Gaozhou People's Hospital

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder associated with chronic low-grade inflammation of the ovary. Sodium glucose co-transporter 2 (SGLT2) inhibitors are a class of antidiabetic drugs that can reduce the weight and hyperglycemia of type 2 diabetes patients. Dapagliflozin is a highly selective, orally active and reversible inhibitor of the human SGLT2. However, the role of dapagliflozin in regulating PCOS remains unclear.

In this study, 24 six-week-old female Sprague Dawley (SD) rats were randomly divided into control, letrozole, and letrozole + dapagliflozin groups. PCOS model rats were produced by gavage administration of letrozole for 21 days. The intervention was conducted after the gavage administration of dapagliflozin for 14 days to evaluate the estrous cycle and ovarian imaging changes of the rats in each group. We observed changes in the weight, ovarian weight, and ovarian morphology of the rats in each group. Pathological changes in the ovaries were examined by H&E staining, changes in ovarian tissue cell apoptosis were identified using TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and changes in inflammation-related factors were detected using immunohistochemistry and Western blotting analysis. Network pharmacology was used to predict the inflammatory targets and pathways affected by dapagliflozin in treating PCOS, and the potential interactions between dapagliflozin and inflammation-related target proteins were evaluated through molecular docking.

Our results demonstrated that dapagliflozin treatment significantly improved PCOS symptoms, recovered ovarian morphology and physiological functions, and reduced the apoptosis of ovarian cells after drug intervention. Dapagliflozin treatment also reduced the levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, indicating its anti-inflammatory properties. Furthermore, network pharmacology identified 26 intersecting target genes relevant to inflammation in PCOS, with subsequent molecular docking simulations revealing strong binding affinities of dapagliflozin to key targets, including AKT1 and TP53.

These findings suggest that dapagliflozin exerts beneficial effects on PCOS by ameliorating ovarian dysfunction and reducing inflammation. Dapagliflozin represents a promising therapeutic candidate for managing PCOS, warranting further clinical investigation to explore its full potential in treating this multifaceted disorder.

The incidence of lumbar disk herniation (LDH) is usually caused by lumbar disk degeneration. Surgery is a common treatment strategy for LDH, but it can recur, resulting in recurrent disk herniation (RDH).

To explore the predictive value of hsa-miR-4741 and LILRB2 in the prognosis of LDH surgery and the mechanism of nucleus pulposus senescence.

The ROC curves of RDH based on hsa-miR-4741 and LILRB2 were constructed to evaluate their predictive values in the prognosis of LDH surgery. Human nucleus pulposus cells (NPC) was treated by TNF-α to construct a cell senescence model, studying the senescence mechanism. Oxidative stress and senescence markers were detected after overexpression of hsa-miR-4741 and LILRB2 to evaluate their effects on the senescence of NPC. Dual luciferase assay and the transfection of hsa-miR-4741 mimics or inhibitor were used to investigate the targeted regulation of it to LILRB2.

The combination of hsa-miR-4741 and LILRB2 showed higher accuracy in predicting the outcome of RDH (AUC = 0.9367), compared with a single molecule. Overexpression of hsa-miR-4741 enhanced TNF-α-induced oxidative stress and senescence, while LILRB2 overexpression had the opposite effect. Hsa-miR-4741 mimics attenuated the luciferase activity of NPC transfected with wt-LILRB2 vector and significantly down-regulated LILRB2 expression. In addition, the antioxidant NAC reversed the promotion of hsa-miR-4741 on NPC senescence.

The combination of hsa-miR-4741 and LILRB2 was a good predictor of LDH prognosis. Hsa-miR-4741 promoted oxidative stress-induced NPC senescence by negatively regulating LILRB2.

Hyaluronic acid (HA)-derived hydrogels signify a noticeable development in biomedical uses, especially in cancer treatment and wound repair. Cancer continues to be one of the foremost causes of death globally, with current therapies frequently impeded by lack of specificity, serious side effects, and the emergence of resistance. HA hydrogels, characterized by their distinctive three-dimensional structure, hydrophilic nature, and biocompatibility, create an advanced platform for precise drug delivery, improving therapeutic results while minimizing systemic toxicity. These hydrogels facilitate the regulated release of medications, genes, and various therapeutic substances, enhancing the effectiveness of chemotherapy, radiotherapy, and immunotherapy. Additionally, they can be designed to react to stimuli like pH, light, and magnetic fields, enhancing their therapeutic capabilities. In the process of wound healing, the hydrophilic and porous characteristics of HA hydrogels establish a moist setting that encourages cell growth and aids in tissue restoration. By imitating the extracellular matrix, they promote tissue regeneration, improve angiogenesis, and influence immune reactions. This review examines the various functions of HA-based hydrogels in cancer treatment and wound healing, highlighting their advancement, uses, and ability to change existing therapeutic methods in these important health sectors.