Insights into the Anti-Adipogenic and Anti-Inflammatory Potentialities of Probiotics against Obesity.

Functional foods with probiotics are safe and effective dietary supplements to improve overweight and obesity. Thus, altering the intestinal microflora may be an effective approach for controlling or preventing obesity. This review aims to summarize the experimental method used to study probiotics and obesity, and recent advances in probiotics against obesity. In particular, we focused on studies (in vitro and in vivo) that used probiotics to treat obesity and its associated comorbidities. Several in vitro and in vivo (animal and human clinical) studies conducted with different bacterial species/strains have reported that probiotics promote anti-obesity effects by suppressing the differentiation of pre-adipocytes through immune cell activation, maintaining the Th1/Th2 cytokine balance, altering the intestinal microbiota composition, reducing the lipid profile, and regulating energy metabolism. Most studies on probiotics and obesity have shown that probiotics are responsible for a notable reduction in weight gain and body mass index. It also increases the levels of anti-inflammatory adipokines and decreases those of pro-inflammatory adipokines in the blood, which are responsible for the regulation of glucose and fatty acid breakdown. Furthermore, probiotics effectively increase insulin sensitivity and decrease systemic inflammation. Taken together, the intestinal microbiota profile found in overweight individuals can be modified by probiotic supplementation which can create a promising environment for weight loss along enhancing levels of adiponectin and decreasing leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and transforming growth factor (TGF)-ß on human health.

Establishment of a porcine bronchial epithelial cell line and its application to study innate immunity in the respiratory epithelium.

In vitro culture models that precisely mirror the porcine respiratory epithelium are needed to gain insight into how pathogens and host interact. In this study, a new porcine bronchial epithelial cell line, designated as PBE cells, was established from the respiratory tract of a neonatal pig. PBE cells assumed a cobblestone-epithelial like morphology with close contacts between the cells when they reached confluence. The PBE cell line was characterized in terms of its expression of pattern recognition receptors (PRRs) and its ability to respond to the activation of the Toll-like receptor 3 (TLR3) and TLR4 signaling pathways, which are key PRRs involved in the defense of the respiratory epithelium against pathogens. PBE cells stimulated with poly(I:C) were able to up-regulate the expression of IFN-ß, IFN-λ1 (IL-29), IFN-λ3 (IL-28B), the antiviral factors Mx1, OAS1, and PKR, as well as the viral PRRs RIG-1 and MDA5. The expression kinetics studies of immune factors in PBE cells allow us to speculate that this cell line can be a useful in vitro tool to investigate treatments that help to potentiate antiviral immunity in the respiratory epithelium of the porcine host. In addition, poly(I:C) and LPS treatments increased the expression of the inflammatory cytokines TNF-α, IL-6, IL-8, and MCP-1/CCL2 and differentially modulated the expression of negative regulators of the TLR signaling pathways. Then, PBE cells may also allow the evaluation of treatments that can regulate TLR3- and TLR4-mediated inflammatory injury in the porcine airway, thereby protecting the host against harmful overresponses.

An In silico Approach towards Finding the Cancer-Causing Mutations in Human MET Gene.

Mesenchymal-epithelial transition (MET) factor is a proto-oncogene encoding tyrosine kinase receptor with hepatocyte growth factor (HGF) or scatter factor (SF). It is found on the human chromosome number 7 and regulates the diverse cellular mechanisms of the human body. The impact of mutations occurring in the MET gene is demonstrated by their detrimental effects on normal cellular functions. These mutations can change the structure and function of MET leading to different diseases such as lung cancer, neck cancer, colorectal cancer, and many other complex syndromes. Hence, the current study focused on finding deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) and their subsequent impact on the protein's structure and functions, which may contribute to the emergence of cancers. These nsSNPs were first identified utilizing computational tools like SIFT, PROVEAN, PANTHER-PSEP, PolyPhen-2, I-Mutant 2.0, and MUpro. A total of 45359 SNPs of MET gene were accumulated from the database of dbSNP, and among them, 1306 SNPs were identified as non-synonymous or missense variants. Out of all 1306 nsSNPs, 18 were found to be the most deleterious. Moreover, these nsSNPs exhibited substantial effects on structure, binding affinity with ligand, phylogenetic conservation, secondary structure, and post-translational modification sites of MET, which were evaluated using MutPred2, RaptorX, ConSurf, PSIPRED, and MusiteDeep, respectively. Also, these deleterious nsSNPs were accompanied by changes in properties of MET like residue charge, size, and hydrophobicity. These findings along with the docking results are indicating the potency of the identified SNPs to alter the structure and function of the protein, which may lead to the development of cancers. Nonetheless, Genome-wide association study (GWAS) studies and experimental research are required to confirm the analysis of these nsSNPs.

In-Silico Exploration of Plant Metabolites as Potential Remedies of Norovirus.

Research is still being carried out to develop specific medications or vaccinations to fight norovirus, a key contributor to foodborne illness. This study evaluated certain plant-based active chemicals as prospective candidates for such treatments using virtual screening techniques and other computer assessments. Twenty (20) plant metabolites were tested against the norovirus VP1, VP2, P48, and P22 protein domains using the molecular docking method. In terms of the lowest global binding energy, Asiatic acid, avicularin, guaijaverin, and curcumin exhibited the highest binding affinity with all selected proteins. Each viral protein's essential binding sites with the potential drugs and drug surface hotspots were uncovered. The ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis was used to further analyze the pharmacological profiles of the top candidates. According to the results, none of the substances showed any adverse consequences that would reduce their drug-like properties. According to the analysis of the toxicity pattern, no detectable tumorigenic, mutagenic, irritating, or reproductive effects of the compounds were discovered. However, among the top four alternatives, curcumin exhibited the highest levels of cytotoxicity and immunotoxicity. These discoveries may open the way for the development of effective norovirus therapies and safety measures. Due to the positive outcomes, we strongly propose more in vivo experiments for the experimental validation of our findings.