The gut microbiota, comprising trillions of microorganisms inhabiting the gastrointestinal tract, is essential to human health and disease. Recent research has illuminated the interactions between many components of human physiology and the gut microbiota, including immune function, metabolism, and neurological health. Central to maintaining this symbiotic relationship is the concept of dysbiosis - an imbalance in the makeup and roles of the gut microbiota. Dysbiosis of the gut microbiota has emerged as a significant factor in the pathogenesis of numerous health conditions, spanning from gastrointestinal disorders like inflammatory bowel disease and irritable bowel syndrome to systemic diseases such as obesity, metabolic syndrome, and even neurological disorders like depression and anxiety. While dysbiosis can result from a myriad of factors including antibiotic use, stress, and genetic predispositions, emerging evidence suggests that diet and lifestyle choices exert profound influences regarding the make-up and capabilities of the gut microbiota. In this review, We explore the complex interactions among lifestyle, nutrition, and gut microbial dysbiosis. In particular, we investigate how the gut microbiota can be modified and dysbiosis can be mitigated by dietary patterns, food composition, prebiotics, probiotics, and lifestyle factors including exercise, stress reduction, and good sleep hygiene. Restoring microbial balance and enhancing general health and well-being can be achieved through preventive and therapeutic measures that can be made more effective by understanding how dietary and lifestyle changes might affect the gut microbiota. Through this exploration, we aim to elucidate the possibility of using lifestyle and dietary modifications as tools for managing gut microbial dysbiosis.

Aim: Present study was done to understand the dimerization of HER2/ERBB2 in normal and cancer cells using in-silico study. Methods: Pathway analysis was done using Reactome. Structure of HER2/ERBB2 protein was obtained from PDB database, and using Schrödinger software protein structure was analysed and dimerization was done. Results: In normal cells, HER2/ERBB2 is present at low levels and forms a stable complex with HSP90 (heat shock protein 90), CDC37 (cell division cycle 37), and ERBIN (an adaptor protein of the HER2/ERBB2 receptor). HER2/ERBB2 lacks a ligand-binding site, so it cannot bind ligands to activate HER2/ERBB2 signaling directly. Instead, it heterodimerizes with other EGFR family members, using their ligand-binding sites to activate cell proliferation signaling cascades. In cancer, overexpression of HER2/ERBB2 leads to ligand-independent activation of signaling through dimerization. During this process, HER2/ERBB2 dissociates from the HSP90 complex. Normally, HSP90 helps to correct misfolded and aggregated proteins, but it fails to correct mutated HER2/ERBB2 in cancer cells. Conclusions: This discussion focuses on the structural changes that HER2/ERBB2 undergoes, particularly in the form of homodimers, under normal and cancerous conditions. This analysis highlights the mutated state of HER2/ERBB2 and the role of HSP90 in this context. Notably, a single-point mutation outside a protein’s active site can significantly alter its structure. This is a critical consideration in drug discovery, underscoring the need to evaluate the entire protein conformation during simulations.

Microsporum gypseum is a dermatophyte with a geophilic nature that is found all over the globe. It mainly causes tinea in the scalp, arms, and legs in humans. Squalene epoxidase (SE) is a crucial enzyme in M. gypseum for the biosynthesis of ergosterol. The medicinal plant Balanites aegyptiaca is an abundant supply of secondary constituents with great therapeutic values. In this research, the fruit epicarp portion was used to inhibit M. gypseum using experimental and computational techniques. The anti-dermatophytic activity of epicarp extracts on M. gypseum was evaluated using the poison plate method at five different concentrations. At 3 mg/mL, the M. gypseum was completely controlled by the fractioned chloroform extract of epicarp. The compounds from previous research were utilized for docking studies (Abuthakir et al., 2022). The ideal compounds and the drug terbinafine were then docked using Schrödinger’s Glide module. It demonstrates that (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside outperforms other substances and the drug terbinafine in docking analysis. Desmond, Schrödinger Molecular Dynamics simulations were also performed for (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside-squalene epoxidase complexes. The complex appears to be more stable, according to the MD simulation research. This study indicates that (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside could be used as a potential inhibitor of M. gypseum growth, and it could be studied further.

A computational approach was exploited towards new molecule designing to target the inhibition of resistant genes mecA and bla_CTX-M in MRSA and ESBL strains cultured from diabetic foot infected patients. The bioinformatic analysis involves the prediction of protein structures for mecA and bla_CTX-M employing the Prime module of Schrodinger. The interactions were examined with the control antibiotics using the modelled protein structures, which revealed that Cefixime and Amikacin showed the highest binding affinity with mecA and bla_CTX-M, respectively. According to the predictions of pharmacophores, the ADHRN hypothesis for mecA protein and the ADHR hypothesis for bla_CTX-M protein were obtained. Subsequently, the antibiotic compound library from Selleckchem was retrieved, and molecular interactions studies were carried out to explore the interaction profiling of mecA with Tobramycin and bla_CTX-M with Acyclovir. Further, the stability of protein-ligand interactions was validated through molecular dynamics simulations. Overall, this study suggests that the predicted pharmacophore model provides in-depth knowledge for repurposing an antibiotic drug with effective inhibition to enhance its therapeutic activity in the currently used ones. Communicated by Ramaswamy H. Sarma