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12 pages, 255 KB  
Article
Influence of Estradiol Levels and Menstrual Cycle Phase on Basal and Exercise-Induced ROS and IL-6 Responses in Eumenorrheic Women
by Markus Gassner, Johanna Diewald, Linda Leichtfried, Lucie Zeller, Serena Ryan, Karl-Heinz Wagner and Daniel König
Sports 2026, 14(5), 168; https://doi.org/10.3390/sports14050168 - 22 Apr 2026
Viewed by 489
Abstract
Biological differences between sexes—particularly due to fluctuating levels of 17β-estradiol and menstrual cycle dynamics—may influence exercise-induced reactive oxygen species (ROS) formation, inflammation and exercise performance. Despite these considerations, there is a lack of research exploring how estradiol and menstrual cycle phases may impact [...] Read more.
Biological differences between sexes—particularly due to fluctuating levels of 17β-estradiol and menstrual cycle dynamics—may influence exercise-induced reactive oxygen species (ROS) formation, inflammation and exercise performance. Despite these considerations, there is a lack of research exploring how estradiol and menstrual cycle phases may impact exercise performance, exercise-induced ROS formation and inflammation. This study aimed to examine whether estradiol concentration or menstrual cycle phase may be significantly associated with resistance circuit high-intensity interval training (HIIT) performance, as well as exercise-induced formation of ROS and Interleukin-6 (IL-6). A total of 30 young healthy female participants completed a single bout of resistance-based HIIT in a fasted state. Blood samples were collected at four time points: at baseline after overnight fasting, two hours after consumption of 0.5 L of water (pre-HIIT), immediately post exercise (post-HIIT) and after 15 min of recovery (15-post-HIIT). Additionally, participants attended six fasting baseline assessments scheduled across various menstrual cycle days. These sessions enabled the assessment of estradiol, ROS and IL-6 concentrations throughout the menstrual cycle without being confounded by nutritional factors. Neither baseline levels of ROS nor IL-6 differed significantly between menstrual cycle phases (luteal vs. follicular ROS: 0.013 µmol/min, p = 0.716; IL-6: 0.052, p = 0.679) menstruation status (yes vs. no ROS: −0.056 µmol/min, p = 0.259; IL-6: −0.302 pg/mL, p = 0.088) or 17β-estradiol concentrations (low (11–≤72.5 pg/mL) vs. high (>72.5–394 pg/mL) ROS: −0.038 µmol/min, p = 0.266; IL-6: +0.015 pg/mL, p = 0.906). On the resistance-circuit-HIIT intervention day, no significant differences in ROS or IL-6 were observed between estradiol concentrations (ROS: p = 0.477; IL-6: p = 0.249), menstrual cycle phase (ROS; p = 0.752; IL-6: p = 0.557) or menstruation status (ROS: p = 0.383; IL-6: p = 0.808) from baseline to pre-HIIT, post-HIIT or 15-post-HIIT. These findings should be interpreted with caution, as the menstrual cycle phases were assigned using a calendar-based approach without biochemical ovulation confirmation and the subgroup sizes were relatively small. These findings suggest that natural 17-beta-Estradiol fluctuations within the menstrual cycle, as well as differences in the menstrual cycle itself, may not substantially modulate ROS or IL-6 responses to acute resistance-based HIIT in young healthy female adults. Full article
(This article belongs to the Special Issue Women's Special Issue Series: Sports)
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18 pages, 4861 KB  
Article
Emodin Promoted Intestinal Secretion of GLP-1 and Limited Cognitive Deficits in Young Bilateral Ovariectomized Rats
by Xin-Yuan Liu, Chao-Yuan Ye, Yuan-Cheng Liu, Meng-Ying Zhao, Ya-Nan Li, Li Lin, Yan-Jun Du, Ying-Yan Fang and Qing Tian
Int. J. Mol. Sci. 2026, 27(8), 3414; https://doi.org/10.3390/ijms27083414 - 10 Apr 2026
Viewed by 425
Abstract
Estrogen deficiency is an established risk factor for menopausal brain dysfunctions in women. Urgent exploration of drugs is needed to improve estrogen deficiency-related brain dysfunctions without the side effects of estrogen supplements. Three-month-old rats had bilateral ovariectomy (OVX) performed and were treated with [...] Read more.
Estrogen deficiency is an established risk factor for menopausal brain dysfunctions in women. Urgent exploration of drugs is needed to improve estrogen deficiency-related brain dysfunctions without the side effects of estrogen supplements. Three-month-old rats had bilateral ovariectomy (OVX) performed and were treated with emodin (EMO, 80 mg/kg/day) and 17 β-estradiol (EST, 0.5 mg/kg/day). Brain functions were evaluated by cognition and emotion-related behavioral tests. Levels of glucagon-like peptide-1 (GLP-1) and estrogen in blood, mRNA levels of estrogen receptor (ER) α, ERβ, GLP-1 receptor (GLP-1R), proprotein convertase subtilisin/kexin type 1 (PCSK1) and proglucagon (proGCG) in intestinal segments, and brain ERα and GLP-1R levels were evaluated. Contractions of isolated intestinal segments were recorded. Additionally, an ERβ antagonist, PHTPP (200 μg/kg/day), was used to clarify the role of ERβ. EST and EMO significantly ameliorated cognition deficit and depressive behaviors in OVX rats, and reduced neuronal loss and synaptic abnormalities in the hippocampus and prefrontal cortex. The blood GLP-1 levels of sham operation rats (sham, 3.09 pg/mL), EMO-treated (2.57 pg/mL) and EST-treated OVX rats (2.64 pg/mL), were higher than that of OVX rats (1.03 pg/mL). EMO had no effect on the blood estrogen level. Furthermore, EMO up-regulated mRNA levels of ERβ in ileum, colon, and cerebral GLP-1R level, while EST increased mRNA levels of ERβ in colon and cerebral ERα level. In vitro intestinal segment spontaneous contraction tests revealed that EMO reduced contraction amplitudes in isolated intestinal segments from OVX rats, with the ileum and proximal colon showing greater sensitivity to EMO. The ileum and colon segments from OVX rats were less sensitive to EST as compared to those of normal rats. Upon PHTPP intervention, the up-regulated intestinal mRNA levels of ERβ, PCSK1, proGCG, blood GLP-1 level by EMO, and the beneficial effects of EMO in abnormal behaviors of OVX rats were significantly inhibited. Overall, it was found that EMO up-regulated blood GLP-1 level via intestinal Erβ-dependent mechanism and increased brain GLP-1R level, which may be involved in the neuroprotection of EMO in OVX animals. Full article
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11 pages, 995 KB  
Article
Effects of Inhaling Clary Sage (Salvia sclarea L.) Essential Oil on Dysmenorrhea-Related Symptoms, Salivary Antioxidant Capacity, and Hormone Levels in Female Collegiate Athletes: A Randomized Crossover Trial
by Tetsuro Kobayashi, Wakana Nakama, Michio Yamashita, Kana Kondo, Shoichi Tsuji, Seiji Shioda and Fumiko Takenoya
Appl. Sci. 2026, 16(7), 3234; https://doi.org/10.3390/app16073234 - 27 Mar 2026
Viewed by 2703
Abstract
Many female athletes experience menstrual cycle issues. We investigated clary sage (Salvia sclarea L.) essential oil inhalation’s effect on dysmenorrhea-related symptoms, antioxidant capacity, and salivary hormone levels in female collegiate athletes. This randomized crossover trial included 20 female collegiate athletes (mean age: [...] Read more.
Many female athletes experience menstrual cycle issues. We investigated clary sage (Salvia sclarea L.) essential oil inhalation’s effect on dysmenorrhea-related symptoms, antioxidant capacity, and salivary hormone levels in female collegiate athletes. This randomized crossover trial included 20 female collegiate athletes (mean age: 20.2 ± 1.2 years). The participants were randomly assigned to one of two conditions: clary sage essential oil (intervention) or water (control) inhalation. Each condition lasted for one menstrual cycle, with inhalation administered at bedtime for 60 min using a diffuser. Dysmenorrhea-related symptoms and their impact on athletic performance were assessed using a visual analog scale. Biochemical analyses included salivary antioxidant capacity and cortisol, estradiol, and progesterone level measurements. Data from 12 participants who completed the study were analyzed. Compared with water inhalation, clary sage essential oil inhalation significantly reduced menstrual pain, sleep disturbances, irritability, and anxiety (all p < 0.05). The impact of dysmenorrhea-related symptoms on performance and total symptom scores was also significantly lower in the intervention condition than in the control condition (both p < 0.05). Additionally, salivary antioxidant capacity was significantly higher following clary sage essential oil inhalation than after water inhalation (p < 0.05). However, no significant differences were observed in the salivary cortisol, estradiol, or progesterone levels between the intervention and control conditions. Clary sage essential oil inhalation may be an effective nonpharmacological approach for alleviating dysmenorrhea-related symptoms and enhancing antioxidant capacity in female collegiate athletes. The results highlight its potential as a noninvasive and easy-to-use daily method for managing menstrual symptoms. Full article
(This article belongs to the Special Issue Biosynthesis and Applications of Natural Products)
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22 pages, 2903 KB  
Article
Antidiabetic Effect of Substituting Processed Meat with Reduced-Fat and Diatomaceous Earth-Enriched Pâtés in Middle-Aged Female Wistar Rats
by Rocío Redondo-Castillejo, Claudia Quevedo-Torremocha, María Luisa de la Cruz Conty, Marina Hernández-Martín, Aránzazu Bocanegra, Adrián Macho-González, Susana Cofrades, María Dolores Álvarez, Sara Bastida, María Elvira López-Oliva, Juana Benedí and Alba Garcimartín
Foods 2026, 15(5), 878; https://doi.org/10.3390/foods15050878 - 4 Mar 2026
Viewed by 569
Abstract
This study evaluates a non-invasive and feasible nutritional strategy as a realistic intervention to prevent or mitigate T2DM in one-year-old female Wistar rats. This strategy is based on replacing a commercial pâté (CP) with a functional one, either a silicon-enriched commercial pâté (Si-CP), [...] Read more.
This study evaluates a non-invasive and feasible nutritional strategy as a realistic intervention to prevent or mitigate T2DM in one-year-old female Wistar rats. This strategy is based on replacing a commercial pâté (CP) with a functional one, either a silicon-enriched commercial pâté (Si-CP), a reduced-fat pâté formulated with a biopolymeric emulsion (BP), or a silicon-enriched and reduced-fat biopolymeric pâté (Si-BP). After consumption of a high-saturated fat high-cholesterol diet, CP rats exhibited elevated fecal excretion, fasting serum glucose, insulin, and LDL cholesterol, and altered islet morphology. Versus the CP group, the Si-CP consumption group exhibited significantly reduced fecal output (1.17 ± 0.02 vs. 2.09 ± 0.44) and serum insulin (12.06 ± 7.89 vs. 20.74 ± 7.44), triglycerides (47.51 ± 4.46 vs. 58.24 ± 9.97), LDL cholesterol (34.63 ± 5.14 vs. 42.20 ± 4.98), and ghrelin (32.49 ± 24.66 vs. 78.35 ± 22.85). Although BP rats also exhibited some positive effects, Si-BP animals presented the most promising results. Compared to the CP group, Si-BP consumption significantly reduced fecal excretion (1.44 ± 0.24) and serum glucose (129.1 ± 10.40 vs. 154.9 ± 15.76), insulin (9.49 ± 6.06), triglycerides (46.91 ± 5.13), and estradiol (528.2 ± 45.00 vs. 634.4 ± 98.87), preserved islet circularity (0.88 ± 0.02 vs. 0.82 ± 0.01), and significantly increased tibia length (4.09 ± 0.12 vs. 3.95 ± 0.09) and wet weight (0.65 ± 0.07 vs. 0.56 ± 0.06). This study demonstrates the antidiabetic effects of silicon from diatomaceous earth (4 mg Si/kg body/day) incorporated into pâté in middle-aged female rats. Replacing CP with a functional alternative improved the health status of diabetic female rats, supporting its potential as an effective nutritional adjuvant. Full article
(This article belongs to the Special Issue Advances in Biological Activities of Functional Food (3rd Edition))
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17 pages, 1394 KB  
Review
Dietary Caffeine, Cold Exposure, and the Estrogen–TRPM8 Axis: A Nutri-Environmental Model for Lower Urinary Tract Symptoms in the Menopause Transition: A Narrative Review
by Dong Hee Lee and Jeong Jun Park
Nutrients 2026, 18(5), 825; https://doi.org/10.3390/nu18050825 - 3 Mar 2026
Viewed by 760
Abstract
Background/Objectives: Lower urinary tract symptoms (LUTSs), particularly nocturia and urgency, often intensify during the menopause transition and may worsen with caffeine intake and cold exposure. This review aims to synthesize evidence relevant to a hypothesized caffeine–cold interaction in transitional menopause, focusing on [...] Read more.
Background/Objectives: Lower urinary tract symptoms (LUTSs), particularly nocturia and urgency, often intensify during the menopause transition and may worsen with caffeine intake and cold exposure. This review aims to synthesize evidence relevant to a hypothesized caffeine–cold interaction in transitional menopause, focusing on water homeostasis and the estrogen–transient receptor potential melastatin 8 (TRPM8) cold-sensory axis, and to propose potentially actionable, nutrition-centered intervention candidates for future testing. Methods: Structured narrative review of PubMed, Embase, Web of Science, and citation tracking (inception–January 2026). Evidence was mapped into a mechanistic framework distinguishing established from hypothesis-generating links; no formal systematic-review study selection or meta-analysis was performed. Results: Caffeine can increase urine output via renal mechanisms (adenosine receptor antagonism and natriuresis) and may lower bladder sensory thresholds. Because half-life is long and variable, afternoon intake can extend into sleep, potentially increasing awakenings and nocturnal voids. Human studies link colder indoor environments to nocturia/overactive bladder, and passive pre-bedtime heating is associated with fewer nocturnal voids. We propose that repeated nighttime cold may amplify caffeine-related diuresis and may shift urine production toward the night, while estradiol decline may heighten TRPM8-mediated cold sensory gain, potentially contributing to urgency/frequency flares. A testable 2 × 2 cold × caffeine framework can operationalize dose, timing, and metabolism, pairing voiding diaries and bedroom temperature sensing with copeptin profiling. Conclusions: Transitional menopause may represent a susceptibility window in which endocrine instability and estradiol decline could plausibly increase sensitivity to indoor cold exposure and caffeine intake, potentially contributing to nocturia and urgency. The hypothesis label ‘dual hormone suppression’ (attenuated nocturnal AVP signal plus estradiol decline) may provide a mechanistic substrate for cold-exacerbated nocturnal polyuria, while an estrogen–TRPM8 axis may amplify cold-evoked urgency. Potentially actionable candidates include chronobiological caffeine timing/management and low-burden thermal strategies; nevertheless, menopause-stage-specific epidemiologic and clinical evidence for a caffeine × cold interaction remains limited and several mechanistic links are extrapolated, so prospective diary- and biomarker-enabled studies and controlled trials are needed to validate mechanisms and refine cold-sensitive endotypes. Full article
(This article belongs to the Special Issue Nutrition, Lifestyle and Women’s Health)
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19 pages, 8536 KB  
Article
Anthocyanins Alleviate Persistent Corpus Luteum and Ovarian Quiescence in Beef Cows by Modulating Gut Microbiota and Reducing Granulosa Cell Apoptosis
by Jiandong Wang, Xue Zhang, Youli Yu, Yi Wu and Yanan Guo
Animals 2026, 16(5), 762; https://doi.org/10.3390/ani16050762 - 1 Mar 2026
Viewed by 463
Abstract
Persistent corpus luteum (PCL) and ovarian quiescence (OQ) are key manifestations of ovarian dysfunction (OD) that lead to reduced reproductive capacity in beef cattle, posing a serious challenge to the industry. Anthocyanins (ACNs) are known for their antioxidant properties. This study aimed to [...] Read more.
Persistent corpus luteum (PCL) and ovarian quiescence (OQ) are key manifestations of ovarian dysfunction (OD) that lead to reduced reproductive capacity in beef cattle, posing a serious challenge to the industry. Anthocyanins (ACNs) are known for their antioxidant properties. This study aimed to investigate the regulatory effects of ACNs on PCL and OQ and to explore the underlying mechanisms. Forty-eight beef cows diagnosed with both OQ and PCL were selected and continuously fed ACNs for 60 days. The results showed that the regulatory effects of ACNs were dose-dependent. A high dose of ACNs (ACNH) significantly increased the number of large follicles and reduced the occurrence of PCL. ACNH treatment significantly decreased serum progesterone (P4) levels and increased estradiol (E2) levels. Furthermore, ACNH reduced microbial diversity in OD cows but significantly increased the abundance of Patescibacteria, Actinobacteriota, Proteobacteria, and Chloroflexi, while decreasing the abundance of Desulfobactera, indicating that ACNs may affect ovarian function by regulating the gut microbial environment. In an ovarian granulosa cell model of oxidative damage, ACN intervention could reduce oxidative stress levels and mitigate oxidative damage. ACNs downregulated various pro-apoptotic genes, such as P53, Fas, and Bax, while upregulating anti-apoptotic genes Bcl-2 and Bcl-xL, suggesting that ACNs significantly inhibit cell apoptosis. To conclude, these results demonstrate that ACNs improve the ovarian function of beef cows by regulating gut microbiota and reducing oxidative stress-induced apoptosis in ovarian granulosa cells, thereby enhancing the reproductive capacity of beef cattle that show reproductive disorders. These findings provide a theoretical basis for the application of ACNs in the cattle industry and showcase their potential value as natural antioxidants. Full article
(This article belongs to the Section Animal Reproduction)
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12 pages, 548 KB  
Article
17β-Estradiol Does Not Designate Non-Sex-Specific Early Ventricular Arrhythmia in Acute Myocardial Infarction, in Contrast to C-Reactive Protein
by Niya E. Semedzhieva, Adelina Tsakova, Vesela Lozanova, Petar I. Atanasov and Dobrinka Dineva
Int. J. Mol. Sci. 2026, 27(2), 970; https://doi.org/10.3390/ijms27020970 - 19 Jan 2026
Viewed by 477
Abstract
Despite the evidence from experimental studies that endogenous hormones have sex-related effects on action potential duration, the relationship between gonadal steroids and ventricular repolarization in acute myocardial infarction (AMI) is not clear. We tested the hypothesis that endogenous 17β-estradiol (E2) and 17β-estradiol-to-testosterone ratio [...] Read more.
Despite the evidence from experimental studies that endogenous hormones have sex-related effects on action potential duration, the relationship between gonadal steroids and ventricular repolarization in acute myocardial infarction (AMI) is not clear. We tested the hypothesis that endogenous 17β-estradiol (E2) and 17β-estradiol-to-testosterone ratio (E2/T) are associated with inflammation, influencing the occurrence of early ventricular arrhythmia (VA) in AMI. Electrocardiographic (ECG) repolarization indices, including resting heart rate (HR), corrected QT (QTc) interval, QTc minimum (QTcmin), QTc maximum (QTcmax), and QTc dispersion (QTcd), along with E2, total T, and the ratio of E2 to T (E2/T), were measured and analyzed after percutaneous coronary intervention in 86 patients (36 women, 41.9%). In a non-specific sex analysis, the incidence of early VA in the course of AMI was determined by the ejection fraction of the left ventricle (OR 0.876, p = 0.054), and by the peak levels of plasma C-reactive protein (OR 1.026, p = 0.077). Endogenous plasma 17β-estradiol tended to be higher in cases with early ventricular arrhythmia (124.5 ± 79 vs. 181 ± 192.8, p = 0.089). 17β-estradiol levels were significantly predicted by C-reactive protein (OR 1.050, p = 0.042). This study found that reduced systolic function of the left ventricle and higher peak CRP levels are associated with endogenous plasma 17β-estradiol in the acute phase of MI, and predicted the risk of early in-hospital ventricular arrhythmia. Full article
(This article belongs to the Special Issue Steroids in Human Disease and Health)
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18 pages, 563 KB  
Article
Effects of Supervised Physiotherapy-Based Exercise on Ovarian Reserve and Spontaneous Pregnancy in Women with Diminished Ovarian Reserve: A Controlled Pilot Study
by Barbara Petra Kovács, Júlia Balog, Judit F. Szigeti, Barbara Sebők, Marianna Török and Szabolcs Várbíró
Life 2026, 16(1), 120; https://doi.org/10.3390/life16010120 - 13 Jan 2026
Viewed by 1120
Abstract
Diminished ovarian reserve (DOR) is a major cause of female infertility with limited treatment options, and lifestyle interventions such as supervised, structured exercise therapy may support ovarian function. In this pilot study, we evaluated the effect of a supervised, physiotherapy-based exercise program combined [...] Read more.
Diminished ovarian reserve (DOR) is a major cause of female infertility with limited treatment options, and lifestyle interventions such as supervised, structured exercise therapy may support ovarian function. In this pilot study, we evaluated the effect of a supervised, physiotherapy-based exercise program combined with antioxidant supplementation on ovarian reserve markers and spontaneous pregnancy rates in 24 infertile women aged 20–42 years, with body mass index (BMI) 18.5–30 kg/m2, regular menstruation, anti-Müllerian hormone (AMH) < 1.1 ng/mL, and antral follicle count ≥3 measured on days 2–4 of the cycle. Participants were randomized into two groups of 12: Both groups received standardized oral therapy, while the intervention group additionally participated in a three-month supervised, structured exercise therapy programme. Analysis of covariance was used to adjust for baseline differences in AMH and BMI, as groups differed significantly in BMI at baseline. At post-treatment assessment, AMH levels were significantly higher in the intervention group, whereas FSH, LH, estradiol, prolactin, and TSH levels did not change significantly. Spontaneous pregnancies were recorded both during the intervention period and throughout a follow-up period of up to six months. Spontaneous pregnancy occurred in 7 out of 12 participants in the intervention group versus 1 out of 12 in the control group, resulting in four and one live births, respectively. These findings suggest that combining supervised, structured exercise therapy with antioxidant supplementation may enhance ovarian reserve and improve the likelihood of spontaneous pregnancy in women with diminished ovarian reserve. Full article
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19 pages, 1624 KB  
Article
Mycotoxin-Induced Oxidative Stress and Its Impact on Human Folliculogenesis: Examining the Link to Reproductive Health
by Zsuzsanna Szőke, Eszter Ruff, Patrik Plank, Zsófia Molnár, Lili Hruby, Apolka Szentirmay, Márkó Unicsovics, Bernadett Csókay, Katalin Varga, Tímea Buzder, Miklós Sipos, Katalin Sára-Popovics, Dóra Holéci, Katalin Posta and Levente Sára
Toxins 2025, 17(12), 574; https://doi.org/10.3390/toxins17120574 - 28 Nov 2025
Cited by 1 | Viewed by 1902
Abstract
Climate change has contributed to increased mycotoxin contamination in food systems, posing a growing threat to human health, including reproductive health. Our study aimed to investigate how mycotoxins entering the follicular fluid affect oxidative stress processes. We analyzed 88 follicular fluid samples from [...] Read more.
Climate change has contributed to increased mycotoxin contamination in food systems, posing a growing threat to human health, including reproductive health. Our study aimed to investigate how mycotoxins entering the follicular fluid affect oxidative stress processes. We analyzed 88 follicular fluid samples from infertile patients for common mycotoxins, including deoxynivalenol (DON), zearalenone (ZEN), its main metabolite alpha-zearalenol (aZOL), and aflatoxin M1 (AfM1), and examined their relationship with oxidative stress markers (MDA, SOD, GPx, CAT, and TAOC) and hormones (cortisol, estradiol, and anti-Müllerian hormone). Higher mycotoxin levels were associated with increased oxidative stress, particularly elevated MDA levels, and disrupted antioxidant enzyme activity. Notably, DON showed a positive correlation with SOD and estradiol levels, indicating a compensatory antioxidant response, while AfM1 served as a negative predictor. The metabolite aZOL was strongly linked to cortisol, with effects influenced by estradiol levels, implying endocrine-disrupting activity. Importantly, the interaction between DON and AMH appeared to impact dominant follicle development, suggesting a potential mechanism by which environmental toxins impair fertility without directly reducing oocyte or embryo counts. These results highlight the complex, dose-dependent effects of mycotoxins on oxidative and hormonal balances within the follicular environment, with implications for oocyte quality and reproductive success. Better understanding these mechanisms could help develop early diagnostic markers and targeted interventions to improve fertility outcomes in women exposed to changing environmental conditions. Full article
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15 pages, 449 KB  
Article
Impact of a High-Fat High-Carbohydrate (HFHC) Diet at a Young Age on Steroid Hormone Hair Concentrations in Mice: A Comparison with a Control Diet and Nutraceutical Supplementation
by Isabella Pividori, Tanja Peric, Antonella Comin, Natalia Rosso, Silvia Gazzin, Mirco Corazzin and Alberto Prandi
Life 2025, 15(11), 1722; https://doi.org/10.3390/life15111722 - 7 Nov 2025
Viewed by 1509
Abstract
An unhealthy prepubertal diet can have long-lasting effects throughout life. This study investigated hair concentrations of adrenal and sex steroids, in an in vivo mouse model of juvenile obesity subjected to control (CTRL), obesogenic (HFHC) diet, or nutraceutical supplementation (silymarin or coconut oil) [...] Read more.
An unhealthy prepubertal diet can have long-lasting effects throughout life. This study investigated hair concentrations of adrenal and sex steroids, in an in vivo mouse model of juvenile obesity subjected to control (CTRL), obesogenic (HFHC) diet, or nutraceutical supplementation (silymarin or coconut oil) diets. 87 3-week-old C57BL/6 mice (42 females, 45 males) were fed CTRL or HFHC diets for 8 weeks. Afterward, the CTRL group continued on CTRL diet while the HFHC diet group was divided into five groups: HFHC, HFHC→CTRL, HFHC→CTRL + silymarin (SIL), HFHC→HFHC + SIL and HFHC→HFHC + Coconut oil. At 4 weeks, the HFHC group showed increased cortisol/dehydroepiandrosterone (DHEA) ratio compared to CTRL group. At 20 weeks, the HFHC→HFHC group showed higher levels of progesterone (P4) and dehydroepiandrosterone sulfate (DHEA-S) and lower levels of estradiol (E2) compared to the CTRL→CTRL group. The switch from HFHC→CTRL was the optimal therapy because the body weight and almost all the hormones were close to those observed for the CTRL diet group. Supplement with SIL or Coconut oil reduced DHEA-S and increased in E2 compared with the endocrine setting seen with the HFHC diet. These interventions should be considered as supportive measures rather than substitutes for dietary correction. Full article
(This article belongs to the Section Medical Research)
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30 pages, 778 KB  
Review
Matrix Metalloproteinase-9 (MMP-9) as a Therapeutic Target: Insights into Molecular Pathways and Clinical Applications
by Marta Wolosowicz, Slawomir Prokopiuk and Tomasz W. Kaminski
Pharmaceutics 2025, 17(11), 1425; https://doi.org/10.3390/pharmaceutics17111425 - 4 Nov 2025
Cited by 21 | Viewed by 6058
Abstract
Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that plays a central role in extracellular matrix (ECM) remodeling, angiogenesis, immune cell trafficking, and cytokine activation. Dysregulated MMP-9 activity has been implicated in the pathogenesis of diverse conditions, including atherosclerosis, aneurysm formation, chronic obstructive pulmonary [...] Read more.
Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that plays a central role in extracellular matrix (ECM) remodeling, angiogenesis, immune cell trafficking, and cytokine activation. Dysregulated MMP-9 activity has been implicated in the pathogenesis of diverse conditions, including atherosclerosis, aneurysm formation, chronic obstructive pulmonary disease (COPD), asthma, neurodegeneration, and malignancy. Although broad-spectrum synthetic MMP inhibitors were initially developed as therapeutic agents, clinical trials failed due to lack of selectivity, poor tolerability, and impairment with physiological tissue repair. This outcome has shifted attention toward indirect pharmacological modulation of MMP-9 using drugs that are already approved for other indications. In this paper, we review the evidence supporting MMP-9 modulation by established therapeutics and adjunctive strategies. Cardiometabolic agents such as statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), metformin, and pioglitazone reduce MMP-9 expression and enzymatic activity, contributing to vascular protection, improved insulin sensitivity, and attenuation of aneurysm progression. Anti-inflammatory and respiratory drugs, including glucocorticoids, phosphodiesterase-4 (PDE4) inhibitors, macrolide antibiotics, montelukast, and nonsteroidal anti-inflammatory drugs (NSAIDs), suppress MMP-9-driven airway inflammation and pathological tissue remodeling in asthma, COPD, and acute lung injury. Tetracycline derivatives, particularly sub-antimicrobial dose doxycycline, directly inhibit MMP-9 activity and are clinically validated in the treatment of periodontal disease and vascular remodeling. Hormone-related therapies such as rapamycin, estradiol, and tamoxifen exert tissue- and disease-specific effects on MMP-9 within endocrine and oncologic pathways. In parallel, nutritional interventions—most notably omega-3 polyunsaturated fatty acids and antioxidant vitamins—provide adjunctive strategies for mitigating MMP-9 activity in chronic inflammatory states. Taken together, these findings position MMP-9 as a modifiable and clinically relevant therapeutic target. The systematic integration of approved pharmacologic agents with lifestyle and nutritional interventions into disease-specific treatment paradigms may facilitate safer, context-specific modulation of MMP-9 activity and unveil novel opportunities for therapeutic repurposing. Full article
(This article belongs to the Section Drug Targeting and Design)
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17 pages, 2966 KB  
Article
Cryptotanshinone Suppresses BVDV Propagation by Suppressing Cell Apoptosis and Restoring Hormone Secretion in Bovine Granulosa Cells
by Xiaoliang Chen, Haipeng Feng, Lei Wang, Jingyan Zhang, Xiaorong Lu, Guowei Xu, Siqi Liu, Qinxin Yang, Xiaowei Feng, Junyan Wang, Kang Zhang and Jianxi Li
Viruses 2025, 17(11), 1433; https://doi.org/10.3390/v17111433 - 28 Oct 2025
Viewed by 847
Abstract
Bovine viral diarrhea virus (BVDV) constitutes a significant pathogen adversely threatening reproductive performance in the cattle industry, primarily by inducing ovarian dysfunction characterized by aberrant hormone synthesis and impaired follicular development. Although several commercial vaccines are available, they are insufficient for prevention and [...] Read more.
Bovine viral diarrhea virus (BVDV) constitutes a significant pathogen adversely threatening reproductive performance in the cattle industry, primarily by inducing ovarian dysfunction characterized by aberrant hormone synthesis and impaired follicular development. Although several commercial vaccines are available, they are insufficient for prevention and control BVDV infection, underscoring the necessity for the development of novel therapeutic drugs. This study aimed to investigate the antiviral activity of cryptotanshinone (CRY) against BVDV infection and its protective effects on bovine ovarian granulosa cells (BOGCs). An in vitro infection model was established by exposing BOGCs to BVDV. The results demonstrated that CRY exhibits anti-BVDV activity and alleviates detrimental effects on BOGCs through multiple mechanisms. Comparative analysis revealed that therapeutic administration of CRY constitutes the most effective mode of intervention. Furthermore, CRY promotes the secretion of estradiol (E2) and progesterone (P4) in BOGCs, counteracting the BVDV-induced reduction in these hormones. Moreover, CRY shows protective activity by mitigating BVDV-induced apoptosis in BOGCs. In summary, this study is the first to elucidate the inhibitory effect of CRY on BVDV and its regulatory role in BOGCs function, suggesting that CRY holds potential application value in the clinical treatment of BVDV-related reproductive disorders. Full article
(This article belongs to the Section Animal Viruses)
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18 pages, 6175 KB  
Article
Metabolomic Analysis of Sea Cucumber Ovum Hydrolysates in Cyclophosphamide-Induced Premature Ovarian Failure
by Xinxin Wang, Leilei Sun, Mingbo Li, Shunmin Gong, Shijia Huang, Jiarun Gao, Yu Zhang and Liqin Sun
Foods 2025, 14(21), 3605; https://doi.org/10.3390/foods14213605 - 23 Oct 2025
Viewed by 1046
Abstract
Sea cucumber ovum are high-value compounds that remain after the processing of sea cucumbers, and their optimal utilization has long posed a challenge. In this research, we systematically examined the therapeutic effects of sea cucumber ovum hydrolysate (SCH) on premature ovarian failure (POF) [...] Read more.
Sea cucumber ovum are high-value compounds that remain after the processing of sea cucumbers, and their optimal utilization has long posed a challenge. In this research, we systematically examined the therapeutic effects of sea cucumber ovum hydrolysate (SCH) on premature ovarian failure (POF) and its underlying mechanism. We utilized a model of ICR mice induced with 100 mg/kg cyclophosphamide (CP) to evaluate the therapeutic influence of SCH on ovarian performance. The ovarian and uterine indices were significantly decreased in the POF group compared to the control group; however, these trends were notably reversed following SCH intervention. The therapeutic effects of SCH were positively reflected by the alterations induced by CP in levels of estradiol (E2), follicle-stimulating hormone (FSH), testosterone (T), luteinizing hormone (LH), and anti-Müllerian hormone (AMH). Regarding oxidative stress, SCH was found to enhance superoxide dismutase (SOD) activity and decrease malondialdehyde (MDA) levels, while also alleviating apoptosis in ovarian granulosa cells. Metabolomics analysis revealed hypoxanthine, mannitol, neocnidilide, tryptophan, palmitoleic acid, and protoporphyrinogen IX as potential biomarkers. In conclusion, SCH effectively improves POF induced by CP, thereby reinforcing the potential application of SCH in the domain of functional foods. Full article
(This article belongs to the Section Foodomics)
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13 pages, 1668 KB  
Article
Sex Steroids in COVID-19 Patients with Hypertension: An Exploratory Study
by Pavitra Kotini-Shah, Shaveta Khosla, Felipe Borges Almeida, Luca Spiro Santovito, Heather Prendergast and Graziano Pinna
Int. J. Mol. Sci. 2025, 26(18), 8976; https://doi.org/10.3390/ijms26188976 - 15 Sep 2025
Viewed by 2222
Abstract
Sex and gender disparities have emerged as critical determinants of COVID-19 outcomes, with males exhibiting higher hospitalization and mortality rates than females. Sex steroids such as estradiol, progesterone, and testosterone have been proposed as modulators of these differences, given their known roles in [...] Read more.
Sex and gender disparities have emerged as critical determinants of COVID-19 outcomes, with males exhibiting higher hospitalization and mortality rates than females. Sex steroids such as estradiol, progesterone, and testosterone have been proposed as modulators of these differences, given their known roles in inflammation, immune function, and vascular health. However, the precise hormonal mechanisms underlying COVID-19 severity, particularly among individuals with comorbid hypertension—a major risk factor for adverse outcomes—remain unclear. In this study, we investigated circulating levels of key sex hormones and their neuroactive metabolites in 116 hypertensive COVID-19 patients enrolled through an urban academic emergency department. Our findings revealed distinct sex-based hormonal profiles and associations with disease severity. Males exhibited higher serum estradiol and testosterone levels, while progesterone levels were significantly higher in postmenopausal females. Notably, hospitalized patients showed elevated estradiol and progesterone levels compared to non-hospitalized individuals, whereas ICU-admitted patients had significantly lower concentrations of all three hormones. A unique exception was ICU-admitted postmenopausal females, who exhibited increased serum testosterone levels relative to non-ICU females. Additionally, in males, elevated 3α-diol was associated with hospitalization and ICU admission, while lower allopregnanolone and estradiol levels correlated with hypoxia in males and females, respectively. These results highlight a dynamic, sex-specific hormonal response to COVID-19 progression in hypertensive individuals, suggesting early upregulation and late depletion of protective sex steroids. Understanding these patterns may improve clinical risk stratification and inform the development of sex-targeted therapeutic interventions for COVID-19 and related inflammatory conditions. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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26 pages, 842 KB  
Review
The Effect of Curcumin on Postmenopausal Symptoms: A Systematic Review Based on Randomized Controlled Trials
by Buket Akyakar, İrem Nur Şahin, Duygu Ağagündüz, Dávid Szép and Ferenc Budán
Int. J. Mol. Sci. 2025, 26(17), 8260; https://doi.org/10.3390/ijms26178260 - 26 Aug 2025
Cited by 1 | Viewed by 5110
Abstract
Menopause is a natural and inevitable part of life for women, leading to many physical and psychological changes accompanied by declining estrogen levels. This systematic review aimed to evaluate the effect of curcumin, due to its antioxidant and anti-inflammatory properties, on postmenopausal outcomes [...] Read more.
Menopause is a natural and inevitable part of life for women, leading to many physical and psychological changes accompanied by declining estrogen levels. This systematic review aimed to evaluate the effect of curcumin, due to its antioxidant and anti-inflammatory properties, on postmenopausal outcomes in women. This comprehensive analysis of RCTs (randomized controlled trials) published in the last decade was selected through a search of PubMed, Wiley, Scopus, and Web of Science (PROSPERO Identifier: CRD42024549735). Study selection and data extraction were performed using exclusion and inclusion criteria according to the PICOS framework (P: Population, I: Intervention, C: Comparison, O: Outcomes, S: Study designs). Of the twelve studies that met the criteria, 11 had a low-risk bias, but reports were conflicting on serum estradiol levels, bone density markers, and vasomotor symptoms; no significant effects on physical, psychological, or sexual functions were observed. For cardiometabolic biomarkers, short-term curcumin intake showed no significant effects, while long-term interventions using bioavailable forms of curcumin showed improvements in serum fasting glucose, fasting insulin, HOMA-IR (Homeostatic Model Assessment of Insulin Resistance), and lipid parameters. There are a limited number of studies examining the effect of curcumin intake on menopause-related outcomes. While overdose has been observed in some studies attempting to restore estradiol levels, no significant effects have been observed. However, curcumin intake impacts postmenopausal symptoms (e.g., improving symptoms of osteoporosis) through its antioxidant and anti-inflammatory effects. Different forms and doses, combinations, and durations of interventions may influence outcomes. Better-designed studies are needed to understand the potential effects of curcumin intake during menopause. Full article
(This article belongs to the Special Issue The Biological Activities of Curcumin and Its Analogues)
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