Hexonic derivatives as human GABA-AT inhibitors: A molecular docking approach

Human ?-aminobutyric acid aminotransferase (GABA-AT), a pyridoxal phosphate dependent enzyme is responsible for the degradation of the inhibitory neurotransmitter GABA. Currently, GABA-AT is a potential drug target for epilepsy due to the selective inhibition in brain. In this computational study, we mainly focus on screening of novel lead candidates against GABA-AT using hexonic derivatives. Structure based virtual screening is performed in Vina that screened top hits based on least binding affinity. Further re-docking on hits is performed in AutoDock results in identification of leads with favorable binding energy and hydrogen bond interactions confirmed the effective inhibition. In conclusion, leads 3-aminohex-5-enoic acid and AG-E-60842 can acts as specific leads for GABA-AT and assist in discovery of novel anti-epileptic drugs

Evolutionary analysis of galectins and identification of potential galectin-1 inhibitors: A computational approach

Galectins are a family of structurally related carbohydrate-binding proteins and some galectins play a major role in initiation, progression and dissemination of different types of tumors. Multiple sequence alignment was performed for 15 types of galectins and phylogenetic tree was constructed for studying evolutionary relationship. Among galectins, galectin-1 contributes to various events associated with cancer biology including tumor transformation, cell cycle regulation and apoptosis. Hence a rational computational approach was followed for the design of new class of glycol-mimetic inhibitors with high affinity and stability. Ten N-39-triazole analogs have been used for molecular docking with galectin-1. Based on docking studies, hexaconazole is identified as a potential inhibitor of galectin-1 for the inhibition of the tumor activity. The binding mechanism of hexaconazole to galectin-1 in the dynamics system was studied by 10 ns Molecular Dynamics simulation. Thus, our study favors more insight on hexaconazole as a promising inhibitor for galectin-1

Stomach carcinoma in the Indian subcontinent: A 16-year trend

<b>Background:</b> Gastric malignancy is one of the most common causes for cancer-related deaths. Reports from the west have shown a paradigm shift in the site of occurrence with malignancies of the gastric cardium increasing in frequency, reports which are contrary to information from the Middle East and South Asia. <b> Aim:</b> To determine trend changes in distribution of gastric malignancy between 1989 and 2004 in the southern state of Tamil Nadu in India. <b> Materials and Methods:</b> The study period was divided into four cohorts of four years each (1989-1992, 1993-1996, 1997-2000 and 2001-2004) for the analysis of the changes in trend for subsite specificity, age and gender predilection. <b> Results:</b> Clinically, there were no significant differences in the presenting symptoms or physical signs in the four cohorts. The antrum was the most common site of predilection, no site-specific change was noted and males continued to be more commonly affected of the two sexes. Gastric cancer was significantly higher above the age of 40 years in all the four subsites and cohorts. A decrease in the mean age was observed for men with cancers of the esophagogastric junction (OGJ) (<i> P</i> &lt; 0.0001) and the proximal stomach (<i> P</i> &lt; 0.0001), while junctional malignancy (<i> P</i> &lt; 0.0001), cancers of the proximal stomach (<i> P</i> &lt; 0.0001) and the antrum (<i> P</i> = 0.03) tended to occur progressively later among women. <b> Conclusion:</b> No change in site specificity or gender predilection for gastric adenocarcinoma has been noted in the past 16 years. However, a gender-dependent paradigm shift in the mean age of presentation is discernible for cancers involving the OGJ, proximal stomach and antrum

Assessment of factors related to poly cystic ovarian syndrome – A comparative and correlational study

AbstractPolycystic ovarian syndrome (PCOS) is a common endocrine disorder that primarily affects women of reproductive age. It is particularly prevalent among adolescent females who receive an insufficient diagnosis despite having potentially adverse consequences. The use of PCOS screening questionnaires has the potential to aid in the early detection of symptoms. The goal of this study is to observe if a self-administered questionnaire may be useful for a clear cognizance of the associated conditions like mental stress and menstrual characteristics correlated to polycystic ovary syndrome. In this study, we selected women within an age group of 17–40 with and without PCOS based on the modified Rotterdam criteria to fill out a self-administrated questionnaire based on the signs and symptoms of PCOS majorly focusing on mental stress and menstrual characteristics. SPSS software, univariate analyses were employed to elucidate the associations among the components of PCOS, demographic factors, and lifestyle characteristics, hence providing insights into the interrelationships among those variables. 64 women with PCOS and 141 women without PCOS participated in the present study. The present study revealed PCOS is greatly influenced by age at menarche (p-value= .043), typical cycle length (p-value = .000) mental health problems during menstruation (p-value = .032), and body mass index (p-value = .001). Multivariate hierarchical logistic regression analysis showed only 2 variables BMI (a-OR 1.156,95% CI (1.067–1.242), p-value = .000), and typical cycle length (a-OR 2.278, 95% CI (1.079–4.809), p-value = .003) were significant. The present study showed that BMI and menstrual cycle length were most closely associated with the incidence of PCOS, which is important in diagnosing and treating the condition. Considering the high incidence of PCOS among women of reproductive age and its potential for significant health implications, it would be prudent to incorporate inquiries regarding mental health concerns and menstrual patterns into routine medical assessments for this demographic analysis. This approach aims to ascertain whether additional diagnostic evaluations and screenings for PCOS are warranted

Identification of key biomarkers and associated pathways of pancreatic cancer using integrated transcriptomic and gene network analysis

Pancreatic cancer shows malignancy around the world standing in 4th position for causing death globally. This cancer is majorly divided into exocrine and neuroendocrine where exocrine pancreatic ductal adenocarcinoma is observed to be nearly 85% of cases. The lack of diagnosis of pancreatic cancer is considered to be one of the major drawbacks to the prognosis and treatment of pancreatic cancer patients. The survival rate after diagnosis is very low, due to the higher incidence of drug resistance to cancer which leads to an increase in the mortality rate. The transcriptome analysis for pancreatic cancer involves dataset collection from the ENA database, incorporating them into quality control analysis to the quantification process to get the summarized read counts present in collected samples and used for further differential gene expression analysis using the DESeq2 package. Additionally, explore the enriched pathways using GSEA software and represented them by utilizing the enrichment map finally, the gene network has been constructed by Cytoscape software. Furthermore, explored the hub genes that are present in the particular pathways and how they are interconnected from one pathway to another has been analyzed. Finally, we identified the CDKN1A, IL6, and MYC genes and their associated pathways can be better biomarker for the clinical processes to increase the survival rate of of pancreatic cancer

Screening of potent phytochemical inhibitors against SARS-CoV-2 protease and its two Asian mutants

Background: COVID-19, declared a pandemic in March 2020 by the World Health Organization is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus has already killed more than 2.3 million people worldwide. Object: The principal intent of this work was to investigate lead compounds by screening natural product library (NPASS) for possible treatment of COVID-19.Methods: Pharmacophore features were used to screen a large database to get a small dataset for structure-based virtual screening of natural product compounds. In the structure-based screening, molecular docking was performed to find a potent inhibitor molecule against the main protease (Mpro) of SARS-CoV-2 (PDB ID: 6Y7M). The predicted lead compound was further subjected to Molecular Dynamics (MD) simulation to check the stability of the leads compound with the evolution of time.Results: In pharmacophore-based virtual screening, 2,361 compounds were retained out of 30,927. In the structure-based screening, the lead compounds were filtered based on their docking scores. Among the 2,360 compounds, 12 lead compounds were selected based on their docking score. Kazinol T with NPASS ID: NPC474104 showed the highest docking score of -14.355 and passed criteria of Lipinski's drug-like parameters. Monitoring ADMET properties, Kazinol T showed its safety for consumption. Docking of Kazinol T with two Asian mutants (R60C and I152V) showed variations in binding and energy parameters. Normal mode analysis for ligand-bound and unbound form of protease along with its mutants, revealed displacement and correlation parameters for C-alpha atoms. MD simulation results showed that all ligand-protein complexes remained intact and stable in a dynamic environment with negative Gibbs free energy.Conclusions: The natural product Kazinol T was a predicted lead compound against the main protease of SARSCoV-2 and will be the possible treatment for COVID-19