Search Results (1,449)

The weaning-to-estrus interval (WEI) is an important indicator of sow reproductive performance, yet the mechanisms underlying post-weaning anestrus in Tibetan sows remain unclear. In this study, multiparous Tibetan sows were classified into an estrus group (FQ) and an anestrus group (WQ) based on estrus status after weaning. Serum reproductive hormones, hematological parameters, gut microbiota (16S rRNA sequencing), and fecal metabolites (untargeted metabolomics) were analyzed. Compared with the FQ group, the WQ group showed significantly lower estradiol (E₂) and higher progesterone (P) levels (p < 0.01), along with a decreased proportion of neutrophils and an increased proportion of lymphocytes (p < 0.05). No significant differences in alpha diversity were observed, whereas PLS-DA revealed differences in microbial community structures between groups. LEfSe analysis indicated that Methanobrevibacter and Acinetobacter were enriched in the FQ group, whereas Muribaculaceae and Prevotella were enriched in the WQ group. Differential metabolites were mainly involved in amino acid and lipid metabolism and enriched in pathways related to steroid hormone biosynthesis, oocyte maturation, and tryptophan metabolism. These findings suggest that post-weaning anestrus may be associated with endocrine imbalances, immune changes, and gut microbiota–metabolite interactions. They may provide a basis for future studies in Tibetan pig breeding and genetic improvement. 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/Objective: With rising per capita sugar consumption, skin glycation-related issues including dullness, homeostasis disruption and accelerated wrinkling have gained widespread attention. However, globally standardized and rigorous evaluation criteria for anti-glycation efficacy remain lacking. This study aimed to establish stage-specific glycation injury cell models and elucidate the stage-dependent molecular mechanisms of glycation-induced fibroblast damage, providing a standardized reference for anti-glycation efficacy assessment. Methods: Three glycation injury models were constructed in human foreskin fibroblasts (HFF-1): early-stage (glucose-induced), intermediate-stage (glyoxal-induced), and late-stage (advanced glycation end products (AGEs)-induced). Core biomarkers including Nε-(carboxymethyl)lysine (CML), collagen type I (Col I) and elastin (ELN) were used to optimize modeling conditions via Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). Untargeted metabolomics based on ultra-high-performance liquid chromatography (UHPLC)-Q Exactive Orbitrap was applied to identify differential metabolites and perturbed pathways, following Metabolomics Standards Initiative (MSI) Level 2 identification criteria. Results: Optimal conditions were determined as 50 mmol/L glucose for 48 h, 0.5 mmol/L glyoxal for 48 h, and 200 μg/mL AGEs for 24 h. A total of 319, 34 and 148 differential metabolites were identified in the three groups, respectively. Six key pathways were significantly perturbed. Early and intermediate models shared similar mechanisms (purine metabolism disturbance), while the late model showed distinct alterations in pyrimidine, nicotinate, arachidonic acid and steroid hormone metabolism. Conclusions: Three stable stage-specific glycation models were successfully established in HFF-1 cells. Significant differences in metabolic profiles and mechanisms exist across the three stages, providing a rational basis for model selection and theoretical support for anti-glycation efficacy evaluation. Full article

Background: Growth disorders, including central precocious puberty and delayed puberty, can significantly affect linear growth, skeletal maturation, metabolic regulation, and psychosocial development during childhood and adolescence. This systematic review synthesizes the current evidence regarding the effectiveness and safety of hormone-based therapies used in children with disorders of pubertal maturation. Methods: A PRISMA-guided systematic search was carried out between January 2016 and March 2026 in different databases, such as MEDLINE (PubMed), EMBASE, CENTRAL, Scopus, Web of Science, CINAHL, LILACS and OpenGrey; the protocol was previously registered in the PROSPERO database (CRD420251068048). Non-randomized, randomized controlled trials and observational research including participants aged 0–18 years receiving hormone therapies were eligible. Risk of bias was assessed using validated, design-specific tools. Results: Twenty studies involving 21,812 participants were included. GnRHa therapy improved final adult height (+3.5 to +4.5 cm) and reduced bone age advancement (−0.6 to −1.3 years) in children with central precocious puberty. rhGH therapy increased growth velocity (+3.0 to +5.0 cm/year) and height SDS (+0.3 to +0.9), particularly in idiopathic short stature and Prader–Willi syndrome. Combined GnRHa plus rhGH therapy showed greater short-term growth benefits than GnRHa alone. Both therapies showed favorable safety profiles, with predominantly mild adverse events and discontinuation rates below 2%. However, the evidence was limited by substantial heterogeneity and moderate-to-serious risk of bias. Conclusions: GnRHa and rhGH therapies are generally effective and safe for improving growth and pubertal outcomes in pediatric endocrine disorders. However, further long-term studies are needed to clarify their metabolic and psychosocial effects in adulthood. Nevertheless, these conclusions should be interpreted with caution due to the study’s moderate-to-serious risk of bias and heterogeneity. Full article

The study investigated the effects of high-intensity interval training (HIIT) on cardiorespiratory fitness, hormonal, and psychological markers in adolescents. Twenty-eight healthy male adolescents were randomized to a HIIT group or a non-training control group. HIIT comprises three sessions per week for 10 weeks, alternating 30 s runs at high-intensity and low-intensity. VO_2max was estimated using the incremental running test. Plasma testosterone and cortisol were assessed by ELISA methods. Depression, anxiety, and stress scores were determined using the Depression Anxiety Stress Scales-21. Data were analyzed using two-way ANOVA with repeated measures. Significant “group × time” interactions were detected for VO_2max, testosterone, cortisol, testosterone-to-cortisol ratio, and stress score, but not for anxiety and depression scores. HIIT resulted in increased VO_2max (p < 0.001, d = 1.04), testosterone (p = 0.005, d = 0.52), and testosterone-to-cortisol ratio (p = 0.008, d = 1.05), and decreased cortisol (p = 0.036, d = 1.09) and stress score (p = 0.020, d = 0.98). Ten-week HIIT resulted in an improvement in physical fitness, steroid hormonal balance, and self-reported stress symptoms, but no changes in depressive and anxiety symptoms in comparison to the control group. The findings should be interpreted with caution due to limitations, including the small sample size and the lack of assessment of sex-related differences. Further research is required to elucidate the topic. Full article

Endometriosis is a chronic, estrogen-dependent disorder defined by ectopic endometrial-like tissue growth, persistent inflammation, and aberrant innervation. Emerging evidence indicates that disease progression and symptom severity are driven by a reciprocal interaction between hormonal dysregulation and neuroinflammatory signaling. This narrative review synthesizes human-based mechanistic and clinical evidence on the hormonal–neuroinflammatory interface in endometriosis, drawing on peer-reviewed publications retrieved from PubMed and Scopus through November 2025. The publications comprised studies using data from patient-derived tissues, primary endometriotic cells, and clinical cohorts. Several convergent molecular nodes at this interface were identified: the prostaglandin E₂–prostaglandin E receptor 2/prostaglandin E receptor 4–aromatase axis, estrogen receptor beta—nuclear factor kappa B signaling, interleukin-6/signal transducer and activator of transcription 3-mediated fibrosis, neurotrophin pathways, transient receptor potential channels (TRPV1/TRPA1), and neurokinin 1 receptor signaling. In this integrated model, endocrine dysfunction fuels neuroinflammation, which in turn impairs steroid responsiveness. This cycle explains the frequent pain–lesion mismatch and the persistence of symptoms despite standard hormonal suppression. Targeting these druggable interface pathways enables better patient stratification and more effective combination therapies for endometriosis. Full article

Enhancing egg production in geese without antibiotics remains a challenge in poultry science. This study compared the effects of Lactobacillus (LAB) and Bacillus (BAC) probiotics on laying performance, gut microbiota, and serum metabolism in Zhedong White geese. Birds were fed a control diet or diets supplemented with LAB or BAC. Egg production and quality were monitored throughout the trial. Serum metabolomics and fecal 16S rRNA sequencing were integrated with KEGG enrichment and correlation analyses to uncover functional mechanisms. Both probiotics improved laying performance and egg quality. Total egg production of the LAB group was 8.5% higher than that of the BAC group (p < 0.05). The LAB group’s advantage in egg production was consistent with its stronger activation of the steroid hormone biosynthesis pathway (elevated serum corticosterone and tetrahydrocorticosterone indicated an overall enhancement of steroidogenic flux). Simultaneously, the LAB group exhibited a more efficient conversion of L-phenylalanine to catecholamine precursors, which drove activation of the neuroendocrine reproductive axis. The BAC group showed more significant changes in nitrogen and energy metabolism pathways and a more pronounced expansion of energy-harvesting Firmicutes. These findings reveal two strain-specific regulatory pathways: LAB functions through the “aromatic amino acid–neuroendocrine–steroid hormone axis,” while BAC relies on the “gut microbiota–energy metabolism” pathway, with direct implications for the precise application of probiotics under antibiotic-free farming conditions. 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

The placenta produces a variety of steroid hormones through the catalytic activity of steroidogenic enzymes, including cytochrome P450 (CYP) hydroxylases and hydroxysteroid dehydrogenases (HSD). Large amounts of progesterone produced by the placenta are essential for the maintenance of pregnancy. Although androgens and estrogens are also elevated in maternal circulation during gestation, there are conflicting reports on whether de novo synthesis of these steroids occurs in the human placenta. To address this issue, we performed a comprehensive analysis of steroidogenic gene expression in early and term placenta. While none of the genes examined showed binary expression changes, 17β-HSDs, including HSD17B1 and AKR1C3, were markedly upregulated in the term placenta. CYP19A1 and HSD11B2 genes were also markedly upregulated. In contrast, CYP17A1, CYP21A2, CYP11B1, CYP11B2, and HSD17B3 were almost undetectable. Consistent with these findings, the plasma ratios of active to precursor sex steroids (estradiol/estrone and testosterone/androstenedione) were higher in pregnant than in non-pregnant women, although concentrations of all steroids increased. In contrast, plasma levels and profiles of 11-oxygenated androgens were unchanged. These results indicate that the human placenta does not significantly contribute to circulating levels of either classical or novel classes of androgens. Therefore, this study provides new insights into the tissue of origin and the physiological significance of sex steroids during gestation. Full article

Cerebrovascular and neurodegenerative diseases are often linked to dysregulated cerebral blood flow, which results in oxidative stress and alterations in energy metabolism. Targeting the underlying initiators and exacerbating factors could offer protective benefits. Among the proposed therapeutic agents, the steroid hormone progesterone (P4) has shown considerable potential. This study evaluates the protective effects of P4 (1.7 mg/kg, administered subcutaneously once daily for a week) in a rat model of chronic cerebral hypoperfusion (CCH), provoked by the permanent bilateral ligation of the common carotid arteries. Redox and metabolic imbalances, specifically lipid and adenine nucleotide metabolism, were examined in serum and striatal crude synaptosomal fractions. Additionally, sensorimotor functions were assessed using non-invasive neurological tests. Biochemical analyses showed that P4 in CCH conditions contributed to the normalization of redox and metabolic homeostasis in both the serum and striatum. In the serum, this was accompanied by increased adenine nucleotide turnover, likely favoring protective adenosine signaling. In parallel, P4 alleviated the striatal oxidative burden while augmenting antioxidant response and promoting nucleotide catabolism. Our findings demonstrate that P4-mediated protection is accomplished through coordinated biochemical serum–striatum responses, linking systemic and synaptic metabolic regulation with improved sensorimotor function and recovery from CCH-induced deficits. Full article

Clutch persistence, defined as the ability to sustain consecutive egg-laying cycles, is a pivotal determinant of profitability in the poultry industry, particularly for aging laying hens (≥65 weeks). However, the molecular mechanisms governing this trait remain elusive, largely due to the traditional “ovary-centric” paradigm that overlooks systemic regulation by the gut microbiota. To address this knowledge gap, the present study aimed to dissect the comprehensive regulatory network governing clutch persistence using integrated multi-omics analyses. A total of 20 sixty-five-week-old Rhode Island Red (RIR) laying hens with cumulative egg production exceeding 300 eggs but distinct clutch persistence were stratified into a high-clutch persistence group (HCP, ≥25 clutches, n = 10) and a low-clutch persistence group (LCPLCP, ≤15 clutches, n = 10). Multi-omics profiling, including ovarian transcriptomics, proteomics, and metabolomics; serum metabolomics; and cecal microbiota 16S rRNA sequencing was performed. Data integration and association mining were conducted via Spearman correlation analysis with stringent thresholds (r > 0.6, p < 0.01). Integrated analyses revealed a “gut–ovary axis” regulatory model mediated by a lipid mediator network, operating through a three-tiered mechanism: (1) Gut Initiation: The HCP group exhibited enriched cecal γ-Proteobacteria, which promoted biosynthesis of lipid precursors. (2) Serum Transport: Key serum lipid mediators, most notably LysoPC (22:6) (VIP = 4.5) and cholesterol ester CE (20:4), served as critical carriers transducing gut-derived signals to the ovary. (3) Ovarian Execution: These lipid signals activated a core ovarian metabolic pathway centered on the PLA2G6-ALOX15B-AGPAT3 axis, which coordinated follicular development and ovulation by supplying steroid hormone synthesis substrates, exerting anti-inflammatory effects, and stabilizing membrane structures. Collectively, this study demonstrates that gut microbiota modulates clutch persistence in aging laying hens via lipid mediators, orchestrating a systemic “gut–serum–ovary” regulatory cascade. These findings provide a novel molecular framework for extending the economic egg-laying cycle through the targeted manipulation of intestinal microbiota or serum lipid metabolism. Full article

Background: Endogenous estradiol/progesterone (E2/P4) regulates neuronal mitochondrial bioenergetics and redox balance. However, the effects of combined oral contraceptive (COC) steroids under physiologically relevant hormonal conditions remain poorly understood. Therefore, this study aims to investigate how COC steroids modulate mitochondrial function within the defined E2/P4 hormonal milieus. Methods: Human SH-SY5Y cells (Cytion) were starved for 48 h in Cytion medium without FBS and with 1% ITS, and then exposed for 48 h to six conditions: vehicle (F0); follicular-like E2/P4 (F1); luteal-like E2/P4 (F2); F1 + dienogest/ethinylestradiol (DNG/EE; F3); F2 + DNG/EE (F4); and DNG/EE alone (F5). The primary endpoints were mitochondrial membrane potential (JC-1 red/green ratio) and ROS (H₂DCFDA/DCF); nitric oxide (DAF-FM) was also recorded. Hoechst 33342 nuclear fluorescence served both as a per-well proxy of cell number and as a proportionality factor for normalization. Results: Follicular- and luteal-like backgrounds were associated with distinct ΔΨm/ROS set-points. The addition of DNG/EE was accompanied by background-dependent shifts, generally characterized by higher DCF signals and lower JC-1 ratios relative to the vehicle, whereas DAF-FM did not reveal statistically robust changes in NO. Hoechst-based normalization preserved these patterns, suggesting that the observed effects likely reflect per-cell functional modulation rather than differences in cell number, although modest, background-dependent variations in proliferation were observed, with DNG/EE associated with a greater increase in ROS under follicular-like conditions and a more pronounced ΔΨm membrane potential in a luteal-like milieu. Conclusions: These findings suggest that neuroendocrine background may influence mitochondrial ΔΨm/ROS states in SH-SY5Y cells, with physiologically inspired E2/P4 milieus potentially shaping baseline conditions onto which COC components exert context-dependent effects at 48 h. These preliminary findings provide a standardized framework for subsequent image-based analyses of mitochondrial function. Full article

Androgen receptor (AR) signaling has emerged as a potential molecular target in triple-negative breast cancer (TNBC), a clinically aggressive and biologically heterogeneous subtype of breast cancer with limited targeted treatment options. Androgens, the main ligands of AR, have been reported to exert antiproliferative and anti-estrogenic effects in normal mammary epithelium; however, the role of AR signaling in TNBC remains controversial and appears to depend strongly on tumor molecular context. In certain experimental settings, elevated androgen levels have been associated with reduced tumor growth, whereas AR activation has also been linked to signaling pathways involved in cell survival, migration, and invasiveness. AR signaling can occur through classical androgen-dependent mechanisms, as well as through ligand-independent activation mediated by protein kinases and intracellular pathways. Increasing interest in AR biology has led to the evaluation of several anti-androgen therapies in AR-positive TNBC, including agents such as enzalutamide, enobosarm, orteronel, bicalutamide, and seviteronel. Although clinical activity has generally been modest, these studies highlight the potential relevance of AR-targeted strategies in selected patient subgroups. This review summarizes current knowledge on androgen and AR signaling in TNBC, integrating molecular mechanisms, preclinical evidence, and clinical studies, and discusses emerging therapeutic strategies aimed at improving patient treatment outcomes. Full article

Background/Objectives: Women exposed to high psychosocial stress in pregnancy have higher risk of postpartum health conditions, but it still is unknown whether high pregnancy stress exposure alters the maternal metabolome at one-month postpartum. Methods: We analyzed data from 625 women participating in the PROGRESS study, a longitudinal pregnancy cohort. Women answered validated psychometric tests (i.e., EPDS, PSS and NLE) during the second or third trimester of pregnancy and provided serum samples at one-month postpartum for metabolomic assessment. Untargeted metabolomics were analyzed using chromatography high-resolution mass spectrometry (LC-HRMS). We used a metabolome-wide association study, using both traditional robust regressions and variance tests, to evaluate associations between pregnancy psychosocial stress and one-month postpartum serum metabolomics. Results: We found a few nominally significant associations between prenatal psychosocial stress scores and the maternal metabolome. However, these findings did not remain after adjusting for multiple testing, with the only exception of epiandrosterone glucuronide, a steroid hormone metabolite, and lithocholyltaurine, a lipid-like molecule. Conclusions: We did not find significant associations between prenatal psychosocial stress and postpartum serum metabolomic profiles, except for two metabolites showing suggestive associations warranting further investigation. Full article

Newborn screening for congenital adrenal hyperplasia (CAH) is effective in identifying patients with severe forms before a potentially lethal crisis, but has a relatively high false-positive rate. The aim of this study was to improve the national neonatal screening program in Sweden and the positive predictive value by implementing LC-MS/MS second-tier testing. A combination of two independent parameters, the steroid hormone ratio (androstenedione+17-hydroxyprogesterone)/cortisol and the concentration of 21-deoxycortisol and adjustment of cut-off levels resulted in an increase in the positive predictive value (PPV) from 14% to 84% for full-term infants. In total, the false-positive screening cases decreased by 88%. CYP21A2 genotyping was used to determine the severity of CAH in identified cases. We report on the stepwise approach that was used to optimize the cut-off levels for full-term and preterm infants in order not to miss any true cases in the process. Full article