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 long-term prognostic implications of free triiodothyronine to free thyroxine ratio in patients with obstructive sleep apnea and acute coronary syndrome.

Objective: Obstructive sleep apnea (OSA) and thyroid dysfunction frequently overlap clinically and are risk factors for cardiovascular disease. The free triiodothyronine to free thyroxine (FT3/FT4) ratio as a novel biomarker of cardiovascular disease prognosis, but the impact of the FT3/FT4 ratio on the prognosis of OSA in patients with acute coronary syndromes (ACS) remains uncertain. Methods: In this prospective cohort study, 2160 patients with ACS were recruited and underwent portable sleep monitoring at Beijing Anzhen Hospital from June 2015 to January 2020. OSA was diagnosed when apnea-hypopnea index of ≥15 events/h. Patients were further divided into tertiles according to FT3/FT4 ratio. All patients had scheduled follow-up visits at 1, 3, 6, 9 and 12 months after discharge, with subsequent outpatient visits or telephone follow-up visits every 6 months. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction (MI), stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Results: Among 1,547 euthyroid patients enrolled (mean age, 56.0 ± 10.5 years), 812 patients (52.5%) had OSA. The FT3/FT4 ratio between OSA and non-OSA patients was not significantly different. During 2.8 (1.4, 3.5) years follow up, the risk of MACCE increased with the decreasing FT3/FT4 tertiles in patients with OSA (tertile3 as reference, tertile2: hazard ratio (HR) 1.26, 95% CI: 0.85-1.86, P = 0.255; tertile1: 1.60, 95% CI 1.11-2.32; P = 0.013). After adjustment for confounders, the lowest FT3/FT4 tertile was still independently associated with an increased risk of MACCE (adjusted HR 1.66, 95% CI 1.11-2.50, P = 0.015). Conclusion: Lower FT3/FT4 ratio associated with poor prognosis in patients with ACS and OSA.

Hormonal influence on maize inflorescence development and reproduction.

KEY MESSAGE: Different plant hormones contribute to maize reproductive success. Maize is a major crop species and significantly contributes directly and indirectly to human calorie uptake. Its success can be mainly attributed to its unisexual inflorescences, the tassel and the ear, whose formation is regulated by complex genetic and hormonal networks, and is influenced by environmental cues such as temperature, and nutrient and water availability. Traditional genetic analysis of classic developmental mutants, together with new molecular approaches, have shed light on many crucial aspects of maize reproductive development including the influence that phytohormones exert on key developmental steps leading to successful reproduction and seed yield. Here we will review both historical and recent findings concerning the main roles that phytohormones play in maize reproductive development, from the commitment to reproductive development to sexual reproduction.

Biocompatibility, antimicrobial efficacy, and therapeutic potential of cobalt carbonate nanoparticles in wound healing, sex hormones, and metabolic regulation in diabetic albino mice.

Nanotechnology enables the manipulation of materials at the nanoscale, offering innovative solutions in various fields. Nanoparticles, with their small size and unique properties, have significant applications in the biomedical filed. The current study was designed to assess the biological applications of self-synthesized cobalt carbonate (CoCO3) nanoparticles. The crystalline structure and chemical composition of the CoCO3-NPs were confirmed by SEM, XRD, and FTIR techniques. We observed the 16.58 nm size of novelly synthesized CoCO3 NPS. The scanning electron microscope study confirmed a uniform cubic spinel structure. The biocompatibility and antimicrobial activity were checked in an invitro setup. We exposed albino mice to these synthesized NPs to study wound healing and metabolic effects. The results of biocompatibility analysis indicated hemolytic activity in a dose-dependent way, which showed no cytotoxic effect except at a higher concentration. Furthermore, the results showed enhanced wound healing processes in CoCO3-NP-treated albino mice as compared to the control group. CoCO3-NPs have considerable effect on the thyroid hormone and insulin levels in albino mice. The levels of T3, T4, and insulin were increased in a dose-dependent manner. Interactions between CoCO3-NPs and thyroxine and insulin were confirmed through molecular docking. We confirmed the antimicrobial efficiency of the nanoparticles using MIC values and zones of inhibition against Staphylococcus haemolyticus and Staphylococcus aureus. Despite their concentration-dependent biocompatibility concerns, the results are promising, as CoCO3-NPs hold potential for use in medical practice, particularly in advanced wound management and microbe inhibition.

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.

Pectin methylesterase activity is required for RALF1 peptide signalling output.

The extracellular matrix plays an integrative role in cellular responses in plants, but its contribution to the signalling of extracellular ligands largely remains to be explored. Rapid alkalinisation factors (RALFs) are extracellular peptide hormones that play pivotal roles in various physiological processes. Here, we address a crucial connection between the de-methylesterification machinery of the cell wall component pectin and RALF1 activity. Pectin is a polysaccharide, contributing to the structural integrity of the cell wall. Our data illustrate that the pharmacological and genetic interference with pectin methyl esterases (PMEs) abolishes RALF1-induced root growth repression. Our data suggest that positively charged RALF1 peptides bind negatively charged, de-methylesterified pectin with high avidity. We illustrate that the RALF1 association with de-methylesterified pectin is required for its FERONIA-dependent perception, contributing to the control of the extracellular matrix and the regulation of plasma membrane dynamics. Notably, this mode of action is independent of the FER-dependent extracellular matrix sensing mechanism provided by FER interaction with the leucine-rich repeat extensin (LRX) proteins. We propose that the methylation status of pectin acts as a contextualizing signalling scaffold for RALF peptides, linking extracellular matrix dynamics to peptide hormone-mediated responses.

Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.

Thyroid hormone dysfunction is frequently observed in patients with chronic illnesses including heart failure which increases risk of adverse events. This study examined effects of thyroid hormones (TH) on cardiac T-tubule (TT) integrity, Ca2+ sparks, and nanoscale organization of ion channels in excitation-contraction (EC)-coupling, including L-type calcium channel (Cav1.2), ryanodine receptor-type 2 (RyR2), and junctophilin-2 (Jph2). TH deficiency was established in adult female rats by propyl-thiouracil (PTU) ingestion for 8 weeks; followed by randomization to continued PTU without or with oral triiodo-L-thyronine (T3; 10 ug/kg/d) for two additional weeks (PTU+T3). Confocal microscopy of isolated cardiomyocytes (CM) showed significant misalignment of TTs, and increased Ca2+ sparks in thyroid-deficient CMs. Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis of STochastic Optical Reconstruction Microscopy (STORM) images showed decreased (p<0.0001) RyR2 cluster number per cell area in PTU CMs compared to euthyroid (EU) control myocytes, and this was normalized by T3-treatment. Cav1.2 channels and Jph2 localized within 210 nm radius of the RyR2 clusters were significantly reduced in PTU myocytes, and these values were increased with T3 treatment. A significant percentage of the RyR2 clusters in the PTU myocytes had neither Cav1.2 or Jph2, suggesting fewer functional clusters in EC-coupling. Nearest neighbor distances between RyR2 clusters were greater (p<0.001) in PTU cells compared to EU and T3-treated CMs that corresponds to disarray of TTs at the sarcomere z-discs. These results support a regulatory role of T3 in the nanoscale organization of RyR2 clusters and co-localization of Cav1.2 and Jph2 in optimizing EC-coupling.

Characterizing Vascular and Hormonal Changes in Women Across the Lifespan: A Cross-Sectional Analysis.

INTRODUCTION: Vascular dysfunction, marked by lower endothelial function and increased aortic stiffness, are non-traditional risk factors that precede the development of CVD. However, the age at which these changes in vascular function occur in women and the degree to which reproductive hormones mediate these changes has not been characterized. METHODS: Women free from major disease were enrolled across the adult lifespan (aged 18-70, n=140). Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery during reactive hyperemia using duplex ultrasound and expressed as percent dilation. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Blood samples were obtained to quantify reproductive hormone concentration. Regression models determined age-related breakpoints and mediating factors between age and vascular outcomes. RESULTS: FMD declined with age with a breakpoint and steeper decline occurring at age 47. Thereafter, age was independently associated with lower FMD (B=-0.13, P<0.001). cfPWV was relatively stable until a breakpoint at age 48, and age was independently associated with higher cfPWV thereafter (B=0.10, P<0.001). Path analysis revealed that the association between age and FMD was partially mediated by follicle stimulating hormone (abind=0.051, P=0.01) and progesterone (abind=0.513, P<0.001) but not estradiol (abind=-0.004, P=0.08). No mediation was present for cfPWV. CONCLUSIONS: Age was associated with endothelial dysfunction and aortic stiffness in women beginning at 47 and 48 years, respectively, 3-4 years prior to the average age of menopause. The association between age and endothelial dysfunction was explained in part by elevations in follicle stimulating hormone and progesterone, but not declining estradiol.

Influence of sire plane of nutrition and targeted body weight gain on ewe lamb growth, glucose metabolism, and ovarian reserve.

Rambouillet rams were managed on either a positive (POS; gain 12% body weight [BW]; n = 8), maintenance (MAINT; maintain BW; n = 8), or negative (NEG; lose 12% BW; n = 8) plane of nutrition before breeding. Rams were bred to ewes (n = 10 per ram) that were managed similarly throughout gestation, and lambs were fed a common diet postnatally. Two ewe lambs (7.6 ± 0.02 months of age, BW = 47.1 ± 1.17 kg) from each sire were selected and within pair, randomly assigned to be managed for a moderate (MOD, 0.11 kg/d; n = 23) or accelerated (ACC, 0.20 kg/d; n = 22) rate of gain for 56 d. Ewe lamb BW was recorded on a weekly basis and blood was collected on d 0, 28, and 56 for analysis of insulin-like growth factor 1 (IGF-1), triiodothyronine (T3), thyroxine (T4), glucose, blood urea nitrogen (BUN), and non-esterified fatty acids (NEFA). Intravenous glucose tolerance tests (IVGTT) were conducted from d -7 to -4 and d 57 to 64. A unilateral ovariectomy was performed and ovarian follicles were staged and counted macro and microscopically. Sire treatment × day and ewe treatment × day interactions were present for BW (P ≤ 0.05), where POS had slower growth than MAINT and NEG, and tended (P = 0.10) to have reduced average daily gain (ADG) when managed at an accelerated rate of gain.By design, ACC had greater BW and ADG than MOD (P < 0.05). Concentrations of IGF-1 and T4 were greater in ACC than MOD (P ≤ 0.05), and NEG tended to have greater concentrations of IGF-1 than POS and MAINT (P = 0.08). At the first IVGTT, concentration of insulin was influenced by a sire treatment × time interaction (P ≤ 0.05), suggesting impaired secretion in NEG-sires ewes, but no differences in area under the curve (AUC) for glucose, insulin, or their ratio (P ≥ 0.11). No interactive effects of sire and ewe treatment (P ≥ 0.52) were observed at the second IVGTT, but insulin and insulin:glucose ratio were influenced by sire treatment × time (P ≤ 0.02), as NEG had greater insulin concentration at 60 min than MAINT (P = 0.03) and greater AUC than POS and MAINT (P ≤ 0.04). No differences in ovary size, weight, or total counts of macro and microscopic follicles were observed (P ≥ 0.23). Ewes fed ACC had a greater number of small surface follicles (P = 0.02), whereas MOD tended to have a greater number of large surface follicles and tertiary follicles (P < 0.06). These findings suggest that paternal plane of nutrition influences female offspring physiology, particularly at varying growth rates.

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.

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.

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.

The impact of hormones on lung development and function: an overlooked aspect to consider from early childhood.

The impact of hormones on the respiratory system constitutes a multifaceted and intricate facet of human biology. We propose a comprehensive review of recent advancements in understanding the interactions between hormones and pulmonary development and function, focusing on pediatric populations. We explore how hormones can influence ventilation, perfusion, and pulmonary function, from regulating airway muscle tone to modulating the inflammatory response. Hormones play an important role in the growth and development of lung tissues, influencing them from early stages through infancy, childhood, adolescence, and into adulthood. Glucocorticoids, thyroid hormones, insulin, ghrelin, leptin, glucagon-like peptide 1 (GLP-1), retinoids, cholecalciferol sex steroids, hormones derived from adipose tissue, factors like insulin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and glucagon are key players in modulating respiratory mechanics and inflammation. While ample evidence underscores the impact of hormones on lung development and function, along with sex-related differences in the prevalence of respiratory disorders, further research is needed to clarify their specific roles in these conditions. Further research into the mechanisms underlying hormonal effects is essential for the development of customizing therapeutic approaches for respiratory diseases. Understanding the impact of hormones on lung function could be valuable for developing personalized monitoring approaches in both medical and surgical pediatric settings, in order to improve outcomes and the quality of care for pediatric patients.

Prevalence of hypogonadism in men with and without chronic obstructive pulmonary disease: A cross-sectional study.

BACKGROUND: Hypogonadism is a common finding of chronic obstructive pulmonary disease (COPD). However, the prevalence of hypogonadism in COPD varies among studies. The aim of this study was to determine and compare the prevalence of hypogonadism in men with and without COPD. METHODS: We conducted a cross-sectional study with 134 patients with stable COPD and 70 age-matched men with non-COPD. Hypogonadism was defined by the presence of symptoms according to the Androgen Deficiency in Aging Males questionnaire, along with total testosterone deficiency (<300ng/dL). RESULTS: Patients had a mean age of 68 years (SD, 6), a body mass index of 28kg/m2 (SD, 6), and 17% were current smokers. The prevalence of hypogonadism was 41.8% in COPD men (N=56, 95%CI, 33-51) and 10.0% in non-COPD men (N=7, 95%CI, 4-20), with a prevalence ratio of 4.2 (95%CI, 2.0-8.7, p<0.001). The prevalence of low total testosterone concentrations (<300ng/dL) were significantly higher in COPD patients vs the control group (47.0% vs 15.7%, p=<0.001). In the COPD group, 89.3% of patients had hypogonadotropic hypogonadism and 10.7%, hypergonadotropic hypogonadism. The prevalence of hypogonadism was higher in severe vs non-severe COPD patients (55.8% vs 35.2%; p=0.024). CONCLUSIONS: The prevalence of hypogonadism was high and greater in COPD vs non-COPD men. This study suggests that COPD patients should be screened for hypogonadism.

Unique cardiometabolic factors in women that contribute to modified cardiovascular disease risk.

Major risk factors of cardiovascular disease (CVD) include hypertension, obesity, diabetes mellitus and metabolic syndrome; all of which are considered inflammatory conditions. Women are disproportionately affected by inflammatory conditions, with sex differences emerging as early as adolescence. Hormonal fluctuations associated with reproductive events such as menarche, pregnancy and menopause, are hypothesized to promote a pro-inflammatory state in women. Moreover, women who have experienced inflammatory-type conditions such as polycystic ovarian syndrome (PCOS), gestational diabetes or pre-eclampsia, have a cardiometabolic phenotype that pre-disposes to increased risk of myocardial infarction, stroke and coronary heart disease. Women with no notable CVD risk factors are often relatively protected from CVD pre-menopause; but overtake men in risk of major cardiovascular events when the cardiovascular protective effects of oestrogen begin to wane. Sex differences and female-specific factors have long been considered challenging to study and this has led to an underrepresentation of females in clinical trials and lack of female-specific data from pre-clinical studies. However, there is now a clear prerogative to include females at all stages of research, despite inherent complexities and potential variability in data. This review explores recent advancements in our understanding of CVD in women. We summarise the underlying factors unique to women that can promote CVD risk factors, ultimately contributing to CVD burden and the emerging therapies aimed to combat this.

Experimentally Elevated Levels of Testosterone Advance Daily Onset of Activity in Short-Day Housed Male House Sparrows (Passer domesticus).

Seasonal changes in sleep/wake cycles and behaviors related to reproduction often co-occur with seasonal fluctuations in sex hormones. Experimental studies have established that fluctuations in circulating testosterone mediate circadian rhythms. However, most studies are performed under constant lighting conditions and fail to investigate the effects of testosterone on the phenotypic output of circadian rhythms, that is, chronotype (daily activity patterns under light:dark cycles). Here, we experimentally elevated testosterone with implants during short nonbreeding daylengths in male house sparrows (Passer domesticus) to test if observed seasonal changes in chronotype are directly in response to photoperiod or to testosterone. We fitted individuals with accelerometers to track activity across treatment periods. Birds experienced three treatments periods: short day photoperiods before manipulation (SD), followed by testosterone implants while still on short days (SD + T). Implants were then removed. After a decrease in cloacal protuberance size, an indicator of low testosterone levels, birds were then photostimulated on long days (LD). Blood samples were collected at night, when testosterone peaks, to compare testosterone levels to daily onset/offset activity for experimental periods. Our results indicate that experimentally elevated testosterone under short nonbreeding photoperiods significantly advanced daily onset of activity and total daily activity relative to daylength. This suggests that testosterone, independent of photoperiod, is responsible for seasonal shifts in chronotypes and daily activity rhythms. These findings suggest that sex steroid hormone actions regulate timing of daily behaviors, likely coordinating expression of reproductive behaviors to appropriate times of the day.

Erratum: Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy.

[This corrects the article DOI: 10.3389/fimmu.2022.930947.].

Humulus lupulus L.: Evaluation of Phytochemical Profile and Activation of Bitter Taste Receptors to Regulate Appetite and Satiety in Intestinal Secretin Tumor Cell Line (STC-1 Cells).

SCOPE: Inflorescences of the female hop plant (Humulus lupulus L.) contain biologically active compounds, most of which have a bitter taste. Given the rising global obesity rates, there is much increasing interest in bitter taste receptors (TAS2Rs). Intestinal TAS2Rs can have beneficial effects on obesity when activated by bitter agonists. This study aims to investigate the mechanism of action of a hydroalcoholic hop extract in promoting hormone secretion that reduces the sense of hunger at the intestinal level through the interaction with TAS2Rs. METHODS AND RESULTS: The results demonstrate that the hop extract is a rich source of bitter compounds (mainly α-, ß-acids) that stimulate the secretion of anorexigenic peptides (glucagon-like peptide 1 [GLP-1], cholecystokinin [CCK]) in a calcium-dependent manner while reducing levels of hunger-related hormones like ghrelin. This effect is mediated through interaction with TAS2Rs, particularly Tas2r138 and Tas2r120, and through the activation of downstream signaling cascades. Knockdown of these receptors using siRNA transfection and inhibition of Trpm5, Plcß-2, and other calcium channels significantly reduces the hop-induced calcium response as well as GLP-1 and CCK secretion. CONCLUSIONS: This study provides a potential application of H. lupulus extract for the formulation of food supplements with satiating activity capable of preventing or combating obesity.

Genome-wide association study of maternal plasma metabolites during pregnancy.

Metabolites are key indicators of health and therapeutic targets, but their genetic underpinnings during pregnancy-a critical period for human reproduction-are largely unexplored. Using genetic data from non-invasive prenatal testing, we performed a genome-wide association study on 84 metabolites, including 37 amino acids, 24 elements, 13 hormones, and 10 vitamins, involving 34,394 pregnant Chinese women, with sample sizes ranging from 6,394 to 13,392 for specific metabolites. We identified 53 metabolite-gene associations, 23 of which are novel. Significant differences in genetic effects between pregnant and non-pregnant women were observed for 16.7%-100% of these associations, indicating gene-environment interactions. Additionally, 50.94% of genetic associations exhibited pleiotropy among metabolites and between six metabolites and eight pregnancy phenotypes. Mendelian randomization revealed potential causal relationships between seven maternal metabolites and 15 human traits and diseases. These findings provide new insights into the genetic basis of maternal plasma metabolites during pregnancy.