A biochemical, theoretical and immunohistochemical study comparing the therapeutic efficacy of curcumin and taurine on T-2 toxin induced hepatotoxicity in rats

Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity.Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done.Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin’s therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin’s higher binding affinity than taurine.Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin

NAFLD and nutraceuticals: a review of completed phase III and IV clinical trials

BackgroundNonalcoholic Fatty Liver Disease (NAFLD) has become a significant public health concern, affecting approximately one-fourth of the population. Despite its prevalence, no FDA-approved drug treatments specifically target NAFLD.AimTo provide a review of clinical trials investigating the use of herbal remedies and dietary supplements in NAFLD management, utilizing the ClinicalTrials.gov database.MethodsThis review evaluates the current evidence by examining completed phase III and IV clinical trials registered on ClinicalTrials.gov. An exhaustive search was performed on April 17, 2023, using the terms “Nonalcoholic Fatty Liver Disease” and “NAFLD.” Two independent reviewers appraised eligible trials based on pre-defined inclusion and exclusion criteria.ResultsAn initial search yielded 1,226 clinical trials, with 12 meeting the inclusion criteria after filtration. The majority of trials focused on Omega-3 fatty acids (20.0%) and vitamin D (26.7%), followed by caffeine, chlorogenic acid, ginger, phosphatidylcholine, Trigonella Foenum-graecum seed extract, vitamin C, and vitamin E (each 6.7%). Most studies were Phase 3 (75.0%) and used a parallel assignment model (91.7%). Quadruple masking was the most prevalent technique (58.3%), and Iran was the leading country in terms of trial locations (25.0%). These interventions constitute two herbal interventions and nine supplement interventions.ConclusionThis reveals a diverse range of nutraceuticals, with Omega-3 fatty acids and vitamin D being predominant in the management of NAFLD. The global distribution of trials highlights the widespread interest in these therapeutics. However, more rigorous, large-scale trials are needed to establish safety, efficacy, and optimal dosages

Role of CD27 and SAMHD1 and their genetic susceptibility to COVID-19

SARS-CoV-2, which initiated the worldwide COVID-19 epidemic in 2019, has rapidly emerged and spread, resulting in significant public health challenges worldwide. The COVID-19 severity signs and their association with specific genes have been investigated to better comprehend this phenomenon. In this study, several genes were investigated to see whether they correspond with COVID-19 sickness severity. This research aims to determine and evaluate certain gene expression levels associated with the immune system, as these genes were reported to play important roles in immune control during the COVID-19 outbreak. We analyzed two immunity-linked genes: CD27 and SAMHD1 in COVID-19 patients’ samples using RT-PCR, compared them to the samples from recovered, immunized, and healthy individuals. These data were examined to determine the potential relationships between clinical patterns, illness severity, and progression, and SARS-CoV-2 infection immunology.We observed that CD27 gene expression was higher in COVID-19 vaccinated and control groups, but lower in active and recovered COVID-19 patients. On the other hand, SAMHD1 gene expression was elevated in infected and recovered COVID-19 groups. According to our study, the proteins CD27 and SAMHD1 are essential for controlling the immunological response to COVID-19. Changes in their expression levels could increase the susceptibility of patients to severe complications associated with the disease. Therefore, the gene expression level of these proteins could serve as viable prognostic markers for COVID-19

T Cells Immunophenotyping and CD38 Overexpression as Hallmarks of the Severity of COVID-19 and Predictors of Patients’ Outcomes

Background: By the end of 2019, the COVID-19 pandemic spread all around the world with a wide spectrum of clinical presentations ranging from mild to moderate to severe or critical cases. T cell subtype dysregulation is mostly involved in the immunopathogenic mechanism. The present study aimed to highlight the role of monitoring T cell subtypes and their activation (expression of CD38) in COVID-19 patients compared to healthy subjects and their role in predicting severity and patients’ outcomes. Materials: The study involved 70 adult COVID-19 confirmed cases stratified into three groups: a mild/asymptomatic group, a clinically moderate group, and a clinically severe/critical group. Flow cytometry analysis was used for the assessment of CD3+ cells for total T cell count, CD4+ cells for helper T cells (Th), CD8+ cells for cytotoxic T cells (Tc), CD4+CD25+ cells for regulatory T cells (T reg), and CD38 expression in CD4+ T cells and CD8+ T cells for T cell activation. Results: A statistically significant difference was found between COVID-19 cases and healthy controls as regards low counts of all the targeted T cell subtypes, with the lowest counts detected among patients of the severe/critical group. Furthermore, CD38 overexpression was observed in both CD4+ and CD8+ T cells. Conclusion: Decreased T cell count, specifically CD8+ T cell (Tc), with T cell overactivation which was indicated by CD38 overexpression on CD4+ and CD8+ T cells had a substantial prognostic role in predicting severity and mortality among COVID-19 patients. These findings can provide a preliminary tool for clinicians to identify high-risk patients requiring vigilant monitoring, customized supportive therapy, or ICU admission. Studies on larger patient groups are needed

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis

Omar E Hegazi,1,2 Samer O Alalalmeh,1,2 Moyad Shahwan,1,2 Ammar Abdulrahman Jairoun,3,4 Mansour M Alourfi,5,6 Ghfran Abdulrahman Bokhari,6 Abdullah Alkhattabi,6 Saeed Alsharif,7 Mohannad Abdulrahman Aljehani,8 Abdulmalik Mohammed Alsabban,9 Mohammad Almtrafi,9 Ysear Abdulaziz Zakri,9 Abdullah AlMahmoud,10 Khalid Mohammed Alghamdi,10 Ahmed M Ashour,11 Nasser M Alorfi11 1Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates; 2Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates; 3Health and Safety Department, Dubai, United Arab Emirates; 4School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia; 5Internal medicine Department, King Faisal Medical City for Southern Region, Abha, Saudi Arabia; 6Department of gastroenterology, East Jeddah hospital, Jeddah, Saudi Arabia; 7Gastroenterology Department, Armed force Hospital of southern region, Khamis Mushait, Saudi Arabia; 8Division of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia; 9Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia; 10Gastroenterology Section, Internal Medicine Department, King Fahad Hospital, Jeddah, Saudi Arabia; 11Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Nasser M Alorfi, Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia, Email [email protected]: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD.Methods: The terms “Non-alcoholic Fatty Liver Disease” and “NAFLD” were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review.Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%.Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.Keywords: NAFLD, hepatology, clinical trials, therapeutics, metabolic disorde