Endocrine Research Articles

An Integrated Approach to the High-Quality, Safe and Healthy Nutrition Provision for Schoolchildren

Schoolchildren nutrition is one of the urgent problems and is currently one of the most important aspects for federal executive authorities. The study aims at the integrated approach development to ensure high-quality, safe and healthy nutrition for schoolchildren at the municipal level. The study object is the school nutrition system in Ekaterinburg. Nutrition satisfaction assessments results in 2019–2020 revealed that 81 % of headmasters, 48 % of teachers, and 62% of school medical staff believed that children liked to eat in the school canteen. At the same time, a man determined that 40 % of elementary school students, 31 % of high school students, 31 % of parents of elementary school students and 28 % of parents of high school students were satisfied with the catering at school, generally. The thesis presents the proportion data on the unsatisfactory samples of nutritional value identified in the course of inspections in schools in Ekaterinburg in 2019–2022, as well as the dynamics of satisfaction with catering in the school canteen and menu. The researchers systematized data on the reasons for nutrition refusal and (or) limited nutrition in the school canteen; on the attainment of the macro- and micronutrients consumption norms compared to the actual daily rations of schoolchildren in Ekaterinburg. The proportion of children with diseases of the endocrine system in schools varies from 0 to 37 %, including those with obesity – from 0 to 15 %, with diseases of the circulatory system – from 0 to 10 %, digestive system – from 0 to 72 %, musculoskeletal system – from 0 to 65 %. The researchers interrelate the number of unsatisfactory laboratory test samples of food products in public catering enterprises in schools with the digestive diseases in schoolchildren. Based on the research results, a man developed draft municipal program.

Abstract 1985: Ablation of adenylosuccinate lyase retarded the cell proliferation and induces mitochondrial dysfunction in endocrine therapy resistant breast cancer cells

Abstract Approximately 75% of breast tumors express estrogen receptors (ER+); recurrent ER+ breast cancer is generally incurable. Endocrine therapy (ET) is the mainstay of treatment for ER+ breast cancer and works by targeting either ER activity (Tamoxifen or Fulvestrant) or availability of its ligand estrogen (Letrozole, Exemestane). Unfortunately, endocrine therapies are limited by the emergence of resistance; resistance to endocrine therapies (ET) remains a significant clinical challenge. We have explored the role of adenylosuccinate lyase (ADSL), an enzyme of the de-novo purine biosynthesis pathway, in ET-resistant breast cancer cells. Protein expression of ADSL was significantly higher in two different ET-resistant cells (LCC9 and T47D-4HT) when compared with their respective parental ET-sensitive cells (MCF-7 and T47D). siRNA mediated ablation of ADSL in LCC9 and T47D-4HT cells blocked cell proliferation and both colony and spheroid formation. Depletion of ADSL in LCC9 cells obstructed cell cycle progression from G1 to S phase and elevated the protein expression of cyclin D1/D3, CDK2/4, and cyclin E. In T47D-4HT cells, ADSL depletion led to an accumulation of cells in S-phase with reduced protein expression of cyclin D1. Notably, ADSL ablation in LCC9 cells lead to DNA replication stress, resulting in activation (phosphorylation) of ataxia-telangiectasia-mutated-and-Rad3-related kinase (ATR) and its key downstream effector checkpoint kinase 1 (Chk1), which further limited the phosphatase activity of cdc25A leading to deactivation (phosphorylation) of Cyclin-Dependent Kinase 2 (CDK2). ADSL knockdown reduced the mitochondrial membrane potential and impaired the oxygen consumption (OCR) and extracellular acidification (ECAR) rates in both LCC9 and T47D-4HT cells. Of note, addition of AICAR to ADSL-depleted LCC9 cells significantly increased cell proliferation, colony formation, and restored mitochondrial membrane potential. RNA sequencing data revealed the effect of ADSL depletion on enrichment of different pathways in LCC9 and TH47D-4HT cells. Importantly, p53 signaling was significantly enriched in LCC9 cells but not in T47D-4HT cells after ADSL knockdown (T47D cells have a mutated p53 gene). ER+ breast cancer patients treated with ET showed high ADSL expression that is associated with poor recurrence-free survival. In summary, our findings indicate that ADSL-mediated de novo purine synthesis is crucial for cell proliferation. Therefore, targeting ADSL may be a novel therapeutic approach for ER, ET-resistant breast cancer. Citation Format: ANIL KUMAR Yadav, Lu Jin, Robert Clarke, Surojeet Sengupta. Ablation of adenylosuccinate lyase retarded the cell proliferation and induces mitochondrial dysfunction in endocrine therapy resistant breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1985.

SAEM systematic online academic resource (SOAR) review: Gastrointestinal illnesses.

Free open access medical education (FOAM) has become an essential tool for emergency medicine (EM) education and can be valuable to clinicians as a point-of-care resource. The development of the revised Medical Education Translational Resources Impact and Quality (rMETRIQ) tool provides a standardized means of quality assessment. Previous entries of the Society for Academic Emergency Medicine systematic online academic resource (SOAR) series have focused on renal, endocrine, and sickle cell disorders. In this iteration, we strive to identify, curate, and describe FOAM topics specific to acute gastrointestinal (GI) illnesses. We searched 389 keywords across 11 GI topics that were modified from the 2019 Model of the Clinical Practice of EM (EM Model) using the search engine Google FOAM and within the top 50 websites listed on Academic Life in Emergency Medicine's Social Media Index. The sites underwent preliminary screening to eliminate resources that were not relevant to EM or GI illnesses. Identified resources were evaluated with the rMETRIQ tool by five board-certified EM physicians who received rMETRIQ tool rater training. After duplicates of the initial 39,505 resources were eliminated, 8059 remained. Primary screening resulted in a final 1202 resources. The most common categories were large bowel (18%), small bowel (13%), stomach (11%), esophagus (11%), biliary (11%), and liver (10%). Many resources covered multiple topics and subtopics. The final mean intraclass correlation coefficient among the five physicians was 0.95 (95% CI 0.92-0.98) for rMETRIQ scoring. We identified 256 sites considered "high quality" with a rMETRIQ score of 16 or higher as designated in prior reviews. This iteration of the SOAR review resulted in the highest number of high-quality resources compared to other SOAR reviews, with 21% of resources thus far scoring ≥ 16. A final list of high-quality resources can guide trainees, educator recommendations, and FOAM authors.

Abstract 434: Understanding metabolic heterogeneity of estrogen receptor positive metastatic breast tumors using spatial transcriptomics and geographic information systems approaches

Abstract The tumor microenvironment consists of numerous cell populations showing diverse metabolic preferences, causing metabolic heterogeneity and therapy resistance. Fulvestrant, a clinically approved selective estrogen receptor (ER) degrader, is the standard of care for ER-positive breast cancer, yet resistance has been reported among metastatic breast cancer patients. In our previous studies, we showed such resistance is attributable to metabolic heterogeneity in the tumor microenvironment. Despite metabolic heterogeneity posing a common challenge in cancer research, current methods, such as histology and Magnetic Resonance Imaging, cannot explore nutrient uptake at transcript-level resolution with spatial context, making it difficult to understand the heterogeneity that affects cellular growth and metabolism. Visium Spatial Transcriptomics, a method that shows regional gene expression, is emerging as a powerful spatial analysis tool, and we integrated this method with geographic information systems to investigate the tumor microenvironment heterogeneity and highlight the importance of cell-microenvironment interactions. We developed a computational pipeline to visualize hotspots of spatially relevant genes using breast cancer metastatic samples from xenograft models and human patients. This pipeline integrates Visium tools and geospatial methods for processing transcriptome profiling data. We analyzed the degree of local spatial association based on Local Moran’s I to estimate regions with significant co-localization of single and multiple gene expressions within a tumor. We then leveraged the co-localized areas in the process of biomarker identification and revealing biological pathways. We also used unsupervised clustering of the complete transcriptome profiles to test the resemblance between identified clusters and hotspots as well as any disruption in the spatial structure of clusters in response to therapy or metastasis. Gene set enrichment analysis of these clusters revealed several glucose or lipid metabolism pathways, and mapping of the genes corresponding to each pathway showed mutually exclusive gene expression patterns in the sample. We also observed minimal co-localization of two metabolic pathways but extensive co-localization between metabolic genes and ER target genes, suggesting distinct metabolic preferences and spatial distributions of endocrine therapy resistant cell populations. Altogether, our analysis pipeline established a computational framework for characterizing the link between tumor microenvironment, local metabolism, and changes in transcriptional response to external stimuli. Our findings support the development of strategies to target different endocrine resistant regions using a combination of ER and metabolic signaling inhibitors. Citation Format: Jin Young Yoo, Sabrina Akter, Nandana Varma, Atharva Jain, Aiman Soliman, Zeynep Madak Erdogan. Understanding metabolic heterogeneity of estrogen receptor positive metastatic breast tumors using spatial transcriptomics and geographic information systems approaches [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 434.

Magnetic Solid-Phase Extraction (MSPE) Coupled With Gas Chromatography-Barrier Discharge Ionization Detection (GC-BID) for the Simultaneous Determination of 16 Phthalates in Baijiu

Prolonged exposure to phthalates (PAEs) can adversely affect the human endocrine system. This study proposes a method for quantitatively determining the PAE content in Baijiu using magnetic solid-phase extraction (MSPE) coupled with gas chromatography-barrier discharge ionization detection (GC-BID). A hydrophobic reversed-phase (C18) magnetic adsorbent was used to extract and enrich the PAEs in Baijiu, and GC-BID was used for their separation and detection. The pretreatment and detection conditions were investigated and optimized to improve the recovery of the PAEs. Under the optimized conditions, the method performed effectively in the linear range (20.0–3000.0 ng/mL), with limits of detection ranging from 0.04 to 0.62 ng/mL, relative standard deviations from 1.5 to 8.7% and enrichment factors from 26.6 to 50.0. The MSPE-GC-BID method successfully detected PAEs in the Baijiu samples. The recovery of the 16 PAEs in the spiked Baijiu ranged from 42.3 to 143.9%, with a relative standard deviation of less than 7.2%. This method shows good repeatability and precision, making it suitable for the determination of phthalates in Baijiu.

Heterozygous missense variant in GLI2 impairs human endocrine pancreas development

Missense variants are the most common type of coding genetic variants. Their functional assessment is fundamental for defining any implication in human diseases and may also uncover genes that are essential for human organ development. Here, we apply CRISPR-Cas9 gene editing on human iPSCs to study a heterozygous missense variant in GLI2 identified in two siblings with early-onset and insulin-dependent diabetes of unknown cause. GLI2 is a primary mediator of the Hedgehog pathway, which regulates pancreatic β-cell development in mice. However, neither mutations in GLI2 nor Hedgehog dysregulation have been reported as cause or predisposition to diabetes. We establish and study a set of isogenic iPSC lines harbouring the missense variant for their ability to differentiate into pancreatic β-like cells. Interestingly, iPSCs carrying the missense variant show altered GLI2 transcriptional activity and impaired differentiation of pancreatic progenitors into endocrine cells. RNASeq and network analyses unveil a crosstalk between Hedgehog and WNT pathways, with the dysregulation of non-canonical WNT signaling in pancreatic progenitors carrying the GLI2 missense variant. Collectively, our findings underscore an essential role for GLI2 in human endocrine development and identify a gene variant that may lead to diabetes.

Effect of quercetin administration on electron microscopic changes in testicular interstitial endocrinocytes during long-term central blockade of luteinising hormone in rats

Quercetin is a flavonoid with potential health benefits and it may help prevent cardiovascular diseases, reduce the risk of degenerative brain processes and cancer, and has antioxidant properties that neutralise free radicals. Substances in this group also have antioxidant properties, which help the body protect itself from the harmful effects of free radicals by neutralising these unstable molecules. Research indicates that the impact of free radicals on cell structure is associated with the development of chronic diseases such as diabetes, cancer, and cardiovascular pathologies. The aim of the study was to investigate the effect of quercetin administration on electron microscopic changes in the interstitial endocrinocytes of the testes under long-term central blockade of the synthesis of luteinising hormone by tryptorelin. The experiment involved 35 sexually mature male white rats. They were divided into two groups: the control group (I) received saline, while group II received subcutaneous injections of tryptorelin at a dose of 0.3 mg of active ingredient per kg of rat body weight to induce experimental central deprivation of luteinising hormone synthesis and additionally, quercetin was administered three times a day by gastric tube in terms of body weight. The study has demonstrated that the administration of tryptorelin results in structural and functional changes in the connective tissue components of rat testes. Specifically, there are quantitative and qualitative disorders in the population of interstitial endocrine cells, as well as electron microscopic changes at the subcellular level. Various pathological changes and abnormalities in the functional activity of the internal components of the cell were detected on days 270 and 365 of the experiment. The frequency, number, and size of Reinke crystals in relation to the cell volume correlated with changes in cells and increased at later stages of the study. A similar correlation with testosterone levels has not been found in the literature, which leads us to classify Reinke crystals as the result of degenerative processes in the cell. Thus, additional administration of quercetin reduces the adverse effect of tryptorelin and delays the onset of changes in the structure of interstitial endocrinocytes from day 180 to later observation periods.

Intestinal Acyl-CoA synthetase 5 (ACSL5) deficiency potentiates postprandial GLP-1 & PYY secretion, reduces food intake, and protects against diet-induced obesity

ObjectiveIn the small intestine, the products of digestion of dietary triacylglycerol (TAG), fatty acids (FA) and monoacylglycerol, are taken up by absorptive cells, enterocytes, for systemic energy delivery. These digestion products can also bind receptors on endocrine cells to stimulate the release of hormones capable of influencing systemic energy metabolism. The initial phase of intestinal FA absorption involves the acylation of FAs to acyl-CoA by the acyl-CoA long chain synthetase (ACSL) enzymes. ACSL5 is abundantly expressed in the small intestinal epithelium where it is the major ACSL isoform, contributing approximately 80% of total ACSL activity. In mice with whole body deficiency of ACSL5, the rate of dietary fat absorption is reduced and energy expenditure is increased. However, the mechanisms by which intestinal ACSL5 contributes to intestinal FA metabolism, enteroendocrine signaling, and regulation of energy expenditure remain undefined. Here, we test the hypothesis that intestinal ACSL5 regulates energy metabolism by influencing dietary fat absorption and enteroendocrine signaling. MethodsTo explore the role of intestinal ACSL5 in energy balance and intestinal dietary fat absorption, a novel mouse model of intestine specific ACSL5 deficiency (ACSL5IKO) was generated by breeding ACSL5 floxed (ACSL5loxP/loxP) to mice harboring the tamoxifen inducible, villin-Cre recombinase. ACSL5IKO and control, ACSL5loxP/loxP mice were fed chow (low in fat) or a 60% high fat diet (HFD), and metabolic phenotyping was performed including, body weight, body composition, insulin and glucose tolerance tests, energy expenditure, physical activity, and food intake studies. Pair-feeding studies were performed to determine the role of food intake in regulating development of obesity. Studies of dietary fat absorption, fecal lipid excretion, intestinal mucosal FA content, and circulating levels of glucagon like peptide 1 (GLP-1) and peptide YY (PYY) in response to a TAG challenge were performed. Treatment with a GLP-1 receptor antagonist was performed to determine the contribution of GLP-1 to acute regulation of food intake. ResultsWe found that ACSL5IKO mice experienced rapid and sustained protection from body weight and fat mass accumulation during HFD feeding. While intestine specific deficiency of ACSL5 delayed gastric emptying and reduced dietary fat secretion, it did not result in increased excretion of dietary lipid in feces. Energy expenditure and physical activity were not increased in ACSL5IKO mice. Mice deficient in intestinal ACSL5 display significantly reduced energy intake during HFD, but not chow feeding. When HFD intake of control mice was matched to ACSL5IKO during pair-feeding studies, no differences in body weight or fat mass gain were observed between groups. Postprandial GLP-1 and PYY were significantly elevated in ACSL5IKO mice secondary to increased FA content in the distal small intestine. Blockade of GLP-1 signaling by administration of a long-acting GLP-1 receptor antagonist partially restored HFD intake of ACSL5IKO. ConclusionsThese data indicate that intestinal ACSL5 serves as a critical regulator of energy balance, protecting mice from diet-induced obesity exclusively by increasing satiety and reducing food intake during HFD feeding. The reduction in food intake observed in ACSL5IKO mice is driven, in part, by increased postprandial GLP-1 and PYY secretion. These effects are only observed during HFD feeding, suggesting that altered processing of dietary fat following intestinal ACSL5 ablation contributes to GLP-1 and PYY mediated increases in satiety.

Secretion of glucagon, GLP-1 and GIP may be affected by circadian rhythm in healthy males.

Glucagon is secreted from pancreatic alpha cells in response to low blood glucose and increases hepatic glucose production. Furthermore, glucagon enhances hepatic protein and lipid metabolism during a mixed meal. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from gut endocrine cells during meals and control glucose homeostasis by potentiating insulin secretion and inhibiting food intake. Both glucose homeostasis and food intake have been reported to be affected by circadian rhythms and vice versa. In this study, we investigated whether the secretion of glucagon, GLP-1 and GIP was affected by circadian rhythms. A total of 24 healthy men with regular sleep schedules were examined for 24h at the hospital ward with 15h of wakefulness and 9h of sleep. Food intake was standardized, and blood samples were obtained every third hour. Plasma concentrations of glucagon, GLP-1 and GIP were measured, and data were analyzed by rhythmometric statistical methods. Available data on plasma glucose and plasma C-peptide were also included. Plasma concentrations of glucagon, GLP-1, GIP, C-peptide and glucose fluctuated with a diurnal 24-h rhythm, with the highest levels during the day and the lowest levels during the night: glucagon (p < 0.0001, peak time 18:26h), GLP-1 (p < 0.0001, peak time 17:28h), GIP (p < 0.0001, peak time 18:01h), C-peptide (p < 0.0001, peak time 17.59h), and glucose (p < 0.0001, peak time 23:26h). As expected, we found significant correlations between plasma concentrations of C-peptide and GLP-1 and GIP but did not find correlations between glucose concentrations and concentrations of glucagon, GLP-1 and GIP. Our results demonstrate that under meal conditions that are similar to that of many free-living individuals, plasma concentrations of glucagon, GLP-1 and GIP were observed to be higher during daytime and evening than overnight. These findings underpin disturbed circadian rhythm as a potential risk factor for diabetes and obesity. ClinicalTrials.gov Identifier: NCT06166368. Registered 12 December 2023.

The Adrenal Gland and Pancreatic Islets - A Beneficial Endocrine Alliance.

Intraportal islet transplantation in patients with type 1 diabetes enables restoration of glucose-regulated insulin secretion. However, several factors hamper a widespread application and long-term success: chronic hypoxia, an inappropriate microenvironment and suppression of regenerative and proliferative potential by high local levels of immunosuppressive agents. Therefore, the identification of alternative and superior transplant sites is of major scientific and clinical interest. Here, we aim to evaluate the adrenal as an alternative transplantation site. The adrenal features a particular microenvironment with extensive vascularization, anti-apoptotic and pro-proliferative, anti-inflammatory and immunosuppressive effects. To validate this novel transplantation site, an in vitro co-culture system of adrenal cells and pancreatic islets was established and viability, islet survival, functional potency and antioxidative defense capacity were evaluated. For in vivo validation, an immune-deficient diabetic mouse model for intra-adrenal islet transplantation was applied. The functional capacity of intra-adrenally grafted islets to reverse diabetes was compared to a standard islet transplant model and measures of engraftment such as vascular integration were evaluated. The presence of adrenal cells positively impacted on cell metabolism and oxidative stress. Following transplantation, we could demonstrate enhanced islet function in comparison to standard models with improved engraftment and superior re-vascularization. This experimental approach allows for novel insights into the interaction of endocrine systems and may open up novel strategies for islet transplantation augmented through the bystander effect of other endocrine cells or the active factors secreted by adrenal cells modulating the microenvironment.

High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesis

To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited. In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10×Genomics platform. We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia. We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule. This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).

Сучасний стан та просторово-часові тенденції аліментарно-залежної захворюваності дитячого населення України

The purpose of the study is a spatio-temporal analysis of the peculiarities of the national and regional dynamics of nutritional morbidity among the children of Ukraine. Research materials and methods: The study design included a retrospective analysis of official statistical data on the prevalence and incidence of food addiction in children and a review of the results of original studies. The research materials included statistical data of the State Statistics Service of Ukraine on certain food-dependent pathologies of the children’s population of Ukraine. The retrospective evaluation of statistical data was 18 years (2000-2017), national and regional data were evaluated. Research methods included statistical evaluation of factual and analytical material. The results: The analysis of trends in the prevalence and incidence of foodborne diseases in children in different age periods during 2000-2017 determines important features of the dynamics of these indicators in different age groups. The total share of alimentary diseases in the total structure of diseases is 9.88-10.00% at the age of 0-14 years old and 17.98% at the age of 15-17 years old. The general analysis shows a trend towards a decrease in the prevalence and incidence of food borne diseases among children of certain age groups over the course of 18 years. This especially applies to diseases of blood organs and the endocrine system. In the group of children aged 0-6 years old, there is an intense decrease in the registration of primary forms of diseases. At the age of 7-14 years old, during 2000-2017, there is an intensive decrease in the incidence and prevalence of diseases of the endocrine system and digestive organs, and at the age of 15-17 years old, there is a significant increase in growth and growth rates according to most indicators. Conclusions: the age-specific features of food-dependent pathology of the children's population, spatial-temporal trends in national and regional sections are determined. The need for further research and monitoring in order to form a policy for the management of food-dependent pathology is shown.

Diabetes as a Pancreatic Microvascular Disease-A Pericytic Perspective.

Diabetes is not only an endocrine but also a vascular disease. Vascular defects are usually seen as consequence of diabetes. However, at the level of the pancreatic islet, vascular alterations have been described before symptom onset. Importantly, the cellular and molecular mechanisms underlying these early vascular defects have not been identified, neither how these could impact the function of islet endocrine cells. In this review, we will discuss the possibility that dysfunction of the mural cells of the microvasculature-known as pericytes-underlies vascular defects observed in islets in pre-symptomatic stages. Pericytes are crucial for vascular homeostasis throughout the body, but their physiological and pathophysiological functions in islets have only recently started to be explored. A previous study had already raised interest in the "microvascular" approach to this disease. With our increased understanding of the crucial role of the islet microvasculature for glucose homeostasis, here we will revisit the vascular aspects of islet function and how their deregulation could contribute to diabetes pathogenesis, focusing in particular on type 1 diabetes (T1D).

Serotonin transporter imaging agent as a probe for β-cells of pancreas

ObjectiveDiabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic β cells in vivo, which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [125I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic β-cell mass (BCM). MethodsIn vitro cell studies were evaluated in INS-1 cells (rat islet β cell line). Biodistribution studies were performed in male normal Sprague-Dawley rats and alloxan-induced type 1 diabetes mellitus (T1DM) rats. Distribution and expression of SERT protein in pancreas of rats were also measured by immunofluorescence staining and Western blot. ResultsIn vitro cell studies showed that the concentration of [125I]ADAM associated with the INS-1 cells was increased gradually with incubation time, and the SERT specific inhibitor, escitalopram, exhibited the inhibitory effect on this interaction. Biodistribution studies also showed that the uptake of [125I]ADAM in the pancreas of normal rats was decreased in the presence of escitalopram. However, in the T1DM rat model with a significant β cells reduction, the uptake of pancreas was increased when compared with the control. Through immunofluorescence staining and Western blot, it was found that both the endocrine and exocrine cells of the normal pancreas expressed SERT protein, and the level of SERT protein in the exocrine cells was higher than islets. In the diabetic state, the expression of SERT in the exocrine cells was further increased. ConclusionsThe SERT imaging agent, [125I]ADAM, at the present form will not be suitable for imaging β cells, specifically because there were extraordinarily high non-specific signals contributing from the exocrine cells of pancreas. In addition, we noticed that the level of SERT expression was abnormally elevated in the diabetic state, which might provide an unexpected target for studying the pathological mechanisms of diabetes.

Serotonin Immunoreactive Cells in Extrahepatic Bile Ducts, Major Duodenal Papilla and Gallbladder in the Domestic Pig

Abstract The main part of serotonin in the body is synthesized and released by a certain type of enteroendocrine cells in the intestinal mucosa called enterochromaffin cells. The scarce qualitative and quantitative data on enterochromaffin and serotonin-positive mast cells in porcine extrahepatic bile ducts and gallbladder, motivated us to undertake the present study. The aim of this study was to determine the localization and density of serotonin-positive cells in the wall of the extrahepatic bile ducts and gallbladder in pigs. An immunohistochemical method was used to identify enterochromaffin cells and determine their percentage relative to the total number of endocrine cells labeled with chromogranin A. Serotonin-positive mast cells were identified after tryptase staining of serial sections. The endocrine function of mast cells was demonstrated by chromogranin A immunolabeling. The highest number of enterochromaffin cells were found in the intramural part of the ductus choledochus, followed by the papilla duodeni major, extramural part of the ductus choledochus, ductus hepaticus comunis, ductus cysticus, and gallbladder. In all parts of the extrahepatic bile ducts, the highest number of mast cells was found in the muscle layer, followed by the serosal layer and the propria. The expression of serotonin in the enterochromaffin cells of the biliary glands and in the mast cells of the analyzed organs suggests a possible synthesis of serotonin, which probably regulates physiological and pathological processes.

Endocrine disruption in teleosts and amphibians is mediated by anthropogenic and natural environmental factors: implications for risk assessment.

Environmental variation in the Anthropocene involves several factors that interfere with endocrine systems of wildlife and humans, presenting a planetary boundary of still unknown dimensions. Here, we focus on chemical compounds and other impacts of anthropogenic and natural originsthat are adversely affecting reproduction and development. The main sink of these endocrine disruptors (EDs) is surface waters, where they mostly endanger aquatic vertebrates, like teleost fish and amphibians. For regulatory purposes, EDs are categorized into EATS modalities (oestrogenic, androgenic, thyroidal, steroidogenesis), only addressing endocrine systems being assessable by validated tests. However, there is evidence that non-EATS modalities-and even natural sources, such as decomposition products of plants or parasitic infections-can affect vertebrate endocrine systems. Recently, the disturbance of natural circadian light rhythms by artificial light at night (ALAN) has been identified as another ED. Reviewing the knowledge about EDs affecting teleosts and amphibians leads to implications for risk assessment. The generally accepted WHO-definition for EDs, which focuses exclusively on 'exogenous substances' and neglects parasitic infections or ALAN, seems to require some adaptation. Natural EDs have been involved in coevolutionary processes for ages without resulting in a general loss of biodiversity. Therefore, to address the 'One Health'-principle, future research and regulatory efforts should focus on minimizing anthropogenic factors for endocrine disruption. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Dual-targeted nano-encapsulation of neonatal porcine islet-like cell clusters with triiodothyronine-loaded bifunctional polymersomes

There is growing evidence that neonatal porcine islet-like cell clusters (NPCCs) isolated from piglets can be used to treat type 1 diabetes in humans. However, graft rejection is a common complication in humans owing to the prevalence of xenoantigens in porcine. Therefore, researchers have investigated various islet encapsulation techniques that could protect against these antigens. To this end, this study presents a robust nano-encapsulation method based on bifunctional polymersomes (PSomes), in which N-hydroxysuccinimide (NHS) and maleimide (Mal) groups conjugated to the PSomes terminal interact with the amine and thiol groups on the surface of NPCCs to induce dual targeting via two covalent bonds. The findings indicate that the ratio of NHS to Mal on PSomes is optimal for dual targeting. Moreover, triiodothyronine (T3) is known to promotes pancreatic islet maturation and differentiation of endocrine cells into beta cells. T3 encapsulated in PSomes is shown to increase the glucose sensitivity of NPCCs and enhance insulin secretion from NPCCs. Furthermore, improvements in the nano-encapsulation efficiency and insulin-secreting capability of NPCCs through dual targeting via dual-Psomes are demonstrated. In conclusion, the proposed nano-encapsulation technique could pave the way for significant advances in islet nano-encapsulation and the imprevement of NPCC immaturity via T3 release.

Bioengineered in vitro three-dimensional tumor models in endocrine cancers.

Endocrine tumors are a heterogeneous cluster of malignancies that originate from cells that can secrete hormones. Examples include, but are not limited to, thyroid cancer, adrenocortical carcinoma, and neuroendocrine tumors. Many endocrine tumors are relatively slow to proliferate, and as such, they often do not respond well to common antiproliferative chemotherapies. Therefore, increasing attention has been given to targeted therapies and immunotherapies in these diseases. However, in contrast to other cancers, many endocrine tumors are relatively rare, and as a result, less is understood about their biology, including specific targets for intervention. Our limited understanding of such tumors is in part due to a limitation in model systems that accurately recapitulate and enable mechanistic exploration of these tumors. While mouse models and 2D cell cultures exist for some endocrine tumors, these models often may not accurately model nuances of human endocrine tumors. Mice differ from human endocrine physiology and 2D cell cultures fail to recapitulate the heterogeneity and 3D architectures of in vivo tumors. To complement these traditional cancer models, bioengineered 3D tumor models, such as organoids and tumor-on-a-chip systems, have advanced rapidly in the past decade. However, these technologies have only recently been applied to most endocrine tumors. In this review we provide descriptions of these platforms, focusing on thyroid, adrenal, and neuroendocrine tumors and how they have been and are being applied in the context of endocrine tumors.

Health dynamics of children and adolescents in the Far Eastern federal district in 2013–2020

Aim. To identify trends in the primary morbidity of children and adolescents in the Far Eastern Federal District.Materials and methods. A retrospective analytical study of the dynamics of primary morbidity in children and adolescents by disease class was conducted.Results. Among the children population, a very high and high stability of the decrease in morbidity rates was established (R = -0.714– (-1.0)) for all classes of diseases. Among the adolescent population, a weak stability in the decrease in morbidity rates was characteristic of VII Diseases of the eye and adnexa (R = -0.262) and X Respiratory diseases (R = -0.262); a moderate stability of IV Diseases of the endocrine system, nutritional disorders, and metabolic disorders (R = -0.333); a moderate stability of IX Diseases of the circulatory system (R = -0.623); and a high stability among all other classes (R= -0.738 – (-0.928)). In the older age group, weak resistance to growth dynamics was determined in classes III Diseases of the blood, hematopoietic organs, and certain disorders involving the immune mechanism (R = 0.024) and VIII Diseases of the ear and mastoid process (R = 0.095).Conclusion. The data obtained forms a basis for further research into regional risk factors that contribute to poor health of the population. The findings can also be used to predict the health status of younger generations.

Conversion of spikers to bursters in pituitary cell networks: Is it better to disperse for maximum exposure or circle the wagons?

The endocrine cells of the pituitary gland are electrically active, and in vivo they form small networks where the bidirectional cell-cell coupling is through gap junctions. Numerous studies of dispersed pituitary cells have shown that typical behaviors are tonic spiking and bursting, the latter being more effective at evoking secretion. In this article, we use mathematical modeling to examine the dynamics of small networks of spiking and bursting pituitary cells. We demonstrate that intrinsic bursting cells are capable of converting intrinsic spikers into bursters, and perform a fast/slow analysis to show why this occurs. We then demonstrate the sensitivity of network dynamics to the placement of bursting cells within the network, and demonstrate strategies that are most effective at maximizing secretion from the population of cells. This study provides insights into the in vivo behavior of cells such as the stress-hormone-secreting pituitary corticotrophs that are switched from spiking to bursting by hypothalamic neurohormones. While much is known about the electrical properties of these cells when isolated from the pituitary, how they behave when part of an electrically coupled network has been largely unstudied.