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

Background: 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.

Saudi Adults' Understanding and Views of Weight Management Practices and Obesity.

Background and Objective: The rising prevalence of overweight and obesity presents a significant global challenge. This study aimed to investigate the understanding and views of weight management practices and obesity among Saudi adults. Methodology: A cross-sectional online survey was conducted from October 2022 to January 2023 among adults residing in Saudi Arabia. Participants completed a self-administered 41-item questionnaire designed to assess their understanding and views regarding weight management practices and obesity. Results: A total of 1066 participants completed the survey. Gender distribution showed a majority of males (55.7%). Age-wise, the majority fell below 51 years, with 37.7% (young) between 18-24, 32.7% (young adult) between 25-33, and 21.3% (adult) between 34-51. Employment was reported by one-third (n = 315) of respondents, while 22.0% (n = 234) had a history of chronic diseases. Furthermore, 77.3% (n = 824) engaged in regular physical activity.The study results revealed that participants' mean score for understanding obesity was 3.28 ± 2.37 (range 0-6), while the average views score was 28.08 ± 8.79 (range 0-34). Furthermore, females displayed a higher level of understanding compared to males. Employment status also played a significant role, with employed individuals having a better understanding of obesity than those who were unemployed. Moreover, participants with higher qualifications demonstrated a more comprehensive understanding of obesity compared to those with lower qualifications. Additionally, individuals with higher monthly income levels displayed a greater understanding of obesity compared to those with lower incomes. Lastly, participants who engaged in regular physical activity exhibited a higher level of understanding compared to those who were physically inactive. Conclusion: The study indicates that factors such as being older, being female, being employed, having higher education and income, and engaging in regular physical activity are associated with increased understanding and favorable views regarding weight management practices and obesity.

Amphetamines in child medicine: a review of ClinicalTrials.gov.

Background: Globally, the use of amphetamines as therapeutic agents in pediatric medicine is a crucial area of concern, especially given the population's vulnerability. Methods: On 6 August 2023, a search was conducted on ClinicalTrials.gov using "amphetamine" as the keyword. Two independent examiners screened trials against set criteria, including a focus on amphetamine, completion status, an interventional approach, and included children. Ongoing or observational studies were excluded. Data extracted from the qualified trials encompassed primary objectives, participant counts, study duration, and outcomes, with the aim of analyzing children disorders treated by amphetamine. Results: On 6 August 2023, a search of the ClinicalTrials.gov database with the term "amphetamines" identified 179 clinical trials. After extensive exclusion criteria, 19 trials were ultimately selected for analysis. The predominant condition under investigation was attention deficit hyperactivity disorder (ADHD), present in 84.2% of studies. Key study characteristics included: phase 4 trials (36.8%), randomized allocation (63.2%), and the parallel intervention model (42.1%). Masking techniques varied, with no masking in 42.1% of studies, and double and quadruple masking both accounting for 21.1%. Geographically, 78.9% of the studies' participants were from the United States. Conclusion: This study highlights the notable therapeutic potential of amphetamines in pediatric ADHD populations and emphasizes the importance of recognizing potential side effects and addiction risks. As pharmacogenomics offers the prospect of personalized treatments, there is potential to increase therapeutic efficacy and decrease adverse reactions. It is vital to balance these benefits against the inherent risks, understanding the need for continued research to optimize the use of amphetamines in medicine.

The Impact of Intermittent Fasting on Non-Alcoholic Fatty Liver Disease in Older Adults: A Review of Clinicaltrials.gov Registry.

Background: Non-alcoholic fatty liver disease (NAFLD) is a predominant health condition across the world due to its rising prevalence and association with various metabolic disorders. Intermittent fasting (IF) has attracted increasing attention as a dietary approach to addressing weight management and enhancing metabolic well-being, and its potential effects on NAFLD have been a topic of growing research interest. Aim: This review aims to critically evaluate the current evidence on IF's impact on NAFLD, including the mechanisms underlying the observed effects in older adults (65+). Methods: A comprehensive search of Clinicaltrials.gov was conducted to identify relevant studies that investigated the effects of IF on NAFLD in older adults (65+). Data on study design, sample size, intervention details, and outcomes related to NAFLD were extracted and analyzed. Results: As of April 12th, 2023, there were 1304 clinical trials on NAFLD. Most of these were interventional studies. The investigation focused on completed studies and found that limited clinical trials were identified with limited interventional measures. Only five out of the 1304 studies on NAFLD involved IF. Basic and advanced outcome measures were examined. Conclusion: Although some studies suggest that IF may have potential benefits for NAFLD, the evidence is still limited and inconclusive.

Community pharmacists' perspectives on cardiovascular disease pharmaceutical care in the United Arab Emirates: a questionnaire survey-based analysis.

Background: Community pharmacists play an intermediary role between prescribing physicians and patients in the United Arab Emirates (UAE) and thus are responsible for ensuring that patients receive optimal cardiovascular disease (CVD) pharmaceutical care. Methods: we used a cross-sectional design to assess the perceptions and practices of community pharmacists concerning pharmaceutical care for patients with CVD. A trained researcher visited randomly selected community pharmacies and used a structured questionnaire to conduct in-person interviews with pharmacists. The questionnaire collected demographic data and information on perceptions and practices regarding CVD pharmaceutical care. Results: Five hundred and fifty-one participants were recruited. The average participant age (mean ± SD) was 35 ± 2.7 years. The average perception score regarding CVD prevention and management was 75.6% (95% confidence interval [CI] 77.1%-74.2%), and the average practice score for CVD prevention and management was 87.1% (95% CI 76.5%-79.6%). Bivariate analysis revealed that gender (p = 0.001), education level (p < 0.001), pharmacy position (p = 0.004), work experience (p < 0.001), number of patients served per day (p < 0.001) and being trained on CVD prevention and management (p < 0.001) were significantly associated with perceptions about the prevention and management of CVD. Better practice scores were seen among older participants (OR 1.01; 95% CI 1-1.019), postgraduates (OR 1.77; 95% CI 1.66-1.89), workers at chain pharmacies (OR 1.24; 95% CI 1.11-1.39), pharmacists in charge (OR 1.22; 95% CI 1.01-1.47), pharmacists with >10 years of experience (OR 11.3; 95% CI 6.01-15.62), pharmacists with 6-10 years of experience (OR 4.42; 95% CI 3.90-5) and pharmacists trained on CVD prevention and management (OR 1.29; 95% CI 1.15-1.46). Conclusion: Pharmacy practitioners working in community pharmacies in the UAE actively engage in delivering pharmaceutical care to patients, playing a role in CVD management and prevention. However, they showed low levels of involvement in other healthcare services, specifically in screening and measuring patients' weight, glucose levels, and blood pressure, monitoring treatment responses, maintaining medical records, and reviewing medication refill histories. Activities such as educating patients, providing medication counseling, offering support for treatment adherence, and fostering collaborative relationships with other healthcare providers should be encouraged among UAE community pharmacists to ensure the provision of high-quality patient care.

Community pharmacists' skills and practice regarding dispensing fiscalized substances: a cross-sectional survey.

Background: The use of drugs containing fiscalized substances is essential in different medical areas, including pain management, obstetric emergencies, and the treatment of mental disorders. However, due to their potential for abuse and negative health effects, the dispensing of these substances demands pharmacists with the requisite skills and practice. Objective: This study assesses the skills and practices of pharmacy personnel in the United Arab Emirates (UAE) regarding the dispensing of tramadol, a medication containing fiscalized substances, in community pharmacies. Methodology: A cross-sectional study was conducted. Community Pharmacies were chosen via random sampling, and seven well-trained final year pharmacy students visited them and conducted face-to-face interviews. The survey tool covered items highlighting the demographic data of the subjects, and items on the practice and skills regarding dispensing the fiscalized substances. The content validity ratio values of all tool questions were more than 0.78, suggesting acceptable validity and the Cronbach's α of 0.75 showed as acceptable internal reliability. The primary outcome measures of interest were the skills and practice regarding dispensing Fiscalized substances. Results: A total of 612 pharmacists were recruited in the study. The average practice score was 80%. There was a statistically significant association (p < 0.05) between practices about dispensing fiscalized substances and gender, age group, pharmacy type, work experience, university of graduation, and receiving training on epilepsy and antiepileptic drugs. Conclusion: The results implied that competency and experience are vital factors for the dispensing of tramadol. Contextually, the majority of the pharmacists evidently have the requisite competencies to provide high-quality and proper medical care, with regards to dispensing tramadol, which will minimize drug abuse and medication errors, and assist outpatients to manage their drugs containing fiscalized substances.

Factors influencing community pharmacists' knowledge about women's issues in epilepsy.

Background: Previous studies have highlighted instances where pharmacists lacked knowledge regarding women's health issues related to epilepsy. Objectives: To assess UAE community pharmacists' knowledge, toward women's issues in epilepsy. Methods: a cross-sectional research method was employed. A team of seven pharmacy students in their final year visited a randomly selected sample of community pharmacies in the UAE and face-to-face interviews were conducted with the pharmacists using a structured questionnaire. The questionnaire includes two parts; Eight questions designed to elicit data about the demographics of the study participants and 12 questions eliciting insights into the participants' knowledge of women's issues in epilepsy. Results: A total of 412 community pharmacist were recruited in the study. The overall level of knowledge about women's issues in epilepsy was good and the average knowledge score was 81% with a 95% confidence interval (CI) [79.1, 82.7%]. The results of multivariate analysis showed higher knowledge scores in chain pharmacies (OR 1.37; 95% CI 1.12-1.67), Chief pharmacists (OR 1.44; 95% CI 1.01-2.06), Pharmacists in charge (OR 3.46; 95% CI 2.7-4.45), pharmacists with 1-5 Years of experience (OR 2.87; 95% CI 1.71-4.82), pharmacists with 6-10 Years (OR 2.63; 95% CI 1.58-4.38), pharmacists with >10 years (OR 3.13; 95% CI 2.03-4.83), graduation form regional universities (OR 1.37; 95% CI 1.12-1.67), graduation form international universities (OR 1.73; 95% CI 1.36-2.20) and receiving a training on epilepsy (OR 1.36; 95% CI 1.12-1.67). Conclusion: While the findings reveal an overall promising level of knowledge among community pharmacists regarding the issues faced by women with epilepsy, pinpointing which clinical and demographic factors have the most significant impact on this knowledge would permit the implementation of tailored educational interventions. Workshops and modules targeting the issues faced by women with epilepsy would further raise the knowledge and competence among community pharmacists in this area, ensuring better pharmaceutical care for this population.

Comprehensive Review of Ustekinumab Utilization in Inflammatory Bowel Diseases: Insights from the ClinicalTrials.gov Registry.

Background: Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic inflammatory conditions affecting the gastrointestinal tract. To achieve and sustain remission, effective treatment strategies are necessary. Ustekinumab, a biologic agent targeting interleukin-12 and interleukin-23, has emerged as a significant therapeutic option for moderate to severe IBD. Aim: To gain insights into the utilization of Ustekinumab for IBD, we conducted a comprehensive review of the ClinicalTrials.gov registry. Methods: A comprehensive search of the ClinicalTrials.gov was conducted to find all clinical trials involving the use of Ustekinumab in IBD patients. As of December 30th, 2022, 69 clinical trials were identified that included IBD and Ustekinumab. The study list was saved, and those clinical trials that fitted the definition of targeted therapy were included in the review. Results: The results showed that Ustekinumab was associated with significant improvements in the clinical response and remission rates, in both Crohn's disease and ulcerative colitis patients. Additionally, the safety profile of Ustekinumab was generally favourable, with low rates of adverse events reported. In terms of study design, most of the relevant studies found in the database were interventional studies. The investigation focused on completed studies and found that there were a limited number of clinical trials with interventional measures. Conclusion: Ustekinumab appears to be a promising treatment option for patients with IBD, with the potential to provide significant clinical benefits and a favourable safety profile. Further research is warranted to confirm these findings and explore optimal dosing and treatment regimens.

Pharmacological Methods of Pain Management: Narrative Review of Medication Used.

Background: Pain management is a critical aspect of healthcare, aimed at alleviating discomfort and improving the quality of life for individuals experiencing acute or chronic pain. Pharmacological methods constitute a primary approach to pain management, including a diverse array of drugs that work through different mechanisms. Aim: Identifying medications commonly employed in pain management, focusing on their mechanism of actions, uses, efficacy and pharmacological applications. Methods: The methodology involved a systematic search of scientific literature using various databases, including PubMed, Scopus, and Google Scholar. Relevant articles published between 2000 and 2023 were screened for inclusion. The selected studies encompassed original research, review articles, therapeutic guidelines and randomized controlled trials. Results: The findings of this review suggest that a multimodal approach combining various analgesics can enhance pain relief while minimizing adverse effects. It emphasizes the importance of assessing pain intensity, determining the underlying etiology, and utilizing evidence-based guidelines to optimize pain management outcomes. Conclusion: Pharmacological methods of pain management are an essential component of pain management strategies to achieve optimal pain relief while minimizing adverse effects. The article concludes with a discussion on emerging trends and future directions in pharmacological pain management, including novel drug targets and advances in drug delivery systems.

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

Background: Nonalcoholic 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. Aim: To provide a review of clinical trials investigating the use of herbal remedies and dietary supplements in NAFLD management, utilizing the ClinicalTrials.gov database. Methods: This 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. Results: An 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. Conclusion: This 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.

A Study to Assess Prescription Transfer and Medicines Collection Through a New Electronic Prescription Service: A Cross-Sectional Survey.

Introduction: The introduction of electronic prescription services has been a significant development in healthcare systems worldwide. In Saudi Arabia, the Wasfaty electronic prescription service was recently introduced, aiming to streamline prescription transfer and medicine collection. Aim: This study assesses the implementation of Wasfaty by investigating prescription transfer, patient satisfaction, and medicine availability among beneficiaries at the University of Jeddah. Methods: A cross-sectional online questionnaire was distributed to students and staff at the University of Jeddah who had received e-prescriptions from the University Medical Centre (n = 2067) in July-December 2022. The questionnaire consisted of three sections: demographics, patient perceptions and satisfaction with the Wasfaty service, and the availability of prescribed medicines. A total of 217 completed questionnaires were received and analyzed. Results: Among the respondents, a majority were female (n = 125, 57.6%). A significant proportion of participants expressed satisfaction with the initial registration process of the Wasfaty service (n = 183, 84.1%). However, a noteworthy finding was that nearly one-third of the participants reported difficulties in locating their prescribed medicines (n = 64, 29.7%). Consequently, a majority of these individuals had to seek alternative pharmacies to obtain their prescribed treatment (n = 138, 63.9%). Of concern were reports of limited access to specific pharmaceuticals, such as anti-hypertensives and antidiabetic medications, which elicited dissatisfaction among respondents. Conclusion: This study sheds light on the challenges associated with the implementation of the Wasfaty electronic prescription service in Saudi Arabia. While initial registration satisfaction is notable, the study highlights issues concerning medicine availability and access to essential pharmaceuticals. Addressing these challenges requires the attention of service providers, and further investigation on a national scale is warranted to better understand and address these issues effectively.

Usage of Glucagon-Like Peptide-1 for Obesity in Children; Updated Review of Clinicaltrials.gov.

Background: Obesity in both adults and children is a primary health concern that can lead to many complications at a young age, including insulin resistance, type 2 diabetes, and other diseases. Glucagon-like peptide-1 receptor agonists (GLP-1) are drugs utilized to treat diabetes, but they are also approved as an adjunct to a low-calorie diet to reduce body weight and to enhance the metabolic profile readings for diabetic and non-diabetic patients. However, their efficacy and safety in children have not been extensively examined. Aim: To identify glucagon-like peptide-1 medications for obesity in pediatric participants (aged up to 17 years old). Methods: Analysis of all clinical trials registered on ClinicalTrials.gov for obesity using GLP-1 as a treatment for children. Results: As of January 26th, 2023, 10,828 clinical trials were found. The search included childhood obesity using GLP-1. The number of trials on the use of GLP-1 to treat childhood obesity is limited. The final number of analyzed trials was 19. GLP-1 has been shown to result in the effective management of body gain among children. Conclusion: Exenatide, semaglutide, and liraglutide were the only GLP-1 medications used as the pharmacotherapy option. It has been studied in many circumstances eg, to treat children with severe obesity, PCOS, hypothalamic obesity, glucose tolerance, and as a complementary treatment alongside behavior-lifestyle change and surgery for obesity.

Assessment of community pharmacists' knowledge about drug-drug interactions in Jeddah, Saudi Arabia.

Background: Drug-drug interactions (DDIs) have the potential to result in severe adverse drug events and profoundly affect patient outcomes. The pivotal role community pharmacists assume in recognizing and effectively managing these interactions necessitates a comprehensive understanding and heightened awareness of their implications. Such knowledge and awareness among community pharmacists are fundamental for ensuring the delivery of safe and efficacious care to patients. Aim: This study aimed to assess the knowledge of community pharmacists in Jeddah, Saudi Arabia, regarding drug-drug interactions (DDIs). Method: A cross-sectional survey was administered to a cohort of 147 community pharmacists through the utilization of a self-administered questionnaire. The questionnaire encompassed a comprehensive range of 30 multiple-choice questions, encompassing various facets pertaining to drug-drug interactions (DDIs). Results: A total of 147 community pharmacists working in Jeddah City, Saudi Arabia, completed the survey. The majority of them were male (89.1%, n = 131), and had bachelor's degrees in pharmacy. Results showed that the lowest correct response of DDIs was between Theophylline/Omeprazole, while the highest was between amoxicillin and acetaminophen. Results revealed that among the 28 drug pairs, only six pairs were determined correctly by most participants. The study found that majority of the studied community pharmacist could not determine the correct answer on drug-drug interaction knowledge, as also seen with the measured below half mean DDIs knowledge of 38.22 ± 22.0 (min = 0, max = 89.29, median = 35.71). Conclusion: The study highlights the need for ongoing training and education programs for community pharmacists in Saudi Arabia to enhance their knowledge and understanding of DDIs, ultimately leading to improved patient care and safety.

Evaluation of Pharmacology and Pathophysiology Knowledge of Epilepsy among Senior Pharmacy Students: A Single Center Experience.

Background and Objectives: Epilepsy is a chronic disease that causes substantial morbidity and mortality. Pharmacists represent an integral role in managing patients with epilepsy. The aim of this study was to evaluate the level of knowledge about the pharmacology and pathophysiology of epilepsy among senior pharmacy students. Materials and Methods: Cross-sectional study using a designed questionnaire to measure the pharmacological and physiological knowledge of senior pharmacy students regarding epilepsy who are studying at Umm Al-Qura University, Makkah, Saudi Arabia, from August to October 2022. Results: A total of 211 senior clinical pharmacy students responded to the questionnaire. The majority of the respondents were 4th year pharmacy students. The numbers of female and male participants were equal (106 and 105 students, respectively). The participants represented an acceptable level of knowledge about the pathophysiology aspects of epilepsy, with a mean total score of 6.22 ± 1.9 out of a maximum score of 10. The respondents reported that epilepsy could be due to genetic predisposition combined with environmental conditions (80.1%) or brain stroke (17.1%). Regarding the respondent knowledge about the pharmacology of epilepsy, the total score was 4.6 ± 2.1 (maximum attainable score: 9). Conclusions: The majority of pharmacy students had knowledge about the pathophysiology concept of the disease; however, low knowledge was shown by the respondents regarding the pharmacology of epilepsy. Thus, there is a need to identify better strategies to improve students' education.

Characterization of interventional clinical trials for monkeypox; systematic review of ClinicalTrials.gov database.

Background: Monkeypox (mpox), a zoonotic viral infection, poses a global threat that is being acknowledged at the national and international levels. This systematic review aims to identify and characterize interventional clinical trials for mpox. Method: All interventional clinical trials registered at ClinicalTrials.gov for mpox were searched up to January 6, 2023. We described the characteristics of interventional clinical trials, and drug interventions (including drugs and vaccines). Results: As of January 6, 2023, there were 10 clinical trials in the ClinicalTrials.gov registry that met our criteria. Most of the interventional clinical trials were focused on the treatment (N = 4, 40%) and prevention (N = 4, 40%) of mpox. From the 10 trials, 50% used random treatment allocation, and six (60%) chose the parallel assignment intervention model. All 10 studies were blinded, and six were open-label blinded. The largest proportion of the clinical trials (N = 4, 40%) were registered in Europe, followed by America (N = 3, 30%) and Africa and others (N = 3, 30%). The JYNNEOS vaccine (40%), followed by Tecovirimat (30%) were the most frequently studied drugs used against mpox. Conclusion: A limited number of clinical trials have been registered on ClinicalTrials.gov since the first case of mpox was reported. Therefore, there is an urgent need to conduct large-scale randomized clinical trials to assess the safety and efficacy of the drugs and vaccines being used against the mpox virus.

Protective role of resveratrol against VCM-induced hepatotoxicity in male wistar rats.

Background: Vancomycin is a glycopeptide antibiotic with a high risk of acute liver injury. Resveratrol is believed to protect the liver against toxicity. Aim: To investigate the ability of resveratrol to attenuate vancomycin-induced liver toxicity in rats injected with vancomycin. Method: Twenty-four adult male Wistar rats were distributed into three groups. The control group received only a vehicle, while the treated group received either vancomycin 200 (mg/kg, i. p.) only or vancomycin (200 mg/kg, i. p.) with resveratrol (20 mg/kg, oral gavage). All groups received their dose once daily for 7 days. Hepatic damage was assessed by measuring biochemical parameter levels in serum, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Also, antioxidants and inflammation biomarkers such as Interleukin-6 (IL-6), malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) were measured. Furthermore, the vancomycin-induced pathological changes in the liver were evaluated by histopathological studies. Results: In the vancomycin-treated group, hepatic serum biomarkers such as AST, ALT, ALP, IL-6, and MDA were elevated, while NO and GSH were depleted. However, resveratrol co-treatment with vancomycin prevented the elevation of AST, ALT, ALP, IL-6, and MDA and it protected the liver from NO and GSH depletion. Also, regarding vancomycin-induced degeneration of hepatocytes, resveratrol co-treatment with vancomycin prevented such degeneration and improved mononuclear cells in the liver. Conclusion: The results showed that oral administration of resveratrol has a significant hepatoprotective effect against vancomycin-induced hepatotoxicity.

Linagliptin and Empagliflozin Inhibit Microtubule Affinity Regulatory Kinase 4: Repurposing Anti-Diabetic Drugs in Neurodegenerative Disorders Using In Silico and In Vitro Approaches.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are significant public health burdens. Many studies have revealed the possibility of common pathophysiology between T2DM and AD. Thus, in recent years, studies deciphering the action mechanism of anti-diabetic drugs with their future use in AD and related pathologies are on high demand. Drug repurposing is a safe and effective approach owing to its low cost and time-saving attributes. Microtubule affinity regulating kinase 4 (MARK4) is a druggable target for various diseases and is found to be linked with AD and diabetes mellitus. MARK4 plays a vital role in energy metabolism and regulation and thus serves as an irrefutable target to treat T2DM. The present study was intended to identify the potent MARK4 inhibitors among FDA-approved anti-diabetic drugs. We performed structure-based virtual screening of FDA-approved drugs to identify the top hits against MARK4. We identified five FDA-approved drugs having an appreciable affinity and specificity toward the binding pocket of MARK4. Among these identified hits, two drugs, linagliptin, and empagliflozin, favorably bind to the MARK4 binding pocket, interacting with its critical residues and thus subjected to detailed analysis. All-atom detailed molecular dynamics (MD) simulations revealed the dynamics of binding of linagliptin and empagliflozin with MARK4. Kinase assay showed significant inhibition of MARK4 kinase activity in the presence of these drugs, implying them as potent MARK4 inhibitors. In conclusion, linagliptin and empagliflozin may be promising MARK4 inhibitors, which can further be exploited as potential lead molecules against MARK4-directed neurodegenerative diseases.

Desmodin and isopongachromene as potential inhibitors of cyclin-dependent kinase 5: phytoconstituents targeting anticancer and neurological therapy.

Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine-threonine protein kinase vital for neuronal cell cycle arrest and differentiation. It activates by binding with p35 and p39 and is important for the functioning of the nervous system. A growing body of evidence suggests that CDK5 contributes to the onset and progression of neurodegeneration and tumorigenesis and represents itself as a potential therapeutic target. Our research illustrates virtual screening of phytochemicals from the IMPPAT (Indian Medicinal Plants, Phytochemistry and Therapeutics) library to search for potential inhibitors of CDK5. Initially, the compounds from the parent library were filtered out via their physicochemical properties following the Lipinski rule of five. Then sequentially, molecular docking-based virtual screening, PAINS filter, ADMET, PASS analysis, and molecular dynamics (MD) simulation were done using various computational tools to rule out adversities that can cause hindrances in the identification of potential inhibitors of CDK5. Finally, two compounds were selected via the extensive screening showing significant binding with CDK5 ATP-binding pocket and ultimately were selected as potent ATP-competitive inhibitors of CDK5. Finally, we propose that the elucidated compounds Desmodin and Isopongachromene can be used further in the drug discovery process and act as therapeutics in the medical industry to treat certain complex diseases, including cancer and neurodegeneration.Communicated by Ramaswamy H. Sarma.

Role of lisinopril in the therapeutic management of cardiovascular disease by targeting microtubule affinity regulating kinase 4: molecular docking and molecular dynamics simulation approaches.

Cardiovascular diseases (CVDs) are a major cause of premature adult death. Various factors contribute to the development of CVDs, such as atherosclerosis leading to myocardial infarction (MI), and compromised cardiac function after MI leads to chronic heart failure with systemic health complications and a high mortality rate. Microtubule detyrosination has rapidly evolved as an essential mechanism to regulate cardiomyocyte contractility. Microtubule affinity regulating kinase 4 (MARK4) regulates cardiomyocyte contractility in a way that it promotes phosphorylation of microtubule-associated protein 4, thereby facilitating the access of vasohibin 2-a tubulin carboxypeptidase-to microtubules for the detyrosination of α-tubulin. Lisinopril, a drug belonging to the class of angiotensin-converting enzyme inhibitors, is used to treat high blood pressure. This is also used to treat heart failure, which plays a vital role in improving the survival rate post-heart attack. In this study, we will evaluate the MARK4 inhibitory potential of lisinopril employing molecular docking and molecular dynamics (MD) simulation approaches. Molecular docking analysis suggested that lisinopril binds to MARK4 with a significant binding affinity forming interactions with functionally essential residues of MARK4. Additionally, MD simulation deciphered the structural dynamics and stability of the MARK4-lisinopril complex. The findings of MD studies established that minimal structural deviations are observed during simulation, affirming the stability of the MARK4-lisinopril complex. Altogether, this study demonstrates lisinopril's crucial role in the therapeutic management of CVD by targeting MARK4.Communicated by Ramaswamy H. Sarma.

Assessment of the Community Pharmacists' Knowledge and Attitudes Toward Pain and Pain Management in Saudi Arabia.

Background: Pain is a global health issue that affects an individual's quality of life. Its alleviation and management will enhance patients' experience. Community pharmacists can help manage pain severity through their valuable roles in medical teams and by managing the consequences of pain. Objective: This study aimed to evaluate community pharmacists' knowledge and attitudes toward pain and pain management in Saudi Arabia. Methods: A cross-sectional study was performed to evaluate community pharmacists' knowledge and attitudes toward pain and pain management in Saudi Arabia. Pharmacists aged ≥ 21 years, with a degree in pharmacy were included in this study. Each respondent participated in an online survey covering cancer-oriented pain and assessment of pain; pharmacology; abuse of substances; and physical dependence. An independent t-test and One-way ANOVA, with least significant difference as a post-hoc test, were employed, in addition to the General Linear Regression Model using Main Effect as the model. Results: This study revealed that the pain-related knowledge and attitude among community pharmacists in Saudi Arabia were inadequate. Age (p = 0.003), work experience (p = 0.036), nature of work (p = 0.001), and work location (p = 0.003) were determined as significant factors affecting their overall knowledge and attitude toward pain. Conclusion: Overall, attempts to expand community pharmacists' knowledge and foster an appropriate attitude toward pain management among them in Saudi Arabia are highly recommended. Additional academic courses, studies, and tailored neuroscience courses will improve their awareness and knowledge of pain and pain management.