High-throughput screening and molecular dynamics simulations of natural products targeting LuxS/AI-2 system as a novel antibacterial strategy for antibiotic resistance in Helicobacter pylori.

The main goal of treating any Helicobacter pylori (H. pylori)-related gastrointestinal disease is completely eradicating infection. Falling eradication efficiency, off-target effects, and patient noncompliance with prolonged and broad spectrums have sparked clinical interest in exploring other effective, safer therapeutic choices. As natural substances are risk-free and privileged with high levels of antibacterial activity, most of these natural chemical's specific modes of action are unknown. With the aid of in silico molecular docking-based virtual screening studies and molecular dynamic simulations, the current study is intended to gather data on numerous such natural chemicals and assess their affinity for the S-ribosyl homocysteine lyase (LuxS) protein of H. pylori. The ligand with the highest binding energy with LuxS, glucoraphanin, catechin gallate and epigallocatechin gallate were rationally selected for further computational analysis. The solution stability of the three compounds' optimal docking postures with LuxS was initially assessed using long-run molecular dynamics simulations. Using molecular dynamics simulation, the epigallocatechin gallate was found to be the most stable molecule with the highest binding free energy, indicating that it might compete with the natural ligand of the inhibitors. According to ADMET analysis, his phytochemical was a promising therapeutic candidate for an antibacterial action since it had a range of physicochemical, pharmacokinetic, and drug-like qualities and had no discernible adverse effects. Additional in vitro, in vivo, and clinical trials are needed to confirm the drug's precise efficacy during H. pylori infection.Communicated by Ramaswamy H. Sarma.

Domain Architecture Based Methods for Comparative Functional Genomics Toward Therapeutic Drug Target Discovery.

Genes duplicate, mutate, recombine, fuse or fission to produce new genes, or when genes are formed from de novo, novel functions arise during evolution. Researchers have tried to quantify the causes of these molecular diversification processes to know how these genes increase molecular complexity over a period of time, for instance protein domain organization. In contrast to global sequence similarity, protein domain architectures can capture key structural and functional characteristics, making them better proxies for describing functional equivalence. In Prokaryotes and eukaryotes it has proven that, domain designs are retained over significant evolutionary distances. Protein domain architectures are now being utilized to categorize and distinguish evolutionarily related proteins and find homologs among species that are evolutionarily distant from one another. Additionally, structural information stored in domain structures has accelerated homology identification and sequence search methods. Tools for functional protein annotation have been developed to discover, protein domain content, domain order, domain recurrence, and domain position as all these contribute to the prediction of protein functional accuracy. In this review, an attempt is made to summarise facts and speculations regarding the use of protein domain architecture and modularity to identify possible therapeutic targets among cellular activities based on the understanding their linked biological processes.

Hypolipidemic and antioxidant effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice.

CONTEXT: The plant Cassia fistula L. (Caesalpiniaceae) fruit was widely used by traditional practitioners to treat cardiovascular diseases (CVDs) in India. Hyperlipidemia is a lipid metabolism disorder and the major risk factor for the development of CVDs. Although most of the current hypolipidemic drugs are expensive and have potential side effects, the research focusing on natural alternative medicines is relevant. OBJECTIVE: To investigate the hypolipidemic and antioxidant effects of ethanol extract of C. fistula fruit (CFE) in high-fat diet (HFD) induced hyperlipidemia in mice. MATERIALS AND METHODS: Oral administration of CFE at 100, 300 and 500 mg/kg body weight on HFD induced hyperlipidemia mice for 30 days. The standard drug atorvastatin (20 mg/kg) was used to compare the efficacy of CFE. Hypolipidemic effect was evidenced by the measurement of serum lipid profile and further confirmed by Oil Red O staining of adipose tissue. The hepatic and cardiac melondialdehyde (MDA) level and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase were determined. RESULTS: Treatment with CFE at different doses has significantly restored the levels of serum lipid, MDA and enzymes activities in the liver and heart of hyperlipidemia mice. Oil Red O staining of visceral adipose tissue has shown marked reduction of lipid accumulation in adipocytes; whereas, administration of CFE at 500 mg/kg showed remarkable (p < 0.001) hypolipidemic and antioxidant effects in HFD fed mice. CONCLUSION: C. fistula fruit demonstrated hypolipidemic and antioxidant properties in vivo and the results corroborate the use of this plant in traditional medicine for cardiac ailments.

Towards the construction of an interactome for Human WD40 protein family.

WD40 proteins are involved in a variety of protein-protein interactions as part of a multi-protein assembly modulating diverse and critical cellular process. It is known that several proteins of this family have been implicated in different disorders such as developmental abnormalities and cancer. However, molecular functions of many proteins in this family are yet unknown and it is of clinical interest. Therefore, it is of interest to define, construct, understand, analyze, evaluate, redefine and refine an interactome for WD40 protein family. We used data from literature mining using Cytoscape followed by linear regression analysis between Betweenness centrality and stress scores to define a model to filter the nodes in a representative WD40 interactome construction. We identified 10 ranked nodes in this analysis and subsequent microarray data selected three of them in insulin resistance that is further demonstrated in HepG2 cell culture models. We also observed the expression of GRWD1, RBBP5 and WDR5 genes during perturbation. Thus, we report hub nodes of WD40 interactome in insulin resistance. It should be noted that the pipeline using protein interaction network help find new proteins of clinical importance.