Bile acid, an important molecule regulating the endocrine system and metabolism, affects glucose, lipid, and energy homeostasis in the body and has emerged as a therapeutic target for diabetes and metabolic syndrome. Polycystic ovary syndrome (PCOS) is a reproductive endocrine-metabolic disorder that is accompanied by not only obesity and insulin resistance but also bile acid metabolism disorders. In this review, we summarize the role of bile acid metabolism in three typical phenotypes of PCOS, including abnormal glucose and lipid metabolism, abnormal follicular development, and hyperandrogenism, and explore the underlying pathophysiological mechanisms. The findings provide a novel perspective for further research on PCOS and potential targets for its diagnosis and treatment.

IntroductionIt is well-known that different populations and animals, even experimental animals with the same rearing conditions, differ in their susceptibility to obesity. The disparity in gut microbiota could potentially account for the variation in susceptibility to obesity. However, the precise impact of gut microbiota on gut metabolites and its subsequent influence on susceptibility to obesity remains uncertain.MethodsIn this study, we established obesity-prone (OP) and obesity-resistant (OR) mouse models by High Fat Diet (HFD). Fecal contents of cecum were examined using 16S rDNA sequencing and untargeted metabolomics. Correlation analysis and MIMOSA2 analysis were used to explore the association between gut microbiota and intestinal metabolites.ResultsAfter a HFD, gut microbiota and gut metabolic profiles were significantly different between OP and OR mice. Gut microbiota after a HFD may lead to changes in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), a variety of branched fatty acid esters of hydroxy fatty acids (FAHFAs) and a variety of phospholipids to promote obesity. The bacteria g_Akkermansia (Greengene ID: 175696) may contribute to the difference in obesity susceptibility through the synthesis of glycerophosphoryl diester phosphodiesterase (glpQ) to promote choline production and the synthesis of valyl-tRNA synthetase (VARS) which promotes L-Valine degradation. In addition, gut microbiota may affect obesity and obesity susceptibility through histidine metabolism, linoleic acid metabolism and protein digestion and absorption pathways.

Recently, the utilization of nonsteroidal anti-inflammatory drugs (NSAIDs) to sensitize cisplatin (CDDP) has gained substantial traction in the treatment of ovarian cancer (OC). However, even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events, notably thrombosis. Furthermore, the diminished sensitivity to CDDP therapy in OC is multifactorial, rendering the application of NSAIDs only partially effective due to their cyclooxygenase-2 (COX-2) inhibiting mechanism. Hence, in this study, reactive oxygen species (ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV) prodrug (DTP@AP NPs) were prepared to achieve comprehensive chemosensitization. On one front, allicin achieved COX-2 blocking therapy, encompassing the inhibition of proliferation, angiogenesis and endothelial mesenchymal transition (EMT), thereby mitigating the adverse impacts of CDDP chemotherapy. Simultaneously, synergistic chemosensitization was achieved from multifaceted mechanisms by decreasing CDDP inactivation, damaging mitochondria and inhibiting DNA repair. In essence, these findings provided an optimized approach for synergizing CDDP with COX-2 inhibitors, offering a promising avenue for enhancing OC treatment outcomes.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder. Nevertheless, its accurate mechanisms remain unclear. Metabolomics is a powerful technique to identify small molecules that could be used to discover pathogenesis and therapeutical targets of disease. In the present study, a urinary untargeted metabolomics combined with targeted quantification analysis was performed to uncover metabolic disturbance associated with PCOS. A total of thirty-eight metabolites were obtained between PCOS patients and healthy controls, which were mainly involved in lipids (39.5%), organic acids and derivatives (23.7%), and organic oxygen compounds (18.4%). Based on enrichment analysis, fourteen metabolic pathways were found to be perturbed in PCOS, particularly glycerophospholipid metabolism and tryptophan metabolism. Targeted quantification profiling of tryptophan metabolism demonstrated that seven compounds (tryptophan, kynurenine, kynurenic acid, quinolinic acid, xanthurenic acid, 3-hydroxyanthranilic acid and 3-hydroxykynurenine) were up-regulated in PCOS. And these tryptophan-kynurenine metabolites showed significant correlations with PCOS clinical features, such as positively associated with testosterone, free androgen index, and the ratio of luteinizing hormone to follicle stimulating hormone. Thus, this study disclosed urinary metabolome changes associated with PCOS, and might provide new insights into PCOS pathogenesis elucidation and therapeutical target development.

ObjectiveThe purpose of this study was to investigate the specific alterations in gut microbiome and serum metabolome and their interactions in patients with polycystic ovary syndrome (PCOS).MethodsThe stool samples from 32 PCOS patients and 18 healthy controls underwent the intestinal microbiome analysis using shotgun metagenomics sequencing approach. Serum metabolome was analyzed by ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. An integrative network by combining metagenomics and metabolomics datasets was constructed to explore the possible interactions between gut microbiota and circulating metabolites in PCOS, which was further assessed by fecal microbiota transplantation (FMT) in a rat trial.ResultsFecal metagenomics identified 64 microbial strains significantly differing between PCOS and healthy subjects, half of which were enriched in patients. These changed species showed an ability to perturb host metabolic homeostasis (including insulin resistance and fatty acid metabolism) and inflammatory levels (such as PI3K/Akt/mTOR signaling pathways) by expressing sterol regulatory element-binding transcription factor-1, serine/threonine-protein kinase mTOR, and 3-oxoacyl-[acyl-cattier-protein] synthase III, possibly suggesting the potential mechanisms of gut microbiota underlying PCOS. By integrating multi-omics datasets, the panel comprising seven strains (Achromobacter xylosoxidans, Pseudomonas sp. M1, Aquitalea pelogenes, Porphyrobacter sp. HL-46, Vibrio fortis, Leisingera sp. ANG-Vp, and Sinorhizobium meliloti) and three metabolites [ganglioside GM3 (d18:0/16:0), ceramide (d16:2/22:0), and 3Z,6Z,9Z-pentacosatriene] showed the highest predictivity of PCOS (AUC: 1.0) with sensitivity of 0.97 and specificity of 1.0. Moreover, the intestinal microbiome modifications by FMT were demonstrated to regulate PCOS phenotypes including metabolic variables and reproductive hormones.ConclusionOur findings revealed key microbial and metabolite features and their interactions underlying PCOS by integrating multi-omics approaches, which may provide novel insights into discovering clinical diagnostic biomarkers and developing efficient therapeutic strategies for PCOS.

BACKGROUND There is a close relationship between cardiovascular risk factors and polycystic ovary syndrome (PCOS), and omega-3 fatty acids may have a key role in improving cardiovascular risk factors. We conducted the current systematic review and meta-analysis to evaluate the effect of omega-3 fatty acid supplementation on cardiovascular risk factors in patients with PCOS. METHODS We searched 4 databases including PubMed (MEDLINE), Cochrane Library, Embase, and Web of Science from inception to February 2021. We included randomized controlled trials (RCTs) that reported the effects of omega-3 fatty acid treatment for PCOS. According to the Cochrane system evaluation guide manual, 2 researchers independently assessed the methodological quality of the included studies. We pooled results using either a fixed effect model or random effect model. RESULTS We identified 314 articles, of which 10 met the criteria for inclusion, involving 778 participants. The pooled results suggested an association between the supplementation of omega-3 fatty acids and a reduction in serum insulin [-2.58 pmol/L, 95% confidence interval (CI): -3.34 to -1.82 pmol/L, P<0.00001, I2=0], homeostatic model assessment of insulin resistance (HOMA-IR) (-0.57, 95% CI: -0.75 to -0.40 L, P<0.00001, I2=2%), serum total cholesterol (TC) (-6.87 mg/dL, 95% CI: -10.28 to -3.47 mg/dL, P<0.0001, I2=95%), serum triglyceride (-4.03 mg/dL, 95% CI: -5.53 to -2.52 mg/dL, P<0.00001, I2=97%), serum low-density lipoprotein cholesterol (LDL-C) (-6.64 mg/dL, 95% CI: -11.58 to -1.70 mg/dL, P=0.008, I2=99%), serum very low-density lipoprotein cholesterol (VLDL-C) (-3.29 mg/L, 95% CI: -6.54 to -0.05 mg/L, P=0.05, I2=72%), serum high-sensitivity C-reactive protein (hs-CRP) (-8.97mg/dL, 95% CI: -17.66 to -0.28 mg/dL, P=0.04, I2=99%), an improvement in serum high-density lipoprotein cholesterol (HDL-C) (2.94 mg/dL, 95% CI: 0.63 to 5.26 mg/dL, P=0.01, I2=87%), but no effect on serum glucose (-0.76 mg/dL, 95% CI: -1.71 to 0.19 mg/dL, P=0.12, I2=73%) was found. DISCUSSION The current meta-analysis demonstrated that omega-3 fatty acid supplementation for women with PCOS resulted in a statistical improvement in insulin, HOMA-IR, TC, triglyceride, LDL-C, VLDL-C, and HDL-C, but did not affect serum glucose. The limitation of this paper is due to the lack of included research literature.

Background Genetic causes of premature ovarian insufficiency (POI) account for approximately 20 ~ 25% of patients. So far, only a few genes have been identified. Results Here, we first identified the c.1840C > A on G-protein signaling modulator 1 ( GPSM1 ) as a susceptibility locus for POI in 10 sporadic POI patients by whole-exome sequencing. The frequency of GPSM1 c.1840C > A was then verified as 3/20 in a POI sample of 20 patients (including the above 10 patients) by Sanger sequencing. RT-PCR and western blot analysis showed the expression of GPSM1 in rat ovaries was increased in the large antral follicle stage compared to the primordial follicle stage ( P < 0.01). The cell proliferation assay (CCK8) and flow cytometry suggested that the small-interfering RNA-induced silencing of Gpsm1 significantly increased apoptosis and decreased proliferation of rat ovarian granulosa cells (GCs) ( P < 0.01). Furthermore, suppression of Gpsm1 in GCs reduced levels of cAMP, PKAc, p-CREB as well as the ratio of Bcl-2/Bax, and increased the expression of Caspase-3 and Cleaved Caspase-3 ( P < 0.01). Conclusions In summary, this study identified a susceptibility variant GPSM1 c.1840C > A of POI for the first time. Gpsm1 was related to rat follicle development, and silencing of Gpsm1 increased apoptosis and decreased proliferation in rat GCs, possibly through inhibition of the cAMP-PKA-CREB pathway.

Aim To analyse the expression of lncRNA-ANRIL and other related factors in different human body fluids, explore the clinical significance of ANRIL and validate whether ANRIL is interrelated with the renin–angiotensin system and NF-κB signalling pathway. Methods Ninety-one patients were included in this cross-sectional study and were divided into the NDM group (20 patients), DM group (25 patients), NPDR group (21 patients) and PDR group (25 patients). Basic information and samples of serum, aqueous fluid and vitreous fluid were collected before vitrectomy or intravitreal injection. The transcription and levels of ANRIL and other related factors were detected by RT-PCR and ELISA. Statistical Package for Social Sciences software was used for statistical analysis. Results ANRIL expression varied among different groups and body fluids. There was no difference in ANRIL expression between the NDM and DM groups, but the level of ANRIL was significantly lower in the DM group than in the NPDR and PDR group. In vitreous fluid, ANRIL expression was positively correlated with Ang II, p65 and VEGF expression in the PDR group. The expression of ANRIL in serum was not significantly correlated with age or the random blood sugar but was positively correlated with diabetic duration and HbAc1 level. Conclusions Levels of lncRNA-ANRIL are higher in DR patient and correlated with the progression of DR that may be used as an indicator to predict the development of DR. The activation of the RAS and the NF-κB pathway may be closely related to the upregulation of ANRIL. Clinical trial number ChiCTR1800017500. Registry Chinese Clinical Trial Registry.