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Background: Nipah virus (NiV) is a zoonotic paramyxovirus that can cause severe respiratory illness and encephalitis in humans, with no effective targets and treatment. Objective: To investigate potential targets involved in the progression of NiV infection by bioinformatics studies. Methods: To identify the key gene involved in NiV infection, a microarray dataset (GSE32902) was downloaded from the National Centre of Biotechnology Information (NCBI). The differentially expressed genes were unraveled by using Geo2Enrichr, and the functional enrichment analysis was facilitated by using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Search Tool for the Retrieval of Interacting Genes (STRING) was used to construct the Protein-protein interaction (PPI) network and visualized by using Cytoscape. Results: A total of 500 genes (262 up-regulated and 238 down-regulated) were identified among NiV infected cells. Nineteen upregulated genes were found with a node degree of more than 10, Among which MX1, ISG15, and IFIT1 were found to have the highest node degree (degree=20), followed by RSAD2 and IRF7 with node degree 18 and MX2 and IFIT3 with node degree 17. Conclusion: The above results explicitly demonstrate that the expressed genes attribute to a defensive response against the virus. Henceforth finding agonists for these genes would help in the effective management of Niv infection.

Background: Bruton's tyrosine kinase inhibitors (BTKis) are used for treating B-cell leukaemia and lymphomas like chronic lymphocytic leukaemia, mantle cell lymphoma, and Waldenström macroglobulinemia. Tumour lysis syndrome (TLS) is an adverse event associated with this class, the prevalence of which is not well studied in an actual context. Objective: This study aims to detect the possible safety signal of BTKis-associated with TLS through disproportionality analysis in the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Patients and Methods: A case/non-case retrospective disproportionality analysis was performed in a publicly available FAERS database using OpenVigil 2.1 (2014Q1-2021Q3). The preferred term defined by MedDRA v24 used for the study was "tumour lysis syndrome" and the drugs included in the analysis were acalabrutinib, ibrutinib, and zanubrutinib. Reporting odds ratio (ROR) was used as the analysis data mining algorithm. Results: 2852 cases of TLS were identified from FAERS database, of which 121 (4.2%) reports were associated with BTKis. Ibrutinib accounted for 103 (85.1%), acalabrutinib for 15 (12.4%), and zanubrutinib for 3 (2.5%) cases of TLS reports associated with BTKis. Positive signal strength was obtained for ibrutinib [ROR 13.5 (95%CI: 11.1-16.4), acalabrutinib [ROR 42.8 (25.7-71.3), and zanubrutinib [ROR 72.4 (23-227.5)] associated TLS. On gender stratification, acalabrutinib and ibrutinib were found to have a higher value (ROR of 1.7 times) for females than males. Conclusion: Our analysis of spontaneous reporting data identified signals for TLS with acalabrutinib, ibrutinib, and zanubrutinib. More research with a superior epidemiological study design of a defined population is required to validate these findings.

Abstract Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase (AR). Hence, AR inhibitors are considered as potential agents in the management of diabetic cataract. This study explored the AR inhibition potential of Hemidesmus indicus var. pubescens root extract by in silico and ex vivo methods. Molecular docking studies (Auto Dock tool) between β-sitosterol, hemidesminine, hemidesmin-1, hemidesmin-2, and AR showed that β-sitosterol (− 10.2 kcal/mol) and hemidesmin-2 (− 8.07 kcal/mol) had the strongest affinity to AR enzyme. Ex vivo studies were performed by incubating isolated goat lenses in artificial aqueous humor using galactose (55 mM) as cataract inducing agent at room temperature (pH 7.8) for 72 h. After treatment with Vitamin E acetate − 100 µg/mL (standard) and test extract (500 and 1000 µg/mL) separately, the estimation of biochemical markers showed inhibition of lens AR activity and decreased sorbitol levels. Additionally, extract also normalized the levels of antioxidant markers like SOD, CAT, GSH. Our results showed evidence that H. indicus var. pubescens root was able to prevent cataract by prevention of opacification and formation of polyols that underlines its potential as a possible therapeutic agent against diabetic complications. Graphic Abstract

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world. Chronic inflammation of liver and associated wound healing processes collectively contribute to the development of cirrhosis which further progresses to dysplastic nodule and then to HCC. Etiological mediators and ongoing manipulations at cellular level in HCC are well established; however, key protein interactions and genetic alterations involved in stepwise hepatocarcinogenic pathways are seldom explored. This study aims to unravel novel targets of HCC and repurpose the FDA-approved drugs against the same. Genetic data pertinent to different stages of HCC were retrieved from GSE6764 dataset and analyzed via GEO2R. Subsequently, protein–protein interaction network analysis of differentially expressed genes was performed to identify the hub genes with significant interaction. Hub genes displaying higher interactions were considered as potential HCC targets and were validated thorough UALCAN and GEPIA databases. These targets were screened against FDA-approved drugs through molecular docking and dynamics simulation studies to capture the drugs with potential activity against HCC. Finally, cytotoxicity of the shortlisted drug was confirmed in vitro by MTT assay. CDC20 was identified as potential druggable target. Docking, binding energy calculations, and dynamic studies revealed significant interaction exhibited by Labetalol with CDC20. Further, in MTT assay, Labetalol demonstrated an IC50 of 200.29 µg/ml in inhibiting the cell growth of HepG2 cell line. In conclusion, this study discloses a series of key genetic underpinnings of HCC and recommends the pertinence of labetalol as a potential repurposable drug against HCC.

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world. Chronic inflammation of liver and associated wound healing processes collectively contribute to the development of cirrhosis which further progresses to dysplastic nodule and then to HCC. Etiological mediators and ongoing manipulations at cellular level in HCC are well established; however, key protein interactions and genetic alterations involved in stepwise hepatocarcinogenic pathways are seldom explored. This study aims to unravel novel targets of HCC and repurpose the FDA-approved drugs against the same. Genetic data pertinent to different stages of HCC were retrieved from GSE6764 dataset and analyzed via GEO2R. Subsequently, protein-protein interaction network analysis of differentially expressed genes was performed to identify the hub genes with significant interaction. Hub genes displaying higher interactions were considered as potential HCC targets and were validated thorough UALCAN and GEPIA databases. These targets were screened against FDA-approved drugs through molecular docking and dynamics simulation studies to capture the drugs with potential activity against HCC. Finally, cytotoxicity of the shortlisted drug was confirmed in vitro by MTT assay. CDC20 was identified as potential druggable target. Docking, binding energy calculations, and dynamic studies revealed significant interaction exhibited by Labetalol with CDC20. Further, in MTT assay, Labetalol demonstrated an IC

Myostatin, a member of the transforming growth factor-β superfamily, is a genetic determinant of skeletal muscle growth. Mice and cattle with inactivating mutations of myostatin have marked muscle hypertrophy. However, it is not known whether myostatin regulates skeletal muscle growth in adult men and whether increased myostatin expression contributes to wasting in chronic illness. We examined the hypothesis that myostatin expression correlates inversely with fat-free mass in humans and that increased expression of the myostatin gene is associated with weight loss in men with AIDS wasting syndrome. We therefore cloned the human myostatin gene and cDNA and examined the gene’s expression in the skeletal muscle and serum of healthy and HIV-infected men. The myostatin gene comprises three exons and two introns, maps to chromosomal region 2q33.2, has three putative transcription initiation sites, and is transcribed as a 3.1-kb mRNA species that encodes a 375-aa precursor protein. Myostatin is expressed uniquely in the human skeletal muscle as a 26-kDa mature glycoprotein (myostatin-immunoreactive protein) and secreted into the plasma. Myostatin immunoreactivity is detectable in human skeletal muscle in both type 1 and 2 fibers. The serum and intramuscular concentrations of myostatin-immunoreactive protein are increased in HIV-infected men with weight loss compared with healthy men and correlate inversely with fat-free mass index. These data support the hypothesis that myostatin is an attenuator of skeletal muscle growth in adult men and contributes to muscle wasting in HIV-infected men.