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Our results demonstrate that RD selectively exerts estrogenic actions in a different manner from tamoxifen. Moreover, RD interacts with tamoxifen without altering its effects in OVX rats.PCOS is defined as a kind of endocrine and metabolic disorder which affects females at reproductive ages, is becoming much more common, nowadays. Microbiomes are known as microorganisms that inhabit the body to play a vital role in human health. In recent years, several basic and clinical studies have tried to investigate the correlation between the reproductive health/disorder and microbiomes (gut microbiomes and vaginal microbiomes). However, the mechanism is still unclear. In this review, we reviewed the relationship between PCOS and microbiomes, including gut/vaginal microbiomes compositions in PCOS, mechanism of microbiomes and PCOS, and then collectively focused on the recent findings on the influence of microbiomes on the novel insight regarding the therapeutic strategies for PCOS in the future clinical practice.Contaminants of Emerging Concerns (CECs) are defined as chemicals not commonly monitored in aquatic ecosystems, but with the potential to cause adverse effects on biota. CECs include Endocrine Disrupting Chemicals (EDCs) and Neuro-Endocrine disruptors (NEDs) of vertebrates. However, most invertebrates only rely on neuroendocrine systems to maintain homeostatic processes. Although conserved neuroendocrine components have been characterized in ecologically relevant groups, limited knowledge on invertebrate neuroendocrinology makes it difficult to define EDCs and NEDs in most species. The monoamine serotonin (5-hydroxytryptamine, 5-HT) acts both as a neurotransmitter and as a peripheral hormone in mammals. selleck chemicals llc In molluscs, 5-HT is involved in multiple physiological roles and molecular components of the serotonergic system have been identified. This review is focused on the effects of CECs on the serotonergic system of bivalve molluscs. Bivalves are widespread in all aquatic environments, estuarine and coastal areas e marine mussel Mytilus galloprovincialis. Overall, available data point at the serotonergic system as a sensitive target for neuroendocrine disruption in bivalves. The results contribute drawing Adverse Outcome Pathways (AOPs) for model EDCs and SSRIs in larvae and adults. However, basic research on neuroendocrine signaling is still needed to evaluate the potential impact of neuroendocrine disruptors in key invertebrate groups of aquatic ecosystems.This study aimed to investigate the usability of blood markers for predicting controlled ovarian stimulation (COS) outcomes in patients with breast cancer undergoing fertility preservation (FP). In total, 91 patients with breast cancer who had undergone COS using a letrozole-combined gonadotropin-releasing hormone (GnRH) antagonist protocol before chemotherapy were enrolled retrospectively in a single tertiary hospital. FP outcomes were compared in terms of the mean platelet volume (MPV), MPV/platelet count (PC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The cutoff values for obtaining 10 or more mature oocytes as favorable prognoses were obtained for each parameter, and the COS outcomes were compared based on the cutoff values. The optimal cutoff levels for MPV and MPV/PC were 10.15 [sensitivity 90.0%; specificity 45.1%; AUC 0.687; 95% CI (0.563, 0.810)] and 0.41 [sensitivity 65.0%; specificity 67.6%; AUC 0.682; 95% CI (0.568, 0.796)], rin patients with breast cancer. Protocols to acquire more mature oocytes, such as the dual-trigger approach, could be recommended for patients with breast cancer with MPV less then 10.15. Furthermore, a higher dose of gonadotropins was considered to obtain more oocytes in patients with MPV/PC less then 0.41.

Evidence proved the association between gut microbiome dysbiosis and polycystic ovary syndrome (PCOS) in metabolic disorder, decreased fertility, and hyperandrogenism. However, alterations in blood microbiome of PCOS remained unknown.

This study aims to measure the blood microbiome profile of PCOS patients compared with healthy controls by 16S rRNA sequencing and to investigate its association with PCOS.

In this case-control study, bacterial DNA in blood of 24 PCOS patients and 24 healthy controls was investigated by 16S rRNA gene sequencing using the MiSeq technology. Alpha and beta diversity were used to analyze within-sample biodiversity and similarity of one group to another, respectively. Linear discriminant analysis effect size (LEfSe) was calculated to determine biomarkers between groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional prediction was performed at genera level.

Alpha diversity of blood microbiome decreased significantly in women with PCOS, and beta diversity analysis demonstrated a major separation between the two groups. In the PCOS group, the relative abundance of

,

, and

decreased significantly, while

increased significantly. Cladogram demonstrated the microbiome differences between the two groups at various phylogenic levels. Meanwhile, linear discriminant analysis (LDA) presented significant decreases in

,

,

,

, and

and significant increases in

and

of the PCOS group. KEGG pathway analysis at genera level suggested that 14 pathways had significant differences between the two groups.

Our findings demonstrated that blood microbiome had a significantly lower alpha diversity, different beta diversity, and significant taxonomic variations in PCOS patients compared with healthy controls.

Our findings demonstrated that blood microbiome had a significantly lower alpha diversity, different beta diversity, and significant taxonomic variations in PCOS patients compared with healthy controls.

To report the point prevalence, deaths and disability-adjusted-life-years (DALYs) due to type 2 diabetes and its attributable risk factors in 204 countries and territories during the period 1990-2019.

We used the data of the Global Burden of Disease (GBD) Study 2019 to report number and age-standardised rates per 100 000 population of type 2 diabetes. Estimates were reported with 95% uncertainty intervals (UIs).

In 2019, the global age-standardised point prevalence and death rates for type 2 diabetes were 5282.9 and 18.5 per 100 000, an increase of 49% and 10.8%, respectively, since 1990. Moreover, the global age-standardised DALY rate in 2019 was 801.5 per 100 000, an increase of 27.6% since 1990. In 2019, the global point prevalence of type 2 diabetes was slightly higher in males and increased with age up to the 75-79 age group, decreasing across the remaining age groups. American Samoa [19876.8] had the highest age-standardised point prevalence rates of type 2 diabetes in 2019. Generally, the burden of type 2 diabetes decreased with increasing SDI (Socio-demographic Index). Globally, high body mass index [51.9%], ambient particulate matter pollution [13.6%] and smoking [9.9%] had the three highest proportions of attributable DALYs.

Low and middle-income countries have the highest burden and greater investment in type 2 diabetes prevention is needed. In addition, accurate data on type 2 diabetes needs to be collected by the health systems of all countries to allow better monitoring and evaluation of population-level interventions.

Low and middle-income countries have the highest burden and greater investment in type 2 diabetes prevention is needed. In addition, accurate data on type 2 diabetes needs to be collected by the health systems of all countries to allow better monitoring and evaluation of population-level interventions.

Orlistat, a reversible inhibitor of pancreatic and gastric lipase, is known to have anti-obesity and antioxidant properties. Cholesterol intermediates and metabolites have diverse and important functions in cardiovascular disease. Therefore, we aimed to evaluate the effect of orlistat on sterol metabolism in overweight and obese adults after weight loss during the intervention or weight loss at 12 weeks.

A total of 51 (27 in the control group and 24 in the experimental group), patients with a BMI of 27 or greater were randomly assigned in a 11 ratio to receive either orlistat (120 mg) three times a day plus phentermine hydrochloride (37.5 mg) once daily or a placebo three times a day plus phentermine hydrochloride (37.5 mg) once daily. The primary study outcome was sterol metabolism.

The experimental group exhibited significantly decreased metabolic signatures of serum sterols, free cholesterol, sitosterol, 7α-hydroxycholesterol (7α-OHC), and 7β-OHC at 12 weeks. The experimental group also exhibited significantly decreased metabolic ratios of sitosterol and 7α-OHC to cholesterol at 12 weeks. Regarding changes in sterol signatures from baseline to 6-month follow-up, free cholesterol, plant sterols, and cholesterol precursors tended to decrease with weight loss during the intervention and increase again as the weight was regained in both groups.

Orlistat treatment improves oxysterol metabolism in overweight and obese adults. Our findings support that orlistat plays a crucial role in the process of endothelial dysfunction and atherosclerosis

oxysterol modulation.

Orlistat treatment improves oxysterol metabolism in overweight and obese adults. Our findings support that orlistat plays a crucial role in the process of endothelial dysfunction and atherosclerosis via oxysterol modulation.

Despite an improved understanding of pheochromocytoma and extra-adrenal sympathetic parganglioma (PPGL), including diagnosis and management, some PPGLs are postoperatively diagnosed. Clinical characteristics and intraoperative haemodynamic instability (HI) in postoperatively diagnosed PPGL patients have been poorly defined. Thus, we investigated the clinical characteristics and HI in patients with postoperatively diagnosed PPGLs compared to patients with preoperatively diagnosed PPGLs.

We obtained clinical and haemodynamic data from the electronic medical records of 256 patients with pathologically confirmed PPGLs at our institution from January 2005 to December 2019. We assessed the intraoperative HI (systolic blood pressure [SBP]>160 mmHg (min) or mean blood pressure [MBP]<60 mmHg (min)) over time.

Twenty-nine patients (11.3%) were diagnosed with PPGLs postoperatively. Hypertension (34.5%

63.0%,

=0.006) and pheochromocytoma (17.2%

81.1%,

<0.001) case rates were lower in postoperativtypical symptoms related PPGLs.

Patients diagnosed with PPGLs postoperatively may have no further higher risk of intraoperative hypertension than those diagnosed preoperatively despite insufficient preoperative management for PPGLs. Further study will be needed to ascertain intrinsic tumour characteristics, and need for universal preoperative use of α- and β-blockers in PPGL patients postoperatively diagnosed or without typical symptoms related PPGLs.The PI3K/AKT pathway, negatively regulated by PTEN, plays a paramount role in glucose metabolism regulation due to its activation by the insulin receptor signaling pathway. We generated a PTEN-KO mouse to evaluate the systemic effect of the overactivation of the PI3K/AKT pathway in insulin signaling and glucose homeostasis. Our results demonstrate that PTEN-KO mice show very low glucose levels in the fasted state, which poorly respond to glucose and pyruvate administration. Insulinemia decreased without alterations in pancreatic islets. Among the possible reasons, we uncover the deregulation of the expression of proximal tubule glucose transporter and consequent glycosuria. Moreover, we evidence an altered activation of hepatic gluconeogenesis-related genes. In addition, the expression of several genes related to β-oxidation showed a delayed or even absent response to fasting, suggesting that the lack of PTEN not only impairs glucose metabolism but also slows down the use of lipids as a metabolic fuel. We conclude that the inducible full PTEN-KO mice could be a good model to study the metabolic interactions between glycidic and lipidic metabolism in hypoinsulinemic hypoglycemia and that PTEN could be an important mediator in the disease and/or a potential drug target.