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Abstract Purpose Cervical cancer (CC), a significant global health threat, necessitates comprehensive understanding for improved therapeutic interventions. Many research indicates that dysregulation of the Hippo-YAP1 pathway leads to uncontrolled proliferation and invasion of tumor cells, promoting the progression of various cancers. This article aims to elucidate the role of RNF6 in CC and its regulation of the Hippo-YAP1 signaling pathway. Methods The public tumor dataset analyses, immunohistochemistry, and western blotting were used to explore the expression of RNF6 in CC. Gain- and loss-of-function assays were conducted to elucidate the role of RNF6 in the proliferation and invasion of CC cells. Transcriptome sequencing was used to explore RNF6’s role in cervical cancer, with validation of its regulation of the Hippo-YAP1 pathway through western blotting and RT-qPCR. Co-transfection of YAP overexpression plasmids into RNF6-silenced CC cells were preformed to confirm YAP1’s pivotal role in RNF6-mediated CC progression. Animal experiments were preformed to further validate RNF6 interference’s inhibitory effect on CC proliferation in vivo. Results Clinical samples and bioinformatics analysis revealed high expression of RNF6 in CC, and closely associated with advanced FIGO (International Federation of Gynecology and Obstetrics) stage, larger tumor size, and poor prognosis. Cellular functional experiments demonstrate that RNF6 promotes the proliferation, invasion, and migration of CC cells, while knockdown of RNF6 yields the opposite effect. Transcriptome sequencing further reveals that RNF6 may promote CC progression through the Hippo-YAP signaling pathway. Western blotting and RT-qPCR further unveil that RNF6 enhances the upregulation of YAP1 protein levels, thereby activating downstream oncogenes CTGF and CYR61 transcription. Additionally, exogenous overexpression of YAP1 reverses the inhibitory effect of RNF6 silencing on CC proliferation and invasion. Furthermore, RNF6 interference significantly attenuates tumor growth in vivo experiments. Conclusion Our research reveals that RNF6 is highly expressed in CC, driving malignant progression by upregulating YAP1 protein expression and enhancing the transcription of downstream target genes CTGF and CYR61, offering potential therapeutic targets for CC treatment.

Abstract Background The factors affecting the cumulative live birth rate (CLBR) of PCOS (Polycystic ovary syndrom) patients who received in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) needs more research for a better outcome. Methods Here we carried out a retrospective analysis of 1380 PCOS patients who received IVF/ICSI-ET for the first time from January 2014 to December 2016. We divided them into cumulative live birth group (group A) and non-cumulative live birth group (group B) according to whether there were live births. Results The conservative cumulative live birth rate was 63.48%. There were 876 cumulative live births (group A) and 504 non-cumulative live births (group B) according to whether the patients had live births or not. Competition analysis showed that duration of infertility, primary/secondary type of infertility, stimulation protocols, starting dose of gonadotrophins and oocyte retrieved numbers were significantly correlated with CLBR. The Cox proportional risk regression model of PCOS patients showed that stimulation protocols had a significant impact on CLBR. Patients in the GnRH (Gonadotropin-releasing hormone)-antagonist protocol group and the mild stimulation protocol had lower CLBR than those in the prolonged GnRH-agonist protocol, which was statistically significant. PCOS patients with the starting dose of gonadotrophins greater than 112.5u had lower CLBR than those with less than 100u, which was statistically significant. Women with 11–15 oocytes and 16–20 oocytes had higher CLBR than women with 1–9 oocytes, which was statistically significant. Conclusions When we used Prolonged GnRH-agonist protocol, or the first starting dose of gonadotrophins was 100u-112.5u, or the number of oocytes obtained was 11–15 and 16–20, the CLBR of PCOS patients increased significantly after the 1st oocyte collection.

Abstract Background Our previous two-dimensional electrophoresis experiment showed that the expression of LASP1 in patients with endometriosis was significantly higher than that of control endometrium. However, the molecular mechanism by which LASP1 is regulated in endometriosis/adenomyosis is unknown. Methods Herein, qPCR was performed to analyze the expression levels of LASP1 and miR-218-5p between endometriosis (Ems) cells and control cells. Fluorescence in situ hybridization was carried out to measure the expression level of miR-218-5p in ectopic endometrium versus normal endometrium. After miR-218-5p mimic or inhibitor were transfected, the transwell experiment was carried out to see the effect of miR-218-5p on the migration of endometrial stromal cells (ESCs). EdU was used to measure cell proliferation rate. Dual-luciferase reporter assay was used to verify the binding of hsa-miR-218-5p to the 3’UTR of LASP1. Western blot and immunofluorescence analysis were carried out to identify the protein expression pattern of LASP1 and EMT markers in endometrial tissue. Results The miR-218-5p is mainly secreted from blood vessels and expressed in the muscle layer around the endometrium, which inhibits the expression level of LASP1 by binding the 3’UTR region of LASP1 in normal ESCs. Overexpression of miR-218-5p impedes the epithelial-to-mesenchymal transition (EMT) and prevents the migration of ESCs and the expression of Vimentin in Ems. Conclusions Our findings revealed that miR-218-5p in endometrial microenvironment prevents the migration of ectopic endometrial stromal cells by inhibiting LASP1.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is currently the major cause of chronic liver disease globally. Bile acids (BAs) have emerged as relevant signaling molecules that are associated with NAFLD development. This study was aimed to examine the association of serum total bile acids (TBAs) with NAFLD in a large population of Chinese subjects. Methods This cross sectional study recruited 152,336 participants from the Second Xiangya Hospital, China. NAFLD was diagnosed based on the presence of hepatic steatosis on ultrasonography, without significant alcohol consumption and other known causes for chronic liver disease. A multivariate logistic regression model was used to test for the association of serum TBAs with NAFLD, adjusting for conventional risk factors of NAFLD. Results A total of 27.4% of the participants had NAFLD. Patients with NAFLD had slightly higher TBA levels than those without, 3.4 vs. 3.0 μmol/L (p

Abstract Apolipoprotein C3 (apoC3) and apolipoprotein A5 (apoA5), encoded by APOA1/C3/A4/A5 gene cluster, are two critical regulators of plasma triglyceride (TG) metabolism. Deficiency of apoC3 or apoA5 led to significant decreased or increased plasma TG levels, respectively. Recent studies indicated apoC3 and apoA5 also played roles in plasma remnant cholesterol, high density lipoprotein (HDL) and hepatic TG metabolisms. Moreover, large scale population genetic studies indicated that loss of function mutations in APOC3 and APOA5 gene conferred decreased and increased risk of coronary artery disease (CAD), respectively. This manuscript mainly reviewed existing evidences suggesting the opposite role of apoC3 and apoA5 in lipid metabolism and CAD risk, and discussed the potential correlation between these two apolipoproteins.

Abstract Background The contributions of inflammation, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) to the residual risk of cardiovascular events have not been determined in a large cohort of Chinese population before. This study was aimed to investigate the association of serum levels of high sensitive C reactive protein (hs-CRP), TG and HDL-C with the residual risk of cardiovascular events in patients with stable coronary artery disease (CAD). Methods We enrolled 4090 patients with stable CAD from 13 hospitals in China. All participants received optimal medical treatment (OMT) for stable CAD suggested by guidelines and were followed. The endpoint measures were the first occurrence of a major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or unplanned coronary revascularization. Cox proportional regression analysis was conducted to identify independent predictors of MACE. Results We found that hs-CRP and HDL-C levels were associated with coronary lesion severity at baseline (both p

Abstract Background It is well known that angiopoietin-like protein 8 (ANGPTL8) exerts its effects on lipid metabolism through the inhibition of lipoprotein lipase and subsequent elevation of plasma triglyceride. However, it is not clear whether ANGPTL8 could affect lipid metabolism via other pathways. The study was aimed to investigate the effects of ANGPTL8 on the function of high-density lipoprotein (HDL), which plays a protective role in atherosclerosis progression. Methods Two hundred and ten subjects were recruited. Plasma ANGPTL8 was measured by enzyme-linked immunosorbent assays. Cholesterol efflux capacity was chosen as the biomarker of HDL function and measured via H3-cholesterol loading THP-1 cell models. Results ANGPTL8 exhibited no significant difference between CAD group and nonCAD group, but ANGPTL8 in DM group was significantly higher than that in the nonDM group [568.3 (406.2–836.8) vs 458.2 (356.8–755.6), P = 0.023]. Compared to controls, subjects in CAD group and DM group exhibited significantly lower cholesterol efflux capacity [CAD: 14.58 ± 2.06 vs 12.51 ± 2.83%, P