Search

Outbreaks of human Nipah virus (NiV) cases have recently been reported in several countries. With a mortality rate of around 80% and no known therapy, there is an urgent need to test existing antivirals repurposed for it. Due to its central role in virus replication, the RNA-dependent RNA polymerase (RdRp) of NiV-L protein is a potential target for such antiviral therapies. In this study, Favipiravir, Remdesivir, Ribavirin, and their metabolites, including monophosphate (MP), diphosphate (DP), and triphosphate (TP), were virtually screened against RdRp. Using molecular dynamics (MD) simulations, lead hits from the docking study were examined for conformational changes. Additional analyses, including MM-PBSA, residual decomposition energy, and principal component analysis, were performed on the MD trajectory. Remdesivir-TP, Favipiravir-TP, and Ribavirin-TP exhibited the lowest binding energies of –7.8, −7.4, and −6.9 kcal/mol, respectively, and displayed an affinity for pocket 1, forming interactions with active site residues Asp726 and Asn727. During the 100 ns MD simulation, Remdesivir-TP demonstrated a more stable binding mode compared to Favipiravir-TP and Ribavirin-TP. The relative binding energies were −94.709 kJ/mol, −68.882 kJ/mol, and −46.98 kJ/mol for Remdesivir-TP, Favipiravir-TP, and Ribavirin-TP, respectively. This research anticipates Remdesivir-TP to be a potential candidate for an antiviral drug against NiV infection. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of trigonelline on bleomycin-induced idiopathic pulmonary fibrosis (IPF) and to explore its underlying mechanisms using network pharmacology. Methods: IPF was induced in C57BL/6 mice by a single intratracheal instillation of bleomycin (5 mg/kg). Trigonelline was administered at doses of 25, 50, and 100 mg/kg/day orally from the 2nd day post-bleomycin induction up to the 14th day. In IPF-induced mice, lung coefficient, immune cell infiltration in bronchoalveolar lavage fluid, and oxidative stress were measured. Histological alterations in lung tissues were also assessed. Moreover, network pharmacology approach was conducted to reveal molecular interactions of bleomycin and trigonelline with targets of IPF. Results: Trigonelline treatment reduced bleomycin-induced oxidative stress and immune cell infiltration, and mitigated physiological changes in the lung tissues of mice. Moreover, trigonelline alleviated bleomycin-induced histological alterations in lung tissues. Network pharmacology analysis showed that bleomycin and trigonelline interacted with IPF targets, such as NFKB1, HDAC2, HIF1A, and TLR4. Conclusions: The interaction of trigonelline with key IPF targets and its ameliorative effects on lung damage and oxidative stress highlight its potential in treating IPF. It may be considered an antifibrotic agent for further clinical development. [ABSTRACT FROM AUTHOR]

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is most prevalent global health problem, develops due to accumulation lipids in the hepatocytes in the form of Triglycerides (TG) and Free Fatty Acids (FFA). Traditional healers recommend seeds of Cucumis melo Linn as a liver tonic as well as for its treatment of liver cirrhosis, however its hepatoprotective mechanism have not been explored. Objectives: To investigate significant molecular mechanism of C. melo against liver cirrhosis via in vivo analysis followed by in silico. Materials and Methods: HFD was used for the induction of hepatotoxicity in mice and Silymarin as a standard control. The physical parameters were measured throughout the study along with antioxidant, serum biomarkers and histology of liver. Further, System biology tools were used to predict the possible mechanism of action. Docking studies were carried out with modulated phytocompounds against FXR protein target. Results: C. melo. Extract and fraction ameliorated the HFD induced oxidative stress and histological changes. Additionally, improved liver biochemical parameters such as AST, ALT, ALP, serum bilirubin, total bilirubin, LDL, VLDL, TC and, TP were seen remarkable significant effects. Furthermore, System biology revealed the 16 phytocompounds of C. melo Linn. potentially regulate the PPAR signaling. Among them, Euphol phytocompound was predicted to interact with secreted FXR and may contribute to reduced hepatotoxicity. Conclusion: The results suggests C. melo as a promising therapeutic agent for hepatotoxicity by reducing the symptoms and stress associated with diseases condition which may be due to the regulation of multiple protein via multiple phytocompounds. [ABSTRACT FROM AUTHOR]

Osteochondral Fractures (OCFs) of the patella are common in adolescents due to ligament laxity and weak osteochondral junctions. OCFs following patellar dislocation are particularly challenging in this age group. Magnetic Resonance Imaging (MRI) aids in comprehensive evaluation, and surgical fixation with bioabsorbable sutures is a reliable treatment option. Early intervention and proper rehabilitation are essential to ensure optimal outcomes and prevent long-term complications. The present case report details the presentation, diagnosis, surgical intervention and outcome of a 16-year-old male with an OCF following patellar dislocation. Examination revealed significant ligament laxity and patellar hypermobility, along with patella alta (Insall-Salvati ratio of 2.1) on the affected side. The neurovascular examination was normal. Initial X-rays showed no abnormalities; however, Computed Tomography (CT) and MRI scans revealed a displaced OCF fragment in the anterior intercondylar region, along with lateral patellar tilt, marrow contusion, chondral delamination and partial thickness tearing of the Medial Patellofemoral Ligament (MPFL). Surgical intervention involved open reduction and internal fixation using absorbable Vicryl sutures. Postoperatively, the patient was immobilised for six weeks, followed by a structured rehabilitation program. The patient achieved a full range of motion and restored knee function within six months, with satisfactory radiographic and functional outcomes. At the latest follow-up, the knee range of motion was from 0 degrees of extension to 130 degrees of flexion, with complete pain alleviation. OCFs of the patella in adolescents require timely diagnosis and intervention to prevent degenerative changes. MRI is essential for evaluating soft tissue injuries. Surgical fixation using bioabsorbable sutures provides effective treatment, offering strong fixation without the need for implant removal. Addressing associated injuries, such as MPFL tears, is crucial to prevent recurrent dislocation. [ABSTRACT FROM AUTHOR]

Background: Momordica charantia (MC), Nigella sativa (NS), and Anethum graveolens (AG) are widely utilized vegetables and as an herbal medicines, despite widespread use, there is no evidence of molecular mechanisms of compound-protein-pathway interaction for the treatment of metabolic syndrome (MetS). Materials and Methods: Reported phytochemicals were collated from the botanical databases and SwissTargetPrediction was utilized to predict likely protein targets. Both the STRING and KEGG databases were used to infer the protein target pathway analysis. Cytoscape v3.6.1 was employed to build the compound-protein-pathway network. AutoDock vina executed through POAP pipeline was employed for therapeutic target and compounds docking study. Molecular dynamics was performed by GROMACS. Results: 34, 19, 34 phytocompounds from three plants MC, NS, and AG were predicted to target 30, 30, 28 protein targets and these targets modulated 20, 18, 22 molecular pathways respectively involved in metabolic syndrome. Neuroactive ligand-receptor interaction, Calcium, cGMP-PKG, cAMP, AMPK, PI3K-Akt, PPAR, Metabolic signaling pathways, etc were modulated by compounds. PPARG was hub gene within the network. Nigellidine from NS, Nigellimine-N-Oxide from NS, Cryptoxanthin from MC scored lowest BE with PPARG (-7.5kcal/mol), FABP1 (-8.8kcal/mol), and HMGCR (-7.1kcal/mol) protein targets respectively. MD simulation for 100ns revealed stable interactions of phytocompounds comparable to standard molecules. Conclusion: The current study identified multi-compounds containing enhanced fraction of MC, NS, and AG could be the effective therapy regimen for diabetes, obesity, and MetS. [ABSTRACT FROM AUTHOR]