[Mechanism of mitochondrial dysfunction in polycystic ovary syndrome and traditional Chinese medicine intervention: a review].

Polycystic ovary syndrome(PCOS) is a highly prevalent endocrine and reproductive disorder characterized by ovulatory dysfunction, hyperandrogenism(HA), and polycystic ovarian morphology(PCOM). It is often accompanied by insulin resistance(IR), obesity, and metabolic disorders and can lead to cardiovascular diseases, endometrial carcinoma and many other late complications, seriously affecting the physical and mental health and quality of life in premenopausal women. The etiology of PCOS is still unknown and many scholars assume that mitochondrial dysfunction may represent a major pathogenic factor in PCOS in recent years. With a holistic view, treatment based on syndrome differentiation, and multi-system and multi-target treatment manner, traditional Chinese medicine(TCM) can mitigate the symptoms and signs of PCOS from multiple aspects. Although there have been reviews on the mechanism of mitochondrial dysfunction in PCOS, there is still a lack of reviews on the intervention of mitochondrial function by TCM to treat PCOS. Therefore, this paper focuses on the role of mitochondrial dysfunction in PCOS and summarizes the studies about the TCM intervention of PCOS by regulating the mitochondrial function, inflammation, oxidative stress(OS), autophagy, and apoptosis in the last five years, aiming to shed new light on the prevention and treatment of PCOS with TCM.

Effect of acupuncture and metformin on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance: a three-armed randomized controlled trial.

STUDY QUESTION: Does acupuncture improve insulin sensitivity more effectively than metformin or sham acupuncture in women with polycystic ovary syndrome (PCOS) and insulin resistance (IR)? SUMMARY ANSWER: Among women with PCOS and IR, acupuncture was not more effective than metformin or sham acupuncture in improving insulin sensitivity. WHAT IS KNOWN ALREADY: Uncontrolled trials have shown that acupuncture improved insulin sensitivity with fewer side effects compared with metformin in women with PCOS and IR. However, data from randomized trials between acupuncture and metformin or sham acupuncture are lacking. STUDY DESIGN, SIZE, DURATION: This was a three-armed randomized controlled trial enrolling a total of 342 women with PCOS and IR from three hospitals between November 2015 and February 2018, with a 3-month follow-up until October 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged from 18 to 40 years with PCOS and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.14 were randomly assigned (n = 114 per group) to receive true acupuncture plus placebo (true acupuncture), metformin plus sham acupuncture (metformin, 0.5 g three times daily) or sham acupuncture plus placebo (sham acupuncture) for 4 months, with an additional 3-month follow-up. True or sham acupuncture was given three times per week, and 0.5 g metformin or placebo was given three times daily. The primary outcome was change in HOMA-IR from baseline to 4 months after baseline visit. Secondary outcomes included changes in the glucose AUC during an oral glucose tolerance test, BMI and side effects at 4 months after baseline visit. MAIN RESULTS AND THE ROLE OF CHANCE: After 4 months of treatment, the changes of HOMA-IR were -0.5 (decreased 14.7%) in the true acupuncture group, -1.0 (decreased 25.0%) in the metformin group and -0.3 (decreased 8.6%) in the sham acupuncture group, when compared with baseline. True acupuncture is not as effective as metformin in improving HOMA-IR at 4 months after baseline visit (difference, 0.6; 95% CI, 0.1-1.1). No significant difference was found in change in HOMA-IR between true and sham acupuncture groups at 4 months after baseline visit (difference, -0.2; 95% CI, -0.7 to 0.3). During the 4 months of treatment, gastrointestinal side effects were more frequent in the metformin group, including diarrhea, nausea, loss of appetite, fatigue, vomiting and stomach discomfort (31.6%, 13.2%, 11.4%, 8.8%, 14.0% and 8.8%, respectively). Bruising was more common in the true acupuncture group (14.9%). LIMITATIONS, REASONS FOR CAUTION: This study might have underestimated the sample size in the true acupuncture group with 4 months of treatment to enable detection of statistically significant changes in HOMA-IR with fixed acupuncture (i.e. a non-personalized protocol). Participants who withdrew because of pregnancy did not have further blood tests and this can introduce bias. WIDER IMPLICATIONS OF THE FINDINGS: True acupuncture did not improve insulin sensitivity as effectively as metformin in women with PCOS and IR, but it is better than metformin in improving glucose metabolism (which might reduce the risk of type 2 diabetes) and has less side effects. Metformin had a higher incidence of gastrointestinal adverse effects than acupuncture groups, and thus acupuncture might be a non-pharmacological treatment with low risk for women with PCOS. Further studies are needed to evaluate the effect of acupuncture combined with metformin on insulin sensitivity in these women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants 2017A020213004 and 2014A020221060 from the Science and Technology Planning Project of Guangdong Province. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov number: NCT02491333. TRIAL REGISTRATION DATE: 8 July 2015. DATE OF FIRST PATIENT'S ENROLLMENT: 11 November 2015.

Qi Gong Wan ameliorates adipocyte hypertrophy and inflammation in adipose tissue in a PCOS mouse model through the Nrf2/HO-1/Cyp1b1 pathway: Integrating network pharmacology and experimental validation in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Initially recorded in Yifang Jijie (an ancient Chinese text), Qi Gong Wan (QGW) is used to treat obese women with infertility. QGW can help promote follicular development and maturation, regulate the balance of serum hormones between testosterone and estradiol, enhance endometrial receptivity, improve waist circumference, and ameliorate insulin resistance. It contains eight herbs: Pinellia ternata (Thunb.) Makino (Banxia), Citrus maxima (Burm.) (Juhong), Poria cocos (Schw.) Wolf. (Fuling), Atractylodes macrocephala Koidz (Baizhu), Cyperus rotundus L. (Xiangfu), Conioselinum anthriscoides 'Chuanxiong' (Chuanxiong), Massa Medicata Fermentata (Shenqu), and Glycyrrhiza uralensis Fisch. ex DC. (Gancao). However, the underlying mechanism of how QGW affects women with PCOS remains unclear. AIM OF THE STUDY: QGW has been widely used to treat PCOS patients with obesity clinically. This study was designed to identify its chemical and pharmacological properties. MATERIALS AND METHODS: Network pharmacology was used to predict the active compounds, potential targets, and pathways of QGW. Female C57BL/6J mice were injected with letrozole and fed a high-fat diet to establish a PCOS-insulin resistance (PCOS-IR) model. Body weight, estrous cycles, ovarian pathology, and serum insulin resistance were measured. qRT-PCR was used to examine the inflammation-related and steroid hormone biosynthesis-related mRNA expression in adipose tissue. Western blotting was used to determine the protein levels of Nrf2, HO-1, and Cyp1b1 in adipose tissue. Molecular docking was used to reveal the key chemical compounds of QGW. RESULTS: Network pharmacology revealed a total of 91 active ingredients in QGW that were associated with 167 targets. QGW could potentially treat PCOS-IR via nitrogen metabolism, steroid hormone biosynthesis, and ovarian steroidogenesis pathways. In the PCOS-IR mouse model, we found that QGW decreased the mean diameter of adipocytes and the total adipocyte area. Furthermore, QGW was found to significantly lower the expression of inflammation-related genes including Tnfɑ and C4a/b and the steroid hormone biosynthesis-related gene Cyp1b1. QGW showed a tendency to improve cystic follicles, fasting insulin, and HOMA-IR index in the PCOS-IR mouse model. Combining these findings with the results of KEGG analysis, we conclude that QGW promotes the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue under conditions of PCOS. Molecular docking revealed that rutin, nicotiflorin, and baicalein may be the key chemical compounds of QGW through which it improves adipocyte hypertrophy and inflammation. CONCLUSIONS: QGW improved adipocyte hypertrophy and inflammation in the PCOS-IR mouse model by activating the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue. Our work thus provides a new research avenue for the study of traditional Chinese medicine in the treatment of PCOS.

Overactivation of the androgen receptor exacerbates gravid uterine ferroptosis via interaction with and suppression of the NRF2 defense signaling pathway.

The mechanisms through which the androgen-dependent activation of the androgen receptor (AR) regulates gravid uterine ferroptosis remain unknown. We show that while co-exposure of pregnant rats to the androgen 5α-dihydrotestosterone (DHT) and insulin (INS) triggered uterine ferroptotic signaling cascades, additional treatment with the anti-androgen flutamide increased expression of the key ferroptosis-inhibitory proteins SLC7A11, GSH, and GPX4; reduced iron content; normalized levels of ferroptosis-associated Tfrc, Fpn1, and Ho1 mRNAs; reduced levels of proteins modified by 4-HNE (a marker of ferroptosis); and restored protein levels of NRF2, a key transcription factor regulating antioxidant defense signaling, in the gravid uterus. Furthermore, exposure to DHT alone increased uterine ferroptosis, and NRF2 abundance was negatively correlated with AR status. Co-immunoprecipitation and Western blot assays revealed that the AR physically interacted with endogenous NRF2, and this interaction was increased by DHT exposure in vivo. Our results suggest that AR overactivation and NRF2 suppression cooperate in the regulation of NRF2-targets in uterine ferroptosis.

A prognosis-predictive nomogram of ovarian cancer with two immune-related genes: CDC20B and PNPLA5.

Ovarian carcinoma (OV) is one of the most lethal gynecological malignancies globally, and the overall 5-year survival rate of OV was 47% in 2018 according to American data. To increase the survival rate of patients with OV, many researchers have sought to identify biomarkers that act as both prognosis-predictive markers and therapy targets. However, most of these have not been suitable for clinical application. The present study aimed at constructing a predictive prognostic nomogram of OV using the genes identified by combining The Cancer Genome Atlas (TCGA) dataset for OV with the immune score calculated by the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm. Firstly, the algorithm was used to calculate the immune score of patients with OV in the TCGA-OV dataset. Secondly, differentially expressed genes (DEGs) between low and high immune score tissues were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed to predict the functions of these DEGs. Thirdly, univariate, multivariate and Lasso Cox's regression analyses were carried out step by step, and six prognosis-related DEGs were identified. Then, Kaplan-Myer survival curves were generated for these genes and validated by comparing their expression levels to further narrow the range of DEGs and to calculate the risk score. Two genes were identified, cell division cycle 20B and patatin-like phospholipase domain containing 5, which were both shown to have higher expression levels in OV tissues and to be significantly associated with the prognosis of OV. Next, a nomogram was created using these two genes and age, and using the receiver operating characteristic (ROC) curve and calibration curve, the effectiveness of the nomogram was validated. Finally, an external validation was conducted for this nomogram. The ROC showed that the areas under the curve (AUCs) of the 3- and 5-year overall survival predictions for the nomogram were 0.678 and 0.62, respectively. Moreover, the ROC of the external validation model showed that the AUCs of the 3- and 5-year were 0.699 and 0.643, respectively, demonstrating the effectiveness of the generated nomogram. In conclusion, the present study has identified two immune-related genes as biomarkers that reliably predict overall survival in OV. These biomarkers might also be potential molecular targets of immune therapy to treat patients with OV.

Facile Synthesis of Mo2C Nanoparticles from Waste Polyvinyl Chloride.

The resource utilization of waste plastic can not only control environmental pollution but can also ease up the problems of lack of energy resources. In this study, molybdenum carbide (Mo2C) nanoparticles have been synthesized by utilizing waste polyvinyl chloride as a carbon source in a stainless-steel autoclave at 600 °C. X-ray diffraction pattern indicates that the product is orthorhombic phase Mo2C. Electron microscopy photographs show that the obtained Mo2C product consisted of crystalline nanoparticles with an average size of 50 nm. The possible formation mechanisms of Mo2C have been also briefly discussed on the basis of the structures of the products synthesized with different reaction times. The effects of reaction temperature on the crystallinity and microstructure of the obtained products have been investigated. The results show that higher reaction temperature promotes the formation of Mo2C with high crystallinity.