Hormonal Dysregulation Research Articles

Decoding the obesity-cancer connection: lessons from preclinical models of pancreatic adenocarcinoma.

Obesity is a metabolic state of energy excess and a risk factor for over a dozen cancer types. Because of the rising worldwide prevalence of obesity, decoding the mechanisms by which obesity promotes tumor initiation and early progression is a societal imperative and could broadly impact human health. Here, we review results from preclinical models that link obesity to cancer, using pancreatic adenocarcinoma as a paradigmatic example. We discuss how obesity drives cancer development by reprogramming the pretumor or tumor cell and its micro- and macro-environments. Specifically, we describe evidence for (1) altered cellular metabolism, (2) hormone dysregulation, (3) inflammation, and (4) microbial dysbiosis in obesity-driven pancreatic tumorigenesis, denoting variables that confound interpretation of these studies, and highlight remaining gaps in knowledge. Recent advances in preclinical modeling and emerging unbiased analytic approaches will aid in further unraveling the complex link between obesity and cancer, informing novel strategies for prevention, interception, and therapy in pancreatic adenocarcinoma and other obesity-associated cancers.

Exploring thyroxine binding globulin structural changes and its release from human hepatoblastoma cells upon interaction with silica particles: A prelude to unrevealing the mechanism of thyroid hormone dysregulation

Endocrine dysregulation in the presence of environmental chemical risk factors is a global adverse health concern. The aim of this investigation was to explore the structural changes and binding affinity of thyroxine (T4) binding protein (TBG) upon interaction with SiO2 particles as the second largest mineral in the Earth's crust and one of the most important constituents of rock, soil, and dust. Therefore, the interaction of TBG with SiO2 particles was assessed by fluorescence quenching, molecular docking, ANS and synchronous fluorescence, and far-UV CD analyses. Also, the release of TBG from human hepatoblastoma cell line, Hep G2, was assessed by ELISA assay. The results displayed that the value of stoichiometry of binding site (n) of TBG for T4 was approximately equal to one, which was reduced to 0.36 in the presence of SiO2 particles. Also, the binding affinity (Kb) values revealed that the binding affinity between T4 and TBG was strong (97.90 × 105 L/mol), while the presence of SiO2 particles resulted in the calculation of a Kb around 0.00159 × 105 L/mol, which was significantly lower than that of the absence of SiO2 particles. This data was also verified by molecular docking analyses which indicated that SiO2 particles interacted with the T4 binding pocket of TBG. Moreover, further studies exhibited that although the equimolar concentration of T4 to TBG resulted in the superior stability of TBG-T4 complex relative to free TBG, the presence of SiO2 particles with the same concentration led to denaturation of the secondary structure of TBG. Furthermore, it was seen that the amount of released TBG in the cell culture medium of Hep G2 was about 2.21 ng/mL protein, whereas this amount in SiO2 particles-treated cell group was significantly reduced to 1.71 ng/mL protein (*P < 0.05). In conclusion, this study implies that SiO2 particles show the potential to result in inhibition of TBG release, TBG denaturation, and interfere with TBG binding affinity which may lead to dysregulation of the thyroid hormone transport and associated signaling pathways.

Assessment of the Role of Endothelial and Vascular Smooth Muscle EGFR for Acute Blood Pressure Effects of Angiotensin II and Adrenergic Stimulation in Obese Mice.

(1) Background: Obesity is associated with hypertension because of endocrine dysregulation of the adrenergic and the renin-angiotensin-aldosterone systems. The epidermal growth factor receptor (EGFR) is an important signaling hub in the cardiovascular system. In this study, we investigate the role of smooth muscle cell (VSMC) and endothelial cell (EC) EGFRs for blood pressure homeostasis and acute vascular reactivity in vivo. (2) Methods: Mice with deletion of the EGFR in the respective cell type received either a high-fat (HFD) or standard-fat diet (SFD) for 18 weeks. Intravascular blood pressure was measured via a Millar catheter in anesthetized animals upon vehicle load, angiotensin II (AII) and phenylephrine (PE) stimulation. (3) Results: We confirmed that deletion of the EGFR in VSMCs leads to reduced blood pressure and a most probably compensatory heart rate increase. EC-EGFR and VSMC-EGFR had only a minor impact on volume-load-induced blood pressure changes in lean as well as in obese wild-type animals. Regarding vasoactive substances, EC-EGFR seems to have no importance for angiotensin II action and counteracting HFD-induced prolonged blood pressure increase upon PE stimulation. VSMC-EGFR supports the blood pressure response to adrenergic and angiotensin II stimulation in lean animals. The responsiveness to AII and alpha-adrenergic stimulation was similar in lean and obese animals despite the known enhanced activity of the RAAS and the sympathetic nervous system under a high-fat diet. (4) Conclusions: We demonstrate that EGFRs in VSMCs and to a lesser extent in ECs modulate short-term vascular reactivity to AII, catecholamines and volume load in lean and obese animals.

How do eating disorders can affect the endocrine system? - literature review

Introduction: Eating disorders (ED) are complex psychological disorders with low rates of detection and early intervention. High rates of morbidity and mortality in eating disorders, especially anorexia nervosa (AN), is still continued. ED mostly refers to adolescent and lead to many significant complications, including many changes in endocrine system. Hormonal disorders in AN occur among sex hormones, thyroid hormones, adrenal hormones, growth hormones, as well as the entire hypothalamic-pituitary axis. &#x0D; Purpose of the study: The aim of this study is to collect and summarize the latest views on endocrine dysregulation in anorexia nervosa and highlights the complications associated with it.&#x0D; Material and method: Literature review was performed in English different databases, using keywords: eating disorders, anorexia nervosa, menstruation, menses, irregular menstruation, estrogen, bone mineral density, cortisol, hipercortisolemia, insulin, leptin, ghrelin, growth hormone, thyroid, tyrosine.&#x0D; Results and conclusions: In our systematic review we would like to present the most significant hormone dysregulation in anorexia nervosa and how they can affect the whole organism, such as gonadal axis disregulation, menstrual disorders, bone mineral density, hipercortisolemia, hypoglycemia and other that anorexia nervosa may cause. The phenomenon of eating disorder is becoming more and more frequent – for this reason it is important to put attention to that and be aware of many complication ED can lead to, including hormonal changes.

CYP17A1 (rs74357) polymorphism and polycystic ovary syndrome risk: a systemic review and meta-analysis.

To investigate the association between CYP17A1 (rs74357) polymorphism and the risk of Polycystic Ovary Syndrome (PCOS). Literature on the association of CYP17rs74357 gene polymorphism and susceptibility to PCOS was retrieved by searching databases such as PubMed, Science Direct, Google Scholar and Embase from. The association measure was analyzed using an Odds Ratio (OR) and 95% Confidence Interval (CI). All the statistical analyses were executed using CMA 3.0 Software. In the present meta-analysis,24 studies including 3462 PCOS and 2898 controls were analyzed. The overall results validated that the 17 CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in 5 genetic models: recessive model (fixed and random effect), dominant model (random effect), CC vs. TT (fixed effect), CT vs. TT (fixed effect), and allele contrast (random effect). Stratified analyses by ethnicity/country also detected significant association between Asian and Caucasian under the recessive, dominant, CC vs. TT, CC vs. CT, and the allele contrast models. In the present study, CYP17 T/C (rs74357) gene polymorphism increase the susceptibility of PCOS, and the recessive C allele, can be proposed as a predictive factor for the risk of PCOS or an important pathway in PCOS associated metabolic and hormonal dysregulation especially insulin resistance.However, larger sample size andmultiracial studies are needed in the future to confirm the findings.

Insulin level, lipid profile, and HOMA index in lean and obese patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent endocrinopathy characterized by insulin resistance, hyperinsulinemia, and increased ovarian androgen production. While obesity has been linked to the pathogenesis of PCOS, the condition is also observed in individuals with normal BMI. This cross-sectional study aimed to evaluate the biochemical profile of lean and obese patients with PCOS. Fifty female patients with previously diagnosed PCOS were included in the study, attending the outpatient clinic at AL-Zahraa Teaching Hospital in Al-Najaf between September 2021 and March 2022. Blood samples were collected from each patient to assess insulin levels, lipid profiles, and fasting blood sugar. The results showed a comparable percentage of lean and obese PCOS patients, with a slightly higher proportion of obese individuals. Statistically significant differences were observed in obese patients with higher fasting blood sugar levels, insulin, HDL cholesterol, and triglycerides. Additionally, the HOMA index, an indicator of insulin resistance, was higher in obese individuals. Lean PCOS patients exhibited metabolic, hormonal, and hematopoietic dysregulations comparable to or less pronounced than those affecting the obese phenotype. Regardless of BMI, insulin resistance is part of PCOS and must be treated immediately.

Probiotic-fermented Qushi decoction alleviates reserpine induced spleen deficiency syndrome by regulating spleen function and gut microbiota dysbiosis.

Spleen deficiency syndrome (SDS) is associated with elevated inflammatory factors and dysregulation of gastrointestinal motility hormones and intestinal microbiota. Qushi Decoction (QD), a traditional formula, has not been reported using modern scientific research methods for changes in its probiotic fermented QD (FQD) composition and its potential mechanisms to alleviate SDS. Therefore, the aim of this study was to investigate the splenic protection of FQD in SDS rats by modulating gastrointestinal motility hormones and intestinal microbiota. The results showed that FQD increased total polysaccharides, total protein, total flavonoids and the other active ingredients compared to QD, effectively improved splenic inflammation and apoptosis in SDS rats, and modulated gastrointestinal motility hormones to alleviate diarrhoea and other symptoms. In addition, the dysregulation of the gut microbiota was reversed by increasing the levels of bifidobacterium and decreasing the levels of Escherichia-Shigella and Proteobacteria, which may be related to the regulation of bacterial metabolites to alleviate SDS. These results suggest that FQD is an effective formula for improving SDS. Our findings are beneficial to the implications for the treatment of SDS. This article is protected by copyright. All rights reserved.

Salivary testosterone and cortisol levels in borderline personality disorder before and after a 12-week group dialectical behavior therapy intervention.

Borderline Personality Disorder (BPD) is a chronic, debilitating, and difficult to treat condition. BPD has recently been linked to steroid hormone dysregulation and medical conditions characterized by disturbed androgen metabolism. This study aimed to investigate cortisol and testosterone levels in BPD, and changes in hormones following psychological treatment. Participants with BPD (n = 33) completed a 12-week Dialectical Behavior Therapy group program. Pre and post salivary testosterone and cortisol were analyzed. Baseline hormones in the BPD group were compared to age-and-sex matched controls (n = 33). Non-parametric tests were utilized to investigate group differences, pre-post treatment hormone and symptom changes, and associations between symptoms and hormone levels. Participants with BPD had significantly higher testosterone levels than controls. Mean testosterone levels in females with BPD were double that of female controls. Testosterone and cortisol levels were related, and some BPD symptoms were associated with with hormone levels. BPD symptoms reduced significantly with treatment, however pre to post hormone levels did not change. This study supports an association between BPD symptoms and neuroendocrine dysfunction at baseline, however we found no reduction in hormone dysfunction post treatment. Further research into relationships between stress signaling and neuroendocrine disturbances in BPD may inform aetiological and treatment models. Australian New Zealand Clinical Trials Registry ACTRN12618000477224. Registered on 3 April 2018.

Sex and stress hormone dysregulation as clinical manifestations of hypothalamic function in migraine disorder: A meta-analysis.

Migraine is a leading cause of disability in young adults. It occurs more frequently in females, often comorbidly with stress disorders, suggesting an association with hypothalamic sex and stress hormonal function and a likely interaction with autonomic nervous system activation. Thus, this study aimed to meta-analyse current literature pertaining to female and male sex hormones (estrogen, progesterone and testosterone concentration), hypothalamic-pituitary-adrenal axis (HPA axis) cortisol responses and heart rate variability (HRV) in migraineurs and controls aged 13-65 years. A systematic search of MEDLINE, Embase, PsycINFO, PubMed, CINAHL and Web of Science databases on 29/08/2022 identified 29 studies for meta-analysis (encompassing 719 migraineur and 592 control participants) that met inclusion and NHLBI risk of bias criteria. Results demonstrated that estrogen concentrations of female migraineurs were reduced (g = -.60, 95% CI [-.91, -.29], p < .001) in the luteal phase of the menstrual cycle, compared to controls. No differences were found in progesterone levels overall in female migraineurs, nor in testosterone levels in male migraineurs compared to controls. Further, early diurnal cortisol concentrations were elevated (g = .32, 95% CI [.00, .63], p = .036) in female and male migraineurs compared to controls, though no differences were found in HRV of female or male migraineurs compared to controls. These findings of dysregulation of estrogen in females and cortisol dysregulation in female and male migraineurs indicate perturbed hypothalamic function and highlight the association of migraine with stress and the need for further rigorous investigation of hypothalamic neuroendocrine functions in migraineurs of both sexes.

Maternal preconception thyroid autoimmunity is associated with neonatal birth weight conceived by PCOS women undergoing their first in vitro fertilization/intracytoplasmic sperm injection

BackgroundThyroid autoimmunity and polycystic ovary syndrome (PCOS) are the most common endocrinopathies and have close relationships based on common etiology and pathogenesis, including genetic susceptibility, metabolic disorders, hormonal dysregulation, immune response, and inflammatory activation. The co-occurrence of both diseases is associated with adverse reproductive outcomes, but its effect on neonatal outcomes remains largely unknown. We aim to explore the effect of thyroid autoimmunity on neonatal birth weight in PCOS women undergoing IVF/ICSI.MethodsThis is a retrospective analysis of 486 PCOS women who underwent the first IVF/ICSI cycles and gave birth to 361 singletons and 125 twins during 2018 – 2020 at a reproductive center. The associations between maternal preconception serum thyroid function and autoimmunity indicators and birth weights of the singleton and twin groups were evaluated using generalized linear models (GLMs) and generalized estimate equations (GEEs), respectively. Analyses were further stratified by neonatal sex, maternal age, and maternal preconception BMI to assess the possible interaction effects.ResultsMaternal preconception serum TPOAb had a significant negative association with singleton birth weight (P for trends = 0.03). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in singleton birth weight of − 119.72 g (95% CI: − 222.68 g, − 16.70 g). Maternal preconception serum TPOAb had a significant positive association with twin birth weight (P for trends = 0.01). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in twin birth weight of 138.62 g (95% CI: 33.96 g, 243.30 g). Besides, maternal preconception serum TPOAb had a specific association with increased twin birth weight for female neonates, a specific association with decreased singleton birth weight for PCOS women under 35 years, and a specific association with decreased twin birth weight for overweight PCOS women (all P for interactions < 0.05).ConclusionsMaternal preconception thyroid autoimmunity may affect the birth weights of both singleton and twin neonates. Further large cohorts and experimental studies are required to confirm these findings and explore the underlying mechanisms.

Exploring the repairing mechanisms of reduced graphene oxide (rGo) on the dysregulation of Xenopus Laevis larva hypothalamus-pituitary-thyroid (HPT) axis caused by chiral triazole fungicide metconazole

Replacing chair fungicide racemate marketed product by its enantiomer with high activity and low environmental risk for application is a more environmentally friendly methods to control crop diseases. Moreover, carbon-based nanomaterials, with the desirable chemical and mechanical properties, exhibits latent reduce fungicide toxicity capability, while the mechanism is still poorly understood. Therefore, the present study characterized the toxicity of rac-metconazole (Mez; (1RS,5RS;1RS,5SR)-5-(4-chlorobenzyl)-2,2-dimethyl-1-(1H)) and its two cis-enantiomers as well as the repairing effect of reduced graphene oxide (rGo) on Xenopus Laevis larva by examining growth appearance indexes, Mez bioaccumulation, and hypothalamus-pituitary-thyroid (HPT) axis related hormone contents and gene expression after 14 and 28 days exposure. Compared with two cis-Mez, rac-Mez was preferentially bioaccumulated in tadpoles, and rac-Mez treatment showed a higher toxicity effect on tadpole including growth stage and body weight inhibition by dysregulating tadpole thyroid stimulating hormone (TSH) and thyroid hormone (TH) contents and related gene expression. Enantioselectivity was observed in two cis-Mez treatments. Compared with R,S-Mez, S,R-Mez treatment showed more severe damage on tadpole HPT axis related physiological and biochemical processes. rGo could effectively decrease the toxicity of Mez, especially shown the capacity of repairing the hormone dysregulation caused by R,S-Mez treatment. Moreover, the addition of rGo can decrease the bioaccumulation of Mez in tadpoles. Therefore, R,S-Mez is less toxic to Xenopus Laevis larva growth, and its toxicity could be effectively repaired by the addition of rGO.

Hormonal changes in veterans with Gulf War Illness

AimsGulf War Illness (GWI) is a multi-system condition of complex etiology and pathophysiology without specific treatment. There is an overlap between the symptoms of GWI and endocrinopathies. This study aimed to identify hormonal alterations in 1990–91 Gulf War (GW) veterans and the relationship between GWI and hormonal dysregulation. Main methodsData from 81 GW veterans (54 with GWI and 27 controls without GWI) was analyzed in a cross-sectional, case-control observational study. Participants completed multiple questionnaires, neuropsychiatric assessments, and a comprehensive set of hormone assays including a glucagon stimulation test (GST) for adult growth hormone deficiency (AGHD) and a high-dose adrenocorticotropic hormone (ACTH) stimulation test for adrenal insufficiency. Key findingsThe GWI group had lower quality of life and greater severity of all symptoms compared to controls. Pain intensity and pain-related interference with general activity were also higher in the GWI group. AGHD was observed in 18 of 51 veterans with GWI (35.3 %) and 2 of 26 veterans without GWI (7.7 %) (p = 0.012 for interaction). Veterans with GWI also exhibited reduced insulin-like growth factor 1 (IGF-1) levels and IGF-1 Z-scores compared to controls. One participant with GWI met the criteria for adrenal insufficiency. No significant changes were observed in other hormonal axes. SignificanceThe frequency of AGHD was significantly higher in veterans with GWI compared to controls. Recombinant human growth hormone replacement therapy (GHRT) may become a breakthrough therapeutic option for this subgroup. A large clinical trial is needed to evaluate the efficacy of GHRT in patients with GWI and AGHD.

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.

Laboratory Findings and Biomarkers in Long COVID: What Do We Know So Far? Insights into Epidemiology, Pathogenesis, Therapeutic Perspectives and Challenges.

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

Germline loss-of-function PAM variants are enriched in subjects with pituitary hypersecretion.

Pituitary adenomas (PAs) are common, usually benign tumors of the anterior pituitary gland which, for the most part, have no known genetic cause. PAs are associated with major clinical effects due to hormonal dysregulation and tumoral impingement on vital brain structures. PAM encodes a multifunctional protein responsible for the essential C-terminal amidation of secreted peptides. Following the identification of a loss-of-function variant (p.Arg703Gln) in the peptidylglycine a-amidating monooxygenase (PAM) gene in a family with pituitary gigantism, we investigated 299 individuals with sporadic PAs and 17 familial isolated PA kindreds for PAM variants. Genetic screening was performed by germline and tumor sequencing and germline copy number variation (CNV) analysis. In germline DNA, we detected seven heterozygous, likely pathogenic missense, truncating, and regulatory SNVs. These SNVs were found in sporadic subjects with growth hormone excess (p.Gly552Arg and p.Phe759Ser), pediatric Cushing disease (c.-133T>C and p.His778fs), or different types of PAs (c.-361G>A, p.Ser539Trp, and p.Asp563Gly). The SNVs were functionally tested in vitro for protein expression and trafficking by Western blotting, splicing by minigene assays, and amidation activity in cell lysates and serum samples. These analyses confirmed a deleterious effect on protein expression and/or function. By interrogating 200,000 exomes from the UK Biobank, we confirmed a significant association of the PAM gene and rare PAM SNVs with diagnoses linked to pituitary gland hyperfunction. The identification of PAM as a candidate gene associated with pituitary hypersecretion opens the possibility of developing novel therapeutics based on altering PAM function.

Cortisol dysregulation in anxiety infertile women and the influence on IVF treatment outcome.

Dysregulation of the stress-regulatory hormone cortisol is associated with anxiety, but its potential impact on infertile women and in vitro fertilization (IVF) treatment remains unclear. This prospective cross-sectional study aimed at evaluating the dysregulation of cortisol and its correlation to anxiety in infertile women. The influence of stress on IVF outcomes was also investigated. A point-of-care test was used for the measurement of morning serum cortisol in 110 infertile women and 112 age-matching healthy individuals. A Self-Rating Anxiety Scale (SAS) was used for the anxiety assessment of infertile women, and 109 of them underwent IVF treatment starting with the GnRH-antagonist protocol. If clinical pregnancy was not achieved, more IVF cycles were conducted with adjusted protocols until the patients got pregnant or gave up. Higher morning serum cortisol level was identified for infertile patients, especially for the elder. Women with no anxiety showed significant differences in cortisol levels, monthly income, and BMI compared with those with severe anxiety. A strong correlation was found between the morning cortisol level and the SAS score. When the cutoff value is 22.25 μg/dL, cortisol concentration could predict the onset of anxiety with high accuracy (95.45%) among infertile women. After IVF treatments, women with high SAS scores (>50) or cortisol levels (>22.25 μg/dL) demonstrated a lower rate of pregnancy (8.0%-10.3%) and more IVF cycles, although the impact of anxiety was not affirmative. Hypersecretion of cortisol related to anxiety was prevalent among infertile women, but the influence of anxiety on multi-cycle IVF treatment was not affirmative due to the complicated treatment procedures. This study suggested that the assessment of psychological disorders and stress hormone dysregulation should not be overlooked. An anxiety questionnaire and rapid cortisol test might be included in the treatment protocol to provide better medical care.

Acupuncture regulates the apoptosis of ovarian granulosa cells in polycystic ovarian syndrome-related abnormal follicular development through LncMEG3-mediated inhibition of miR-21-3p

BackgroundThe main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulatory dysfunction, which are caused by excessive apoptosis of ovarian granulosa cells. Acupuncture has been shown to improve follicular development abnormalities in patients with PCOS, but its mechanism is unknown. This study hypothesized that the mechanism of acupuncture on follicular development abnormalities in PCOS patients is the inhibition of granulosa cell apoptosis through LncMEG3-mediated regulation of miR-21-3p.MethodsA PCOS-like rat model was established using subcutaneous injection of dehydroepiandrosterone (DHEA). Acupuncture was performed on rats for 15 d (CV-4, RN-3, CV-6, SP-6 and EX-CA 1). Ovarian morphology was observed by HE staining, and sex hormone and AMH levels were detected by ELISA. Primary granulosa cells were isolated from each group of rats to assess the association of acupuncture treatment, LncMEG3, miR-21-3p, and granulosa cell apoptosis in rats with PCOS.ResultsLncMEG3 and miR-21-3p were highly expressed in the ovarian granulosa cells of rats with PCOS, and LncMEG3-mediated regulation of miR-21-3p was involved in the development of PCOS in rats. Silencing of MEG3 attenuated sex hormone dysregulation and ovarian histopathological changes in PCOS rats and promoted follicle cell development and maturation. In addition, silencing MEG3 increased the viability and number of granulosa cells. In addition, silencing MEG3 further inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats. Acupuncture improved polycystic ovarian morphology and sex hormone levels in PCOS rats. Acupuncture intervention increased the viability and number of granulosa cells. Acupuncture intervention inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats by targeting miR-21-3p via LncMEG3.ConclusionThese results suggest that acupuncture can downregulate LncMEG3, thereby targeting and regulating miR-21-3p to suppress early and late granulosa cell apoptosis and normalize their proliferation. These factors ultimately compensate for abnormal follicular development. These findings shed light on the clinical potential of acupuncture as a safe treatment for follicular developmental abnormalities in PCOS.

Body Mass Index (BMI) Related Morbidity with Thyroid Surgery.

The increase in incidence of thyroid cancer correlates with strict increases in body mass index (BMI) and obesity in the United States. Thyroid hormone dysregulation has been shown to precipitate circulatory volume, peripheral resistance, cardiac rhythm, and even cardiac muscle health. Theoretically, thyroid surgery could precipitate injury to the cardiopulmonary system. The American College of Surgery National Quality Improvement Program database was queried for thyroidectomy cases in the 2007-2020 Participant User files. Continuous and categorical associations between BMI and cardiopulmonary complications were investigated as reported in the database. The query resulted 186,095 cases of thyroidectomy procedures in which the mean age was 51.3 years and sample was 79.3% female. No correlation was evident in univariate and multivariate analyses between BMI and the incidence of postoperative stroke or myocardial infarction. The incidence of complications was extremely low. However, risk of deep venous thrombosis correlated with BMI in the categorical, univariate, and multivariate (OR 1.036, CI 1.014-1.057, p < 0.01) regression analysis. Additionally, increased BMI was associated with increased risk of pulmonary embolism (PE) (OR 1.050 (1.030, 1.069), p < 0.01), re-intubation (OR 1.012 (1.002, 1.023), p = 0.02), and prolonged intubation (OR 1.031 (1.017, 1.045), p < 0.01). Despite the rarity of cardiopulmonary complications during thyroid surgery, patients with very high BMI carry a significant risk of deep venous thrombosis, PE, and prolonged intubation. 3 Laryngoscope, 133:2823-2830, 2023.

EPS4.06 Alterations in incretin and somatostatin levels by glucose tolerance status in people with cystic fibrosis

Objectives: Insulin deficiency in cystic fibrosis (CF) leads to CF related diabetes (CFRD), and dysregulation of other enteroendocrine hormones may further impair insulin secretion in CF. This study investigated whether glucose intolerance was associated with altered incretin or somatostatin secretion in adults with CF.

Appetite hormone dysregulation and executive dysfunction among adolescents with bipolar disorder and disruptive mood dysregulation disorder.

Appetite hormone dysregulation may play a role in the pathomechanisms of bipolar disorder and chronic irritability. However, its association with executive dysfunction in adolescents with bipolar disorder and those with disruptive mood dysregulation disorder (DMDD) remains unclear. We included 20 adolescents with bipolar disorder, 20 adolescents with DMDD, and 47 healthy controls. Fasting serum levels of appetite hormones, including leptin, ghrelin, insulin, and adiponectin were examined. All participants completed the Wisconsin Card Sorting Test. Generalized linear models with adjustments for age, sex, body mass index, and clinical symptoms revealed that patients with DMDD had elevated fasting log-transformed insulin levels (p = .023) compared to the control group. Adolescents with DMDD performed worse in terms of the number of tries required to complete tasks associated with the first category (p = .035), and adolescents with bipolar disorder performed worse in terms of the number of categories completed (p = .035). A positive correlation was observed between log-transformed insulin levels and the number of tries required for the first category (β = 1.847, p = .032). Adolescents with DMDD, but not those with bipolar disorder, were more likely to exhibit appetite hormone dysregulation compared to healthy controls. Increased insulin levels were also related to executive dysfunction in these patients. Prospective studies should elucidate the temporal association between appetite hormone dysregulation, executive dysfunction, and emotional dysregulation.