Dongfang Liu

Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-aged women and a major cause of infertility. Understanding global patterns and temporal trends of PCOS-related infertility is essential for guiding clinical management and resource allocation. Methods Data on PCOS prevalence and infertility proportion among women aged 15–49 years were obtained from the Global Burden of Disease (GBD) 2021 database, covering 204 countries and territories from 1990 to 2021. Estimated annual percentage changes (EAPC) were calculated to assess temporal trends across age groups, regions, infertility subtypes, and countries. Socio-demographic disparities were evaluated using the Socio-demographic Index (SDI). Results The number of women with PCOS nearly doubled globally, increasing from 34.8 million in 1990 to 65.8 million in 2021. The proportion of infertility among women with PCOS increased from 18.22% to 19.00%. Women aged 35–39 years had the highest infertility proportion (21.9%). Substantial geographic variation was observed, with the largest increase in infertility cases occurring in Equatorial Guinea (772%), whereas the United States Virgin Islands and Latvia showed declines. The highest infertility proportion was observed in the Central African Republic (21.84%) and the lowest in Australia (11.89%). Higher SDI regions had more infertility cases, while infertility proportions were inversely associated with SDI levels. Conclusion The global burden of PCOS and related infertility has increased substantially over the past three decades. Significant socioeconomic disparities persist, with low-SDI regions experiencing higher infertility proportions. Improving early diagnosis, healthcare accessibility, and targeted interventions is essential to reduce the global burden of PCOS-related infertility.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and is characterized by excessive lipid accumulation in hepatocytes. Endoplasmic reticulum (ER) stress and inflammation play important roles in hepatic lipid accumulation. Although CILP2 has been implicated in lipid metabolism, its role in MASLD remains unclear. Hepatic steatosis was induced in mice by a high-fat diet in this study. CILP2 was overexpressed in mouse livers and in vitro hepatocytes using the Ad-CILP2 adenovirus. CILP2 KO mice were also used in the experiments. Liver tissues and hepatocytes were collected for further analysis. CILP2 expression was upregulated in steatotic liver tissue and hepatocytes. CILP2 overexpression upregulated genes related to fatty acid synthesis (Srebp-1c, Fasn, Acc, Scd1, and Cd36), promoted lipid accumulation, and elevated the expression of proinflammatory cytokines (Il6, Tnf, and Il1b). Conversely, CILP2 knockout reduced high-fat diet-induced hepatic steatosis and improved glucose metabolism. Mechanistically, CILP2 activated the IRE1α/XBP1 branch of the ER stress pathway, thereby promoting lipid synthesis and inflammation, effects that were partially alleviated by 4-PBA and STF-083010 treatments. Our findings indicate that CILP2 contributes to hepatic lipid accumulation and inflammation via the IRE1α/XBP1 pathway and may represent a potential therapeutic target for MASLD intervention.

Age-related renal impairment often occurs insidiously and has become an important cause of chronic renal failure, especially when individuals with other chronic diseases. However, there is lack of effective treatments. Research on diabetic patients has revealed that empagliflozin (EMPA), one of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, exhibits a distinct protective effect on aging kidneys. EMPA has been shown to improve renal fibrosis and ameliorate inflammatory cytokines, including IL-1 and IL-8, which are closely associated with the aging process in db/db mouse models. As a result, we assessed markers indicative of kidney senescence P16 and senescence-associated β-galactosidase (SA-β-gal) in the renal tissue of male C57 mice undergoing natural aging, following treatment with EMPA. Our findings showed that in Old-EMPA group, the expression of P16 and SA-β-gal were downregulated compared to Old-vehicle group, while these markers were expressed lower in Young group. RNA sequencing analysis indicated that our findings correlated with increased expressions of Six1 and Wnt4 in the kidney. Protein–protein interaction (PPI) analysis confirmed an interaction between Six1 and Wnt4. After treatment with EMPA, the expression of Six1 and Wnt4 was observed to increase in both aging Primary renal tubular epithelial cells (PRTECs) and HK-2 cells, whereas the expression of NF-κB and its downstream effectors IL-1β and TNF-α decreased, leading to an improvement in aging-related changes.

Osteoprotegerin (OPG) has emerged as a pivotal factor in metabolic disease pathology; however, its role in hepatic glucose metabolism remains poorly understood. We demonstrated a pronounced reduction in hepatic OPG expression in obese mice, attributable to DNA hypermethylation mediated by DNMT3α. Opg overexpression in the liver reduced the basal metabolic rate and exacerbated glucose metabolism disorders in mice with high-fat diet–induced obesity, whereas Opg knockout yielded opposite effects. Furthermore, mammalian target of rapamycin complex 1 (mTORC1; Raptor)/S6K1/IRS1/AKT signaling was found to be required for the regulation of hepatic glucose metabolism. Mechanistic investigations revealed that OPG interacts with Raptor within the mTORC1 complex, facilitating its phosphorylation at Ser863 and Ser877, influencing the mTORC1 (Raptor)/S6K1/IRS1/AKT signaling pathway, and thereby affecting glucose metabolism and insulin sensitivity. These findings underscore the integral role of OPG in glucose homeostasis and suggest it as a novel therapeutic target in type 2 diabetes. Article Highlights: Methylation of the Opg promoter inhibits hepatic OPG expression in obese mice. Hepatic OPG regulates glucose metabolism and insulin sensitivity in obese mice. OPG regulates glucose metabolism through interaction with mammalian target of rapamycin complex 1 (Raptor). Opg deficiency in mice reduces age-related metabolic dysfunction.

Vascular aging was reported to be closely related to diabetes. This study investigates the inhibitory effects and mechanism of curcumin on diabetic vascular aging by regulating mitophagy through the PINK1 pathway. The diabetic rat model was established by feeding with a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and treated with high-dose (200 mg/kg), low-dose (50 mg/kg) curcumin, or metformin (200 mg/kg), respectively. The role of mitophagy in high glucose (HG)-induced human aortic smooth muscle cells (HASMCs) aging in vitro were investigated. The results indicated that curcumin ameliorated weight loss and improved elevated blood glucose levels in diabetic rats. Curcumin also improved the vascular pathological changes of the common carotid artery, decreased the vascular interstitial collagen fiber and vascular calcium salt deposition, and improved vascular ultrastructure. Furthermore, curcumin significantly decreased ET-1, VCAM-1, and p16 expressions. In addition, curcumin increased the expression of LC3II/I, Beclin1, and PINK1 proteins, while decreasing p62 expression. High-dose curcumin could improve mitochondrial morphology and increase mitochondrial autophagy. Additionally, curcumin increased HASMCs viability and inhibited HG-induced vascular aging by promoting mitophagy in vitro. WB confirmed that LC3II/I, Beclin1, and PINK1 levels were increased, while p62 and p16 levels were decreased. The improvement effect of curcumin on vascular aging was reversed by the mitophagy inhibitor Mdivi-1 or PINK1 siRNA. In conclusion, curcumin alleviates vascular aging in diabetic rats and HG-induced senescence in HASMCs by enhancing mitochondrial autophagy. These results suggest that curcumin has therapeutic potential in alleviating diabetic vascular aging.

Renal fibrosis is a critical factor in chronic kidney disease progression, with limited diagnostic and therapeutic options. Emerging evidence suggests RNA-binding proteins (RBPs) are pivotal in regulating cellular mechanisms underlying fibrosis. Utilizing an extensive GEO dataset (175 renal fibrosis and 99 normal kidney samples), we identified and validated key RBPs through integrated bioinformatics and machine learning approaches, including lasso and logistic regression models. Differentially expressed genes were analyzed for pathway enrichment using Gene Ontology and KEGG. Single-cell RNA sequencing delineated cell-specific RBP expression, and a murine unilateral ureteral obstruction (UUO) model provided experimental validation. A diagnostic model incorporating five RBPs (FKBP11, DCDC2, COL6A3, PLCB4, and GNB5) achieved high accuracy (AUC = 0.899) and robust external validation. These RBPs are implicated in immune-mediated pathways such as cytokine signaling and inflammatory responses. Single-cell analysis highlighted their expression in specific renal cell populations, underscoring functional diversity. Immunofluorescence linked FKBP11 with macrophage infiltration, suggesting its potential as a therapeutic target. his study identifies novel RBPs associated with renal fibrosis, advancing the understanding of its pathogenesis and offering actionable biomarkers and therapeutic targets. The integration of bioinformatics and machine learning emphasizes their translational potential in kidney care.

Background: In recent years, the prevalence and mortality rates of diabetes have been rising continuously, posing a significant threat to public health and placing a heavy burden on the population. This study was conducted to describe and analyze the burden of diabetes in China from 1990 to 2021 and its attributable risk factors.Methods: Utilizing data from the Global Burden of Disease Study 2021, we analyzed the incidence, prevalence, and disability‐adjusted life years (DALYs) of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in China from 1990 to 2021. We extracted sex‐ and age‐specific data on diabetes, focusing on DALYs, years lived with disability, and years of life lost. Bayesian meta‐regression and spatiotemporal Gaussian process regression were used to estimate disease parameters. Age‐standardized rates (ASRs) and estimated annual percentage changes (EAPC) were calculated using direct standardization and log‐linear regression. The population‐attributable fractions were also determined for each risk factor.Results: In 2021, the absolute number of incident diabetes mellitus (DM) cases was estimated at 4003543.82, including 32 000 T1DM and 3971486.24 T2DM cases. The ASRs were 244.57 for DM, 2.67 for T1DM, and 241.9 for T2DM (per 100 000 population). The absolute number of prevalent DM cases was 117288553.93, including 1442775.09 T1DM and 115845778.84 T2DM cases. The ASRs were 6142.29 for DM, 86.78 for T1DM, and 6055.51 for T2DM (per 100 000 population). In 2021, there were 178475.73 deaths caused by DM, with an ASR of mortality of 8.98 per 100 000 population. The DALYs due to DM in 2021 were 11713613.86, with an ASR of 585.43 per 100 000 population and an EAPC of 0.57. This increase can be attributed to several factors, including high body mass index, air pollution, and dietary habits.Conclusions: The burden of diabetes is considerable, with high prevalence and incidence rates, highlighting the urgent need for public health interventions. Addressing factors like high fasting plasma glucose, body mass index, air pollution, and dietary risks through effective interventions is critical. image

Empagliflozin is currently known to decrease blood glucose levels, delay renal failure, and reduce the risk of cardiovascular death and all-cause mortality