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Systemic acid-base status is primarily determined by the interplay of net acid production (NEAP) arising from metabolism of ingested food stuffs, buffering of NEAP in tissues, generation of bicarbonate by the kidney, and capture of any bicarbonate filtered by the kidney. In chronic kidney disease (CKD), acid retention may occur when dietary acid production is not balanced by bicarbonate generation by the diseased kidney. Hormones including aldosterone, angiotensin II, endothelin, PTH, glucocorticoids, insulin, thyroid hormone, and growth hormone can affect acid-base balance in different ways. The levels of some hormones such as aldosterone, angiotensin II and endothelin are increased with acid accumulation and contribute to an adaptive increase in renal acid excretion and bicarbonate generation. However, the persistent elevated levels of these hormones can damage the kidney and accelerate progression of CKD. Measures to slow the progression of CKD have included administration of medications which inhibit the production or action of deleterious hormones. However, since metabolic acidosis accompanying CKD stimulates the secretion of several of these hormones, treatment of CKD should also include administration of base to correct the metabolic acidosis.

Purpose: Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. Methods: Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. Results: All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. Conclusion: Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) and Western Medicine both have shown efficacy in treating male sexual dysfunction (MSD). The aim of this perspective paper is to discuss a possible link between Western medicine and TCM in the MSD field as represented by the entity of Klotho. Klotho is a recently discovered protein, mainly expressed in the kidney, encoded by the anti‐aging gene klotho. Not only is Klotho significantly correlated with the development and progression of kidney diseases and their complications, but increasing evidence indicates that it is also closely related to MSD. A comprehensive search within PubMed database was performed to retrieve available evidence on Klotho's roles, particularly in kidney and in MSD. Indeed, in the TCM theory, the concept of the "kidney" is entirely different from the Western medicine: it is closely related to metabolism and to the reproductive, nervous, endocrine systems, being more than just a urinary organ. According to the "Kidney storing essence (jīng) and governing reproduction" (KSEGR) theory, a cornerstone in TCM, the treatment of MSD mainly consists of restoring the kidney's function. Signs of decreasing kidney essence show a consistent similarity to deficiencies of Klotho, also for what regards the male sexual function. Based on the current evidence, Klotho may represent a potential biological indicator for sexual desire and sexual function and a kind of new scientific Silk Road between TCM and Western medicine for MSD; nevertheless, there is a need to conduct further high‐quality research to prove this hypothesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: The widespread use of sodium propionate as a preservative in food may affect public health. We aimed to assess the effects of sodium propionate on circadian rhythms and pancreatic development in zebrafish and the possible underlying mechanisms. RESULTS: In this experiment, we analyzed the relationship between circadian rhythms and pancreatic development and then revealed the role of the thyroid endocrine system in zebrafish. The results showed that sodium propionate interfered with the rhythmic behavior of zebrafish, and altered the expression of important rhythmic genes. Experimental data revealed that pancreatic morphology and developmental genes were altered after sodium propionate exposure. Additionally, thyroid hormone levels and key gene expression associated with the hypothalamic–pituitary–thyroid axis were significantly altered. Melatonin at a concentration of 1 μmol L−1, with a mild effect on zebrafish, observably alleviated sodium propionate‐induced disturbances in circadian rhythms and pancreatic development, as well as regulating the thyroid system. CONCLUSION: Melatonin, while modulating the thyroid system, significantly alleviates sodium propionate‐induced circadian rhythm disturbances and pancreatic developmental disorders. We further revealed the deleterious effects of sodium propionate as well as the potential therapeutic effects of melatonin on circadian rhythm, pancreatic development and the thyroid system. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Despite the lack of endogenous synthesis and relevant nuclear receptors, several papers have been published over the decades claiming that the physiology of mollusks is affected by natural and synthetic sex steroids. With scant evidence for the existence of functional steroid nuclear receptors in mollusks, some scientists have speculated that the effects of steroids might be mediated via membrane receptors (i.e. via non-genomic/non-classical actions) - a mechanism that has been well-characterized in vertebrates. However, no study has yet investigated the ligand-binding ability of such receptor candidates in mollusks. The aim of the present study was to further trace the evolution of the endocrine system by investigating the presence of functional membrane sex steroid receptors in a mollusk, the great pond snail (Lymnaea stagnalis). We detected sequences homologous to the known vertebrate membrane sex steroid receptors in the Lymnaea transcriptome and genome data: G protein-coupled estrogen receptor-1 (GPER1); membrane progestin receptors (mPRs); G protein-coupled receptor family C group 6 member A (GPRC6A); and Zrt- and Irt-like protein 9 (ZIP9). Sequence analyses, including conserved domain analysis, phylogenetics, and transmembrane domain prediction, indicated that the mPR and ZIP9 candidates appeared to be homologs, while the GPER1 and GPRC6A candidates seemed to be non-orthologous receptors. All candidates transiently transfected into HEK293MSR cells were found to be localized at the plasma membrane, confirming that they function as membrane receptors. However, the signaling assays revealed that none of the candidates interacted with the main vertebrate steroid ligands. Our findings strongly suggest that functional membrane sex steroid receptors which would be homologous to the vertebrate ones are not present in Lymnaea. Although further experiments are required on other molluscan model species as well, we propose that both classical and non-classical sex steroid signaling for endocrine responses are specific to chordates, confirming that molluscan and vertebrate endocrine systems are fundamentally different. [ABSTRACT FROM AUTHOR]

To reduce the use of antibiotics and chemicals in aquaculture, an edible herb, Bidens pilosa, has been selected as a multifunctional feed additive. Although there has been considerable research into the effects of B. pilosa on poultry, the wider effects of B. pilosa, particularly on the growth and gut microbiota of fish, remain largely unexplored. We aimed to investigate the interactive effects between the host on growth and the gut microbiota using transcriptomics and the gut microbiota in B. pilosa-fed tilapia. In this study, we added 0.5% and 1% B. pilosa to the diet and observed that the growth performance of tilapia significantly increased over 8 weeks of feeding. Comparative transcriptome analysis was performed on RNA sequence profiles obtained from liver and muscle tissues. Functional enrichment analysis revealed that B. pilosa regulates several pathways and genes involved in amino acid metabolism, lipid metabolism, carbohydrate metabolism, endocrine system, signal transduction, and metabolism of other amino acids. The expression of the selected growth-associated genes was validated by qRT–PCR. The qRT–PCR results indicated that B. pilosa may enhance growth performance by activating the expression of the liver igf1 and muscle igf1rb genes and inhibiting the expression of the muscle negative regulator mstnb. Both the enhancement of liver endocrine IGF1/IGF1Rb signaling and the suppression of muscle autocrine/paracrine MSTN signaling induced the expression of myogenic regulatory factors (MRFs), myod1, myog and mrf4 in muscle to promote muscle growth in tilapia. The predicted function of the gut microbiota showed several significantly different pathways that overlapped with the KEGG enrichment results of differentially expressed genes in the liver transcriptomes. This finding suggested that the gut microbiota may influence liver metabolism through the gut–liver axis in B. pilosa-fed tilapia. In conclusion, dietary B. pilosa can regulate endocrine IGF1 signaling and autocrine/paracrine MSTN signaling to activate the expression of MRFs to promote muscle growth and alter the composition of gut bacteria, which can then affect liver amino acid metabolism, carbohydrate metabolism, endocrine system, lipid metabolism, metabolism of other amino acids, and signal transduction in the host, ultimately enhancing growth performance. Our results suggest that B. pilosa has the potential to be a functional additive that can be used as an alternative to reduce antibiotic use as a growth promoter in aquaculture. [ABSTRACT FROM AUTHOR]

A SEND toxicology data transformation, harmonization, and analysis platform were created to improve the identification of unique findings related to the intended target, species, and duration of dosing using data from multiple studies. The lack of a standardized digital format for data analysis had impeded large-scale analysis of in vivo toxicology studies. The CDISC SEND standard enables the analysis of data from multiple studies performed by different laboratories. This work describes methods to analyze data and automate cross-study analysis of toxicology studies. Cross-study analysis can be used to understand a single compound's toxicity profile across all studies performed and/or to evaluate on-target versus off-target toxicity for multiple compounds intended for the same pharmacological target. This work involved development of data harmonization/transformation strategies to enable cross-study analysis of both numerical and categorical SEND data. Four de-identified SEND datasets from the BioCelerate database were used for the analyses. Toxicity profiles for key organ systems were developed for liver, kidney, male reproductive tract, endocrine system, and hematopoietic system using SEND domains. A cross-study analysis dashboard with a built-in user-defined scoring system was created for custom analyses, including visualizations to evaluate data at the organ system level and drill down into individual animal data. This data analysis provides the tools for scientists to compare toxicity profiles across multiple studies using SEND. A cross-study analysis of 2 different compounds intended for the same pharmacological target is described and the analyses indicate potential on-target effects to liver, kidney, and hematopoietic systems. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic–pituitary–adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3β-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE. [ABSTRACT FROM AUTHOR]

Despite their significant impact, comprehensive screenings and detailed analyses of per- and polyfluoroalkyl substance (PFAS) binding strengths at the orthosteric and allosteric sites of NRs are currently lacking. This study addresses this gap by focusing on the binding interaction analysis of both common and uncommon PFAS with the nuclear receptors (NRs) vitamin D receptor (VDR), peroxisome proliferator-activated receptor gamma (PPARγ), pregnane X receptor (PXR), and estrogen receptor alpha (ERα). Advanced docking simulations were used to screen 9507 PFAS chemicals at the orthosteric and allosteric sites of PPARγ, PXR, VDR, and ERα. All receptors exhibited strong binding interactions at the orthosteric and allosteric site with a significant number of PFAS. We verified the accuracy of the docking protocol through multiple docking controls and validations. A mixture modeling analysis indicates that PFAS can bind in various combinations with themselves and endogenous ligands simultaneously, to disrupt the endocrine system and cause carcinogenic responses. These findings reveal that PFAS can interfere with nuclear receptor activity by displacing endogenous or native ligands by binding to the orthosteric and allosteric sites. The purpose of this study is to explore the mechanisms through which PFAS exert their endocrine-disrupting effects, potentially leading to more targeted therapeutic strategies. Importantly, this study is the first to explore the binding of PFAS at allosteric sites and to model PFAS mixtures at nuclear receptors. Given the high concentration and persistence of PFAS in humans, this study further emphasizes the urgent need for further research into the carcinogenic mechanisms of PFAS and the development of therapeutic strategies that target nuclear receptors. [ABSTRACT FROM AUTHOR]

Endocrine disruptive compounds are natural or anthropogenic environmental micropollutants that alter the function of the endocrine system ultimately damaging the metabolism. Bisphenol A (BPA) is the most common of these pollutants and it is often used in epoxy coatings and polycarbonates as a plasticizer. Therefore, monitoring BPA levels in different environments is very important and challenging. In recent years, an increasing number of BPA detection methods have been proposed. This article presents a critical review of aptamer-based electrochemical, fluorescence-based, colorimetric, and several other BPA detection platforms published in the last decade. Furthermore, a statistical evaluation has been made using principle component analysis showing analytical performance parameters do not create very different clusters. Comparisons to other BPA detection methods are also presented so that the reader has an overall literature overview. [ABSTRACT FROM AUTHOR]

• Monitoring of trends in reproductive factors is crucial to gain insight into society from a cultural and sociological point of view and to analyze the impact of these changes on reproductive health and related conditions. • Reproductive factors have relevant impact on diseases and conditions related to the endocrine system, as well as on the risk of hormone-related cancers, such as breast, endometrial, and ovarian cancer. • Mean maternal and paternal age at birth show increasing trends in high-income countries from Europe and North America. • Delaying childbirth involves a decrease in the number of children. • Sweden and the USA had the highest fertility rates, around two children in some years, while Italy and Spain had the lowest ones, with less than 1.5 children over the whole period. To provide a comprehensive picture of trends in parents' age and total fertility rate in selected most populous high-income countries from Europe and North America. Data were retrieved from official statistics published by the United Nations, the World Bank, the European Union (EU), and by national health statistics offices. Mean maternal age at birth showed increasing trends in all considered countries; in 2020, the highest mean age was observed in Italy (32.2) and Spain (32.3), and the lowest one in the USA (28.8). Mean maternal age at first birth also showed upward trends. In the 1990s, mean age at first birth ranged from 25.5 to 26.9 years, except for the USA where it was below 25 years. The countries with the highest average maternal age at first birth were Italy and Spain, reaching 31 years over the most recent years. Data on mean paternal age at birth were scant. In Germany (2019) it was 34.6 and in the USA (2014) 27.9 years. In Italy, mean paternal age increased from 34.2 in 2000 to 35.5 in 2018, in the UK from 30.7 in 1990 to 33.4 in 2017, and in Canada, a decrease was observed from 29.1 in 2006 to 28.3 in 2011. Finally, Sweden and the USA had the highest fertility rates, around two children in some years, while Italy and Spain had the lowest ones, with less than 1.5 children over the whole period. Monitoring of trends in reproductive factors is crucial to gain insight into society from a cultural and sociological point of view and to analyze the impact of these changes on reproductive health and related conditions. [ABSTRACT FROM AUTHOR]

Gut microbiota plays an important role in the regulation of bone homeostasis and bone health. Recent studies showed that these effects could be mediated through microbial metabolites released by the microbiota like short-chain fatty acids, metabolism of endogenous molecules such as bile acids, or a complex interplay between microbiota, the endocrine system, and the immune system. Importantly, some studies showed a reciprocal relationship between the endocrine system and gut microbiota. For instance, postmenopausal estrogen deficiency could lead to dysbiosis of the gut microbiota, which could in turn affect various immune response and bone remodeling. In addition, evidence showed that shift in the indigenous gut microbiota caused by antibiotics treatment may also impact normal skeletal growth and maturation. In this mini-review, we describe recent findings on the role of microbiome in bone homeostasis, with a particular focus on molecular mechanisms and their interactions with the endocrine and immune system. We will also discuss the recent findings on estrogen deficiency and microbiota dysbiosis, and the clinical implications for the development of new therapeutic strategies for osteoporosis and other bone disorders. [ABSTRACT FROM AUTHOR]

Adenomyosis is characterized by ectopic proliferation of endometrial tissue within the myometrium. Histologically, this condition is marked by the presence of islands of benign endometrial glands surrounded by stromal cells. The myometrium appears thinner, and cross-sectional analysis often reveals signs of recent or chronic hemorrhage. The ectopic endometrial tissue may respond to ovarian hormonal stimulation, exhibiting proliferative or secretory changes during the menstrual cycle, potentially leading to bleeding, uterine swelling, and pain. Adenomyosis can appear as either a diffuse or focal condition. It is crucial to understand that adenomyosis involves the infiltration of the endometrium into the myometrium, rather than its displacement. The surgical management of adenomyosis is contingent upon its anatomical extent. The high incidence of the disease and the myths that develop around it increase the need to study its characteristics and its association with pregnancy and potential obstetric complications. These complications often require quick decisions, appropriate diagnosis, and proper counseling. Therefore, knowing the possible risks associated with adenomyosis is key to decision making. Pregnancy has a positive effect on adenomyosis and its painful symptoms. This improvement is not only due to the inhibition of ovulation, which inhibits the bleeding of adenomyotic tissue, but also to the metabolic, hormonal, immunological, and angiogenic changes associated with pregnancy. Adenomyosis affects pregnancy through disturbances of the endocrine system and the body's immune response at both local and systemic levels. It leads to bleeding from the adenomyotic tissue, molecular and functional abnormalities of the ectopic endometrium, abnormal placentation, and destruction of the adenomyotic tissue due to changes in the hormonal environment that characterizes pregnancy. Some of the obstetric complications that occur in women with adenomyosis in pregnancy include miscarriage, preterm delivery, placenta previa, low birth weight for gestational age, obstetric hemorrhage, and the need for cesarean section. These complications are an understudied field and remain unknown to the majority of obstetricians. These pathological conditions pose challenges to both the typical progression of pregnancy and the smooth conduct of labor in affected women. Further multicenter studies are imperative to validate the most suitable method for concluding labor following surgical intervention for adenomyosis. [ABSTRACT FROM AUTHOR]

Postural Orthostatic Tachycardia Syndrome (POTS) affects up to 1% of the US population, predominantly women, and is characterized by a complex, elusive etiology and heterogeneous phenotypes. This review delves into the intricate physiology and etiology of POTS, decoding the roles of the sinoatrial node, the autonomic nervous system, fluid dynamics, and the interplay between the immune and endocrine systems. It further examines key contributing factors such as dysautonomia, thoracic hypovolemia, autonomic neuropathies, sympathetic denervation, autoimmune responses, and associations with conditions such as small-fiber neuropathy and mast cell activation syndrome. Given the numerous mysteries surrounding POTS, we also cautiously bring attention to sinoatrial node and myocardial function, particularly in how the heart responds to stress despite exhibiting a normal cardiac phenotype at rest. The potential of genomic research in elucidating the underlying mechanisms of POTS is emphasized, suggesting this as a valuable approach that is likely to improve our understanding of the genetic underpinnings of POTS. The review introduces a tentative classification system for the etiological factors in POTS, which seeks to capture the condition's diverse aspects by categorizing various etiological factors and acknowledging co-occurring conditions. This classification, while aiming to enhance understanding and optimize treatment targets, is presented as a preliminary model needing further study and refinement. This review underscores the ongoing need for research to unravel the complexities of POTS and to develop targeted therapies that can improve patient outcomes. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome is a clinical syndrome characterized by massive proteinuria, called nephrotic range proteinuria (over 3.5 g per day in adults or 40 mg/m2 per hour in children), hypoalbuminemia, oncotic edema, and hyperlipidemia, with an increasing incidence over several years. Nephrotic syndrome carries severe morbidity and mortality risk. The main pathophysiological event in nephrotic syndrome is increased glomerular permeability due to immunological, paraneoplastic, genetic, or infective triggers. Because of the marked increase in the glomerular permeability to macromolecules and the associated urinary loss of albumins and hormone-binding proteins, many metabolic and endocrine abnormalities are present. Some of them are well known, such as overt or subclinical hypothyroidism, growth hormone depletion, lack of testosterone, vitamin D, and calcium deficiency. The exact prevalence of these disorders is unknown because of the complexity of the human endocrine system and the differences in their prevalence. This review aims to comprehensively analyze all potential endocrine and hormonal complications of nephrotic syndrome and, vice versa, possible kidney complications of endocrine diseases that might remain unrecognized in everyday clinical practice. [ABSTRACT FROM AUTHOR]

Arrhythmias and depression are recognized as diseases of the heart and brain, respectively, and both are major health threats that often co-occur with a bidirectional causal relationship. The autonomic nervous system (ANS) serves as a crucial component of the heart–brain axis (HBA) and the pathway of interoception. Cardiac activity can influence emotional states through ascending interoceptive pathways, while psychological stress can precipitate arrhythmias via the ANS. However, the HBA and interoception frameworks are often considered overly broad, and the precise mechanisms underlying the bidirectional relationship between depression and arrhythmias remain unclear. This narrative review aims to synthesize the existing literature, focusing on the pathological mechanisms of the ANS in depression and arrhythmia while integrating other potential mechanisms to detail heart–brain interactions. In the bidirectional communication between the heart and brain, we emphasize considering various internal factors such as genes, personality traits, stress, the endocrine system, inflammation, 5-hydroxytryptamine, and behavioral factors. Current research employs multidisciplinary knowledge to elucidate heart–brain relationships, and a deeper understanding of these interactions can help optimize clinical treatment strategies. From a broader perspective, this study emphasizes the importance of considering the body as a complex, interconnected system rather than treating organs in isolation. Investigating heart–brain interactions enhance our understanding of disease pathogenesis and advances medical science, ultimately improving human quality of life. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting chemicals are pollutants known to disrupt metabolism, and hormone biosynthesis or alter how the endocrine system works. Research has shown that Bisphenol A (BPA) mimics estrogen and thyroid hormone therefore a potential endocrine system disruptor. Exposures to Bisphenol A above threshold levels leading to endocrine disruption are expected when there is persistent use of products made using bisphenol A. Among the key sources of BPA that leach to the container's contents through hydrolysis are polycarbonate containers. In this study, we monitor levels of bisphenol A exposure to users of polycarbonate containers using cyclic and differential pulse voltammetry in Thika town. Results obtained for the bisphenol A levels using voltammetric method for all the new and old sampled bottles subjected to varying conditions like time and temperature were in the range 0.3-1.6 μgmL-1 for water samples and 2.2-3.7 μgmL-1 for baby milk samples. As temperatures were increased from 25oC to 95oC, the amount of BPA leaching from the polycarbonate containers increased into water and milk. Further, results obtained show that the amount of Bisphenol A leaching increased in all the bottles, both new and used as contact time increased from 1 hour to 12 hours. All the new and old samples overshot the tolerable daily intake for Bisphenol A of 4 μg/kgbw/day allowed by the European Food Safety Authority (EFSA) and this rings an alarm for careful and thorough attention. [ABSTRACT FROM AUTHOR]

A key goal of the field of endocrinology has been to understand the hormonal mechanisms that drive social behavior and influence reactions to others, such as oxytocin. However, it has sometimes been challenging to understand which aspects and influences of hormonal action are conserved and common among mammalian species, and which effects differ based on features of these species, such as social system. This challenge has been exacerbated by a focus on a relatively small number of traditional model species. In this review, we first demonstrate the benefits of using non-traditional models for the study of hormones, with a focus on oxytocin as a case study in adding species with diverse social systems. We then expand our discussion to explore differing effects of oxytocin (and its response to behavior) within a species, with a particular focus on relationship context and social environment among primate species. Finally, we suggest key areas for future exploration of oxytocin's action centrally and peripherally, and how non-traditional models can be an important resource for understanding the breadth of oxytocin's potential effects. [ABSTRACT FROM AUTHOR]

• Overview of recent findings concerning ischemic stroke and the liver. • The liver contributes to post-stroke immunosuppression and stress-induced hyperglycemia. • Increased hepatic glutathione production could combat inflammation and oxidative stress after acute ischemic stroke. Focal brain damage and neurological deficits are the direct consequences of acute ischemic stroke (AIS). In addition, cerebral ischemia causes systemic alterations across peripheral organs. Dysregulation of the autonomic and endocrine systems as well as the release of brain-derived pro-inflammatory mediators trigger a peripheral immune response and systemic inflammation. As a key metabolic organ, the liver contributes not only to post-stroke immunosuppression but also to stress-induced hyperglycemia. At the same time, increased ketogenesis and glutathione production in the liver are likely to combat inflammation and oxidative stress after AIS. The closely linked lipid metabolism could regulate both glucose and glutathione homeostasis. In addition, increased hepatic very low-density lipoprotein (VLDL) secretion may improve the availability of phospholipids, polyunsaturated fatty acids (PUFAs) and glutathione after AIS. This review provides an overview of recent findings concerning ischemic stroke and the liver and discusses the therapeutic potential of targeting the hepatic metabolism to improve patient outcome after stroke. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the impact of Diacerein (DIC) on endocrine and cardio-metabolic changes in polycystic ovarian syndrome (PCOS) mouse model. Methods: A total of 18 adult female mice (Parkes strain), aged 4–5 weeks, were randomly assigned to three groups, each comprising 6 animals, as follows: Group I (control), received normal diet and normal saline as vehicle for 51 days; Group II received Letrozole (LET; 6 mg/kg bw) for 21 days to induce PCOS; Group III received LET, followed by daily oral gavage administration of DIC (35 mg/kg bw) for 30 days. Results: This study indicates that treatment with LET resulted in PCOS with characteristics such as polycystic ovaries, elevated testosterone, weight gain, visceral adiposity, high levels of insulin as well as fasting blood glucose in addition to insulin resistance, improper handling of ovarian lipids, atherogenic dyslipidemia, impaired Na + /K + -ATPase activity and serum, cardiac, and ovarian oxidative stress. Serum/ovarian adiponectin levels were lowered in LET-treated mice. In mice treated with LET, we also discovered a reduction in cardiac and serum paraoxonase 1 (PON1). Interestingly, DIC restored ovarian andcardio-metabolic abnormalities in LET-induced PCOS mice. DIC prevented the endocrine and cardio-metabolic changes brought on by letrozole-induced PCOS in mice. Conclusion: The ameliorative effects of DIC on letrozole-induced PCOS with concurrent oxidative stress, abdominal fat deposition, cardiac and ovarian substrate mishandling, glucometabolic dysfunction, and adiponectin/PON1 activation support the idea that DIC perhaps, restore compromised endocrine and cardio-metabolic regulators in PCOS. [ABSTRACT FROM AUTHOR]

Aging is an inevitable biological process that affects the function of all organs, including the adrenal gland, which is essential for producing steroid hormones that regulate metabolism, stress response, and immune activation. Understanding how aging affects the morphology of this gland is crucial to developing interventions to mitigate its adverse effects. Thus, this study aimed to describe the morphoquantitative alterations of the adrenal gland in senescent Sprague Dawley rats compared to adult rats. Twelve male rats were divided into 6 adult rats aged 6 months (group A) and 6 senescent rats aged 36 months (group S). Histopathological studies, quantification of collagen fibers types I and III, and stereological analysis were performed to determine the volume density (Vv), surface area (Sv), and number (Nv) of the nuclei of the zona fasciculata cells. Adrenal gland tissue from group S presented dysplasia, metaplasia, intracellular fat accumulation, fibrosis, blood vessel dilation, and increased presence of apoptotic cells. Capsule thickening and increased collagen type I were also observed. There was a significant decrease in Vv, Sv, and Nv of zona fasciculata nuclei in group S compared to group A. The results indicate that aging induces significant morphoquantitative changes in the adrenal gland, which could contribute to the decrease in glucocorticoid production and alterations in aldosterone and cortisol secretion observed in senescence. Understanding these alterations is crucial to developing interventions that mitigate the adverse effects of aging on the endocrine system. [ABSTRACT FROM AUTHOR]

Blue nevus is a type of uncommon benign pigmented lesion in the skin or the mucosa of human body which is featured by pigmented dendritic melanocytes and spindled melanocytic cells. Sinonasal blue nevus is extremely rare. We reported a sinonasal blue nevus case with the background of pituitary adenoma, type 2 diabetes mellitus, and hypertension (including endoscopic and histological pictures). Further, the existing literature about blue nevus is reviewed. This paper puts a spotlight on the potential correlation between blue nevus with the endocrine system disorder and provides support for further experimental research. [ABSTRACT FROM AUTHOR]

All organisms require the ability to engage in either sexual or asexual reproduction in order to ensure their own survival. In aquaculture, when one sex outgrows the other faster, farmers use hormones to stimulate growth. Furthermore, the production of fish based on sexual dimorphism is predominantly executed through the utilization of estrogens and androgens. Environmentally, these compounds may pollute the ecosystem and cause endocrine system alterations that cause harmful effects; thus, they must be handled carefully to assure environmental, biological, and food safety. Phytoestrogens as natural non-steroidal phenolic plant chemicals that resemble 17-β-estradiol, could be employed as a safe alternative source of natural estrogens. The phytoestrogens have many biological effects due to their ability to compete with estrogen receptors, but they may negatively affect fish production, reproduction, and behaviors under controlled conditions. Thus, the current literature emphasizes on the beneficial effects of phytoestrogens on aquatic animal performance, behaviors, and some reproductive features. [ABSTRACT FROM AUTHOR]

For endocrine disrupting chemicals (EDC) the existence of "safe exposure levels", that is exposure levels that do not present an appreciable risk to human health is most controversially discussed, as is the existence of health-based reference values. Concerns have been especially raised that EDCs might not possess a threshold level such that no exposure level to EDCs can be considered safe. To explore whether or not threshold levels can be identified, we performed a screening exercise on 14 pesticidal and biocidal active substances previously identified as EDCs in the European Union. The respective substances are ideal subjects for case studies to review for endocrine activity and disruptive potential following well-defined regulatory assessment based on solid data to effectually establish adversity as consequence of endocrine disruption. Dimethomorph, metiram and propiconazole for which the weight of evidence demonstrating endocrine disruption was the strongest were used as subjects for further study. Epoxiconazole was additionally selected as its effects on the endocrine system are extensive. For all four substances, analysis of the toxicological data clearly indicated thresholds of adversity below which no adverse effects mediated through an endocrine mechanism were observed. Particular emphasis was placed on mechanistic considerations including homeostasis and the concept of adversity. As a proof of concept this study provides evidence that like other substances of toxicological concern EDCs have threshold levels for adversity. While for some EDCs the respective thresholds might indeed be very low this shows that, data allowing, for other EDCs sufficiently protective reference values can be derived. [ABSTRACT FROM AUTHOR]

Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances. Among these parabens, particular concerns have been raised regarding the potential adverse effects of iso-butylparaben (IBP). Studies have specifically highlighted its potential for inducing hormonal disruption, significant ocular damage, and allergic skin reactions. This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague–Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50 mg/kg/day for 13 weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including mortality rates, clinical signs, body weights, food and water consumption, ophthalmological findings, urinalysis, hematological and clinical biochemistry tests, organ weights, necropsy and histopathological findings, estrus cycle regularity, semen quality, and toxicokinetic behavior. The findings revealed that IBP induced local irritation at the injection site in males at doses ≥ 10 mg/kg/day and in females at 50 mg/kg/day; however, systemic toxicity was not observed. Consequently, the no-observed-adverse-effect level (NOAEL) for IBP was determined to be 50 mg/kg/day in rats of both sexes, indicating no impact on the endocrine system. The toxicokinetics of IBP exhibited dose-dependent systemic exposure, reaching a maximum dose of 50 mg/kg/day, and repeated administration over 13 weeks showed no signs of accumulation. [ABSTRACT FROM AUTHOR]

Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes. [ABSTRACT FROM AUTHOR]

This article presents two case studies of zebra finches that exhibited unusual symptoms. The first bird had infertility and swelling around the eyes, with abnormalities found in the oviduct and periocular skin. The second bird had oviductal prolapse, periocular dermatitis, and osteomyelitis. The cause of the symptoms in both cases was not definitively determined, but mycobacterium was found in the second bird. These findings emphasize the need for further research on the causes and impacts of these symptoms in zebra finches. [Extracted from the article]

Thyroid carcinoma ranks as the 9th most prevalent global cancer, accounting for 586,202 cases and 43,636 deaths in 2020. Computerized image analysis, utilizing artificial intelligence algorithms, emerges as a potential tool for tumor evaluation. This study aims to assess and compare chromatin textural characteristics and nuclear dimensions in follicular neoplasms through gray-level co-occurrence matrix (GLCM), fractal, and morphometric analysis. A retrospective cross-sectional study involving 115 thyroid malignancies, specifically 49 papillary thyroid carcinomas with follicular morphology, was conducted from July 2021 to July 2023. Ethical approval was obtained, and histopathological examination, along with image analysis, was performed using ImageJ software. A statistically significant difference was observed in contrast (2.426 (1.774–3.412) vs 2.664 (1.963–3.610), p =.002), correlation (1.202 (1.071–1.298) vs 0.892 (0.833–0.946), p =.01), and ASM (0.071 (0.090–0.131) vs 0.044 (0.019–0.102), p =.036) between NIFTP and IFVPTC. However, morphometric parameters did not yield statistically significant differences among histological variants Computerized image analysis, though promising in subtype discrimination, requires further refinement and integration with traditional diagnostic parameters. The study suggests potential applications in scenarios where conventional histopathological assessment faces limitations due to limited tissue availability. Despite limitations such as a small sample size and a retrospective design, the findings contribute to understanding thyroid carcinoma characteristics and underscore the need for comprehensive evaluations integrating various diagnostic modalities. [ABSTRACT FROM AUTHOR]

One of the reasons of the development of pathologies causing death is hypoxia. The purposes of this study were (1) to study some physiological and biochemical mechanisms of α2-adrenoblockers, which ensure the tissue resistance increase to hypoxia; (2) to offer new drugs contributing to the increase of tissues' stability towards the hypoxic affection; and (3) to submit new medications to surpass by their anti-hypoxic activity of those already used in modern medicine and have some advantages. The reactivity of postsynaptic vascular α2-adrenoceptors was determined on the damaged spinal cord expressed by the blood pressure increase in response to intravenous administration of azepexole that selectively binds to α2-adrenoceptors. Determination of the systemic hemodynamic values and the vascular resistance to the blood flow was performed by the method with plastic microspheres of marked isotopes. pO2 in the blood and the oxygen-transporting function were determined in a sample of 0.1 ml of blood in 30, 90, and 180 min after the α2-adrenoblockers' injections. It has been found that one of the major hemodynamic effects of mesedin and beditin was an improvement in cardiac output, as well as a prolonged increase in coronary blood flow and vasodilation of the heart vessels. Some anti-hypoxic mechanisms of the studied α2-adrenoblockers are an improvement of blood oxygen-transporting function followed by tissue oxygenation and the increased level of corticosterone and resistance to hypoxia. Revealing the mechanisms of action of the postsynaptic α2-adrenoceptors suggests that mesedin and beditin are potentially effective therapeutic means for many hypoxic conditions. [ABSTRACT FROM AUTHOR]

The emergence of the COVID-19 pandemic has led to the rapid and worldwide development and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aimed to explore the current knowledge on potential adverse endocrine effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pituitary, adrenal, diabetes, and gonadal events are also reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar searches were performed. Case reports, case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines are accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of the endocrine disorders linked to COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Background: Thyroid disorders, relatively common diseases of the endocrine system, have risen gradually in recent years. Early detection and accurate diagnosis of thyroid cancer hold exceptional importance. This study aimed to determine the efficacy of a modified TI-RADS and BRAFV600E mutation testing for thyroid cancer (PTC) diagnosis. Methods: Ninety five thyroid nodules (48 benign and 47 malignant) from 81 patients were examined using Kwak Thyroid Imaging Reporting and Data System (TI-RADS) were subjected to shear wave elasticity (SWE), BRAFV600E genotyping and fine needle aspiration (FNA) cytology. Results: The modified TI-RADS exhibited superior diagnostic accuracy compared to TI-RADS in differentiating benign nodules from malignant thyroid nodules. Moreover, the AUC of modified TI-RADS in conjunction with BRAFV600E was the highest at 95% CI (0.898– 0.992, p=0.003), surpassing other diagnostic methods in enhanced sensitivity and maintaining high specificity. Conclusion: The diagnostic efficiency of this combination surpassed that of individual diagnostic methods. [ABSTRACT FROM AUTHOR]

Testosterone boosters (TB) are multi-ingredient dietary supplements that have gained popularity among athletes and the general population. However, certain ingredients in TB are associated with adverse events. The aim of the present study was to analyze dietary TB supplements available for sale online on shop.bodybuilding.com and amazon.com in ten distribution area markets. We evaluated the top five best-selling TB and the most frequently used ingredients of 50 selected TB and the evidence for their efficacy and safety, as well as legislation, statements in the European Union (EU) and sports organizations such as International Olympic Committee (IOC), International Society of Sports Nutrition (ISSN), Australian Institute of Sport (AIS) and World Anti- Doping Agency (WADA). Among 50 TB, 361 components and 98 ingredients were identified. The following ingredients were included in the final review: fenugreek, D- aspartic acid (DAA), 3,3′-diindolylmethane (DIM) or indole-3-carbinol (I3C), Eurycoma longifolia, Cordyceps spp., and ecdysteroids. In EU an authorized health claims refer to few ingredients in TB, mainly minerals, vitamins. Some ingredients were recognized by international sports organizations such as the ISSN, AIS, and WADA and some were identified as unauthorized ingredients/novel food in the EU. Selected ingredients can possibly increase the risk of endocrine system dysregulation. [ABSTRACT FROM AUTHOR]

Diabetic wounds pose an enduring clinical hurdle, marked by delayed recovery, persistent inflammation, and an elevated susceptibility to infections. Conventional treatment approaches often fall short of delivering optimal outcomes, prompting the exploration of innovative methods to enhance the healing process. Electrospun wound dressings offer superior healing, controlled drug release, enhanced cell proliferation, biocompatibility, high surface area, and antimicrobial properties. In the current study, polycaprolactone/gelatin-based nanofibrous wound dressings were developed for the delivery of Wharton's jelly stem cells and curcumin into the diabetic wounds bed. Curcumin was loaded into the polycaprolactone/gelatin solution and electrospun to produce curcumin-loaded scaffolds. In vitro experiments including scanning electron microscopy, cell viability assay, release assay, hemocompatibility assay, cell proliferation assay, and antibacterial assay were utilized to characterize the delivery system. Then, curcumin-loaded scaffolds were seeded with 30,000 Wharton's jelly stem cells and implanted into a rat model of diabetic wounds. Study showed that the scaffolds containing both Wharton's jelly stem cells and curcumin significantly improved diabetic wound closure (86.32 3.88% at the end of 14th day), augmented collagen deposition, and improved epithelial tissue formation. Gene expression studies showed that VEGF and IGF genes were significantly upregulated by the co-delivery system. Our developed system may have augmented diabetic wound healing via upregulating pro-healing genes.

The endocrine system regulates many functions of the human body to maintain optimal performance and homeostasis of various organs and systems. Playing sports and various physical activities changes the regulatory function of the endocrine organs in the form of successive phases, and the magnitude of the response depends on the intensity and duration of the physical stress exerted. Hormonal regulation during physical activity facilitates the adaptation of the functional activity of the cardiovascular system, the activation of energy depots, and the maintenance of adequate tissue hydration. Physical activity leads to an increase in the production of growth hormone, insulin-like growth factor-1, total and free testosterone, which enhances the anabolic reactions of the body. It is important to understand the relationship and impact of physical activity on the functioning of the endocrine system for the development of physical exercise’s complexes, patient rehabilitation, research and treatment of endocrine disorders. The effect of physical activity on the endocrine system for women has been studied to a greater extent, in contrast to men, where the data is contradictory. Therefore, in this article we will highlight the features of various endocrine organs and hormones during sports activities in men.

With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most life‐threatening neoplasias in terms of incidence and mortality worldwide. Vitamin D deficiency has been associated with an increased risk of CRC. 1α,25‐Dihydroxyvitamin D3 [1,25(OH)2D3], the most active vitamin D metabolite, is a pleiotropic hormone that, through its binding to a transcription factor of the nuclear receptor superfamily, is a major regulator of the human genome. 1,25(OH)2D3 acts on colon carcinoma and stromal cells and displays tumor protective actions. Here, we review the variety of molecular mechanisms underlying the effects of 1,25(OH)2D3 in CRC, which affect multiple processes that are dysregulated during tumor initiation and progression. Additionally, we discuss the epidemiological data that associate vitamin D deficiency and CRC, and the most relevant randomized controlled trials of vitamin D3 supplementation conducted in both healthy individuals and CRC patients. [ABSTRACT FROM AUTHOR]

Cover IllustrationThe vitamin D endocrine system and colorectal cancer. Image provided by Antonio Barbáchano, José Manuel González‐Sancho, authors of the State‐of‐the‐Art Review included in this issue, pages 2485–2518.. [Extracted from the article]

Spaceflight and terrestrial spaceflight analogs can alter immune phenotypes. Macrophages are important immune cells that bridge the innate and adaptive immune systems and participate in immunoregulatory processes of homeostasis. Furthermore, macrophages are critically involved in initiating immunity, defending against injury and infection, and are also involved in immune resolution and wound healing. Heterogeneous populations of macrophage-type cells reside in many tissues and cause a variety of tissue-specific effects through direct or indirect interactions with other physiological systems, including the nervous and endocrine systems. It is vital to understand how macrophages respond to the unique environment of space to safeguard crew members with appropriate countermeasures for future missions in low Earth orbit and beyond. This review highlights current literature on macrophage responses to spaceflight and spaceflight analogs. [ABSTRACT FROM AUTHOR]

Developing time‐sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from the mammalian endocrine system it has generated non‐toxic microscale amyloid materials through the coordination between divalent metals and poly‐histidine stretches. Like their natural counterparts that keep the functionalities of the assembled protein, those synthetic structures release biologically active proteins during a slow self‐disintegration process occurring in vitro and upon in vivo administration. Being these granules formed by a single pure protein species and therefore, chemically homogenous, they act as highly promising time‐sustained drug delivery systems. Despite their enormous clinical potential, the nature of the clustering process and the quality of the released protein have been so far neglected issues. By using diverse polypeptide species and their protein‐only oligomeric nanoscale versions as convenient models, a conformational rearrangement and a stabilization of the building blocks during their transit through the secretory granules, being the released material structurally distinguishable from the original source is proved here. This fact indicates a dynamic nature of secretory amyloids that act as conformational arrangers rather than as plain, inert protein‐recruiting/protein‐releasing granular depots. [ABSTRACT FROM AUTHOR]

The optic afferent nervous system (OANS) plays a significant role in generating vision and circadian behaviors based on light detection and signals from the endocrine system. However, the bionic simulation of this photochemically mediated behavior is still a challenge for neuromorphic devices. Herein, stimuli of neurotransmitters at ultralow concentrations and illumination are coupled to artificial synapses with the aid of biofunctionalized heterojunction and tunneling to successfully simulate a circadian neural response. Furthermore, the mechanisms underlying the photosensitive synaptic current in response to stimuli are described. Interestingly, this OANS is demonstrated to be capable of mimicking normal and abnormal circadian learnability by combining the measured synaptic current with a three‐layer spike neural network. Strong theoretical and experimental evidence, as well as applications, are provided for the proposed biomimetic OANS to demonstrate that it can reproduce biological circadian behavior, thus establishing it as a promising candidate for future neuromorphic intelligent robots. [ABSTRACT FROM AUTHOR]

Background: Xenoestrogens are synthetic or naturally occurring chemicals capable of altering the endocrine system of humans and animals owing to their molecular similarity to endogenous hormones. There is limited data regarding their effects on women´s health. Chronic exposure to xenoestrogens can promote the development of estrogen-related diseases. Objectives: To examine xenoestrogen concentration (TEXB-α) differences between women with leiomyomas or endometriosis and control women, and to study the relationship between the clinical and sociodemographic characteristics of these patients and their xenoestrogen levels. Methods: Prospective case-control study. We selected 221 women who underwent surgery at Quironsalud Madrid University Hospital between 2017 and 2021. The cases included 117 patients: 74 women who underwent surgery for uterine leiomyomas, 21 with endometriosis, and 22 with both pathologies. The control group comprised 104 healthy women who underwent surgical procedures for other reasons. TEXB-α was determined in the omental fat of all patients. Using a questionnaire and reviewing the patients' medical records, we collected sociodemographic data and other relevant variables. Results: A significant majority of study participants (68.8%) had detectable levels of xenoestrogens. We found no association between TEXB-α levels in omental fat and the presence of myomas or endometriosis. In the case group, women living or working in Madrid Community exhibited, on average, 3.12 Eeq pM/g higher levels of TEXB-α compared to those working in other areas (p = 0.030). Women who referred to the use of estrogen-containing hormonal contraceptives had, on average, 3.02 Eeq pM/g higher levels of TEXB-α than those who had never used them (p = 0.022). Conclusions: This study found no association between omental xenoestrogen levels and leiomyomas or endometriosis. However, their presence in most participants and their association with highly polluted areas emphasizes the importance of limiting environmental exposure to these substances. We also identified an association between hormonal contraceptive use and xenoestrogen concentration. [ABSTRACT FROM AUTHOR]

The renin‐angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity‐associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein‐coupled receptor (MasR) and Mas‐related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity‐associated metabolic effects. [ABSTRACT FROM AUTHOR]

The intestinal microbiota, comprised of bacteria, archaea, and phages, inhabits the gastrointestinal tract of the organism. Male reproductive sterility is currently a prominent topic in medical research. Increasing research suggests that gut microbiota dysbiosis can result in various reproductive health problems. This article specifically investigates the impact of gut microbiota dysbiosis on male reproductive infertility development. Gut microbiota imbalances can disrupt the immune system and immune cell metabolism, affecting testicular growth and sperm production. This dysfunction can compromise the levels of hormones produced and secreted by the endocrine glands, affecting male reproductive health. Furthermore, imbalance of the gut microbiota can disrupt the gut–brain–reproductive axis, resulting in male reproductive infertility. This article explores how the imbalance of the gut microbiota impacts male reproductive infertility through immune regulation, endocrine regulation, and interactions of the gut–brain–reproductive axis, concluding with recommendations for prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: Premature ovarian failure may be a consequence of radiotherapy administered for the treatment of various female oncologic diseases. Before radiotherapy, fertility may be preserved through ovarian transposition (OT), which consists of moving the ovaries away from the radiation field. Objective: To ascertain all types of surgical techniques employed for OT, outline the endocrine and reproductive outcomes of each one, and discover if one works better than the others. Search strategy: The authors performed a systematic search of the English literature looking for all studies related to OT before radiotherapy published up to June 2023. Nine studies were included. Selection criteria: The eligible studies were assessed based on the presence of a description of the surgical technique employed for OT before pelvic radiotherapy and a report of the endocrine and reproductive outcomes. Data collection and analysis: Odds ratios (OR) with 95% confidence intervals were used to compare endocrine and reproductive outcomes The χ2 test was employed for the statistical analysis and a P value less than 0.05 was considered significant. Main results: A total of 323 female patients aged between 7 and 51 years—198 (61.3%) with non‐gynecologic cancer and 125 (38.7%) with gynecologic cancer—underwent OT, either bilateral (221, 68.4%) or unilateral (102, 31.6%), before radiotherapy. Essentially, two types of OT were employed: lateral and medial. A total of 71 (22%) patients underwent medial OT and 252 (78%) patients (127 with non‐gynecologic tumors and 125 with gynecologic tumors) had a lateral OT. The latter was used in a similar percentage of cases for gynecologic (50.4%) and non‐gynecologic (49.6%) tumors, whereas the medial approach was performed only for non‐gynecologic cancers (Hodgkin's lymphoma). The difference between medial OT and lateral OT was not significant regarding the preservation of endocrine function (OR 0.65, P = 0.120). However, midline OT worked better in terms of reproductive outcomes. In fact, the percentage of patients with pregnancy (49.2%) and live births (45%) associated with medial OT was significantly higher than that associated with lateral OT, 6.5% and 13.4%, respectively, and the difference between such data was statistically significant (OR 7.04, P = 0.001 and OR 5.29, P = 0.003, respectively). Conclusions: Ovarian transposition is an important method to preserve fertility before radiotherapy, considering the worldwide ongoing use of this treatment for various cancers arising in young women. The surgical method depends on the type of disease, but OT—especially medial OT when feasible—is effective in terms of ovarian function preservation and reproductive outcomes. Synopsis: The difference in endocrine function preservation between medial and lateral ovarian transposition was not significant, but midline ovarian transposition yielded better reproductive outcomes. [ABSTRACT FROM AUTHOR]

The endocrine system functions by interactions between ligands and receptors. Ligands exhibit potency for binding to and interacting with receptors. Potency is the product of affinity and efficacy. Potency and physiological concentration determine the ability of a ligand to produce physiological effects. The kinetic behavior of ligand-receptor interactions conforms to the laws of mass action. The laws of mass action define the relationship between the affinity of a ligand and the fraction of cognate receptors that it occupies at any physiological concentration. We previously identified the minimum ligand potency required to produce clinically observable estrogenic agonist effects via the human estrogen receptor-alpha (ERα). By examining data on botanical estrogens and dietary supplements, we demonstrated that ERα ligands with potency lower than one one-thousandth that of the primary endogenous hormone 17β-estradiol (E2) do not produce clinically observable estrogenic effects. This allowed us to propose a Human-Relevant Potency Threshold (HRPT) for ERα ligands of 1 × 10–4 relative to E2. Here, we test the hypothesis that the HRPT for ERα arises from the receptor occupancy by the normal metabolic milieu of endogenous ERα ligands. The metabolic milieu comprises precursors to hormones, metabolites of hormones, and other normal products of metabolism. We have calculated fractional receptor occupancies for ERα ligands with potencies below and above the previously established HRPT when normal circulating levels of some endogenous ERα ligands and E2 were also present. Fractional receptor occupancy calculations showed that individual ERα ligands with potencies more than tenfold higher than the HRPT can compete for occupancy at ERα against individual components of the endogenous metabolic milieu and against mixtures of those components at concentrations found naturally in human blood. Ligands with potencies less than tenfold higher than the HRPT were unable to compete successfully for ERα. These results show that the HRPT for ERα agonism (10–4 relative to E2) proposed previously is quite conservative and should be considered strong evidence against the potential for disruption of the estrogenic pathway. For chemicals with potency 10–3 of E2, the potential for estrogenic endocrine disruption must be considered equivocal and subject to the presence of corroborative evidence. Most importantly, this work demonstrates that the endogenous metabolic milieu is responsible for the observed ERα agonist HRPT, that this HRPT applies also to ERα antagonists, and it provides a compelling mechanistic explanation for the HRPT that is grounded in basic principles of molecular kinetics using well characterized properties and concentrations of endogenous components of normal metabolism. [ABSTRACT FROM AUTHOR]

The skin–brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson's disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly and indirectly regulate behaviour. Conversely, CNS-driven neural and hormonal responses have been demonstrated to regulate pigmentation, e.g., under stress. Additionally, due to the shared neuroectodermal origins of the melanocytes and neurons in the CNS, certain CNS diseases may be linked to pigmentation-related changes due to common regulators, e.g., MC1R variations. Furthermore, the HPA analogue of the skin connects skin pigmentation to the endocrine system, thereby allowing the skin to index possible hormonal abnormalities visibly. In this review, insight is provided into skin pigment production and neuromelanin synthesis in the brain and recent findings are summarised on how signalling pathways in the skin, with a particular focus on pigmentation, are interconnected with the central nervous system. Thus, this review may supply a better understanding of the mechanism of several skin–brain associations in health and disease. [ABSTRACT FROM AUTHOR]

This article provides a narrative summary of current understanding of football injuries in female athletes. We summarize the epidemiological data and compare differences between levels of competition, from amateur through professional. Underlying intrinsic risk factors such as anatomic, biomechanics and endocrine factors are outlined. Extrinsic risk factors such as football boot design and playing surface are detailed. We briefly report on the outcomes of women's injury prevention programmes and their success in reducing ankle injuries. [ABSTRACT FROM AUTHOR]