labeling. From the ADME gene–drug pairs with both FDA and CPIC PGx classification, the majority of the drugs were for depression, cancer, and pain medications. The ADME gene–drug pairs with FDA PGx labeling considerably overlap with CPIC classification; however, a large number of ADME gene–drug pairs have only CPIC evidence levels but not FDA classification. PGx actionable labeling was the most common classification, with CYP2D6 as the most prevalent ADME gene in the FDA PGx labeling. Health professionals can impact therapeutic outcomes via pharmacogenetic interventions by analyzing and reconciling the FDA labels and CPIC database. Citation: Medicines PubDate: 2024-02-20 DOI: 10.3390/medicines11030006 Issue No: Vol. 11, No. 3 (2024)
- Medicines, Vol. 11, Pages 7: Triple Silencing of HSP27, cFLIP, and CLU
Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells Authors: Jeong Man Cho, Sojung Sun, Eunji Im, Hyunwon Yang, Tag Keun Yoo First page: 7 Abstract: Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer. Citation: Medicines PubDate: 2024-02-21 DOI: 10.3390/medicines11030007 Issue No: Vol. 11, No. 3 (2024)
- Medicines, Vol. 11, Pages 4: A Multi-Modality Intervention Improves
Obesity Bias among Medical Students Authors: Stephanie Trofymenko, Randa Kutob, Amit Algotar First page: 4 Abstract: Background: Obesity is linked to chronic diseases in adults and children. Its prevalence continues to grow in the United States, necessitating the need for healthcare provider training and presenting an opportunity for the education of future medical providers. Despite this need, effectively implementing obesity education into medical school curricula has been challenging. Anti-obesity bias amongst healthcare providers and trainees represents a significant obstacle to the care of patients with obesity. Obesity bias may affect up to 1/3 of medical students. Methods: This study describes the development and preliminary testing of a brief, 2.5 h multi-modality teaching intervention consisting of online, interactive, and independent learning modules for first-year medical students and a patient panel focused on obesity, obesity bias, and motivational interviewing. The participants took Crandall’s anti-fat attitude (AFA) questionnaire before and after an online independent learning module on motivational interviewing and obesity bias. The AFA consists of three subscales (“dislike”, “fear of fat”, and “willpower”). Individual responses were measured using a nine-point Likert-type response format (0 = very strongly disagree; 9 = very strongly agree). An average composite score was calculated for each subscale. Results: Data were analyzed from 103 first-year medical students enrolled at a college of medicine in the southwestern United States in 2022. The AFA mean composite scores decreased significantly, indicating a decrease in explicit anti-obesity attitude bias after completing the online module. This decrease was present in all three domains of fear (4.63 vs. 3.72, p < 0.001), dislike (1.25 vs. 0.88, p < 0.001) and willpower (3.23 vs. 2.31, p < 0.001). Conclusions: Relatively brief educational interventions can positively impact students’ anti-obesity attitudes. Citation: Medicines PubDate: 2024-01-28 DOI: 10.3390/medicines11020004 Issue No: Vol. 11, No. 2 (2024)
- Medicines, Vol. 11, Pages 5: Can a Low-Phosphate Diet for Chronic Kidney
Disease Treat Cancer' An Interdisciplinary Literature Review Authors: Ronald B. Brown, Philip Bigelow First page: 5 Abstract: Background: Cancer therapeutics have a low success rate in clinical trials. An interdisciplinary approach is needed to translate basic, clinical, and remote fields of research knowledge into novel cancer treatments. Recent research has identified high dietary phosphate intake as a risk factor associated with cancer incidence. A model of tumor dynamics predicted that reducing phosphate levels sequestered in the tumor microenvironment could substantially reduce tumor size. Coincidently, a low-phosphate diet is already in use to help patients with chronic kidney disease manage high serum phosphate levels. Methods: A grounded-theory literature-review method was used to synthesize interdisciplinary findings from the basic and clinical sciences, including oncology, nephrology, nutritional epidemiology, and dietetic research on cancer. Results: Findings of tumor remission associated with fasting and a ketogenic diet, which lower intake of dietary phosphate, support the hypothesis that a low-phosphate diet will reduce levels of phosphate sequestered in the tumor microenvironment and reduce tumor size. Additionally, long-term effects of a low-phosphate diet may reverse dysregulated phosphate metabolism associated with tumorigenesis and prevent cancer recurrence. Conclusions: Evidence in this article provides the rationale to test a low-phosphate diet as a dietary intervention to reduce tumor size and lower risk of cancer recurrence. Citation: Medicines PubDate: 2024-01-30 DOI: 10.3390/medicines11020005 Issue No: Vol. 11, No. 2 (2024)
- Medicines, Vol. 11, Pages 3: Dimeric 3,5-Bis(benzylidene)-4-piperidones:
Tumor-Selective Cytotoxicity and Structure-Activity Relationships Authors: Swagatika Das, Praveen K. Roayapalley, Hiroshi Sakagami, Naoki Umemura, Dennis K. J. Gorecki, Mohammad Hossain, Masami Kawase, Umashankar Das, Jonathan R. Dimmock First page: 3 Abstract: Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers of 3,5-bis(benzylidene)-4-piperidones against human malignant cells (promyelocytic leukemia HL-60 and squamous cell carcinoma HSC-2, HSC-3, and HSC-4). Methods: Tumor specificity was evaluated by the selectivity index (SI), that is the ratio of the mean CC50 for human non-malignant oral cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) to that for malignant cells. Results: The compounds were highly toxic to human malignant cells. On the other hand, these molecules were less toxic to human non-malignant cells. In particular, a potent lead molecule, 3b, was identified. A QSAR study revealed that the placement of electron-releasing and hydrophilic substituents into the aryl rings led to increases in cytotoxic potencies. The modes of action of a lead compound discovered in this study designated 3b were the activation of caspases-3 and -7, as well as causing PARP1 cleavage and G2 arrest, followed by sub-G1 accumulation in the cell cycle. This compound also depolarized the mitochondrial membrane and generated reactive oxygen species in human colon carcinoma HCT116 cells. In conclusion, this study has revealed that, in general, the compounds described in this report are tumor-selective cytotoxins. Citation: Medicines PubDate: 2024-01-11 DOI: 10.3390/medicines11010003 Issue No: Vol. 11, No. 1 (2024)
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