Polyketide synthases mutation in tuberculosis transmission revealed by whole genomic sequence, China, 2011-2019.

Introduction: Tuberculosis (TB) is an infectious disease caused by a bacterium called Mycobacterium tuberculosis (Mtb). Previous studies have primarily focused on the transmissibility of multidrug-resistant (MDR) or extensively drug-resistant (XDR) Mtb. However, variations in virulence across Mtb lineages may also account for differences in transmissibility. In Mtb, polyketide synthase (PKS) genes encode large multifunctional proteins which have been shown to be major mycobacterial virulence factors. Therefore, this study aimed to identify the role of PKS mutations in TB transmission and assess its risk and characteristics. Methods: Whole genome sequences (WGSs) data from 3,204 Mtb isolates was collected from 2011 to 2019 in China. Whole genome single nucleotide polymorphism (SNP) profiles were used for phylogenetic tree analysis. Putative transmission clusters (≤10 SNPs) were identified. To identify the role of PKS mutations in TB transmission, we compared SNPs in the PKS gene region between "clustered isolates" and "non-clustered isolates" in different lineages. Results: Cluster-associated mutations in ppsA, pks12, and pks13 were identified among different lineage isolates. They were statistically significant among clustered strains, indicating that they may enhance the transmissibility of Mtb. Conclusion: Overall, this study provides new insights into the function of PKS and its localization in M. tuberculosis. The study found that ppsA, pks12, and pks13 may contribute to disease progression and higher transmission of certain strains. We also discussed the prospective use of mutant ppsA, pks12, and pks13 genes as drug targets.

Efficacy of astragalus in the treatment of radiation-induced lung injury based on traditional Chinese medicine: A systematic review and meta-analysis of 25 RCTs.

BACKGROUND: Astragalus (Hedysarum Multijugum Maxim., Huangqi) is a Chinese herbal medicine, and according to the theory of traditional Chinese medicine (TCM), Chinese medicinal preparations containing astragalus can be used clinically to treat radiation-induced lung injury (RILI). To systematically review the efficacy and safety of Chinese medicinal preparations containing astragalus in the prevention and treatment of RILI by means of meta-analysis. METHODS: A systematic literature on randomized controlled trials (RCTs) of prescriptions containing astragalus in the treatment of RILI by Pubmed, Embase, Web of Science, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, WANFANG Database. The retrieval time is from the establishment of the database to January 18, 2022. Meta-analysis, heterogeneity test and sensitivity analysis were performed on eligible RCTs using Revman 5.4 software and STATA 17.0 software, and a "funnel plot" was used to analyze potential publication bias. RESULTS: A total of 25 RCTs were included, including 1762 patients, and the most widely used drugs were heat-clearing and detoxifying, yin-nourishing and qi-nourishing. The prescriptions containing astragalus can significantly reduce the total incidence of RILI (P < .01), improve the total effective rate and cure rate of RILI (P < .01), improve the quality of life of patients, alleviate breathing difficulties and reduce the expression of inflammatory factors (P < .01), and no adverse reactions related to TCM treatment were reported. CONCLUSION: The traditional Chinese medicinal preparation containing astragalus can effectively alleviate the clinical symptoms of RILI, reduce the toxic side effects, and is safe to use in clinic.

Network pharmacology-based strategy to investigate the active ingredients and molecular mechanisms of Scutellaria Barbata D. Don against radiation pneumonitis.

INTRODUCTION: Herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (RP), and the Scutellaria barbata D. Don (SBD) is a perennial herb that has been reported to protect against radiation-induced pneumonitis. However, the exact molecular mechanism is not known. The objective of this research was to investigate the against radiation pneumonitis ingredients and their functional mechanisms in SBD. METHODS: Based on the network pharmacology approaches, we collected active ingredients and target genes in SBD against RP through Traditional Chinese Medicine System Pharmacology (TCMSP) Database, and the "Herb-Ingredients-Target Genes-Disease" Network was constructed by using of Cytoscape. STRING analysis was performed to reveal the protein-protein interactions, and then we applied enrichment analysis on these target proteins, gene function, and pathways. RESULTS: A total of 18 ingredients in SBD regulate 65 RP related target proteins, which show that quercetin, luteolin, baicalein, wogonin may be the key active ingredients, while IL6, AKT1, VEGFA, MMP9, CCL2, prostaglandin-endoperoxide synthase 2 (PTGS2) (cyclooxygenase-2 [COX-2]), CXCL8, IL1B, mitogen-activated protein kinase (MAPK1), and IL10 were identified as critical targets. Besides, the results of Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that predicted targets of SBD are mostly associated with the pathological process of oxidative stress and inflammation. AGE- Receptor of Advanced Glycation Endproducts (RAGE) signaling pathway in diabetic complications, IL-17 signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, NF-kappa B signaling pathway might serve as the principal pathways for RP treatment. CONCLUSION: In our study, the pharmacological and molecular mechanism of SBD against RP was predicted from a holistic perspective, and the results provided theoretical guidance for researchers to explore the mechanism in further research.