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Search Results (294)

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21 pages, 3388 KB  
Article
Multi-Target Modulation of Metabolic and Steroidogenic Pathways by Cinnamomum burmannii and Myristica fragrans in Polycystic Ovary Syndrome: An Integrative Transcriptomics, Metabolomic, Pharmacoinformatics and Experimental Validation
by Taruna Ikrar, Salmon Charles Siahaan, Hendy Hendarto, Arifa Mustika, Eighty Mardiyan Kurniawati, Wiskara Jatipradresthya, Edwin Hadinata, Nurpudji Astuti Taslim, Dante Saksono Harbuwono, Raymond Rubianto Tjandrawinata and Fahrul Nurkolis
Nutrients 2026, 18(8), 1305; https://doi.org/10.3390/nu18081305 - 21 Apr 2026
Viewed by 231
Abstract
Background: Polycystic ovary syndrome (PCOS) is a complex endocrine–metabolic disorder characterized by interconnected dysregulation of steroidogenesis and insulin signaling. Multi-target therapeutic strategies are increasingly needed to address its heterogeneous pathophysiology. Methods: An integrative approach combining transcriptomic analysis of GSE137684, including stratification of normoandrogenic [...] Read more.
Background: Polycystic ovary syndrome (PCOS) is a complex endocrine–metabolic disorder characterized by interconnected dysregulation of steroidogenesis and insulin signaling. Multi-target therapeutic strategies are increasingly needed to address its heterogeneous pathophysiology. Methods: An integrative approach combining transcriptomic analysis of GSE137684, including stratification of normoandrogenic and hyperandrogenic PCOS subtypes to capture androgen-related heterogeneity, network pharmacology, molecular docking, and in vitro validation was employed. Principal component analysis (PCA), differential expression analysis, and enrichment analyses were used to identify candidate genes and pathways. Molecular docking evaluated interactions between phytochemicals from Cinnamomum burmannii and Myristica fragrans and key PCOS targets. Functional validation was performed in insulin-resistant 3T3-L1 adipocytes and DHEA-induced KGN cells, assessing cell viability, lipid accumulation, glucose uptake, gene expression, and hormone levels. Results: PCA revealed partial separation between PCOS and the control samples, with PC1 and PC2 explaining 44.8% and 12.5% of variance, respectively. No genes remained significant after multiple testing correction; however, nominally significant candidates (p < 0.01) highlighted pathways related to steroidogenesis and metabolic regulation. Network analysis identified key hub genes including CYP17A1, CYP19A1, AKT1, ESR1, and MAPK1. Molecular docking demonstrated strong binding affinities, with top compounds showing binding energies up to −11.4 kcal/mol (CYP17A1) and −10.9 kcal/mol (AKT1). In vitro, cell viability remained above 80% across all tested concentrations, indicating low cytotoxicity. Treatment significantly reduced lipid accumulation and enhanced glucose uptake in insulin-resistant 3T3-L1 cells (p < 0.05). Additionally, expression of AKT1 and MAPK1 was significantly restored (p < 0.05). In KGN cells, testosterone levels were significantly decreased while the estradiol levels increased (p < 0.05), accompanied by the downregulation of CYP17A1 and upregulation of CYP19A1 (p < 0.05). The combination treatment exhibited more consistent effects across metabolic and hormonal endpoints. Conclusions:Cinnamomum burmannii and Myristica fragrans exert multi-target effects on metabolic and steroidogenic pathways relevant to PCOS. This integrative study demonstrates that transcriptomics-guided network pharmacology combined with experimental validation can identify synergistic phytotherapeutic strategies for complex endocrine disorders. Full article
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14 pages, 1330 KB  
Article
Plasma Estrone Concentration Is Associated with Physical Activity Levels in Postmenopausal Breast Cancer Survivors
by Mayra Alejandra Mafla-España, Javier García Sánchez, Lucía Ortega-Pérez de Villar, Guillermo Casero-García, María Dolores Torregrosa and Omar Cauli
Women 2026, 6(2), 27; https://doi.org/10.3390/women6020027 - 20 Apr 2026
Viewed by 276
Abstract
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. [...] Read more.
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
(This article belongs to the Special Issue Breast Cancer: Causes and Prevention)
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15 pages, 2488 KB  
Article
Diagnostic Utility of ACTH, Cortisol, DHEAS, and Their Derived Ratios in Cushing’s Syndrome Subtypes
by Ekin Yiğit Köroğlu, Abbas Ali Tam, Sevgül Faki, Pervin Demir, Fatma Neslihan Çuhaci Seyrek, Didem Özdemir, Oya Topaloğlu, Reyhan Ersoy and Bekir Çakir
J. Clin. Med. 2026, 15(7), 2772; https://doi.org/10.3390/jcm15072772 - 7 Apr 2026
Viewed by 335
Abstract
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 [...] Read more.
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
(This article belongs to the Section Endocrinology & Metabolism)
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16 pages, 283 KB  
Article
The Relationship Between Serum Neurosteroids and Oxytocin Levels and Craving, Aggression and Emotion Regulation in Patients with Methamphetamine Use Disorder
by Hacer Akbas Cakmak, Ahmet Bulent Yazici, Derya Guzel Erdogan, Yavuz Selim Ogur and Esra Yazici
Med. Sci. 2026, 14(2), 169; https://doi.org/10.3390/medsci14020169 - 27 Mar 2026
Viewed by 439
Abstract
Background: This study aimed to investigate the relationship between serum neuroactive steroids (NAS) and oxytocin and craving and psychosocial functioning in men diagnosed with methamphetamine use disorder (MUD). Methods: In this observational cross-sectional study, 40 men with MUD (PG) and 41 [...] Read more.
Background: This study aimed to investigate the relationship between serum neuroactive steroids (NAS) and oxytocin and craving and psychosocial functioning in men diagnosed with methamphetamine use disorder (MUD). Methods: In this observational cross-sectional study, 40 men with MUD (PG) and 41 non-substance-use-disorder controls (CG) completed measures of emotion dysregulation (DERS-16), attachment (ECR-R), aggression (BPAQ), and suicidal ideation (BSS). PG additionally completed the Substance Craving Scale (SCS) and Addiction Profile Index (API). Serum allopregnanolone (ALLO), DHEAS, testosterone, 17β-estradiol (E2), and oxytocin were assayed. Results: The results indicated that the PG exhibited significantly higher scores than the CG across all psychological measures. Robust adjusted group effects were observed for DERS-16 (Model 1: F = 35.507, p < 0.001; Model 2: F = 18.225, p < 0.001) and trait anger (Model 1: F = 41.104, p < 0.001; Model 2: F = 16.732, p < 0.001). Notably, serum levels of ALLO, DHEAS, testosterone, E2, and oxytocin did not differ significantly between groups. However, hormonal measures were strongly intercorrelated within both groups (r ≈ 0.877–0.936, all p < 0.001). In the PG, craving demonstrated positive correlations with DHEAS (r = 0.384, p = 0.014), testosterone (r = 0.415, p = 0.008), E2 (r = 0.360, p = 0.023), and oxytocin (r = 0.350, p = 0.027). A multivariable model analyzing craving was statistically significant (R2 = 0.350; F(3,36) = 6.474, p = 0.001), with composite hormonal factor (B = 2.390, p = 0.016) serving as an independent predictor, while API Excluding Craving(API-EC) (p = 0.094) and DERS-16 did not emerge as a significant factor (p = 0.056). In hormone-specific models controlling for API-EC and DERS-16, DHEAS (p = 0.012), testosterone (p = 0.007), oxytocin (p = 0.023), and E2 (p = 0.023) retained significance after false discovery rate (FDR) correction; ALLO did not (p = 0.055). Conclusions: Despite the absence of significant differences in peripheral NAS and oxytocin levels between groups, men with MUD exhibited pronounced psychosocial impairments. The craving experienced during inpatient treatment was primarily elucidated by an integrated endocrine profile. These findings underscore the necessity for larger longitudinal studies incorporating repeated hormonal assessments to further explore these relationships. Full article
(This article belongs to the Section Neurosciences)
15 pages, 3511 KB  
Article
Integrated Metabolomic and Transcriptomic Analysis Reveals Host Response Mechanisms to Porcine Epidemic Diarrhea Virus Infection in Pigs
by Yajing Zhou, Tongxi Lu, Jie Wang, Shanshen Gu, Ruihua Huang, Shenglong Wu, Wenbin Bao and Haifei Wang
Vet. Sci. 2026, 13(4), 313; https://doi.org/10.3390/vetsci13040313 - 25 Mar 2026
Viewed by 320
Abstract
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 [...] Read more.
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
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
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27 pages, 2495 KB  
Article
The Stimulating Effect of Low-Molecular-Weight Luteinizing Hormone Receptor Agonist on Steroidogenesis and Ovulation in Female Rats with Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome
by Kira V. Derkach, Alena S. Pechalnova, Inna I. Zorina, Irina Yu. Morina, Liubov V. Bayunova, Irina V. Romanova, Irina V. Fedorchuk, Julian R. Ryzhov, Elizaveta E. Chernenko, Viktor N. Sorokoumov and Alexander O. Shpakov
Int. J. Mol. Sci. 2026, 27(6), 2748; https://doi.org/10.3390/ijms27062748 - 18 Mar 2026
Viewed by 492
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Using Model Organisms to Study Complex Human Diseases—2nd Edition)
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21 pages, 1501 KB  
Review
Case-Based Perspectives on the Management of Genitourinary Syndrome of Menopause
by Jissy Cyriac and Richa Sood
Clin. Pract. 2026, 16(3), 60; https://doi.org/10.3390/clinpract16030060 - 12 Mar 2026
Viewed by 1096
Abstract
Background and Objectives: Genitourinary syndrome of menopause (GSM), previously known as vulvovaginal atrophy, is a chronic, progressive hypoestrogenic condition affecting vulvovaginal, urinary and sexual health in women. Common symptoms include vaginal dryness, itching, dyspareunia, urinary urgency and recurrent urinary tract infections (UTIs). Despite [...] Read more.
Background and Objectives: Genitourinary syndrome of menopause (GSM), previously known as vulvovaginal atrophy, is a chronic, progressive hypoestrogenic condition affecting vulvovaginal, urinary and sexual health in women. Common symptoms include vaginal dryness, itching, dyspareunia, urinary urgency and recurrent urinary tract infections (UTIs). Despite the high prevalence, GSM is underdiagnosed and undertreated, thereby negatively impacting women’s quality of life. To illustrate the practical aspects of GSM diagnosis and provide evidence-based management, we present a case-based narrative review synthesizing recently published, high-quality evidence. Materials and Methods: Evidence was drawn from multiple sources through targeted searches of databases, and included the 2025 AUA/SUFU/AUGS guideline (AUA), the 2024 NICE network meta-analyses (NICE), a 2025 systematic review/meta-analysis in breast-cancer survivors, the 2020 Menopause Society GSM Position Statement, the 2018 NAMS/ISSWSH breast cancer consensus, several primary source citations and other high quality peer-reviewed publications. Results: Five illustrative composite case vignettes of GSM are presented to highlight the evaluation strategy and evidence-supported treatment choices. Nonhormonal options are the first line treatments for mild GSM symptoms, either with or without the addition of vaginal estrogen therapy. For moderate to severe GSM, low-dose vaginal estrogen, vaginal DHEA, and ospemifene are all effective FDA-approved options. In breast cancer survivors, individualized decisions with oncology input are warranted. Maximal caution and a shared decision-making approach is required for women using Aromatase Inhibitors (AIs) for breast cancer risk reduction when choosing treatments for GSM. Conclusions: Treating GSM improves vaginal, sexual and urinary outcomes and quality of life of women. Clinicians need to proactively screen for GSM and offer evidence-based treatment options. The treatment decisions in breast cancer survivors are nuanced, requiring a shared-decision approach. Full article
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13 pages, 368 KB  
Article
Physical Activity, Metabolic Risk and the Primary Allostatic Load Mediators: An Explorative Study
by Francis Osei, Pia-Maria Wippert and Andrea Block
Sports 2026, 14(3), 107; https://doi.org/10.3390/sports14030107 - 9 Mar 2026
Viewed by 771
Abstract
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 [...] Read more.
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
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10 pages, 234 KB  
Article
GDF15 in Patients with Autoimmune Primary Adrenal Insufficiency
by Aleksandra Zdrojowy-Wełna, Jowita Halupczok-Żyła, Katarzyna Kolačkov, Justyna Kuliczkowska-Płaksej, Aleksandra Jawiarczyk-Przybyłowska, Barbara Stachowska, Iga Zendran-Zahorska and Marek Bolanowski
Int. J. Mol. Sci. 2026, 27(5), 2260; https://doi.org/10.3390/ijms27052260 - 27 Feb 2026
Viewed by 460
Abstract
Growth differentiation factor 15 (GDF15) is a stress-response protein that conveys cellular distress signals to the brain and activates neural pathways leading to weight loss. GDF15 levels are increased in glucocorticoid deficiency; however, multiple factors may influence its levels in patients with primary [...] Read more.
Growth differentiation factor 15 (GDF15) is a stress-response protein that conveys cellular distress signals to the brain and activates neural pathways leading to weight loss. GDF15 levels are increased in glucocorticoid deficiency; however, multiple factors may influence its levels in patients with primary adrenal insufficiency (PAI). The objective of this study was to determine circulating GDF15 levels in patients with PAI compared with a control group and to assess their associations with other clinical parameters. We included 37 patients (22 females) with autoimmune PAI and 47 healthy controls. Serum GDF15 levels, together with anthropometrical, hormonal and biochemical parameters, were assessed. Patients with PAI had significantly higher circulating GDF15 levels than controls did (1276.8 ± 952.1 vs. 682.8 ± 270.2 pg/mL, p < 0.001). In both groups, GDF15 levels were positively correlated with age (p < 0.001). In patients with PAI, GDF15 showed positive correlations with disease duration and duration of autoimmune thyroid disease, gonadotropin levels, waist-to-hip ratio, and body fat percentage, and negative correlations with DHEAS and sex hormone levels. In conclusion, GDF15 levels are increased in patients with PAI compared with healthy controls and correlate with age and the duration of autoimmune disease. Full article
18 pages, 305 KB  
Article
Sex Hormones and Keratoconus: In Search of the Link
by Iasonas Makrypoulias, Irini Chatziralli, Dimitris Papaconstantinou, Konstantinos Panagiotopoulos, Stylianos A. Kandarakis, Petros Petrou, Anke Messerschmidt-Roth and Konstantinos Droutsas
J. Clin. Med. 2026, 15(4), 1528; https://doi.org/10.3390/jcm15041528 - 14 Feb 2026
Viewed by 535
Abstract
Background: Keratoconus (KC) is the most common ectatic corneal disorder, causing progressive corneal deformation, visual impairment, and reduced quality of life. Although KC pathogenesis is multifactorial, the contribution of systemic factors, including hormonal regulation, remains incompletely understood. This study aimed to investigate [...] Read more.
Background: Keratoconus (KC) is the most common ectatic corneal disorder, causing progressive corneal deformation, visual impairment, and reduced quality of life. Although KC pathogenesis is multifactorial, the contribution of systemic factors, including hormonal regulation, remains incompletely understood. This study aimed to investigate the role of sex hormones and gonadotropins in KC in a predominantly Greek population. Methods: We recruited 105 KC patients and 71 healthy controls (HC). Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin (PRL), testosterone (TES), dehydroepiandrosterone sulfate (DHEA-S), and progesterone (PRG) were measured and analyzed in relation to corneal tomographic and biomechanical parameters, as well as treatment modality. Results: LH showed positive correlations with corneal biomechanical parameters. KC patients who underwent penetrating keratoplasty exhibited higher FSH levels and a reduced LH/FSH ratio compared with those treated with corneal cross-linking. E2 levels were increased in women over 46 years of age, while PRL correlated with Kmax and Q-value. Men with KC demonstrated reduced TES associated with corneal morphology and biomechanics, increased PRG levels, and reduced DHEA-S in keratoplasty-treated patients. Conclusions: These findings suggest that sex hormones and gonadotropins may contribute to KC pathophysiology, supporting a systemic hormonal component in disease progression. Full article
(This article belongs to the Special Issue Keratoconus: Current Status and Prospects)
19 pages, 2743 KB  
Article
Capturing Emotions Induced by Fragrances in Saliva: Objective Emotional Assessment Based on Molecular Biomarker Profiles
by Laurence Molina, Francisco Santos Schneider, Malik Kahli, Alimata Ouedraogo, Mellis Alali, Agnés Almosnino, Julie Baptiste, Jeremy Boulestreau, Martin Davy, Juliette Houot-Cernettig, Telma Mountou, Marine Quenot, Elodie Simphor, Victor Petit and Franck Molina
Biosensors 2026, 16(2), 81; https://doi.org/10.3390/bios16020081 - 28 Jan 2026
Viewed by 696
Abstract
In this study, we describe a non-invasive approach to objectively assess fragrance-induced emotions using multiplex salivary biomarker profiling. Traditional self-reports, physiological monitoring, and neuroimaging remain limited by subjectivity, invasiveness, or poor temporal resolution. Saliva offers an advantageous alternative, reflecting rapid neuroendocrine changes linked [...] Read more.
In this study, we describe a non-invasive approach to objectively assess fragrance-induced emotions using multiplex salivary biomarker profiling. Traditional self-reports, physiological monitoring, and neuroimaging remain limited by subjectivity, invasiveness, or poor temporal resolution. Saliva offers an advantageous alternative, reflecting rapid neuroendocrine changes linked to emotional states. We combined four key salivary biomarkers, cortisol, alpha-amylase, dehydroepiandrosterone, and oxytocin, to capture multidimensional emotional responses. Two clinical studies (n = 30, n = 63) and one user study (n = 80) exposed volunteers to six fragrances, with saliva collected before and 5 and 20 min after olfactory stimulation. Subjective emotional ratings were also obtained through questionnaires or an implicit approach. Rigorous analytical validation accounted for circadian variation and sample stability. Biomarker patterns revealed fragrance-induced emotional profiles, highlighting subgroups of participants whose biomarker dynamics correlated with particular emotional states. Increased oxytocin and decreased cortisol levels aligned with happiness and relaxation; in comparison, distinct biomarker combinations were associated with confidence or dynamism. Classification and Regression Trees (CART) analysis results demonstrated high sensitivity for detecting these profiles. Validation in an independent cohort using an implicit association test confirmed concordance between molecular profiles and behavioral measures, underscoring the robustness of this method. Our findings establish salivary biomarker profiling as an objective tool for decoding real-time emotional responses. Beyond advancing affective neuroscience, this approach holds translational potential in personalized fragrance design, sensory marketing, and therapeutic applications for stress-related disorders. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis—2nd Edition)
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21 pages, 1211 KB  
Article
Memory Retrieval After an Acute Academic Stressor: An Exploratory Analysis of Anticipatory Cortisol and DHEA Responses
by Sara Garces-Arilla, Vanesa Hidalgo, Camino Fidalgo, Teresa Peiró, Alicia Salvador and Magdalena Mendez-Lopez
Appl. Sci. 2026, 16(3), 1306; https://doi.org/10.3390/app16031306 - 27 Jan 2026
Viewed by 572
Abstract
The relationship between hormonal reactivity to acute stress and memory is well established, but the role of anticipatory cortisol and dehydroepiandrosterone (DHEA) levels remains underexplored. This study aimed to assess the psychobiological responses (anxiety, affect, cortisol and DHEA) to an academic examination, subsequent [...] Read more.
The relationship between hormonal reactivity to acute stress and memory is well established, but the role of anticipatory cortisol and dehydroepiandrosterone (DHEA) levels remains underexplored. This study aimed to assess the psychobiological responses (anxiety, affect, cortisol and DHEA) to an academic examination, subsequent memory performance and associations between anticipatory hormonal response and memory retrieval. Seventy-nine undergraduates (10 males) completed an acquisition session involving picture encoding and immediate free recall. Forty-eight hours later, during the recall session, they sat a written examination followed by delayed free recall and recognition tasks. Results showed higher anticipatory anxiety, negative affect and cortisol levels in the recall session than in the acquisition session. Participants showed poorer delayed recall performance and reduced recognition of neutral pictures. In addition, after correction for multiple comparisons, exploratory hierarchical regression analyses indicated that anticipatory cortisol levels and the cortisol/DHEA ratio assessed prior to the recall session were negatively associated with total delayed free recall performance, with the cortisol/DHEA ratio also being negatively associated with delayed free recall of negative pictures. In the absence of a control group, these findings cannot be used to make causal inferences. However, they are consistent with theoretical accounts of DHEA’s anti-glucocorticoid role and highlight associations between cortisol/DHEA balance and delayed free recall performance, particularly for negative emotional material. Full article
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15 pages, 2987 KB  
Article
Altered Plasma Endocannabinoids and Oxylipins in Adolescents with Major Depressive Disorders: A Case–Control Study
by Akash Chakravarty, Abinaya Sreetharan, Ester Osuna, Isabelle Herter-Aeberli, Isabelle Häberling, Jeannine Baumgartner, Gregor E. Berger and Martin Hersberger
Nutrients 2026, 18(2), 280; https://doi.org/10.3390/nu18020280 - 15 Jan 2026
Viewed by 1488
Abstract
Background: Pediatric Major Depressive Disorder (pMDD) is one of the leading causes of disability in adolescents. There is currently no single explanation that fully accounts for the cause of the disorder, but various factors, including dysregulation of the immune and stress responses, have [...] Read more.
Background: Pediatric Major Depressive Disorder (pMDD) is one of the leading causes of disability in adolescents. There is currently no single explanation that fully accounts for the cause of the disorder, but various factors, including dysregulation of the immune and stress responses, have been linked to its onset. Oxylipins and endocannabinoids, derived from metabolization of n-3 and n-6 polyunsaturated fatty acids (PUFAs), regulate inflammation and have been suggested to attenuate inflammation associated with depression. This study aims to understand whether adolescents with pMDD have altered baseline levels of oxylipins and endocannabinoids compared to healthy adolescents. Methods: In this case–control study, we measured 60 oxylipins and endocannabinoids in plasma from 82 adolescents with pMDD and their matching healthy controls. Results: A Principal Component Analysis revealed substantial variability within each group and only a moderate degree of separation between them. In a paired analysis, the lipid mediators of controls exhibited higher concentrations of n-6 PUFA-derived prostaglandins and thromboxanes (PGE2, PGD2, PGF2a and TXB2), n-3 PUFA-derived TxB3, and the endocannabinoids AEA, EPEA, and DHEA. In contrast, cases had higher concentrations of the n-6 PUFA-derived 6-keto-PGF1a and the n-3 PUFA-derived PGD3. In addition, we observed a higher percentage of oxylipins and endocannabinoids derived from DHA (5.65 ± 5.46% vs. 4.72 ± 4.94%) and AA (16.31 ± 11.10% vs. 12.76 ± 13.46%) in plasma from controls, in line with the higher DHA and AA levels observed in erythrocytes from controls compared to cases. Conclusions: Overall, our results show lower plasma levels of endocannabinoids and lower DHA- and AA-derived oxylipins in adolescents with pMDD, supporting their role in the pathophysiology of pMDD. To infer a causative role of the n-3 and n-6 PUFA-derived oxylipins and endocannabinoids in pMDD, an intervention study with n-3 PUFA supplementation and monitoring of oxylipins and endocannabinoids would be necessary. Full article
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12 pages, 719 KB  
Review
Clinical Strategies for Counteracting Human Ovarian Aging: Molecular Background, Update, and Outlook
by Jan Tesarik and Raquel Mendoza Tesarik
Int. J. Mol. Sci. 2025, 26(24), 11973; https://doi.org/10.3390/ijms262411973 - 12 Dec 2025
Viewed by 1730
Abstract
Ovarian aging (OA) results from the senescence of different cell types present in the ovary, decreasing female fertility and quality of life and augmenting the risk of a variety of fertility-unrelated pathological conditions. The changes observed in the ovarian cells are accompanied by [...] Read more.
Ovarian aging (OA) results from the senescence of different cell types present in the ovary, decreasing female fertility and quality of life and augmenting the risk of a variety of fertility-unrelated pathological conditions. The changes observed in the ovarian cells are accompanied by changes occurring in various elements of the hypothalamic–pituitary–ovarian (HPO) axis, the complex endocrine system that regulates the female reproductive cycle. Issues pertaining to the HPO axis have been addressed in animal models via hormonal treatments with preparations inhibiting ovarian follicular recruitment at the level of the receptors of gonadotropin-releasing hormone (GnRH)-secreting neurons, mainly acting on glutamate- and gamma-aminobutyric acid (GABA)-driven signaling. GnRH agonists and antagonists have also been used in women exposed to chemotherapeutics. HPO-independent OA can be delayed through the administration of different antioxidants and mitochondria-protecting agents, among which melatonin has been shown to be particularly useful. Other therapeutic approaches used with success in women include hormonal and growth factor (GF) modulators, such as growth hormone (GH), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factors (VEGF), and dehydroepiandrosterone (DHEA), and the development of patient-tailored combination-based therapies (IGF-1 + VEGF + DHEA) has also been suggested. Intraovarian injection of autologous platelet-rich plasma (PRP), mitochondrial donation through pronuclear transfer, and ovarian tissue cryopreservation and autotransplantation have also yielded promising results in women, and their use can preserve not only fertility but also the ovarian endocrine function. Personalized mixtures of specific agents (desatinib, quercetin, rapamycin, metformin, resveratrol, melatonin, and coenzyme Q10) targeting different cell types in the ovary are currently under investigation. Overall, this review aims to present a global view of the subject, uniting the physiological and molecular background of this pathology with the history and development of potential treatment strategies and new perspectives in this domain. As such, this study may be helpful both to clinicians facing problems resulting from OA and to researchers pursuing further developments in this field. Full article
(This article belongs to the Special Issue Molecular Research on Embryo Developmental Potential: 2nd Edition)
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27 pages, 1055 KB  
Article
Acute Adrenal Suppression Following Resistance Training in Elite Female Athletes: A Comprehensive Steroid Profile
by Sabrina Vollrath, Norman Bitterlich, Dennis Lüdin, Adrian Rothenbühler, Anthony C. Hackney, Silvio R. Lorenzetti, Anna Drewek, Basil Achermann, Therina du Toit and Petra Stute
Sports 2025, 13(12), 426; https://doi.org/10.3390/sports13120426 - 3 Dec 2025
Viewed by 2041
Abstract
Aim: This prospective observational study aimed to evaluate acute adrenal-derived hormonal responses and training performance in elite female athletes during resistance training with respect to the female cycle. Methods: In 19 elite female athletes, acute hormonal responses to resistance training were examined over [...] Read more.
Aim: This prospective observational study aimed to evaluate acute adrenal-derived hormonal responses and training performance in elite female athletes during resistance training with respect to the female cycle. Methods: In 19 elite female athletes, acute hormonal responses to resistance training were examined over four weeks, measured before and 60 min after exercise. Liquid chromatography–mass spectrometry provided a comprehensive steroid profile, including classical and adrenal-specific 11-oxygenated androgens. Performance metrics were tracked using a velocity-based training method. Results: Sixty minutes after resistance training, significant acute changes in steroid hormone concentrations were observed. Levels of 11β-hydroxyandrostenedione (11OHA4) (−0.707 nmol/L; p = 0.012, −20.0%), androsterone (−0.201 nmol/L; p = 0.049, −14.8%), and dehydroepiandrosterone (DHEA) (−3.813 nmol/L; p = 0.006, −17.1%) decreased significantly. The total sum of glucocorticoids, mineralocorticoids, and bioactive androgens decreased. No significant differences in absolute or relative velocity loss and estimated one-repetition maximum were observed, suggesting comparable strength and fatigue across menstrual cycle phases. Conclusions: The observed post-exercise decline in glucocorticoids, mineralocorticoids, and androgens such as DHEA indicates a coordinated acute suppression of adrenal steroidogenesis in response to resistance training in female elite athletes. No differences in strength parameters were observed across menstrual cycle phases. Full article
(This article belongs to the Special Issue Women's Special Issue Series: Sports)
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