Antifibrotic effect of silymarin on arecoline-induced fibrosis in primary human buccal fibroblasts: an in silico and in vitro analysis.

BACKGROUND: This study aimed to assess silymarin's anticancer and antifibrotic potential through in silico analysis and investigate its impact on in vitro arecoline-induced fibrosis in primary human buccal fibroblasts (HBF). METHODS & RESULTS: The study utilized iGEMDOCK for molecular docking, evaluating nine bioflavonoids, and identified silymarin and baicalein as the top two compounds with the highest target affinity, followed by subsequent validation through a 100ns Molecular Dynamic Simulation demonstrating silymarin's stable behavior with Transforming Growth Factor Beta. HBF cell lines were developed from tissue samples obtained from patients undergoing third molar extraction. Arecoline, a known etiological factor in oral submucous fibrosis (OSMF), was employed to induce fibrogenesis in these HBFs. The inhibitory concentration (IC50) of arecoline was determined using the MTT assay, revealing dose-dependent cytotoxicity of HBFs to arecoline, with notable cytotoxicity observed at concentrations exceeding 50µM. Subsequently, the cytotoxicity of silymarin was assessed at 24 and 72 h, spanning concentrations from 5µM to 200µM, and an IC50 value of 143µM was determined. Real-time polymerase chain reaction (qPCR) was used to analyze the significant downregulation of key markers including collagen, epithelial-mesenchymal transition (EMT), stem cell, hypoxia, angiogenesis and stress markers in silymarin-treated arecoline-induced primary buccal fibroblast cells. CONCLUSION: Silymarin effectively inhibited fibroblast proliferation and downregulated genes associated with cancer progression and EMT pathway, both of which are implicated in malignant transformation. To our knowledge, this study represents the first exploration of silymarin's potential as a novel therapeutic agent in an in vitro model of OSMF.

The Slitscope.

Slit lamp biomicroscope is the right hand of an Ophthalmologist. Even though precise, its bulky design and complex working process are limiting constraints, making it difficult for screening at outreach camps, which are an integral part of this field for the purpose of eliminating needless blindness. The torchlight is the main tool used for screening. Recently, the integration of smartphones with instruments and the digitization of slit lamp has been explored, to provide simple and easy hacks. By bringing the slit of the slit lamp to traditional torchlight, we have created "The Slitscope". It combines the best of both worlds as a simple innovative do-it-yourself novel technique for precise cataract screening. It is especially useful in peripheral centers, vision centers, and outreach camps. We present two prototypes which can also be 3D printed.

A comprehensive review on the risks assessment and treatment options for Sarcopenia in people with diabetes.

Objectives: This comprehensive review aims to examine the reciprocal interplay between Type 2 diabetes mellitus (T2DM) and sarcopenia, identify prevailing research gaps, and discuss therapeutic approaches and measures to enhance healthcare practices within hospital settings. Methods: A thorough literature review was conducted to gather relevant studies and articles on the relationship between T2DM and sarcopenia. Various databases were searched, including Google Scholar, PubMed, Scopus, and Science Direct databases. The search terms included T2DM, sarcopenia, inflammation, insulin resistance, advanced glycation end products, oxidative stress, muscle dimensions, muscle strength, muscle performance, aging, nutrition, hormone levels, and physical activity. The collected articles were critically analysed to extract key findings and identify gaps in current research. Results: The prevalence and incidence of metabolic and musculoskeletal disorders, notably T2DM and sarcopenia, have surged in recent years. T2DM is marked by inflammation, insulin resistance, accumulation of advanced glycation end products, and oxidative stress, while sarcopenia involves a progressive decline in skeletal muscle mass and function. The review underscores the age-related correlation between sarcopenia and adverse outcomes like fractures, falls, and mortality. Research gaps regarding optimal nutritional interventions for individuals with T2DM and sarcopenia are identified, emphasizing the necessity for further investigation in this area. Conclusions: The reciprocal interplay between T2DM and sarcopenia holds significant importance. Further research is warranted to address knowledge gaps, particularly in utilizing precise measurement tools during clinical trials. Lifestyle modifications appear beneficial for individuals with T2DM and sarcopenia. Additionally, practical nutritional interventions require investigation to optimize healthcare practices in hospital settings. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01262-w.

Interventions in cerebrovascular emergencies among patients with Paroxysmal nocturnal haemoglobinuria - A word of caution.

INTRODUCTION: Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal hematopoietic disorder, where there is deficiency of glycosylphosphatidylinositol (GPI) anchored proteins in the cell membrane, leading to increased complement sensitivity of red blood cells, intravascular hemolysis and vascular inflammation. Arterial and venous strokes in patients with PNH are a rarity posing significant diagnostic and therapeutic challenges. We report our experience with management of PNH patients with cerebrovascular emergencies. METHODS: We report 2 patients with PNH, one who was previously diagnosed with PNH and had arterial stroke, the other had an index presentation of cerebral venous sinus thrombosis (CVT) and was subsequently diagnosed with PNH. We also present the systematic review of literature reporting similar cases, highlighting the challenges in management. RESULTS: Both patients presented to our centre with cerebrovascular emergency. The first patient was a diagnosed with PNH, and presented with left hemispheric infarction caused by thrombosis of middle cerebral artery. He was thrombolysed and underwent mechanical thrombectomy, which was unsuccessful in view of repeated re - thrombosis of the vessel. The patient survived with significant disability. The second patient had severe cerebral venous sinus thrombosis with large right hemispheric hemorrhagic venous infarction. She underwent emergency decompressive hemicraniectomy complicated by massive blood loss and disseminated intravascular coagulation. She subsequently had recurrent life threatening intracranial bleed secondary to platelet transfusions, thrombocytopenia, and use of contrast agents. She progressed to develop Budd Chiari syndrome and was initiated on Eculuzimab. She became transfusion independent, however remained in minimally conscious state and succumbed to sepsis. CONCLUSIONS: Management of arterial and venous strokes is complex in patients with PNH. Invasive procedures and platelet transfusions are to be avoided in acute thrombosis, till robust evidence is available establishing the safety of the same in patients with PNH. Eculuzimab is a promising option, but far from reach for patients in developing countries.

Cerebral venous sinus thrombosis: changing trends in the incidence, age and gender (findings from the CMC Vellore CVT registry).

BACKGROUND: Multiple cerebral venous sinus thrombosis (CVT) registries from various geographical regions indicate that female gender, the use of contraceptive pills, pregnancy and puerperium are important risk factors. In this study, we report the changes in the epidemiology of patients with CVT managed over the past 26 years. METHODS: The CMC Vellore CVT registry is a prospectively maintained database at the Christian Medical College, Vellore since January 1995. Stata software was used to analyse the data and assess the changes in the incidence, age and gender distribution over the previous 26 years. RESULTS: Among 1701 patients treated during the study period, 908 (53%) were women and 793 (47%) were men. The mean incidence of CVT was 49 per 100 000 admissions before 2010, which increased to 96 per 100 000 after 2010. Male gender had a higher odds of developing CVT (OR - 2.07 (CI 1.68 to 2.55, p<0.001). This could be attributed to the declining incidence of postpartum CVT after 2010 compared with the decade before 2010 (50% vs 20%). The mean age at presentation had increased from 24.5 to 33.2 years in the last decade. CONCLUSIONS: There was a clear change in the gender pattern from being a condition with female preponderance, to one where equal or more men are being affected. Lower incidence of postpartum CVT cases could be the driving factor. An increase in the overall incidence of CVT cases was noted, probably due to a higher index of clinical suspicion and better diagnostic imaging modalities.

Arq Ajib - a wonder Unani formulation for inhibiting SARS-CoV-2 spike glycoprotein and main protease - an in silico approach.

OBJECTIVES: The current pandemic caused by Severe Acute Respiratory Syndrome Corona-Virus 2 (SARS-CoV-2) has become a global health menace with significant morbidity and mortality besides huge socioeconomic implications. Despite the approval of few vaccines for the prevention of the disease, the discovery of safe and effective countermeasures especially from natural sources is of paramount importance, as the number of cases continues escalating. Arq Ajib has long been used for various diseases and its ingredients have been reported for antiviral, antimicrobial, antipyretic, anti-inflammatory, antioxidant activities. The present study investigates the inhibitory effect of phytocompound of Arq Ajib on potential drug targets of SARS-CoV-2. METHODS: The structures of phytocompounds present in Arq Ajib were retrieved from PubChem database and some were illustrated using Marvin Sketch. SARS-CoV-2 S glycoprotein (PDB ID: 6LZG) and 3CLpro (PDB ID: 7BQY) were selected as the target protein. Dock Prep module in UCSF Chimera software was used for receptor structure processing. AutoDock Vina was used to calculate the binding affinities between the protein and ligands and to predict most promising compounds with best scores. RESULTS: Molecular docking results predicted that the phytocompounds of Arq Ajib had good binding affinity and interaction with S glycoprotein and 3CLpro. Quercetin and Isorhoifolin from Mentha arvensis were identified as promising candidates with the potential to interact with 3CLpro and spike glycoprotein and inhibit the viral replication and its entry into the host. CONCLUSIONS: Arq Ajib may prove valuable for developing novel therapeutic candidate for COVID-19; however, it has to be substantiated further with in-vitro and in-vivo studies.

Computational analysis of marine algal compounds for obesity management against pancreatic lipase.

Obesity is considered a global crisis because of its increased risk factors triggered by lifestyle changes. The prevalence of this condition is increasing at an alarming rate, giving rise to development of novel drugs. Pancreatic lipase possesses higher efficacy in inhibiting this condition among the other drug targets. In this study, virtual screening of 126 plant-derived anti-obesity compounds and 1110 marine algal compounds from seaweed metabolite database were screened and targeted against pancreatic lipase and ranked based on their binding affinity values. A total of 530 compounds that possessed best docked scores of less than -6 kcal/mol were checked for Lipinski's properties through Swiss ADME. Furthermore, these compounds were subjected to toxicity prediction using PROTOX II server. As much as 38 compounds were found to be non-toxic and were subjected to molecular docking analysis. Based on the binding energy, the following compounds RG012 (-10.15 kcal/mol), LIG42 (-9.7 kcal/mol), BC010 (-8.47 kcal/mol), RL073 (-8.2 kcal/mol), and LIG46 (-8.03 kcal/mol) were selected exhibiting higher binding affinity when compared to the standard drug (Orlistat) and hence these compounds were subjected to molecular dynamics simulation using GROMACS. BC010 complex revealed a stable interaction within the binding pocket and the binding free energy is -158.208 kJ/mol which is higher when compared to other complexes in 100 ns simulation. BC010 ((7S,11S,12S,14R)-4',14-dimethoxyamentol) from brown algae Cystophora fibrosa could be considered as a potential drug candidate to suppress obesity by inhibiting pancreatic lipase.Communicated by Ramaswamy H. Sarma.

Influence of SGLT2 Inhibitors in Remodeling, Substrate and Ion Metabolism of Myocardium to Prevent Cardiovascular Risks: Recent Work and Advancement.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs that lower blood glucose levels while decreasing blood pressure, volume loss, and weight loss. SGLT2 inhibitors were studied to determine their effectiveness in treating cardiovascular disease and their side effects. Study outcomes related to cardiovascular and metabolic outcomes were examined in patients on SGLT2 inhibitors by searching PubMed, Embase, Cochrane, and SCOPUS. Articles related to clinical trials, reviews, and meta-analyses were considered. A review of SGLT2 inhibitors' mechanisms of action in preventing cardiovascular (CVS) disease progression was described. We then reviewed the possible effects of SGLT2 inhibitors on CVS dysfunction development, composition, and stability. In the following, we discussed the impact of SGLT2 inhibitors on CVD events, such as ischemic strokes and myocardial infarctions, and their role in treating congestive heart failure and cardiovascular mortality.

Navigating a medical mystery in an elite athlete-severe dystonia induced by swimming.

Dystonia is a state of involuntary muscle contractions that cause repetitive or twisting movements. It may affect one or more parts of the body and sometimes the entire body. The condition can be mild or severe. In this unusual case, high-intensity swimming triggered the episodes of atypical functional movement disorder.