Integration of 16 S rRNA gene sequencing, metabonomics and metagenome analysis to investigate the mechanism of Sparganium stoloniferum-Curcuma phaeocaulis in treating of endometriosis in rats.

BACKGROUND: Endometriosis is a gynecological disease that causes severe chronic pelvic pain and infertility in women. The therapeutic efficacy of the traditional herbal combination of Sparganium stoloniferum-Curcuma phaeocaulis (Sangleng-Ezhu, SL-EZ) in the treatment of endometriosis has been established. However, the precise mechanism by which this treatment exerts its effects remains elusive. METHODS: To gain further insights, UPLC-MS/MS was employed to identify the primary chemical constituents of SL-EZ in serum. Additionally, network pharmacology was utilized to analyze the active ingredients and their corresponding targets. Furthermore, the impact of SL-EZ on ectopic endometrial growth in endometrial implants was assessed using a rat model. The therapeutic mechanism of SL-EZ in rats with endometriosis was further investigated through the application of 16 S rRNA gene sequencing, metagenomic sequencing, and metabolomics. RESULTS: The primary compounds in serum were zederone, p-coumaric acid, dehydrocostus lactone, curdione, curcumol. The growth of ectopic lesions in a rat model was effectively inhibited by SL-EZ. In comparison to the control group, the endometriotic rats exhibited a decrease in α-diversity of the gut microbiota, an increase in the Firmicutes/Bacteroidetes ratio, and a reduction in the abundance of Ruminococcaceae. Following SL-EZ intervention, the potential probiotic strains Lactobacillus gasseri and Lactobacillus johnsonii were able to restore the intestinal microenvironment at the species level. The altered metabolites were significantly correlated with Verrucomicrobia, Proteobacteria, and Bacteroidetes. The metabolomic analysis demonstrated significant alterations in intestinal metabolites. And SL-EZ intervention also exerted regulatory effects on various metabolic pathways in gut microbiota, including aminoacyl-tRNA biosynthesis, monobactam biosynthesis, cyanoamino acid metabolism, glycine, serine and threonine metabolism, plant secondary metabolite biosynthesis, and amino acid biosynthesis. CONCLUSION: The identification of novel treatment formulations for endometriosis was achieved through the utilization of network pharmacology and gut microbiota analyses. Our findings revealed simultaneous alterations in the microbiota within the rat model of endometriosis. The therapeutic efficacy of SL-EZ in treating endometriosis is attributed to its ability to restore the gut microbiota and regulate metabolism. This investigation offers valuable insights into the therapeutic mechanisms of traditional Chinese medicine (TCM) for endometriosis.

Identification of key modules and candidate genes associated with endometriosis based on transcriptome data via bioinformatics analysis.

BACKGROUNDS: Endometriosis is a common disease in women, but the signaling pathways and genes involved remain unclear. This study screened genes that were differentially expressed in ectopic endometrium (EC) and eutopic endometrium (EU) in endometriosis and provided clues for subsequent experimental verification. METHODS: Endometriosis samples were harvested from inpatients that underwent surgery from 2017 to 2019 with pathological evidence of endometriosis. We assessed the mRNA expression profiles in endometriosis and further conducted gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) to identify potential biomarkers in endometriosis. Finally, we further validated hub genes using public databases and immunohistochemistry assays. RESULTS: The upregulated DEGs of ectopic endometrium from endometriosis patients were mainly involved in cell adhesion, MAPK signaling, PI3K-Akt signaling pathways, cytokine receptor interactions, and epithelial-mesenchymal transformation (EMT)-associated signaling pathways. The downregulated DEGs between ectopic endometrium and eutopic endometrium were related to decidualization-associated genes in endometriosis. The correlated gene modules in eutopic endometrial cells were mainly enriched in cell adhesion, embryo implantation and inflammation. The eutopic and ectopic endometrial lesions in endometriosis were involved in the EMT process. Furthermore, we identified 18 co-expression modules during WGCNA analysis. Hub genes in the pale turquoise module were FOSB, JUNB, ATF3, CXCL2, FOS, etc. Significantly enriched KEGG pathways included the TNF, MAPK, foxO, oxytocin, and p53 signaling pathways. Enrichment pathways were directly related to immune surveillance, stem cell self-renewal, and epithelial-mesenchymal transformation. Several pathways and modules of endometriosis are related to cancer-associated pathways, which substantiates the correlation between endometriosis and various gynecological tumors. CONCLUSIONS: Endometriosis was tightly correlated with EMT and fibrosis mediated by inflammatory immunity, cytokines, estrogen, kinases and protooncogene through transcriptomics. Overall, our findings lay the groundwork for understanding the pathogenesis of endometriosis and its relationship with malignant transformation.

Impact of exercise on maternal gestational weight gain: An updated meta-analysis of randomized controlled trials.

BACKGROUND: Clinical evidence indicates that women will benefit from regular physical activity during pregnancy. This study aimed to summarize and update the evidence on the effect of exercise on maternal gestational weight gain (GWG). METHODS: We conducted a systematic literature search of Pubmed, Embase, and Cochrane Library from inception until July, 2018 for randomized controlled trials (RCTs) that investigate the effect of physical exercises on the maternal GWG compared with that of no physical exercises or conventional medical care. We extracted data from eligible trials for study characteristics, interventions, patients' baseline characteristics and outcomes for the study populations of interest. We conducted meta-analyses using random effects models. RESULTS: From 844 citations, 23 RCTs including 4462 pregnant women met the inclusion criteria. Meta-analysis indicated that compared with that in women having conventional medical care, GWG was significantly decreased in pregnant women with physical exercise [weighted mean difference (WMD) -1.02, 95% CI -1.35 to -0.70; P < .01; I = 48.4%]. Women appeared to benefit more for gestational weight control for exercise frequency of 3 times per week (WMD -1.22, 95% CI -1.55 to -0.90; I = 40.3%) and exercise duration of 30 to 45 minutes each time (WMD -1.32, 95% CI -1.79 to -0.85; I = 1.5%). CONCLUSION: This meta-analysis provides indications that exercise intervention can reduce maternal GWG for pregnant women, especially for those with exercise frequency of 3 times per week and duration of 30 to 45 minutes each time.

Prognostic Effect of Bisphosphonate Exposure for Patients With Diagnosed Solid Cancer: A Systematic Review With Meta-Analysis of Observational Studies.

Background: Bisphosphonates are widely prescribed for the prevention and treatment of osteoporosis. Recent epidemiological studies indicate that people with bisphosphonate use may have lower cancer risk and have improved survival. The aim of this study is to determine the association between bisphosphonate use and survival outcomes in solid cancer patients using systematic review and meta-analysis. Methods: A systematic literature search was performed using the PubMed, Embase, and Cochrane databases. Original articles published until April, 2018 were selected. The survival outcome measures assessed included overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS). Pooled hazard ratio (HR) and their 95% confidence interval (95% CI) were derived using a random-effects model. Results: Out of 9,742 retrieved citations, six cohort studies and two nested case-control studies satisfying the inclusion criteria were included for analyses. Bisphosphonate use was significantly associated with improved OS (HR 0.84, 95% CI 0.76-0.93), CSS (HR 0.73, 95% CI 0.58-0.90) and RFS (HR 0.72, 95% CI 0.53-0.96). The results of subgroup analyses stratified by major study characteristics were generally consistent with the main findings. For individual cancer type, we found that bisphosphonate use was significantly associated with longer OS for patients with gastroesophageal cancer (HR 0.62, 95% CI 0.40-0.98), as well as longer CSS for patients with breast cancer (HR 0.73, 95% CI 0.55-0.95). Conclusions: Current evidence indicates that bisphosphonate use is significantly associated with improved survival for patients with solid cancer. However, the prognostic effects in specific solid tumors remains to be confirmed by further large prospective cohort studies.