Mesenchymal stem cells (MSCs) have emerged as a promising regenerative tool, owing mainly to their multi-differentiation potential and immunosuppressive capacity. When compared with MSCs classically derived from the adult bone marrow (BM), MSCs of neonatal origins exhibit superior proliferation ability, lower immunogenicity, and possible lower incorporated mutation; hence, they are considered as an alternative source for clinical use. Several researches have focused on the biological differences among some neonatal MSCs cultured in serum-containing medium (SCM). However, since it has been reported that MSCs possess different biological characteristics when cultured in serum-free medium (SFM), these comparative studies in SCM cannot exactly represent the results under the serum-free Good Manufacturing Practice (GMP) standard. Here, MSCs were isolated from three neonatal tissues, namely amniotic membrane (AM), umbilical cord (UC), and chorionic plate (CP), from the same donor, and their morphologies, immunophenotypes, trilineage differentiation potentials, global gene expression patterns, and proliferation abilities were systematically compared under chemical-defined SFM. Our study demonstrated that these three neonatal MSCs exhibited a similar morphology and immunophenotypic pattern but various mesodermal differentiation potentials under SFM: amniotic membrane-derived MSCs showed a higher rate for osteogenic differentiation; chorionic plate-derived MSCs presented better adipogenic induction efficiency; and all these three neonatal MSCs exhibited similar chondrogenic potential. Moreover, by the analysis of global gene expression patterns, we speculated a possible higher proliferation ability of CP-MSCs in SFM, and we subsequently validated this conjecture. Collectively, these results suggest that MSCs of different neonatal origins possess different biological features in SFM and thus may represent an optimal choice for different clinical applications.

Background: GLP-1 receptor agonists (GLP-1 RA) have been proven to treat several metabolic diseases; however, the effects of GLP-1 RA on polycystic ovary syndrome (PCOS) remain unclear. Here, we aimed to investigate whether semaglutide, a novel GLP-1 RA, could alleviate ovarian inflammation in PCOS mice. Methods: Female C57BL/6J mice were subcutaneously injected with dehydroepiandrosterone for 21 days to establish the PCOS model. Then the mice were randomly divided into three groups: PCOS group (n = 6), S-0.42 group (semaglutide 0.42 mg/kg/w, n = 6), and S-0.84 group (semaglutide 0.84 mg/kg/w, n = 6). The remaining six mice were used as controls (NC). After 28 days of intervention, serum sex hormones and inflammatory cytokine levels were measured. Hematoxylin and eosin staining was used to observe the ovarian morphology. Immunohistochemical staining was used to detect the relative expression of CYP19A1, TNF-α, IL-6, IL-1β, and NF-κB in ovaries. CYP17A1 and StAR were detected using immunofluorescence staining. Finally, the relative expressions of AMPK, pAMPK, SIRT1, NF-κB, IκBα, pIκBα, TNF-α, IL-6, and IL-1β were measured using Western blotting. Results: First, after intervention with semaglutide, the weight of the mice decreased, insulin resistance improved, and the estrous cycle returned to normal. Serum testosterone and IL-1β levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1β, NF-κB, CYP17A1, and StAR in the ovary was significantly downregulated, whereas CYP19A1 expression was upregulated after the intervention. Finally, we confirmed that semaglutide alleviates ovarian tissue inflammation and improves PCOS through the AMPK/SIRT1/NF-κB signaling pathway. Conclusion: Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NF‑κB signaling pathway in PCOS mice.

Polycystic ovary syndrome (PCOS) is a prevalent gynecologic endocrine disorder characterized by menstrual irregularities, elevated androgen levels, and ovulatory dysfunction. Its etiology is multifactorial. Emerging evidence indicates that PCOS patients exhibit diminished gut microbiota (GM) diversity and altered microbial ratios, contributing to the metabolic derangements observed in these individuals. This review elucidates the role of GM in the pathogenesis and metabolic disorders of PCOS, encompassing insulin resistance (IR), hormonal imbalances, bile acid metabolic disorders, Interleukin-22-mediated immune dysregulation, and brain-gut axis disturbances. Additionally, it synthesizes current therapeutic strategies targeting the GM, aiming to furnish a theoretical framework for prospective clinical interventions.

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder among women of reproductive age. Although the traditional mechanistic framework has focused on dysregulation of the hypothalamic-pituitary-ovarian axis (HPOA), emerging evidence suggests that PCOS-associated metabolic disturbances predominantly originate from dysregulation of the hypothalamic-sympathetic nerve-adipose tissue axis (HSF axis). This article systematically reviews the mechanisms by which hypothalamic nuclei (including the arcuate nucleus and paraventricular nucleus) regulate adipose tissue metabolism through sympathetic neural pathways. Furthermore, it explores how HSF axis dysfunction exacerbates both metabolic and reproductive abnormalities in PCOS through pathophysiological pathways such as chronic low-grade inflammation and energy sensing dysregulation. This synthesis offers novel insights into PCOS pathogenesis by bridging the gap between neuroendocrine regulation and systemic metabolic dysfunction.

Context: Metrnl is a novel adipokine mainly produced by white adipose tissue, which plays important roles in insulin sensitization, and energy homeostasis. However, information about the function of Metrnl in Metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. Methods: This is a control study, which enrolled 176 adults with MAFLD and 176 normal controls. They were matched in body mass index (BMI), age, and sex. Serum Metrnl was determined by ELISA. Other biochemical data were also collected. Results: Compared to the controls, circulating Metrnl was prominently decreased in the MAFLD adults (P< 0.001). Next, binary logistic regression model indicated that sex, waist circumference (WC), triglyceride, γ-gamma glutamyl transferase(γ-GGT), and Metrnl was independently associated with MAFLD. Further, as Metrnl levels elevated across its tertiles, the rate of MAFLD decreased (67.52, 66.95, and 15.38%; P value for trend< 0.001). Data from multivariate logistic regression models evidenced that compared with the lowest tertile of Metrnl, the odds ratio of MAFLD was 0.023(95% CI 0.006– 0.086, P< 0.001) for the highest tertile after adjusting for potential confounders. Besides, area under ROC curve of Metrnl for diagnosis MAFLD was 0.755(95% CI 0.705– 0.805). Metrnl was positively correlated with diastolic blood pressure, WC, BMI, systolic blood pressure, γ-GGT, and Creatinine in MAFLD. Finally, we found systolic blood pressure and Creatinine were independently related to serum Metrnl in MAFLD. Conclusion: Serum Metrnl is reduced in adult with MAFLD. The results suggest that Metrnl may be a protective factor associated with the pathogenesis of MAFLD.