Gallocin-derived Engineered Peptides Targeting EGFR and VEGFR in Colorectal Cancer: A Bioinformatic Approach.

BACKGROUND: Colorectal cancer (CRC) treatment using time-saving and cost-effective targeted therapies with high selectivity and low toxicity drugs, is a great challenge. In primary investigations on Gallocin, as a most proposed factor in CRC pathogenesis caused by Streptococcus gallolyticus, it was surprisingly found that this bacteriocin has four α-helix structures and some anti- cancer sequences. OBJECTIVE: The aim of this study was to determine the ability of Gallocin-based anticancer peptides (ACPs) against epidermal growth factor receptor (EGFR) and vascular epidermal growth factor receptor (VEGFR) and the evaluation of their pharmacokinetics properties using bioinformatics approaches. METHODS: Support vector machine algorithm web-based tools were used for predicting ACPs. The physicochemical characteristics and the potential of anti-cancer activity of Gallocin-derived ACPs were determined by in silico tools. The 3D structure of predicted ACPs was modeled using modeling tools. The interactions between predicted ACPs and targets were investigated by molecular docking exercises. Then, the stability of ligand-receptor interactions was determined by molecular dynamic simulation. Finally, ADMET analysis was carried out to check the pharmacokinetic properties and toxicity of ACP. RESULTS: Four amino acid sequences with anti-cancer potential were selected. Through molecular docking, Pep2, and Pep3 gained the best scores, more binding affinity, and strong attachments by the formation of reasonable H-bonds with both EGFR and VEGFR. Molecular simulation confirmed the stability of Pep3- EGFR. According to pharmacokinetic analysis, the ACPs were safe and truthful. CONCLUSION: Designed peptides can be nominated as drugs for CRC treatment. However, different in-vitro and in-vivo assessments are required to approve this claim.

Maternal and neonatal outcomes in pregnant women with multiple sclerosis disease: A systematic review and meta-analysis.

OBJECTIVES: Little is known regarding the impact of multiple sclerosis (MS) on maternal and neonatal outcomes. Consequently, this systematic review and meta-analysis aimed to study the impacts of MS on maternal and neonatal outcomes in pregnant women with a history of MS. METHODS: This review was designed in line with the PRISMA guidelines. Two researchers conducted independent reviews of the literature without time restrictions until January 2023 using international databases, including PubMed, Web of Science, CINAHL Plus, Embase, Scopus, Science Direct, and Google Scholar. A random-effect meta-analysis, using the db metan command in Stata 17.2, was used to calculate the pooled measure of association. RESULTS: The meta-analysis identified 15 studies involving 33,174,541 pregnant women (32,191 with MS and 33,142,350 as controls). The findings indicate that women with a history of MS are at an increased risk of cesarean delivery (OR=1.28, 95% Confidence Intervals [CI]: 1.14-1.45, p-value: 0.042). Also, these women are at higher risk of neonatal outcomes, such as preterm birth (OR= 1.39, 95% CI: 1.08-1.78, p-value: 0.02), congenital malformations (OR=1.32, 95%CI: 1.16-1.50, p-value: 0.031), Apgar score <7 (OR=2.13, 95% CI: 1.19-3.79, p-value: 0.03), and small for gestational age (OR=1.27, 95% CI: 1.08-1.51, p-value: 0.040). CONCLUSION: Pregnant women with MS have a greater chance of adverse pregnancy results than pregnant women without MS. Consequently, pregnant women with MS should create detailed before and after pregnancy plans, in consultation with their doctors, spouses, families, and friends, regarding the necessary care and supplements. Future studies applying a prospective cohort design that control for potential confounders are needed to further validate the findings.

Niosome as an Effective Nanoscale Solution for the Treatment of Microbial Infections.

Numerous disorders go untreated owing to a lack of a suitable drug delivery technology or an appropriate therapeutic moiety, particularly when toxicities and side effects are a major concern. Treatment options for microbiological infections are not fulfilled owing to significant adverse effects or extended therapeutic options. Advanced therapy options, such as active targeting, may be preferable to traditional ways of treating infectious diseases. Niosomes can be defined as microscopic lamellar molecules formed by a mixture of cholesterol, nonionic surfactants (alkyl or dialkyl polyglycerol ethers), and sometimes charge-inducing agents. These molecules comprise both hydrophilic and hydrophobic moieties of varying solubilities. In this review, several pathogenic microbes such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Plasmodium, Leishmania, and Candida spp. have been evaluated. Also, the development of a proper niosomal formulation for the required application was discussed. This review also reviews that an optimal formulation is dependent on several aspects, including the choice of nonionic surfactant, fabrication process, and fabrication parameters. Finally, this review will give information on the effectiveness of niosomes in treating acute microbial infections, the mechanism of action of niosomes in combating microbial pathogens, and the advantages of using niosomes over other treatment modalities.

Microbiota metabolites in the female reproductive system: Focused on the short-chain fatty acids.

Several disorders have been linked to modifications in the gut microbial imbalance, intestinal epithelium, and host immune system. In this regard, microbiota derived short-chain fatty acids (SCFAs) play a key function in the regulation of histone deacetylases (HDACs), which affect modulation of immunity and regulation of inflammatory responses in the intestine and other organs. Studies examining the metabolites produced by polymicrobial bacterial vaginosis (BV) states and Lactobacillus-dominated microbiota have noted a dramatic reduction of lactic acid and a shift toward SCFA synthesis. Along with higher levels of SCFAs, acetate is typically the main metabolite in the cervicovaginal fluid of women with symptomatic bacterial vaginosis. The fact that SCFAs made by the vaginal microbiota have been shown to exhibit antibacterial and immune-modulating properties suggests that they may have promise as indicators of disease and/or disease susceptibility. In this review, we overview and summarize the current findings on the detrimental or protective roles of microbiota metabolites especially SCFAs in the health and disease of the female reproductive system.