Search Results (290)

Background: Polycystic ovary syndrome (PCOS) is a frequently encountered endocrine disturbance with a still poorly defined etiology that arises in women during their reproductive years. Increased apoptosis of granulosa cells has been identified as one of the key factors contributing to abnormal follicular development. This study aimed to elucidate the role of six-transmembrane epithelial antigen of prostate 4 (STEAP4) in granulosa cell function using in vitro and in vivo models relevant to PCOS. Methods: We treated KGN cells (a human granulosa-like cell line) and C57BL/6 mice with dehydroepiandrosterone (DHEA) to establish experimental models mimicking PCOS features. STEAP4 expression was assessed by qRT–PCR, Western blot, and immunohistochemistry. Proliferative capacity and apoptotic rates were gauged with CCK-8 assays, EdU labeling, and flow cytometry. The regulatory mechanisms were investigated through immunofluorescence staining for nuclear factor erythroid–2–related factor 2 (Nrf2) nuclear translocation and immunoprecipitation assays for HIF-1α ubiquitination. Results: Exposure to androgen markedly raised both STEAP4 transcript and protein abundance in KGN cells as well as in PCOS model mice. STEAP4 knockdown resulted in increased proliferation and reduced apoptosis in DHEA–treated KGN cells. Mechanistically, STEAP4 enhanced reactive oxygen species levels, promoted Nrf2 nuclear translocation, and stabilized HIF–1α protein by reducing its ubiquitination, leading to increased TERT expression and subsequent TP53 pathway activation. In vivo, STEAP4 silencing significantly alleviated hormonal imbalances, estrous cycle disorders, and reduced oxidative stress levels in ovarian tissue of DHEA-induced PCOS–like mice. Conclusions: Taken together, evidence from these experimental models indicates that STEAP4 shapes oxidative stress and granulosa cell apoptosis by operating through the ROS–TERT–TP53 axis. The data point to a possible contribution of STEAP4 to PCOS pathogenesis and mark it as a candidate therapeutic target that merits additional clinical study. Full article

(1) Background: Ovulatory dysfunction (OD) is frequently the first clinical expression of an underlying polyendocrine or metabolic disturbance. In the context of the international consensus renaming polycystic ovary syndrome (PCOS) as polyendocrine metabolic ovarian syndrome (PMOS), our primary aim was to estimate the prevalence of four OD-associated endocrinopathies—hyperandrogenemia, insulin resistance (IR), thyroid dysfunction, and hyperprolactinemia—in a Chilean symptomatic clinical cohort, and to compare their frequencies between adolescents and young adults. (2) Methods: Cross-sectional study including 251 women (≥2 years post-menarche) with confirmed OD, stratified into Group A (12–18 years; n = 96) and Group B (19–35 years; n = 155). (3) Results: Hyperandrogenemia was the most prevalent endocrinopathy in both groups (50.0% vs. 49.0%; p = 0.882), driven primarily by elevated dehydroepiandrosterone sulfate (DHEAS) in Group A (37.5% vs. 24.5%; p = 0.028). IR was significantly more frequent in adolescents (55.2% vs. 41.3%; p = 0.032). Thyroid dysfunction (primary threshold: thyroid-stimulating hormone [TSH] > 5.0 μIU/mL) was present in 2.1% and 5.2% of Groups A and B (p = 0.226). Hyperprolactinemia (>25 ng/mL; macroprolactin-excluded) was detected in 13.5% and 13.6% (p = 0.999). (4) Conclusions: All four endocrinopathies were detectable during adolescence, with prevalences largely comparable to those observed in young adult women, supporting the rationale for considering structured polyendocrine evaluation in women with OD ≥ 2 years post-menarche within the PAInT (Prolactin, Androgens, Insulin, and Thyroid hormones) framework. Full article

This study validated immunoassays for measuring circulating DHEA and DHEA-S in broiler plasma and compared the two biomarkers. A commercially available RIA kit for DHEA and a species-independent ELISA kit for DHEA-S were tested against each other and available literature data. Blood samples were collected from 68 female broilers at slaughter. Most sample concentrations were close to the lower calibration range. DHEA concentrations ranged from 52 to 354 pg/mL, whereas DHEA-S values ranged from 76 to 7320 pg/mL. Both assays showed satisfactory validation results, including good precision (intra- and inter-assay CV ≤ 15%), accuracy (recovery ≥ 99%), linearity (R² > 0.9; run test p > 0.1), and parallelism between calibrator curves and sample dilutions (ANCOVA p > 0.1). However, the DHEA-S assay showed high cross-reactivity with DHEA (160%), making quantitative DHEA-S determination unreliable; therefore, values should be interpreted as an estimate of combined DHEA/DHEA-S concentrations. Consequently, the higher concentrations measured with the DHEA-S ELISA compared with the DHEA RIA (Bland–Altman bias: −525.8 pg/mL) do not indicate a true predominance of DHEA-S. Nevertheless, both assays may represent useful tools for comparative evaluations among samples, although they do not provide reliable information on the physiological interconversion between the two steroids. Full article

Background/Objectives: Weight loss achieved through lifestyle interventions has been demonstrated to improve the clinical prognosis of female hyperandrogenism. However, the interplay between such interventions, androgens, and glucose–lipid metabolism remains heterogeneous. This study evaluated the effects of lifestyle-induced weight loss on glucose and lipid metabolism and androgen levels in Chinese women of reproductive age with hyperandrogenism and examined the association between the degree of weight loss and changes in androgen levels, glucose and lipid metabolism, exercise capacity, and dietary patterns. Methods: This observational study, based on real-world clinical settings, collected medical records of women of reproductive age with hyperandrogenism who underwent weight-loss interventions between July 2023 and September 2025. Correlation analysis employed Spearman’s rank correlation coefficient, whilst pre- and post-weight-loss comparisons utilised paired t-tests or Wilcoxon signed-rank tests. Results: After a follow-up of 6 to 7 months, a total of 66 participants achieved a mean weight loss of 5.67 ± 4.27 kg. Statistically significant reductions were observed in testosterone (0.40 ± 0.10 vs. 0.30 ± 0.10 ng/mL, p < 0.001), androstenedione (p < 0.001), and the free androgen index (p < 0.001). Glucose metabolism showed statistically significant improvement, with decreases in HOMA-IR (p = 0.040), fasting glucose (p = 0.001), and fasting/2 h postprandial insulin (p < 0.001). However, lipid profiles showed no statistically significant changes. Multiple linear regression revealed that change in testosterone was independently and inversely associated with change in apolipoprotein A1 (β = −0.496, p = 0.008), while change in dehydroepiandrosterone sulfate was inversely associated with change in fasting insulin (β = −0.357, p = 0.032). A non-linear, inverted U-shaped relationship was found between weight loss magnitude and change in sex hormone-binding globulin, with moderate weight loss (5–10%) yielding the greatest increase (p = 0.044). Marked weight loss (≥10%) was associated with the lowest follow-up fasting insulin levels (p = 0.039). Conclusions: Weight loss achieved through lifestyle interventions is associated with improvements in androgen levels and glucose metabolism, though its impact on lipid metabolism remains limited. The degree of improvement in insulin sensitivity correlates more strongly with the magnitude of weight reduction. Full article

All-trans retinoic acid (atRA) is known to regulate lipid metabolism, adipocyte differentiation, and the immune system in mammals and other aquatic species. However, studies on atRA in crustaceans, especially in Eriocheir sinensis, are still scarce. The present study aimed to investigate the regulatory effects of dietary or injected atRA on female crabs during the fattening period. In the dietary regulation experiment, 270 female crabs were fed diets containing different doses of atRA (0, 150, 300, 600, 1200, and 2400 mg/kg) for a total of 49 days. In the in vivo injection experiment, 90 females were divided into an experimental group (injected with a 0.3 μg/g dose of atRA) and a control group (injected with the same amount of DMSO solvent). Injections were given weekly throughout the 35-day experimental period. Results: Both dietary atRA and atRA injection promoted ovarian development, as evidenced by increased GSI, elevated serum Vg levels, decreased GIH, and upregulated expression of vg, vgr, and rxr genes. In terms of mechanism, dietary atRA promoted ovarian development via the upregulation of pyrimidine nucleotides and dehydroepiandrosterone, which supplied nucleic acid precursors and hormonal support. Furthermore, RXR was identified as a potential key target of atRA in inducing ovarian development, as molecular docking revealed that atRA could spontaneously bind to RXR. Moreover, following atRA injection, the expression of rxr, along with key genes involved in ovarian development, lipid synthesis, and lipid transport, was significantly upregulated. In addition, the atRA diet created a favorable microenvironment for ovarian development by reducing pro-inflammatory lipid levels in the ovary. Transcriptomic and metabolomic analyses revealed that atRA modulates energy and lipid metabolism by activating the AMPK pathway. In terms of the bacterial community structure, the atRA diet significantly decreased Fusobacterium abundance and enriched Parabacteroides as the signature beneficial bacterium. In terms of nutritional quality, the atRA diet markedly reduced saturated and trans-fatty acids while increasing monounsaturated fatty acids and various key essential amino acids. Conclusions: This study revealed that atRA plays a key role in promoting ovarian development, improving nutritional quality, and modulating the structure of the microbiota, thereby providing theoretical support for healthy aquaculture of female crabs during the fattening period. Full article

Objective: This study aims to investigate the role of thrombospondin-1 (THBS1) in polycystic ovary syndrome (PCOS) pathogenesis and its mechanism in regulating granulosa cell (GC) function. Methods: Follicular fluid and granulosa cells from 21 PCOS patients and 21 age-matched non-PCOS controls were analysed for THBS1 expression and clinical correlations. A dehydroepiandrosterone (DHEA)-induced PCOS rat model with adeno-associated virus serotype 9 (AAV9)-mediated THBS1 knockdown was used to assess phenotypic changes. The KGN human granulosa-like cell line was employed to evaluate THBS1 overexpression effects on proliferation, apoptosis, and steroidogenesis. Mechanistic studies included RNA sequencing with Gene Set Enrichment Analysis (GSEA), co-immunoprecipitation, molecular docking against the latent TGF-β1 crystal structure (PDB 9VJJ), molecular dynamics simulation, an active/total TGF-β1 ELISA, and pharmacological TGF-β receptor inhibition. Results: THBS1 was elevated in PCOS follicular fluid and granulosa cells and correlated positively with serum AMH and LH after Benjamini–Hochberg FDR correction. AAV9-mediated ovarian THBS1 knockdown (37.4% protein reduction, p = 0.006) ameliorated cystic morphology, restored estrous cyclicity, and normalised serum AMH/LH/T. In KGN cells, THBS1 overexpression suppressed proliferation, induced apoptosis and inflammatory cytokines, and dysregulated steroidogenic enzymes. Transcriptome analysis revealed upregulation of canonical TGF-β/Smad pathway components (SERPINE1, SMAD7, TGFB2, INHBA, CCN2, COL1A1/2). Molecular docking and 100-ns dynamics simulation supported a stable interaction between THBS1 and latent TGF-β1 (ΔG_TOTAL ≈ −120 kcal·mol⁻¹). Co-immunoprecipitation confirmed physical association in cells, and ELISA showed elevated TGF-β1 in PCOS follicular fluid and rat serum, both attenuated by THBS1 knockdown. Pharmacological TGF-β receptor inhibition with SB-431542 rescued THBS1-induced cellular dysfunction. Conclusions: THBS1 is associated with PCOS-related granulosa cell dysfunction through the TGF-β/Smad pathway and represents a candidate biomarker and exploratory therapeutic target that warrants validation in independent multicentre cohorts. Full article

Geroprotective molecules are currently being actively investigated for the prevention of skin aging. An overview of geroprotectors in dermatology encompasses agents such as antioxidants, ultraviolet (UV) photoprotective agents, chemical peels, and carbon dioxide (CO₂) lasers, each with inherent limitations, including poor tolerability in individuals with sensitive skin. Regarding biostimulators, high-molecular-weight peptides (exceeding 500 kDa) exhibit limited cutaneous bioavailability, underscoring the need for low-molecular-weight geroprotective compounds. One such candidate is dehydroepiandrosterone DHEA, a neurosteroid with anti-aging and anti-stress properties, which also serves as a precursor to sex steroids. Although topical hormone replacement therapy with estrogens and androgens is being utilized, it remains confined to formal hormone replacement regimens and is associated with a significant adverse effect profile. The aim of this review was to analyze the key molecular mechanisms underlying the effects of DHEA on the skin, with particular emphasis on its metabolism and sex- and age-dependent mechanisms of action. Additionally, this review seeks to elucidate the factors contributing to the absence of approved topical DHEA formulations and to outline the potential of DHEA as an anti-aging agent in dermatological applications. DHEA has demonstrated significant skin-improving effects in several studies; its investigation has been predominantly confined to postmenopausal women. Furthermore, the outcome measures employed in these studies lacked specificity. DHEA is not permitted for use in cosmetic products within the European Union due to its hormonal activity. Its use is only allowed as an extemporaneous formulation under the established regulatory frameworks of individual countries. The indications for its use and the appropriate dosage for men and women must be clearly defined based on the results of future clinical studies. Promising research directions include the pharmacogenetic characterization of steroidogenic enzymes and sex hormone receptors, as well as the evaluation of DHEA in both sexes, specifically in premenopausal women and in men presenting with late-onset hypogonadism. Additionally, the biological effects of the primary metabolites of DHEA, androstenedione, and 5-androstenediol, on the cutaneous function remain unexplored, including their potential anti-aging activity mediated through retinoid receptor activation. Full article

Background/Obejctives: Sarcopenic obesity (SO) has gained growing attention in metabolic dysfunction-associated steatotic liver disease (MASLD), yet data in Caucasian populations remain limited. The aim of this study was to assess the prevalence of SO using different definitions and to explore its relationship with steroid androgens, physical performance and frailty in MASLD individuals. Methods: Two hundred Caucasian patients with MASLD and available dual-energy X-ray absorptiometry (DEXA) data were evaluated. Clinical, biochemical, hormonal and elastography data were recorded, while physical performance was assessed using the Short Physical Performance Battery (SPPB) and Liver Frailty Index (LFI). Results: SO prevalence ranged from 34.5% to 76.5% depending on the definition applied (AIMSO score, body mass index, and body fat percentage-based criteria). Across definitions, SO individuals showed greater hepatic steatosis, more metabolic comorbidities and demonstrated poorer physical performance. Lower dehydroepiandrosterone sulfate (DHEAS) levels were independently associated with SO when the definition is based on total body fat percentage, and waist circumference (WC) was consistently linked to SO across all definitions. Separate analysis based on gender, confirmed that DHEAS was independently associated with SO in men, while WC represented an independent factor associated with SO in both genders. Conclusions: In conclusion, SO is common among Caucasian MASLD patients and is accompanied by metabolic, hepatic, hormonal, and functional alterations. These findings may help recognize patients at risk of SO and support more focused assessment and monitoring in clinical practice. Full article

Objective: In this study, Dehydroepiandrosterone (DHEA-induced Polycystic Ovary Syndrome (PCOS) mice were used as models to evaluate the improvement effect of Vitexin (Vit) on ovarian fibrosis and explore the mechanism of action of the NR4A1/NLRP3 signaling pathway. Method: Sixty 4-week-old female ICR mice of the same batch number were selected and their systems were divided into 6 groups (n = 10): normal (Control, Ctrl) group, model (Polycystic Ovary Syndrome, PCOS) group, treatment (Vitexin, The Vit group, normal NR4A1 gene silencing group (Ctrl NR4A1^-/-), NR4A1 gene silencing model group (PCOS NR4A1^-/-), and NR4A1 gene silencing treatment group (Vit NR4A1^-/-). Silencing gene modeling was performed by tail vein injection of adeno-associated virus (serotype AAV-8), and the mouse genotypes were detected by qRT-PCR technology 14 days after injection. After the genotype was determined, the PCOS group and the PCOS NR4A1^-/- group were administered dehydroepandrosterone (6 mg/100 g/d) by gavage for 28 consecutive days for modeling, while the Vit group and the Vit NR4A1^-/- group were treated with dehydroepandrosterone + vitexin (10 mg/kg/d) by gavage for 28 consecutive days. All mice were raised with pure water and regular maintenance food. After 4 weeks of drug intervention, the mice were euthanized and samples were collected. The pathological changes in ovarian tissue were observed by H&E staining, and the degree of ovarian tissue fibrosis was observed by Masson staining. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in mouse serum were detected by biochemical kits. The levels of inflammatory factors (IL-1β, IL-6, IL-18, TNF-α) in mouse serum were determined by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect oxidative kinase (Gsta4, Prdx3, Mgst1, Gpx3, Gsr), inflammatory factors (Nlrp3, Caspase-1, Asc, Il-1β, Il-18, Tnf-α) and fibrotic pathway-related genes (Tgf-β1, Smad3, Collagen1, CTGF, α-SMA, Mmp-13, and β-catenin) in ovarian tissues. The levels of inflammatory factors (NLRP3, Caspase-1, ASC, IL-1β, IL-18, TNF-α, IκBα) and fibrosis in mice were determined by Western blot method, and statistical description and analysis were performed using SPSS software. Result: In the wild-type genotype group, compared with the PCOS group, Vit treatment could effectively regulate the metabolic abnormalities of PCOS mice, including inhibiting excessive weight gain, restoring normal glucose tolerance, and reducing body fat content. After Vit treatment, the levels of MDA, TC, TG, LDL, IL-1β, IL-6, IL-18 and TNF-α in the serum of PCOS mice were significantly reduced, while the levels of SOD and HDL in the serum of PCOS mice were increased. The staining results indicated that Vit treatment could significantly inhibit the process of ovarian fibrosis in PCOS mice. The results of WB and PCR demonstrated that after Vit gavage treatment in mice, inflammatory and fibrotic factors such as Nlrp3, Caspase-1, Asc, Il-1β, Il-18, Tgf-β1, Smad3, Collagen1, CTGF, and α-SMA in ovarian tissues could be significantly down-regulated, and the fibrotic level of ovarian tissues could be reduced. Among the same measurement indicators, the silenced NR4A1 group showed a certain degree of increase compared with the wild genotype group, but there was no significant difference. Conclusions: Vit intervention can restore the sex hormone levels and follicular development in ovarian tissues of PCOS mice, regulate reproductive endocrine disorders and abnormal lipid metabolism levels, and regulate the expression of Collagen I, a-SMA and CTGF in the ovaries by inhibiting the NR4A1/NLRP3 signaling pathway, thereby improving the ovarian fibrosis level of PCOS mice. It is suggested that it may play a key role in the treatment of PCOS and the prevention and delay of its long-term complications. Full article

The timing and nature of gestational stress can alter offspring immune function and hypothalamic–pituitary–adrenal (HPA) axis regulation, yet the role of maternal stress history remains poorly understood. This study evaluated the effects of prenatal stress, maternal stress history, and repeated stress exposure on immune and stress reactivity in prenatally stressed (PS) gilts across two farrowings. Eleven PS second-parity sows (197.27 ± 19.22 kg) were sampled at multiple timepoints and compared with their maternally stressed (MS) dams. During the second pregnancy, PS sows received the same maternal treatment as their dams: placebo (CON) or hydrocortisone acetate (HCA) administered twice daily for 21 days during mid (M; d 51–72) or late (L; d 81–102) gestation. Data were analyzed using mixed models with repeated measures in SAS (Version 9.4). During the first pregnancy, PS gilts in the L-HCA group exhibited higher lymphocyte proliferation indices and plasma cortisol concentrations than MS dams (p < 0.05). In the second pregnancy, dehydroepiandrosterone sulfate concentrations were lower in PS sows in the M-HCA group than the CON sows (p < 0.05). Overall, cortisol concentrations were lower in PS sows than PS gilts (p < 0.05), suggesting that maternal stress history modifies physiological responses to gestational stress, though this interpretation is constrained by the small sample size. Full article

The protective effect of physical activity on breast cancer recurrence may be mediated changes in by sex hormone levels. In this study, we examined the association between habitual physical activity and estrogen and androgen plasma levels in postmenopausal women with localised breast cancer. We conducted a cross-sectional study among 47 postmenopausal women who were breast cancer survivors with estrogen receptor-positive tumours (enrolled at the Medical Oncology Department of University Hospital Dr. Peset, Valencia, Spain). Habitual physical activity was assessed using the International Physical Activity Questionnaire (IPAQ), and a weighted estimate of total physical activity per week (MET∙min∙wk⁻¹) was calculated. Total plasma levels of estrone, 17β-estradiol, progesterone, androstenedione, testosterone, and dehydroepiandrosterone-sulphate (DHEA-sulphate) were measured. Bivariate analyses by the Spearman correlation test were done between physical activity and each hormone concentration. Multivariate analyses (linear regression) using concentration of each hormone as the dependent variable and physical activity, age, marital status, BMI, Charlson Comorbidity Index, tumour stage, previous radiotherapy, or previous chemotherapy as predictor variables. Estrone concentration was positively and significantly correlated with BMI (ρ = 0.332, p = 0.022), but no other correlations were found between BMI and the other hormone concentrations, nor were concentrations of any hormone associated with age or Charlson Comorbidity Index (p > 0.05 in all cases). Physical activity was significantly and inversely correlated with estrone concentration (ρ = −0.308; p = 0.035). Linear regression analysis confirmed a statistically significant association between estrone concentration and BMI and physical activity, after adjusting for all potential confounders (for BMI: standardised β coefficient = 0.407; non-standardised β coefficient = 1.054; t = 2.898; p = 0.006; 95% CI for non-standardised beta: 0.318- to 1.790; for physical activity: standardised β coefficient = −0.300; non-standardised β coefficient = −0.005; t = −2.135; p = 0.039; 95% CI for non-standardised beta: −0.010- to 0.000). The relationship between estrone concentration and physical activity may be further explored as a biomarker for evaluating the protective effect of physical activity against breast cancer recurrence in women receiving anti-estrogen therapies. Full article

Background/Objectives: Differentiating Cushing’s disease (CD) from adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome (AICS) remains challenging in patients with equivocal ACTH levels. While dynamic testing is frequently required, baseline hormonal measurements may offer a simpler diagnostic approach. We aim to evaluate the diagnostic value of baseline plasma ACTH, cortisol, and dehydroepiandrosterone sulfate (DHEAS) levels and their derived ratios for differentiation between ACTH-dependent and ACTH-independent Cushing’s syndrome, and to propose a diagnostic algorithm based on these parameters. Methods: This retrospective single-centre study included adult patients with endogenous Cushing’s syndrome aged 18–75 years who were followed at our institution. Patients with ectopic/paraneoplastic Cushing’s syndrome were excluded. The AICS group comprised overt adrenal CS and mild autonomous cortisol secretion cases. Morning baseline plasma ACTH (pg/mL), serum cortisol (µg/dL), and serum DHEAS (µg/dL) levels were measured and ratios calculated: cortisol-to-ACTH ratio (CAR), DHEAS-to-cortisol ratio (DCR), and CAR-to-DHEAS ratio (CAR/D). ROC analysis assessed diagnostic performance with age and sex adjustments. Results: A total of 100 patients were included, comprising 43 patients with CD and 57 with AICS. Plasma ACTH demonstrated high diagnostic accuracy for identifying CD with a cut-off of ≥14.65 pg/mL (sensitivity 100%, specificity 98.25%, AUC 0.998). Serum DHEAS showed strong discriminative power with a cut-off of ≥67.15 µg/dL (sensitivity 88.37%, specificity 91.23%, AUC 0.925), achieving high discriminative power after age–sex adjustment at ≥85.59 µg/dL (sensitivity 100%, specificity 100%, AUC 0.999). CAR showed good performance in identifying CD with a cut-off of ≤0.75 µg/dL per pg/mL (sensitivity 93.02%, specificity 98.25%, AUC 0.980). CAR/D demonstrated high diagnostic power with a cut-off of ≤1.54 (sensitivity 95.35%, specificity 98.25%, AUC 0.974), improving after age–sex adjustment to ≤2.36 (sensitivity 97.87%, specificity 96.23%, AUC 0.992). Conclusions: Baseline plasma ACTH, serum cortisol, and serum DHEAS measurements, along with derived ratios—especially CAR and CAR/D—provide highly accurate differentiation between ACTH-dependent and ACTH-independent Cushing’s syndrome. These widely available measurements may reduce dependence on dynamic testing and improve diagnostic accuracy in patients with equivocal findings. Full article

Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, dehydration and death in piglets, resulting in significant economic losses in the pig industry. It is crucial to identify the pathogenesis and mechanism between host–PEDV interactions. In our study, we performed transcriptomic and metabolomic analyses in PEDV-infected Large White (LW) pigs. PEDV infection caused blunted and fused intestinal villi, necrosis of the intestinal mucosal epithelial cells and atrophy of intestinal glands. Transcriptomic and metabolomic analyses revealed 692 differentially expressed genes and 1485 differential metabolites, respectively. Among them, differentially expressed genes were enriched in virion assembly, lipoprotein metabolic process and PPAR signaling pathway. Differential metabolites were enriched in primary bile acid biosynthesis and lipoic acid metabolism. An integrated analysis of the transcriptome and metabolome revealed that differentially expressed genes and metabolites were co-enriched in steroid hormone biosynthesis and bile secretion. In addition, key metabolites Dehydroepiandrosterone (DHEA) and Estriol in steroid hormone biosynthesis both inhibited PEDV infection and alleviated the excessive inflammatory response in vitro. Collectively, our study constructed a multi-omics landscape of PEDV infection in LW pigs, providing potential targets for developing metabolic-targeted antiviral interventions. Full article

Polycystic ovary syndrome (PCOS) is associated with impaired ovarian steroidogenesis and ovulation, which necessitates the development of effective ovulation inducers for PCOS. The aim of the study was to evaluate the effects of allosteric luteinizing hormone receptor agonist TP03 and human chorionic gonadotropin (hCG) on ovarian steroidogenesis, as well as ovulation in prepubertal female rats with dehydroepiandrosterone(DHEA)-induced PCOS. Taking into account differences in progesterone levels, cohorts with high (PCOS(H)) and low (PCOS(L)) progesterone were formed and treated with Follimag and Cetrotide. After 48 h, TP03 (25 mg/kg) or hCG (25 IU/rat) were injected, and hormone levels, gene expression, and ovarian morphology were assessed. The PCOS(H)-cohort exhibited irregular estrous cycles, ovarian cysts, and increased ovarian mass and estradiol levels, but the number of corpora lutea (CL) was maintained. In the PCOS(L)-cohort, ovarian weight was increased, and Star, Cyp11a1, and Adamts1 gene expression as well as the CL number were decreased. In both cohorts, TP03 and hCG increased progesterone levels and the expression of steroidogenesis (Star, Cyp11a1) and ovulation (Cox2, Adamts1, Egr1) genes, as well as inducing CL formation. Thus, TP03, like hCG, stimulates steroidogenesis and ovulation in PCOS-rats with different progesterone levels, which provides the first evidence of the effectiveness of allosteric LHR agonists as ovulation triggers in PCOS. Full article

Background: Chronic stress is associated with dysregulation of the body’s allostatic systems, contributing to increased allostatic load (AL) and adverse metabolic outcomes. Regular physical activity (PA) is considered a key protective factor that may attenuate AL by enhancing adaptive stress responses and supporting metabolic health. This study examined the differences between PA, primary mediators of AL, and metabolic risk markers in apparently healthy adults in Germany. Methods: Forty-six adults (18–45 years) were categorized into a moderate intensity (regular PA: ≥150 min a week vs. non-regular PA: ≤150 min a week) group according to current PA recommendations. Primary AL mediators were quantified by cortisol (μg/12 h), epinephrine (μg/12 h), norepinephrine (μg/12 h), and dehydroepiandrosterone sulfate (DHEA-S: μg/mL). Group differences in primary AL mediators and metabolic risk markers were examined using the Mann–Whitney U test. Results: A significant group difference was observed for cortisol levels, with higher values in the regular PA group (p = 0.01), with a moderate negative effect size of r = −0.38. No statistically significant differences (p > 0.05) were found between groups for epinephrine, norepinephrine, DHEA-S, or metabolic risk markers, including triglycerides, blood pressure, body mass index (BMI), and high-density lipoprotein cholesterol (HDL-C). Conclusions: The findings suggest that regular PA may be associated with altered stress-regulatory activity, as reflected by differences in cortisol. While no statistically significant group differences were observed for metabolic risk markers, descriptive patterns indicate more favorable lipid profiles and potential variation in primary AL mediators at higher PA levels. Given the exploratory nature of the analyses and the small and unequal group sizes, these findings should be interpreted with caution and warrant confirmation in future studies with larger and more balanced samples. Full article