Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder Typically, it is characterized by hirsutism, hyperandrogenism, ovulatory dysfunction, menstrual disorders and infertility To date, its pathogenesis remains unclear However, insulin resistance (IR) is considered as the primary pathological basis for its reproductive dysfunction On the other hand, a condition in which insulin is over-secreted is called hyperinsulinemia IR/Hyperinsulinemia is associated with chronic inflammation, hormonal changes, follicular dysplasia, endometrial receptivity changes, and abortion or infertility Additionally, it increases incidence of complications during pregnancy and has been associated with anxiety, depression, and other psychological disorders Gut microbiota, the “second genome” acquired by the human body, can promote metabolism, immune response through interaction with the external environment Gut microbiota dysbiosis can cause IR, which is closely linked to the occurrence of PCOS This article reviewed recent findings on the roles of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome

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Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome: a review.

Glucagon like peptide-1 (GLP-1) is an incretin secretory molecule. GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes (T2DM) due to their attributes such as body weight loss, protection of islet β cells, promotion of islet β cell proliferation and minimal side effects. Studies have found that GLP-1R is widely distributed on pancreatic and other tissues and has multiple biological effects, such as reducing neuroinflammation, promoting nerve growth, improving heart function, suppressing appetite, delaying gastric emptying, regulating blood lipid metabolism and reducing fat deposition. Moreover, GLP-1RAs have neuroprotective, anti-infectious, cardiovascular protective, and metabolic regulatory effects, exhibiting good application prospects. Growing attention has been paid to the relationship between GLP-1RAs and tumorigenesis, development and prognosis in patient with T2DM. Here, we reviewed the therapeutic effects and possible mechanisms of action of GLP-1RAs in the nervous, cardiovascular, and endocrine systems and their correlation with metabolism, tumours and other diseases.

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GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in young reproductive-aged women. PCOS is often associated with obesity and impairs reproductive health. Even though several theories have been proposed to explain the pathogenic mechanism of PCOS, the role of insulin resistance (IR) as a key etiological component, independently of (but amplified by) obesity, is well recognized. The consequent hyperinsulinemia activates excessive ovarian androgen production, leading to PCOS. Additionally, the state of chronic inflammation related to obesity impacts ovarian physiology due to insulin sensitivity impairment. The first-line treatment for adolescents with obesity and PCOS includes lifestyle changes; personalized dietary interventions; and, when needed, weight loss. Medical nutrition therapy (MNT) and the use of specific food supplements in these patients aim at improving symptoms and signs, including insulin resistance and metabolic and reproductive functions. The purpose of this narrative review is to present and discuss PCOS in adolescents with obesity, its relationship with IR and the role of MNT and food supplements in treatment. Appropriate early dietary intervention for the management of adolescents with obesity and PCOS should be considered as the recommended approach to restore ovulation and to protect fertility.

https://www.mdpi.com/2072-6643/13/6/1848/pdf

Polycystic Ovary Syndrome in Insulin-Resistant Adolescents with Obesity: The Role of Nutrition Therapy and Food Supplements as a Strategy to Protect Fertility.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women at reproductive age. However, the underlying pathogenic mechanisms have not been completely understood. Hyperandrogenism is an important clinic feature in patients with PCOS, suggesting its pathologic role in the development and progression of PCOS. However, the actual role of androgen and the related signals in PCOS and PCOS-related complications have not yet been clarified. In this review, we surveyed the origin and effects of androgen on PCOS and the related complications, highlighted the cellular signals affecting androgen synthesis and summarized the pathological processes caused by hyperandrogenism. Our review well reveals the important mechanisms referring the pathogenesis of PCOS and provides important clues to the clinic strategies in patients with PCOS.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.16205

The role of androgen and its related signals in PCOS

Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact etiology and pathophysiology are not comprehensively understood yet. We searched PubMed for PCOS pathogenesis and management in this article and ClinicalTrials.gov for information on repurposed medications. All responsible factors behind PCOS were thoroughly evaluated. Furthermore, the complete information on PCOS commonly prescribed and repurposed medications is summarized through tables. Epigenetics, environmental toxicants, stress, diet as external factors, insulin resistance, hyperandrogenism, inflammation, oxidative stress, and obesity as internal factors were investigated. Lifestyle modifications and complementary and alternative medicines are preferred first-line therapy in many cases. Medications, including 3-hydroxy-3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, thiazolidinediones, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucose-like peptide-1 receptor agonists, mucolytic agents, and some supplements have supporting data for being repurposed in PCOS. Since there are few completed clinical trials with a low population and mostly without results on PCOS repurposed medications, it would be helpful to do further research and run well-designed clinical trials on this subject. Moreover, understanding more about PCOS would be beneficial to find new medications implying the effect via the novel discovered routes.

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Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing

Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity.

The roles of retinoic acid in the differentiation of spermatogonia and spermatogenic disorders.

Objective To evaluate the expression profile of MCM6 in HCC and the relationship between MCM6 level and clinicopathological parameters through bioinformatics analysis of several databases. Methods MCM expression level, clinical parameters, survival data, and gene set enrichment analysis were analyzed by bioinformatics database, including Oncomine™, UALCAN, HCCDB, TCGA, cBioPortal, and LinkedOmics. Real-time PCR, western blotting, and IHC staining were conducted to identify the expression of MCM6 in HCC compared to normal liver tissues. Results Bioinformatics analysis indicated that the mRNA of MCM6 was obviously increased in multiple cancer types, especially in HCC. MCM6 level was positively associated with multiple clinical parameters (stage 3 and grades 3 and 4) and negatively associated with patient outcomes (overall survival). Moreover, enrichment of functions and signaling pathways analysis of MCM6 suggested that MCM6 might mediate DNA replication and cellular metabolism to promote the development and progression of HCC. Furthermore, IHC staining and western blotting indicated that the MCM6 was enhanced in HCC tissue, and MCM6 could promote HCC proliferation in activating Notch pathway via WB and bioinformatic analysis. Conclusion This study actually revealed the expression and related functions of MCM6 in HCC. Furthermore, MCM6 is a carcinogenic role in activating Notch pathway to promote HCC cell proliferation, which may be a new prognostic biomarker and therapeutic target for HCC patients.

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Xin Zeng

Papers

Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity.

The roles of retinoic acid in the differentiation of spermatogonia and spermatogenic disorders.

MCM6 Promotes Hepatocellular Carcinoma Progression via the Notch Pathway: Clinical, Functional, and Genomic Insights