Background
The main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulatory dysfunction, which are caused by excessive apoptosis of ovarian granulosa cells. Acupuncture has been shown to improve follicular development abnormalities in patients with PCOS, but its mechanism is unknown. This study hypothesized that the mechanism of acupuncture on follicular development abnormalities in PCOS patients is the inhibition of granulosa cell apoptosis through LncMEG3-mediated regulation of miR-21-3p.
Methods
A PCOS-like rat model was established using subcutaneous injection of dehydroepiandrosterone (DHEA). Acupuncture was performed on rats for 15 d (CV-4, RN-3, CV-6, SP-6 and EX-CA 1). Ovarian morphology was observed by HE staining, and sex hormone and AMH levels were detected by ELISA. Primary granulosa cells were isolated from each group of rats to assess the association of acupuncture treatment, LncMEG3, miR-21-3p, and granulosa cell apoptosis in rats with PCOS.
Results
LncMEG3 and miR-21-3p were highly expressed in the ovarian granulosa cells of rats with PCOS, and LncMEG3-mediated regulation of miR-21-3p was involved in the development of PCOS in rats. Silencing of MEG3 attenuated sex hormone dysregulation and ovarian histopathological changes in PCOS rats and promoted follicle cell development and maturation. In addition, silencing MEG3 increased the viability and number of granulosa cells. In addition, silencing MEG3 further inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats. Acupuncture improved polycystic ovarian morphology and sex hormone levels in PCOS rats. Acupuncture intervention increased the viability and number of granulosa cells. Acupuncture intervention inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats by targeting miR-21-3p via LncMEG3.
Conclusion
These results suggest that acupuncture can downregulate LncMEG3, thereby targeting and regulating miR-21-3p to suppress early and late granulosa cell apoptosis and normalize their proliferation. These factors ultimately compensate for abnormal follicular development. These findings shed light on the clinical potential of acupuncture as a safe treatment for follicular developmental abnormalities in PCOS.
Osteoarthritis (OA) is a major cause of mobility impairment in the elderly. Scavenging excessive reactive oxygen species (ROS) to inhibit oxidative stress damage is a theraupetic strategy for OA. However, low clearance efficiency, rapid clearance by the joint fliud, poor stability and lack of sustainability challenged most ROS scavengers. Herein, we innovatively synthesized a spermidine (SPD)-acrylonitrile (PAN) copolymer nanofiber membrane using electrostatic spinning technology for effective treatment of OA, wherin SPD that has potent antioxidant ability served as ROS scavenger and PAN as backbone for sustainable release of SPD. Compared with the PAN, the PAN-SPD nanofibers not only greatly improved the mechanical properties, but also exhibited the sustainability and high efficiency to scavenge ROS. Moreover, PAN-SPD nanofibers have good biocompatibility, and can effectively reduce oxidative stress damage in H2O2 induced chondrocytes by down-regulating the expression of pro-inflammatory factors like MMP-13, IL-6 and TNF-α while up-regulating the antioxidant factors such as (SOD, CAT, GSH). There was a dramatic reduction in OA severity after PAN-SPD nanofibrous membrane treatment in OA joints compared to the untreated group after a 8-week therapy. Overall, this study provides effective strategies and new ideas for the future clinical treatment of OA or oxidative stress-related diseases.
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