Current understanding of CTLA-4: from mechanism to autoimmune diseases

Autoimmune diseases (ADs) are characterized by the production of autoreactive lymphocytes, immune responses to self-antigens, and inflammation in related tissues and organs. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is majorly expressed in activated T cells and works as a critical regulator in the inflammatory response. In this review, we first describe the structure, expression, and how the signaling pathways of CTLA-4 participate in reducing effector T-cell activity and enhancing the immunomodulatory ability of regulatory T (Treg) cells to reduce immune response, maintain immune homeostasis, and maintain autoimmune silence. We then focused on the correlation between CTLA-4 and different ADs and how this molecule regulates the immune activity of the diseases and inhibits the onset, progression, and pathology of various ADs. Finally, we summarized the current progress of CTLA-4 as a therapeutic target for various ADs

Mental health difficulties of adults with COVID-19-like symptoms in Bangladesh: a case control-study

Introduction The rapid spread of SARS-CoV-2 coupled with inefficient testing capacities in Bangladesh has resulted in a number of deaths from COVID-19-like symptoms that have no official test results. Insufficient test sites and healthcare facilities catered to COVID-19 has led to feelings of fear and frustration in those who are sick. This study was the first study which explored the mental health of adults with the most common COVID-19-like symptoms in Bangladesh. Methods This retrospective case control study gathered data via an online survey to explore the mental health of Bangladeshi adults with symptoms akin to COVID-19. Level of stress, anxiety symptoms, and depressive symptoms were measured with the DASS-21. Chi-square tests and multivariate logistic regression was performed to examine the association of variables. Results The prevalence rates of anxiety symptoms, and depressive symptoms of overall population were 26.9% and 52.0% respectively and 55.6% reported mild to extremely severe levels of stress. Multivariate logistic regression determined that respondents with COVID-19-like symptoms (case) reported higher odds for stress level (AOR: 2.043; CI: 1.51-2.76), anxiety symptoms (AOR: 2.770; CI: 2.04-3.77) and depressive symptoms (AOR: 1.482; CI: 1.12-1.96) than asymptomatic respondents (control). Conclusion Patients with symptoms like those of COVID-19 should be prioritized in the healthcare setting in order to reduce mental health difficulties throughout the pandemic

Mental health difficulties of adults with COVID-19-like symptoms in Bangladesh: A cross-sectional correlational study.

BackgroundThe rapid spread of novel corona virus disease (COVID-19) coupled with inefficient testing capacities in Bangladesh has resulted in a number of deaths from COVID-19-like symptoms that have no official test results. This study was the first study that explored the mental health of adults with the most common COVID-19-like symptoms in Bangladesh.MethodsThis cross-sectional correlational study gathered data via an online survey to explore the mental health of Bangladeshi adults with symptoms akin to COVID-19. Level of stress, anxiety symptoms, and depressive symptoms were measured with the DASS-21. Chi-square tests and multivariate logistic regression was performed to examine the association of variables.ResultsThe prevalence rates of anxiety symptoms and depressive symptoms of the overall population were 26.9% and 52.0% respectively and 55.6% reported mild to extremely severe levels of stress. Multivariate logistic regression determined that respondents with COVID-19-like symptoms reported higher odds for stress level (AOR = 2.043, CI = 1.51 to 2.76), anxiety symptoms (AOR = 2.770, CI = 2.04 to 3.77) and depressive symptoms (AOR = 1.482, CI = 1.12 to 1.96) than asymptomatic respondents.LimitationsThere was a chance of recall bias as it was not possible to validate the information due to the retrospective design of the study. Recruitment methods only captured internet users, which reduces the generalizability of findings.ConclusionsPatients with symptoms like those of COVID-19 should be prioritized in the healthcare setting in order to reduce mental health difficulties throughout the pandemic

Antiemetic activity of trans-ferulic acid possibly through muscarinic receptors interaction pathway: In vivo and in silico study

Current study was conducted to assess the effectiveness of the polyphenol trans-ferulic acid (TFA) as an antiemetic agent using in vivo and in silico methods. To evaluate this, we induced emesis in 3-day-old chicks through the oral administration of copper sulfate (CuSO4·5H2O) at a dose of 50 mg/kg. To ascertain the potential antiemetic mechanism of TFA, we employed various reference drugs such as domperidone (6 mg/kg), ondansetron (5 mg/kg), and hyoscine (21 mg/kg) as positive control groups, while the vehicle acted as a negative control group. TFA was administered orally at the doses of 25, 50 and 100 mg/kg body weight. Both the TFA and reference drug provided alone or in combined groups to assess their synergistic or antagonistic activity on the chicks. Molecular docking of TFA and the selected reference drugs was conducted against 5HT3, D2, H1, NK1, and mAChRs (M1-M5) receptors for determining binding affinity to the receptors. Active binding sites and drug-receptor interactions were predicted with the aid of various computational tools. Various pharmacokinetic features and drug-likeness of all the selected ligands were determined through the SwissADME online server. The results suggest that TFA diminishes the mean number of retches and enhances latency in the chicks at lower doses. In the combined drug therapy, TFA exhibited better antiemetic effects with ondansetron and hyoscine. In silico ADME proposed that TFA retains preferable drug-likeness and better pharmacokinetic properties to be a reliable lead. Additionally, TFA revealed the elevated binding affinity against mAChRs and the ligand (TFA) expressed the highest binding affinity (−7 kcal/mol) with the M5 receptor (6OL9). In conclusion, TFA demonstrated mild antiemetic effects in chicks, possibly through the mAChRs interaction pathway