Gut microbiota and risk of polycystic ovary syndrome: Insights from Mendelian randomization.

Background: Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and metabolic syndrome with complex origins and pathogenesis that has not yet been fully elucidated. Recently, the interconnection between gut microbiota and metabolic diseases has gained prominence in research, generating new insights into the correlation between PCOS and gut microbiota composition. However, the causal link between PCOS and gut microbiota remains relatively unexplored, indicating a crucial gap in current research. Methods: We conducted a two-sample Mendelian randomization analysis using summary statistics obtained from the MiBioGen Consortium's extensive genome-wide association studies (GWAS) meta-analysis, focusing on the gut microbiota. Summary statistics for PCOS were acquired from the FinnGen Consortium R7 release data. Various statistical approaches, including inverse variance weighted, MR-Egger, maximum likelihood, weighted model, and weighted median, have been employed to investigate the causal association between the gut microbiota and PCOS. Additionally, we performed a reverse causal analysis. Cochran's Q statistic was used to assess the heterogeneity of the instrumental variables. Regarding the relationships between PCOS and specific genera within the gut microbiota, a significance level of P < 0.05 was observed, but only when q ≥ 0.1. Results: Our analysis revealed that specific microbial genera, namely Bilophila (P = 4.62 × 10-3), Blautia (P = 0.02), and Holdemania (P = 0.04), displayed a protective effect against PCOS. Conversely, the presence of the Lachnospiraceae family of bacteria was associated with a detrimental effect on PCOS (P = 0.04). Furthermore, reverse Mendelian randomization analysis confirmed the significant influence of Lachnospiraceae on PCOS. No significant variations in instrumental variables or evidence of horizontal pleiotropy were observed. Conclusions: The results revealed a definitive causal link between PCOS and the presence of Bilophila, Blautia, Holdemania, and Lachnospiraceae in the gut microbiota. This discovery could provide pivotal insights, leading to novel preventive and therapeutic approaches for PCOS.

Diagnostic value of IL-22, IL-23, and IL-17 for NK/T cell lymphoma.

NK/T cell lymphoma (NKTCL) is a common blood cancer, and early diagnosis of this disease is crucial. This study is aimed to investigate the roles of IL-17, IL-22 as well as IL-23 for the diagnosis of NKTCL. Sixty-five patients with NKTCL were included and the blood samples were collected, and sixty healthy objectives served as the controls. Serums of the patients and controls were collected. The expression levels of IL-17, IL-22, and IL-23 were examined using enzyme-linked immunosorbent (ELISA) assay. The receiver operator characteristic (ROC) curve was drawn for determining the potential diagnostic value of these cytokines. The serum levels of IL-17 (156.0 ± 67.75 pg/mL), IL-22 (39.98 ± 23.88 pg/mL), and IL-23 (43.05 ± 25.69 pg/mL) were all markedly increased in NKTCL patients (P<0.001); ROC analysis showed the serum level of IL-17, IL-22, and IL-23 could serve as the potential diagnostic biomarker for NKTCL with high sensitivity and specificity. The AUC of IL-17 was 0.9487 (95% confidence interval (CI), 0.9052 to 0.9922). Area under the curve (AUC) of IL-22 was 0.7321 (95% CI, 0.6449 to 0.8192). The AUC of IL-23 was 0.7885 (95% CI, 0.7070 to 0.8699). Our data indicated that IL-17, IL-22, and IL-23 were all increased in NKTCL and may function as potential diagnostic biomarkers for NKTCL.

Research on the Mechanism of Asperosaponin VI for Treating Recurrent Spontaneous Abortion by Bioinformatics Analysis and Experimental Validation.

Asperosaponin VI (AS6), as the quality marker of Dipsaci Radix, is verified to exert therapeutic effect on alleviating recurrent spontaneous abortion (RSA). However, due to the lack of relevant research, its molecular mechanism is still unclear. We retrieved targets for AS6 and RSA, and then used their overlapped targets for PPI analysis. In addition, we used GO and KEGG enrichment analyses, and molecular docking to investigate the anti-RSA mechanisms of AS6. Furthermore, we conducted in vitro experiments to validate the predictions of network pharmacology. Results showed that a total of 103 AS6-associated targets and 2084 RSA-associated targets, with 49 targets overlapped. GO enrichment analysis showed 845 significant biological processes like decidualization, while KEGG pathway enrichment analysis revealed 76 significant entries including 18 signaling pathways, which were closely linked to PI3K-Akt, HIF-1, TNF, IL-17, and VEGF signaling pathways, etc. Molecular docking findings verified that AS6 had tight link with the key targets including JUN, CASP3, STAT3, SRC, and PTGS2. Notably, in vitro experiments revealed that AS6 treatment could exert lower expressions of JUN, pro-CASP3, CASP3, STAT3, SRC, and PTGS2 in decidual cells compared with progesterone despite the expressions of STAT3, SRC, and PTGS2 with no significant difference, and mifepristone could interfere with the effects. In general, numerous targets and multiple pathways involve during the process of AS6 treatment against RSA. Moreover, our in vitro research first reported that AS6 may regulate the expressions of key targets (JUN, CASP3, STAT3, SRC, and PTGS2) in decidual cells to promote decidualization, thus treating RSA.

Mechanical forces on trophoblast motility and its potential role in spiral artery remodeling during pregnancy.

During the first trimester of pregnancy, cytotrophoblasts (CTBs) differentiate into extravillous trophoblasts (EVTs). EVTs migrate from villus to decidua, invade maternal spiral arteries (SAs) and more strikingly, they migrate against blood flow along the vessels and replace endothelial cells (ECs), completing SA remodeling. Studies have indicated that trophoblast cells are mechanosensitive. They assemble ECs, which can align in the direction of fluid flow. However, how they sense blood flow and transform mechanical stimulations into chemical signals remain largely unexplored. What factors trigger their motility? what are the potential and major factors that guide them to find their path and empower them to migrate against flow? To answer these intricate questions, this review provides some of the novel aspects and sheds new insights into clinical applications.