The impact of endocrine-disrupting chemicals on stem cells: Mechanisms and implications for human health.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

The effects of 17ß-trenbolone and bisphenol A on sexual behavior and social dominance via the hypothalamic-pituitary-gonadal axis in male mice.

17ß-Trenbolone (17-TB) is well documented as an environmental endocrine disruptor in aquatic biological studies, but its effects on mammals remain poorly understood. Furthermore, 17-TB acts as a hormone with properties similar to testosterone, and the consequences of juvenile exposure on adult social behavior remain uncertain. Bisphenol A (BPA) acts as an estrogen-like hormone, compared to 17-TB. Three-week-old male Balb/c mice were exposed orally to 17-TB (100 µg/(kg·day)) and BPA (4 mg/(kg·day)) for 28 days. Assessments of social interactions and a three-chamber test showed that 17-TB increased virility in male mice, intensified both male and female sexual behavior, and attracted and accepted female mice. It also increased social dominance through tube tests in male mice and markedly activated the c-Fos+ immune response in the medial prefrontal cortex (mPFC) and basal amygdala (BLA). ELISA data showed that 17-TB and BPA exposure significantly affected serum gonadotropin-releasing hormone (GnRH), growth hormone (GH), estradiol (E2), and luteinizing hormone (LH) levels, as well as testicular lesions and androgen receptor (ARß) and estrogen receptor (ERα) synthesis. Testicular transcriptomic analysis further confirmed that could disrupt steroid synthesis and linoleic acid-related biometabolic processes. These findings suggest the influence of 17-TB and BPA exposure on sexual behavior and fertility in male mice, possibly through modulation of the hypothalamic-pituitary-gonadal axis. This study provides insights relevant to human reproductive health and neuro-social behavioral research, and the potential risk of environmental disturbances should not be overlooked.

Infertility treatments and risk of breast benign diseases: a case‒control study.

BACKGROUND: Theoretically, endocrine fluctuations occurring during infertility treatments, including ovulation induction (OI) and assisted reproductive techniques (ART), could be associated with an increased risk of benign breast diseases (BBDs). To date, no studies have been conducted on this association. Therefore, the present study investigated the association between different types of infertility treatments and BBDs. METHODS: This case‒control study was conducted in Arash Women's Hospital, Tehran, Iran. The case group included infertile women diagnosed with BBDs without atypia, and the control group included infertile women without breast disease. Breast imaging studies (mammography/ultrasound) were performed for BBD screening, and the diagnosis was confirmed by histopathological examination. Study variables were collected retrospectively from medical records, hospital databases, and questionnaires. RESULTS: Finally, 154 infertile women, including 50 cases (BBDs) and 104 controls (no BBDs), were compared. Our data showed that 66% of cases and 61.4% of controls had undergone at least one course of infertility treatment. There was no association between BBD risk and previous infertility treatments (OR = 1.21; 95% CI = 0.59-2.46), ART (OR = 1.14; 95% CI = 0.90-1.44), or OI cycles (OR = 1.13; 95% CI = 0.98-1.32). Stratification by confounding variables did not change these results. CONCLUSIONS: It seems that there is no association between BBDs in infertile women and the type, duration, or number of prior infertility treatments; however, considering the small sample size of the study, the clinical significance of this finding should not be neglected. Therefore, we consider it essential to carry out more extensive, detailed, and prospective studies to distinguish the association of BBDs with different infertility treatments and medications.

Total testosterone, sex hormone-binding globulin, and free testosterone concentrations and risk of primary liver cancer: A prospective analysis of 200,000 men and 180,000 postmenopausal women.

In most countries, males have ~2-3 times higher incidence of primary liver cancer than females. Sex hormones have been hypothesized to contribute to these differences, but the evidence remains unclear. Using data from the UK Biobank, which included ~200,000 males and ~180,000 postmenopausal females who provided blood samples at recruitment, we estimated hazard ratios (HR2) and 95% confidence intervals (CI) for a doubling in hormone concentration from multivariable adjusted Cox regression for circulating total testosterone, sex-hormone binding globulin (SHBG), and free testosterone concentrations and risk of primary liver cancer. After a median of 11.8 years of follow-up, 531 cases of primary liver cancer were observed, of which 366 occurred in males and 165 occurred in females. Total testosterone and SHBG were shown to be positively associated with liver cancer risk in both males and females (Total testosterone HR2: 3.42, 95% CI:2.42-4.84 and 1.29, 0.97-1.72, respectively; SHBG HR2: 5.44, 4.42-6.68 and 1.52, 1.09-2.12, respectively). However, free testosterone was inversely associated with primary liver cancer in males (HR2: 0.42, 0.32-0.55) and no association was observed in females. When analyses compared two main liver cancer subtypes, hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), there was evidence of heterogeneity; associations for total testosterone and SHBG concentrations were only positively associated with HCC in both males (HR2: 3.56, 2.65-4.79 and 7.72, 6.12-9.73, respectively) and females (HR2: 1.65, 1.20-2.27 and 6.74, 3.93-11.5, respectively) but not with ICC. Further research understanding the mechanisms of how sex-steroids may influence liver cancer risk is needed.

Dose and time dependent morphodynamic changes in the ovary of nano-nickel treated rats A SEM study.

AIMS: Present study demonstrates dose and time dependent effects of NiONPs (<30 nm) on the ovaries of Wistar rat. METHODS: Female rats were gavaged NiONPs or NiOMPs (5 mg/kg b.w.) for 24 h, 15 days and 30 days, euthanized and ovaries thus removed were analyzed for nickel bioaconcentration and processed for scanning electron microscopy. Serum samples were analyzed to compare the effects of nickel nano & microparticles on progesterone and estradiol values. RESULTS: Results confirmed the bioaccumulation of Ni in ovarian tissue. Its concentration was higher in NiONPs treated rats than NiOMPs treated rats. Progesterone level increased whereas estradiol values decreased in NiONPs and NiOMPs treated rats. SEM results also exhibited dose dependent effects on the morphology of corpoluteal complex. The structural changes varied from formation of blebs to distorted microvilli and germinal epithelium. CONCLUSION: It is hypothesized that NiONPs/NiOMPs are biodegraded into smaller fragments that conjugate with amino acids and or alter downstream signaling pathways, generate ROS and modulate protein structure activity relationships. Finally, these processes manifest into morphological alterations in the ovary. Biopersistence of nickel in female reproductive system may compromise with fertility and reproductive performance of exposed population.

Hormones in Malaria Infection: Influence on Disease Severity, Host Physiology, and Therapeutic Opportunities.

Human malaria, caused by Plasmodium parasites, is a fatal disease that disrupts the host's physiological balance and affects the neuroendocrine system. This review explores how malaria influences and is influenced by hormones. Malaria activates the Hypothalamus-Pituitary-Adrenal axis, leading to increased cortisol, aldosterone, and epinephrine. Cortisol, while reducing inflammation, aids parasite survival, whereas epinephrine helps manage hypoglycemia. The Hypothalamus-Pituitary-Gonad and Hypothalamus-Pituitary-Thyroid axes are also impacted, resulting in lower sex and thyroid hormone levels. Malaria disrupts the renin-angiotensin-aldosterone system (RAAS), causing higher angiotensin-II and aldosterone levels, contributing to edema, hyponatremia and hypertension. Malaria-induced anemia is exacerbated by increased hepcidin, which impairs iron absorption, reducing both iron availability for the parasite and red blood cell formation, despite elevated erythropoietin. Hypoglycemia is common due to decreased glucose production and hyperinsulinemia, although some cases show hyperglycemia due to stress hormones and inflammation. Hypocalcemia, and hypophosphatemia are associated with low Vitamin D3 and parathyroid hormone but high calcitonin. Hormones such as DHEA, melatonin, PTH, Vitamin D3, hepcidin, progesterone, and erythropoietin protects against malaria. Furthermore, synthetic analogs, receptor agonists and antagonists or mimics of hormones like DHEA, melatonin, serotonin, PTH, vitamin D3, estrogen, progesterone, angiotensin, and somatostatin are being explored as potential antimalarial treatments or adjunct therapies. Additionally, hormones like leptin and PCT are being studied as probable markers of malaria infection.

Prevalencia de hipertirotropinemia neonatal comoindicador de deficiencia de yodo en la provincia de La Pampa: un análisis epidemiológico / Prevalence of high neonatal thyroid stimulating hormone levels as an indicator of iodine deficiency in the province of La Pampa: An epidemiological analysis

Introducción. El yodo desempeña un rol fundamental en el metabolismo, el crecimiento y el desarrollo humano. Durante el embarazo y la infancia, la demanda de este micronutriente aumenta considerablemente. La tirotropinemia neonatal (TSHn) aumentada, definida como TSHn ≥5 mUI/l, es un marcador que señala la deficiencia de yodo en una población cuando su prevalencia supera el 3 %. Objetivo. Determinar la prevalencia de TSHn ≥ 5 en La Pampa durante el período 2021-2022, analizar su correlación con diferentes variables y compararla con datos de una cohorte histórica. Población y métodos. Estudio transversal, de diseño descriptivo-analítico, sobre una población de neonatos nacidos en las cinco zonas sanitarias de la provincia de La Pampa durante los años 2021 y 2022. Resultados. De los 5778 neonatos evaluados, el 9,6 % presentó niveles de TSHn ≥5 mUI/l. El 70,4 % de estas mediciones fueron realizadas después del tercer día de vida. No se observaron diferencias significativas en la frecuencia de niveles elevados de TSHn según el año de nacimiento, peso al nacer o días hasta la extracción. Se registró una mayor prevalencia en el sexo masculino (10,6 % versus 8,5 %; p = 0,007) y entre los neonatos nacidos a término (9,8 % versus 6,6 %; p = 0,02). La prevalencia de hipertirotropinemia fue superior a la observada en una cohorte de 2001-2002. Conclusiones. La prevalencia de hipertirotropinemia neonatal en La Pampa durante los años 2021 y 2022 fue del 9,6 %, lo que indica un estado de deficiencia leve de yodo en la provincia, superior al reportado hace dos décadas.

Introduction. Iodine plays a key role in human metabolism, growth, and development. During pregnancy and childhood, the demand for this micronutrient increases notably. Increased neonatal thyroid stimulating hormone (nTSH) levels, defined as nTSH ≥ 5 mIUL, are a marker of iodine deficiency in a population if its prevalence is higher than 3%.Objective. To establish the prevalence of nTSH ≥ 5 in La Pampa in the 2021­2022 period, analyze its correlation with different variables, and compare it with data from a historical cohort.Population and methods. Cross-sectional, descriptive-analytical study in a population of newborn infants born in the 5 health regions of the province of La Pampa in 2021 and 2022. Results. Of  the  5778  assessed  newborn  infants,  9.6%  had  nTSH  levels  ≥  5  mIU/L. It was reported that 70.4% of these measurements were done after the third day of life. No significant differences were observed in the frequency of high nTSH levels by year of birth, birth weight, or days until samplecollection.A higher prevalence was observed among male infants (10.6% versus 8.5%; p = 0.007) and term infants (9.8% versus 6.6%; p = 0.02). The prevalence of high TSH levels was superior to that observed in the 2001­2002 cohort. Conclusions. The  prevalence of high nTSH levels in La Pampa during 2021 and 2022 was 9.6%, suggesting the presence of mild iodine deficiency in the population of this province, higher that what  had been reported 2 decades ago.

The GhEB1C gene mediates resistance of cotton to Verticillium wilt.

MAIN CONCLUSION: The GhEB1C gene of the EB1 protein family functions as microtubule end-binding protein and may be involved in the regulation of microtubule-related pathways to enhance resistance to Verticillium wilt. The expression of GhEB1C is induced by SA, also contributing to Verticillium wilt resistance. Cotton, as a crucial cash and oil crop, faces a significant threat from Verticillium wilt, a soil-borne disease induced by Verticillium dahliae, severely impacting cotton growth and development. Investigating genes associated with resistance to Verticillium wilt is paramount. We identified and performed a phylogenetic analysis on members of the EB1 family associated with Verticillium wilt in this work. GhEB1C was discovered by transcriptome screening and was studied for its function in cotton defense against V. dahliae. The RT-qPCR analysis revealed significant expression of the GhEB1C gene in cotton leaves. Subsequent localization analysis using transient expression demonstrated cytoplasmic localization of GhEB1C. VIGS experiments indicated that silencing of the GhEB1C gene significantly increased susceptibility of cotton to V. dahliae. Comparative RNA-seq analysis showed that GhEB1C silenced plants exhibited altered microtubule-associated protein pathways and flavonogen-associated pathways, suggesting a role for GhEB1C in defense mechanisms. Overexpression of tobacco resulted in enhanced resistance to V. dahliae as compared to wild-type plants. Furthermore, our investigation into the relationship between the GhEB1C gene and plant disease resistance hormones salicylic axid (SA) and jasmonic acid (JA) revealed the involvement of GhEB1C in the regulation of the SA pathway. In conclusion, our findings demonstrate that GhEB1C plays a crucial role in conferring immunity to cotton against Verticillium wilt, providing valuable insights for further research on plant adaptability to pathogen invasion.

Pituitary stalk thickening in pediatric patients: an underrecognized diagnosis?

Objective: Pituitary stalk thickening (PST) is a rare condition in pediatric patients. Data on PST in Latin American pediatric populations are scarce. The aim of this study was to characterize a comprehensive cohort of pediatric patients diagnosed with PST in Chile between 2020 and 2022. Subjects and methods: Retrospective review of medical records from 2020 to 2022 of patients under 18 years old diagnosed with PST, defined as a pituitary stalk width ≥ 3 mm at the pituitary insertion and/or ≥ 4 mm at the optic chiasm. A literature review was also performed to compare the identified cases with previously published ones. Results: Nine patients with PST were identified. Their mean age at diagnosis was 10.36 years (range 2.4-17 years). The patients' main manifestations were polydipsia and polyuria (100%) and poor growth (77.8%). Eight patients had germ cell tumors, while one patient had Langerhans cell histiocytosis. At the time of diagnosis, all patients had arginine vasopressin (AVP) deficiency, along with a deficiency in at least one anterior pituitary hormone. Germ cell tumor markers were negative in all patients. A biopsy-confirmed diagnosis was obtained in all cases. Four patients required a second biopsy. The frequency of PST due to germ cell tumors was four patients/year during the study period, which is twice the expected frequency in Chile. Conclusion: This study, characterizing the largest cohort of pediatric patients with PST in Latin America, found germ cell tumors to be the main etiology of this condition. It is important to focus diagnostic procedures on obtaining a correct diagnosis and promptly initiating appropriate treatment in patients with PST. Regional cooperation is essential for gathering data from larger cohorts to enhance our understanding of pediatric PST and improve patient outcomes.

A young woman with unexpected panhypopituitarism: Case Report.

Nausea and vomiting are common symptoms most frequently caused by gastrointestinal etiologies. Alternatively, panhypopituitarism is a rare condition in which two or more pituitary hormones are deficient. In this case, we describe a 25-year-old type II diabetic woman with severe and persistent nausea and vomiting. She had lost 9 kg of weight since her symptoms began 5 weeks prior. Vital signs were normal, and laboratory studies showed metabolic acidosis thought to be due to fasting ketosis. She underwent an extensive gastrointestinal workup and treatment plan without successful control or abatement of symptoms. Upon further questioning, she was found to have been experiencing secondary amenorrhea and body hair changes. Testing revealed panhypopituitarism with severe adrenocorticotropic hormone and cortisol deficiency. She was started on immediate treatment, and her symptoms resolved in less than 24 h. Imaging showed suspected Rathke's cyst, which has since been removed. Based on similar cases and neuroanatomy, we suspect that her symptoms were due to her severe cortisol deficiency, such that a lack of sympathetic tone leads to increased vagal tone and increased neuronal signals from the brain's emetic center. This conclusion is further supported by the rapidity of resolution of her nausea and vomiting. This case highlights this rare and severe case of panhypopituitarism and also comments on the importance of a thorough history and physical exam, which ultimately lead to the uncovering of an unexpected diagnosis.

Steroidogenic differentiation of human amniotic membrane-derived mesenchymal stem cells into a progesterone-/androgen-producing cell lineage by SF-1 and an estrogen-producing cell lineage by WT1-KTS.

Background: Sex steroid hormones, primarily synthesized by gonadal somatic cells, are pivotal for sexual development and reproduction. Mice studies have shown that two transcription factors, steroidogenic factor 1 (SF-1) and Wilms' tumor 1 (WT1), are involved in gonadal development. However, their role in human gonadal somatic differentiation remains unclear. We therefore aimed to investigate the roles of SF-1 and WT1 in human gonadal steroidogenic cell differentiation. Methods: Using a transient lentivirus-mediated gene expression system, we assessed the effects of SF-1 and WT1 expression on the steroidogenic potential of human amniotic membrane-derived mesenchymal stem cells (hAmMSCs). Results: SF-1 and WT1-KTS, a splice variant of WT1, played distinct roles in human steroidogenic differentiation of hAmMSCs. SF-1 induced hAmMSC differentiation into progesterone- and androgen-producing cell lineages, whereas WT1-KTS promoted hAmMSC differentiation into estrogen-producing cell lineages. Conclusion: Our findings revealed that SF-1 and WT1-KTS play important roles in human gonadal steroidogenic cell differentiation, especially during ovarian development. These findings may pave the way for future studies on human ovarian differentiation and development.

Identification of a 301 bp promoter core region of the SrUGT91D2 gene from Stevia rebaudiana that contributes to hormone and abiotic stress inducibility.

BACKGROUND: The UDP-glucuronosyltransferase 91D2 (SrUGT91D2) gene is a crucial element in the biosynthetic pathway of steviol glycosides (SGs) and is responsible for creating 1,2-ß-D glucosidic bonds at the C19 and C13 positions. This process plays a vital role in the synthesis of rebaudioside M (RM) and rebaudioside D (RD). The promoter, which regulates gene expression, requires functional analysis to understand gene expression regulation. However, investigations into the function of the promoter of SrUGT91D2 (pSrUGT91D2) have not been reported. RESULTS: The pSrUGT91D2 was isolated from six S. rebaudiana lines, and subsequent multiple sequence comparisons revealed the presence of a 26 bp inDel fragment (pSrUGT91D2-B1188 type) in lines GP, GX, 110, 1114, and B1188 but not in the pSrUGT91D2 of line 023 (pSrUGT91D2-023 type). Bioinformatics analysis revealed a prevalence of significant cis-regulatory elements (CREs) within the promoter sequences, including those responsive to abscisic acid, light, anaerobic conditions, auxin, drought, low temperature, and MeJA. To verify the activity of pSrUGT91D2, the full-length promoter and a series of 5' deletion fragments (P1-P7) and a 3' deletion fragment (P8) from various lines were fused with the reporter ß-glucuronidase (GUS) gene to construct the plant expression vector, pCAMBIA1300-pro∷GUS. The transcriptional activity of these genes was examined in tobacco leaves through transient transformation. GUS tissue staining analysis and enzyme activity assays demonstrated that both the full-length promoter and truncated pSrUGT91D2 were capable of initiating GUS expression in tobacco leaves. Interestingly, P8-pSrUGT91D2-B1188 (containing the inDel segment, 301 bp) exhibited enhanced activity in driving GUS gene expression. Transient expression studies of P8-pSrUGT91D2-B1188 and P8-pSrUGT91D2-023 in response to exogenous hormones (abscisic acid and indole-3-acetic acid) and light indicated the necessity of the inDel region for P8 to exhibit transcriptional activity, as it displayed strong responsiveness to abscisic acid (ABA), indole-3-acetic acid (IAA), and light induction. CONCLUSIONS: These findings contribute to a deeper understanding of the regulatory mechanism of the upstream region of the SrUGT91D2 gene and provide a theoretical basis for future studies on the interaction between CREs of pSrUGT91D2 and related transcription factors.

Pumpkin seed oil lessens the colchicine-induced altered sex male hormone balance, testicular oxidative status, sperm abnormalities, and collagen deposition in male rats via Caspase3/Desmin/PCNA modulation.

This study examined the efficiency of pumpkin seed oil (PSO) to rescue the colchicine (CHC)-induced adverse impacts on sperm characteristics, male sex hormones, testicular architecture, oxidative status, DNA content, collagen deposition, and immune expression of desmin and PCNA. Male Sprague Dawley rats were divided into four experimental groups (n = 10 each): control (distilled water), CHC (0.6 mg/kg b.wt), PSO (4 mL/kg b.wt), and CHC + PSO. After 60 days of dosing, CHC significantly reduced sperm motility (19%), sperm concentration (38%), estradiol (52%), testosterone (37%), luteinizing hormone (54%), and follicle-stimulating hormone (29%) compared to the control. Yet, the testicular tissues of CHC-administered rats exhibited elevated abnormal sperms (156%), malondialdehyde (354%), lactate dehydrogenase (73%), Caspase-3 (66%), and 8-hydroxyguanosine (65%) but lower reduced glutathione (74%), catalase (73%), and superoxide dismutase (78%) compared to the control group. Moreover, CHC induced testicular degeneration, distorted seminiferous tubules, apoptotic cells, exfoliated spermatogenic cells, reduced DNA content, decreased PCNA and desmin immune-expression, and increased collagen deposition. PSO effectively reversed the CHC-induced alterations in sperm quality and testicular function and architecture, likely through its antioxidant, antifibrotic, anti-apoptotic, and DNA-protective properties. These results suggest that PSO may be a beneficial intervention for long-term CHC users and may protect against CHC-induced male reproductive toxicity.

White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored. METHODS: Diffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton. RESULTS: Voxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD than the placebo group in several tracts. CONCLUSION: The main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism. CLINICAL TRIAL REGISTRATION: EUDRA-CT 2016-001719-19; "Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study."; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE.

Prevalence and predictors of cancer screening in transgender and gender nonbinary individuals.

Background: Current cancer screening guidelines for transgender individuals are guided primarily by expert opinion, and are extrapolated from guidelines for cisgender populations, despite the additional unique risks that transgender populations face in cancer risk and cancer care. Aims: We examined adherence to current recommended screening guidelines as well as drivers of cancer screening in 192 transgender and gender-nonbinary (TGNB) individuals participating in Project AFFIRM, a multi-site longitudinal cohort study of TGNB individuals. Methods: We used a chi-squared analysis to look for significant associations between predictors and adherence to breast, cervical, prostate and colon cancer screening. We analyzed predictors by 3 different categories: sex/gender identity, healthcare access, and socioeconomic status. Results: Screening rates were low for breast, cervical, prostate and colon cancer in TGNB populations compared to national rates for cisgender populations. Among several significant predictors, gender-affirming surgery (hysterectomy) (p-value = <0.0001) and telling others they are transgender at a younger age (< 18) (p-value = 0.0344) were associated with increased screening adherence, while having HIV was associated with decreased screening adherence (p-value = 0.0045). Discussion: Our results suggest that interacting with the healthcare system to obtain comprehensive cancer screening can be difficult to navigate among the other healthcare needs of TGNB individuals both on an individual and systems level. Future efforts to mitigate the barriers to screening adherence should be targeted at the healthcare system level.

Comprehensive Analysis of the Association Between Sex Hormones and Body Mass Components Among Men Adults: Results From a Large Population-Based Study.

BACKGROUND: As the human body ages, adverse body composition status such as sarcopenia and obesity become obvious phenotypes which can cause numerous health problems. We aimed to comprehensively investigate the association of sex hormones and body mass components in adult men of various age groups. METHODS: We analysed national representative population data from the US National Health and Nutrition Examination Survey. Generalized linear model regression analyses were used to evaluate the association between sex hormones (total testosterone [TT], bio-available testosterone [BT], sex hormone-binding globulin [SHBG], estradiol [E2] and testosterone to estradiol ratio [T/E ratio]) and body mass components (weight, body mass index (BMI), total lean mass, appendicular lean mass, bone mineral content, total fat and trunk fat). The collection and testing time of blood samples were not fixed and there was no strict fasting, but in subsequent analysis we used statistical methods to minimize the impact of random testing. RESULTS: After screening for inclusion and exclusion, 3759 male participants aged 20-85 years old were included in this study. Higher levels of TT, SHBG, BT and T/E ratios were significantly associated with higher total lean mass, appendicular lean mass and bone mineral content, while lower weight, BMI, total fat and trunk fat. For E2 levels in men, we found an opposite trend, with higher E2 levels significantly associated with lower total lean mass and appendicular lean mass, and higher weight, BMI, total fat and trunk fat. Notably, in subgroup analysis, the results showed that there were significant interaction effects of age and smoking history in the association between sex hormones and body mass components. CONCLUSION: Higher TT levels, BT levels, SHBG levels and T/E ratios are associated with lower body weight and improved body composition in young adult men (characterized by higher lean body mass, higher bone density and lower fat mass). The relationship is especially pronounced among relatively young, nonsmoking men.

Effect of Time-Restricted Eating on Circulating Levels of IGF1 and Its Binding Proteins in Obesity: An Exploratory Analysis of a Randomized Controlled Trial.

Obesity is associated with alterations in circulating IGF1, IGF1-binding proteins (IGFBPs), insulin, inflammatory markers, and hormones implicated in cardiovascular disease, diabetes, cancer, and aging. However, the effects of 4 and 6 h time-restricted eating (TRE) on circulating IGF1 and IGFBPs is uncertain. OBJECTIVE: This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes. Insulin sensitivity, glucose control, adipokines, and inflammatory markers were also examined. DESIGN: An exploratory analysis of an 8-week randomized controlled trial implementing a daily TRE intervention was carried out. PARTICIPANTS/SETTING: This study was conducted at the University of Illinois at Chicago in 2019. Participants with obesity were randomized to 4 or 6 h TRE (n = 35) or a control (n = 14) group. Plasma biomarkers were measured by ELISA at baseline and week 8. In a sub-analysis, participants were stratified into higher- (>3.5%) and lower- (≤3.5%) weight-loss groups. INTERVENTION: Participants fasted daily from 7 p.m. to 3 p.m. in the 4 h TRE group (20 h) and from 7 p.m. to 1 p.m. in the 6 h TRE group (18 h), followed by ad libitum eating for the remainder of the day. Controls received no dietary recommendations. MAIN OUTCOME MEASURES: IGF1, IGFBPs, hsCRP, and adipokines were the main outcome measures of this analysis. STATISTICAL ANALYSIS: Repeated measures ANOVA and mediation analysis were conducted. RESULTS: Body weight significantly decreased with TRE (-3.6 ± 0.3%), contrasting with controls (+0.2 ± 0.5%, p < 0.001). Significant effects of TRE over time were observed on plasma IGFBP2, insulin, HOMA-IR, and 8-isoprostane levels, without affecting other biomarkers. In the sub-analysis, IGFBP2 increased while leptin and 8-isoprostane decreased significantly only in the "higher weight loss" subgroup. Changes in insulin and HOMA-IR were related to TRE adherence. CONCLUSIONS: Eight-week daily 4 to 6 h TRE did not affect IGF1, IGFBP1, or IGFBP3 levels but improved insulin, HOMA-IR, and 8-isoprostane. IGFBP2 increased and leptin decreased when weight loss exceeded 3.5% of baseline.

Proteins and Peptides from Food Sources with Effect on Satiety and Their Role as Anti-Obesity Agents: A Narrative Review.

BACKGROUND/OBJECTIVE: Obesity, clinically defined as a body mass index (BMI) of 30 kg/m2 or higher, is a medical condition characterized by the excessive accumulation of body fat, which can lead to adverse health consequences. As a global public health issue with an escalating prevalence, controlling appetite and satiety is essential for regulating energy balance and managing body weight. Dietary proteins and peptides have gained interest in their potential to prevent and treat obesity by modulating satiety signals. This narrative review analyzes scientific evidence highlighting the role of dietary proteins and peptides in regulating satiety signals and investigates their therapeutic potential in preventing and treating obesity. METHODS: A comprehensive literature search was conducted in multiple electronic databases, including PubMed, Scopus, and Web of Science. The search focused on articles examining the impact of dietary proteins and peptides on satiety and obesity, encompassing both preclinical and clinical trials. RESULTS: Several studies have demonstrated a correlation between the intake of specific proteins or peptides from plant and animal sources and satiety regulation. These investigations identified mechanisms where amino acids and peptides interact with enteroendocrine cell receptors, activating intracellular signaling cascades that promote the release of anorexigenic gut hormones such as cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). Both in vitro and in vivo assays have shown that these interactions contribute to appetite regulation and the sensation of satiety. CONCLUSIONS: Using proteins and peptides in the diet may be an effective strategy for regulating appetite and controlling body weight. However, more research-including clinical trials-is needed to understand the underlying mechanisms better and optimize the application of these bioactive compounds in preventing and treating obesity.

Role of Gonadal Steroid Hormones in the Eye: Therapeutic Implications.

Gonadal steroid hormones are critical regulatory substances involved in various developmental and physiological processes from fetal development through adulthood. These hormones, derived from cholesterol, are synthesized primarily by the gonads, adrenal cortex, and placenta. The synthesis of these hormones involves a series of enzymatic steps starting in the mitochondria and includes enzymes such as cytochrome P450 and aromatase. Beyond their genomic actions, which involve altering gene transcription over hours, gonadal steroids also exhibit rapid, nongenomic effects through receptors located on the cell membrane. Additionally, recent research has highlighted the role of these hormones in the central nervous system (CNS). However, the interactions between gonadal steroid hormones and the retina have received limited attention, though it has been suggested that they may play a protective role in retinal diseases. This review explores the synthesis of gonadal hormones, their mechanisms of action, and their potential implications in various retinal and optic nerve diseases, such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), or retinitis pigmentosa (RP), discussing both protective and risk factors associated with hormone levels and their therapeutic potential.

Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study.

The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies on sex hormones and from the Trøndelag Health Study (HUNT) and large consortia on cancers. There was suggestive evidence of 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio 0.60, 95% confidence interval 0.37-0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry.