Search Results (389)

Postmenopausal osteoporosis is an age-related condition in which estrogen deficiency drives low-grade inflammation and oxidative stress, disrupting the homeostatic balance between bone formation and resorption. Since osteopenia represents a critical intermediate stage, preventive strategies are essential to mitigate its progression. Preclinical studies suggest that hydrogen sulfide (H₂S), a gaseous mediator with antioxidant properties, protects bone metabolism by supporting osteoblast function and suppressing osteoclast activity. Building on this evidence, we conducted the first exploratory clinical trial assessing the effects of inhalation therapy with sulfurous mineral waters on systemic biomarkers in postmenopausal women with osteopenia. Thirty-eight eligible participants underwent a daily inhalation of sulfurous waters (14.6 mg/L sulfide) for 12 consecutive days. Biomarkers of oxidative stress, inflammation, and bone turnover were assessed at baseline, immediately post-treatment, and five days after cessation in the serum of patients. The treatment was well tolerated and did not cause any early adverse effect. Serum H₂S levels, measured in a subset of participants, significantly increased, confirming systemic bioavailability. Sulfurous water inhalation induced a marked change in oxidative stress, with malondialdehyde levels declining by up to 37% from baseline. Pro-inflammatory cytokines, particularly IL-8 and MIP-1α, were significantly decreased (up to 50–70%) at the end of the treatment. Reference bone turnover markers P1NP and CTX-1 did not show significant changes; however, BALP exhibited a significant increase, suggesting the activation of pathways linked to biomineralization. These findings provide preliminary human evidence that inhaled sulfurous waters enhance systemic H₂S bioavailability and modulate redox and inflammatory pathways associated with bone remodeling in osteopenic women, supporting the rationale for further controlled pharmacodynamic investigations evaluating the potential of H₂S in bone health. Full article

Endocrine-disrupting chemicals (EDCs) perturb hormonal homeostasis, dysregulating multiple biological pathways and subsequently resulting in adverse health outcomes, including impaired reproductive function. Bisphenols represent an important subclass of EDCs with widespread use in polycarbonate plastics, thermal paper formulations, epoxy resins, and various everyday consumer products. Bisphenol A (BPA) was the first bisphenol to be synthesized, with extensive industrial applications. However, the concerns over its potential health risks, most notably reproductive dysfunction, prompted the development and introduction of several structurally related BPA analogues. That said, studies on the potential hormonal effects of these BPA analogues remain limited. Therefore, strengthening the evidence base on their reproductive safety evaluation remains an essential priority for ensuring their safe application, and this study contributes to that broader objective. The study aimed to explore the potential endocrine-disrupting activity of two commonly used BPA analogues, bisphenol F (BPF) and bisphenol S (BPS), on reproductive hormone signalling, contributing to ongoing safety assessment efforts. The molecular interactions of these analogues with the estrogen receptor-α (ERα) and estrogen receptor-β (ERβ) were analyzed through structural binding characterization employing the induced fit docking (IFD) approach using the Schrödinger 2019 suite. The overall results revealed that the two indicated BPA analogues were placed successfully in the ligand-binding pockets of ERα and ERβ. Their binding pattern and molecular interactions showed certain similarities; however, they did not fully replicate the amino acid residue environment of the native ligands of ERα and ERβ, estradiol. Notably, the binding energy estimations revealed that BPF and BPS showed substantially lower values than those calculated for native ligands of ERα and ERβ. In summary, this study suggests that BPF and BPS exhibit lower predicted binding affinity toward ERα and ERβ under the applied molecular docking conditions. However, these computational findings do not establish receptor activation, endocrine potency, or safety outcomes, and the potential involvement of other reproductive signalling pathways warrants further investigation. Full article

Breast cancer is the most common malignant tumor among women worldwide, and its occurrence is closely associated with long-term exposure to environmental pollutants. Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants widely present in the living environment. Epidemiological studies indicate that exposure to PAHs increases the risk of breast cancer. PAH derivatives exhibit stronger toxicity or endocrine-disrupting activity than their parent compounds; however, research on their specific effects and mechanisms in breast cancer cells remains limited. For this purpose, this study selected 3-Hydroxybenz[a]anthracene, a PAH derivative with potential estrogenic activity, as the target compound. Using the estrogen receptor-positive breast cancer cell line MCF-7 as the model, we performed EdU staining, colony formation assays, scratch healing assays, Transwell invasion assays, and apoptosis assays and preliminarily examined changes in relevant signaling proteins via Western blot. Results indicate that 3-Hydroxybenz[a]anthracene promotes proliferation and migration in MCF-7 cells while inhibiting apoptosis under certain conditions, but it has no effect on cell invasion. Mechanistically, it upregulates key proteins including AKT, c-Myc, E-Cadherin, Vimentin, MMP2, MMP9 and Bcl-2 while downregulating p-AKT expression. This study confirms through in vitro experiments that 3-Hydroxybenz[a]anthracene exhibits estrogen-like effects and modulates malignant behavior in breast cancer cells by regulating relevant signaling pathways. These findings provide experimental evidence for further evaluating the potential role of this environmental contaminant in breast cancer initiation and progression. Full article

Zearalenone (ZEN), a prevalent estrogenic mycotoxin found in grains and oils, poses significant health risks due to its endocrine-disrupting properties. This study elucidates the application of a laccase-mimicking copper-tannic acid (CuTA) nanozyme as an effective catalyst for the degradation of ZEN. The CuTA nanozyme was capable of directly catalyzing the oxidation of ZEN, with optimal reaction conditions observed at a pH of 7.0 and temperatures ranging from 37 to 57 °C. The degradation products of ZEN were identified as 13-hydroxy-zearalenone (13-OH-ZEN) and 15-hydroxy-zearalenone (15-OH-ZEN). Furthermore, cytotoxicity assessments demonstrated that the CuTA nanozyme-mediated degradation of ZEN effectively reduced the hepatotoxicity of this mycotoxin. The E-screen bioassay revealed a 43.7-fold reduction in the estrogenic activity of ZEN after CuTA-mediated degradation. In corn oil, the CuTA nanozyme achieved 82% ZEN removal within 12 h and maintained 58% efficiency after four reuse cycles. These results highlight the potential use of the CuTA nanozyme to detoxify ZEN in corn oil. Full article

Background: Di(2-ethylhexyl) phthalate (DEHP) is a high-production-volume plasticizer and ubiquitous environ-mental contaminant with established endocrine-disrupting potential. While zebrafish transcriptomic studies have typically used high concentrations and long exposure windows, less is known about genome-wide responses during late embryogenesis/early larval maturation under environmentally relevant exposures. Here we profiled whole-organism transcriptomic responses to a short DEHP exposure during a developmentally sensitive transition (96–120) hours post-fertilization, hpf) and interpreted responses using differential expression, enrichment analyses, and endocrine-focused protein–protein interaction (PPI) network modeling. Methods: Wild-type AB zebrafish lar-vae (96 hpf) were exposed to DEHP at [10⁻⁹ M] or solvent control for 24 h. Larvae were pooled per replicate (25 lar-vae/pool) and processed for poly(A)-selected RNA-seq. Reads were quality-controlled, aligned to the Danio rerio reference genome, and quantified at gene- level. Differential expression was performed using DESeq2. Functional enrichment used KEGG over-representation analysis (ORA) and gene set enrichment analysis (GSEA). Zebrafish genes were mapped to human orthologs for GO/KEGG and STRING-based endocrine subnetworks, which were visualized and interrogated using STRINGdb and visNetwork. Results: Low-dose, short-term exposure does not produce large gene-level effects but induces coordinated, pathway-level transcriptional remodeling. KEGG ORA showed significant enrichment of MAPK signaling and regulation of actin cytoskeleton with additional enrichment of axon guidance and neuroactive ligand–receptor interaction. GSEA detected coordinated downregulation of KEGG neurodegeneration collections with negative normalized enrichment scores reflecting shared gene sets re-lated to mitochondrial function, proteostasis, cytoskeletal organization, and stress-response pathways. Endo-crine-focused STRING subnetworks indicated consistent downregulation of CYP19A1 within estrogen metabo-lism/biosynthesis modules and downregulation of upstream androgen biosynthetic enzymes HSD3B2 and CYP17A1, alongside upregulation of HSD17B3 and proteostasis-associated factors including DNAJA1. Endocrine network to-pology highlighted regulatory and cofactor nodes affecting receptor-linked transcription, consistent with indirect endocrine modulation rather than large receptor-transcript changes. Conclusions: In summary, this study demon-strates that exposure to low-dose DEHP during a critical period of zebrafish embryonic development is associated with modest but coordinated transcriptomic changes across multiple biological pathways. Pathway enrichment and network-based analyses highlight estrogen- and androgen-associated processes, along with broader signaling, met-abolic, and structural pathways, as transcriptionally responsive during this window. Importantly, these findings reflect molecular-level associations rather than direct evidence of functional or physiological endocrine disruption. Instead, they identify candidate pathways and regulatory networks that may be sensitive to low-level environmen-tal exposure and warrant further investigation. Collectively, this work underscores the value of systems-level tran-scriptomic approaches for detecting subtle, pathway-wide responses to environmentally relevant exposures during development. Full article

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin that adversely affects directly exposed individuals, yet the intergenerational consequences of paternal ZEN exposure remain poorly understood. In this study, we investigated the impact of paternal ZEN exposure on hepatic outcomes in F1 offspring, with a focus on the underlying molecular mechanisms. Kunming male mice (F0) were fed a ZEN-supplemented diet (10 mg/kg bw/day) for 5 weeks. Their F1 offspring developed hepatic steatosis, elevated oxidative stress, and a chronic inflammatory state. Proteomic analysis of F1 livers revealed significant dysregulation of immune and inflammatory pathways, including NF-κB and chemokine signaling, with reduced MHC-I and increased MHC-II levels. These findings provide mechanistic insight into how paternal ZEN exposure disrupts hepatic immune-metabolic homeostasis in F1 offspring, highlighting a critical and understudied pathway in intergenerational toxicology. Full article

Zearalenone (ZEA) is a prevalent non-steroidal estrogenic mycotoxin in feed and feedstuffs. This study investigated the effects of graded dietary purified ZEA standard (0, 0.2, 0.5, 1, 2, and 4 mg/kg) on growth performance, blood biochemistry, oxidative stress, immune response, intestinal morphology, histopathology, and gut microbiota in broilers. The use of purified ZEA standard eliminates confounding effects from co-occurring contaminants and the reduced nutritional quality of naturally contaminated feed, allowing an accurate assessment of ZEA-specific effects. A total of 216 one-day-old Arbor Acres male broilers were randomly allocated into six treatment groups, each with six replicates of six birds, for a 42-day trial. At the regulatory limit (0.5 mg/kg) and below, no overt toxic effects were observed on growth performance, hematology, or serum biochemistry. Although alterations in oxidative stress markers, specifically decreased liver superoxide dismutase (SOD) activity and reduced ileal glutathione peroxidase (GSH-Px) activity, and in immune markers, including increased interleukin-2 (IL-2) levels in the jejunum and ileum and decreased ileal interleukin-10 (IL-10) levels, were observed at 0.2–0.5 mg/kg, these changes did not cause tissue damage or functional impairment. Toxicological alterations emerged only at higher doses (1–4 mg/kg), comprising impaired jejunal morphology and moderate lung secretory cell metaplasia. The highest dose (4 mg/kg) further induced severe renal tubular degeneration and necrosis, accompanied by significant disruption of the jejunal microbiota. In conclusion, these findings indicate that purified ZEA at the regulatory limit exhibits no overt toxicity in broilers, although higher contamination levels pose clear risks to intestinal, pulmonary, and renal health. Full article

Background: Follicle-stimulating hormone (FSH)-based vaccines show the potential to disrupt spermatogenesis without disturbing sexual function and libido in males. Herein, we developed a novel FSH vaccine based on the tandem of a conserved 13-amino acid receptor-binding epitope of FSHβ (FSHβ13AA-T) and tested its effect on reproductive physiology and function using the male mouse as a model. Methods: Serum reproductive hormone levels, testicular histology, daily sperm production, sperm motility, libido and fertility of male mice following FSH vaccination were determined. Results: Compared to placebo-immunized controls, FSH vaccination triggered (p < 0.05) marked antibody generation, inhibited spermatogenesis and reduced sperm motility (p < 0.05), without adverse effects on serum LH and testosterone levels as well as the libido of male mice. Mechanistically, FSH vaccination suppressed (p < 0.05) testicular local estrogen production by downregulated aromatase encoding gene Cyp19a1 expression and also downregulated (p < 0.05) expression of key spermatogenic genes in testes, including Creb, INHα, Wnt2, Aqp8, Cmtm2a and Spata19, thus disrupting and impairing spermatogenesis and sperm motility. Conclusions: These results demonstrate that immunization of male mice against FSHβ13AA could substantially inhibit spermatogenesis and reduce sperm motility. Thus, FSHβ13AA-based vaccines hold potential for development as male contraceptives that do not compromise libido in species including men in which FSH is essential for spermatogenesis. Full article

Background: Diminished ovarian reserve is characterized by a decrease in oocyte count and estrogen levels, which leads to infertility. The genetic and epigenetic mechanisms in MI to MII transition or complete MII phase in the oocyte maturation process estrogen receptor alpha and piRNA relationship were evaluated. Methods: This study analyzed 100 cumulus oophorous complex samples from normoresponder and DOR patients undergoing IVF, subdivided into metaphase I and metaphase II stages. To elucidate the ER-α, PIWIL3, piR-651, and piR-823 genes qRT-PCR was used and qualitative ER-α protein expressions were determined by immunohistochemistry. Pearson’s correlation analysis was utilized to evaluate the interactions between genes within each experimental group. Results: The DOR samples exhibited significant downregulation of ER-α gene and protein expression compared to the NOR controls. PIWIL3 gene, piR-651, and piR-823 expressions reduced in DOR MI and MII. Strong positive correlations among ER-α, PIWIL3, piR-651, and piR-823 were observed in NOR, whereas DOR showed weaker correlations and immunohistochemistry verified lower ER-α protein levels in DOR. Conclusions: The disruption of ER-α and piRNA-related gene networks in DOR may underlie the suboptimal maturation of oocytes, and monitoring ER-α, PIWIL3, piR-651, and piR-823 expressions could facilitate early determination of maturation stages and improve assessment of ovarian reserve. The potential for transposition to MII in NOR and DOR oocytes was observed in relation to the association between ER-α protein/gene expression and PIWIL3, which regulates ER-α. Moreover, piR-651 and piR-823, whose expressions depend on estrogen level, indirectly regulate oocyte maturation from MI to MII in both NOR and DOR epigenetically. We suggest that the MI and MII stages of oocytes could be determined earlier in NOR and DOR cases by controlling ER-α, PIWIL3, piR-651 and piR-823 expressions. These molecular markers indicate promise for diagnostic applications in reproductive medicine, warranting further validation in larger cohorts. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disorder that is increasingly recognized as a systemic condition with profound implications for female reproductive potential. In addition to pelvic distortion and impaired folliculogenesis, growing evidence indicates that intrinsic alterations in oocyte morphology, mitochondrial function, and developmental competence contribute to infertility. The disease is driven by a multifactorial interplay of somatic mutations, epigenetic remodeling, immune dysregulation, and aberrant steroid signaling, which together create a pro-inflammatory, oxidative, and fibrotic microenvironment. Elevated cytokines, reactive oxygen species, and disrupted granulosa-cell function within the follicular niche impair meiotic progression, cytoplasmic maturation, and mitochondrial integrity, potentially accelerating oocyte aging and diminishing reproductive longevity. Epigenetic and post-transcriptional disturbances—including altered DNA methylation, histone modifications, and RNA-splicing defects—further reinforce estrogen dominance, progesterone resistance, and impaired decidualization, with downstream consequences for ovarian–endometrial communication. Although morphological abnormalities have been documented in oocytes from women with endometriosis, clinical outcomes remain heterogeneous, highlighting the need for integrative models that connect molecular alterations to functional reproductive endpoints. A deeper understanding of these mechanisms is essential for identifying biomarkers of oocyte competence and modifiable strategies—ranging from nutritional optimization to reduction of environmental risk factors—in clinical care to safeguard the reproductive potential of women with endometriosis. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age worldwide. It is characterized by the presence of endometrial-like tissue outside the uterine cavity, which frequently results in dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. While hormonal medications and surgical procedures are common treatments, they are often constrained by adverse effects and high recurrence rates. The aim was to systematically identify, critically appraise, and synthesize randomized controlled trials evaluating vitamin D, C, and E supplementation in women with endometriosis, focusing on their effects on pelvic pain, dysmenorrhea, dyspareunia, quality of life, oxidative and inflammatory biomarkers, and fertility-related outcomes, and to highlight methodological gaps that can inform future research and integrated therapeutic strategies. Following PRISMA guidelines, seven eligible RCTs were identified from databases including PubMed, Scopus, and ScienceDirect. The quality of these studies was assessed using the Jadad Scoring System and Cochrane RoB 2 tool. High-dose supplementation of vitamin D (50,000 IU) was found to significantly reduce pelvic pain and improve biochemical markers such as hs-CRP and total antioxidant capacity (TAC). Vitamin D appears to modulate endometrial pathways by reducing active β-catenin protein activity, which may disrupt signaling associated with lesion invasion and survival. Additionally, combined Vitamin C and E therapy (typically 1000 mg/day of Vitamin C and 800 IU/day of Vitamin E) acts synergistically to scavenge free radicals. This intervention significantly decreased oxidative stress markers, including malondialdehyde (MDA) and reactive oxygen species (ROS). Patients reported significant improvements in symptoms, including a 43% reduction in daily pelvic pain and a 37% reduction in dysmenorrhea. Despite physiological improvements, there was no statistically significant increase in pregnancy rates observed across the trials. Vitamin supplementation with D, C, and E represents a safe, low-cost adjunct therapy that can effectively mitigate endometriosis-related oxidative stress and pelvic pain. While these vitamins show promise for symptom relief, further research with larger sample sizes is required to determine their long-term impact on fertility outcomes and lesion regression. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking estrogen, progesterone, and HER2 receptors. This characteristic limits the effectiveness of hormonal and targeted therapies, and despite advances in chemotherapy (ChT), radiotherapy (RT), surgery, targeted therapy (TT) and immunotherapy (IT), clinical outcomes remain poor, highlighting an urgent need for new therapeutic strategies. The development of advanced nanotechnology-based strategies has opened new avenues for the diagnosis and therapy of TNBC. This review focuses on photothermal therapy (PTT) combined with nanotechnology-based strategies. PTT constitutes an emerging modality for oncological treatment that leverages light irradiation, mostly in the near-infrared (NIR) spectral region, to induce the localized thermal ablation of malignant tissues. When combined with gold nanoparticles (AuNPs), PTT is significantly potentiated. AuNPs have distinctive optical and physicochemical characteristics, rendering them highly effective as multifunctional nanoplatforms. Upon irradiation, AuNPs act as efficient photothermal agents, inducing localized hyperthermia. This thermal effect disrupts cellular homeostasis and initiates a cascade of cell death pathways, including apoptosis and necrosis, culminating in tumor regression. This review describes the latest therapeutic advances of PTT and AuNPs. As this innovative approach progresses toward clinical application, future studies and trials will be crucial in determining its potential for TNBC management and improving patient outcomes. Full article

Background and Objectives: Recurrent urinary tract infection (rUTI) remains common and burdensome, with growing emphasis on antibiotic stewardship and non-antibiotic prevention. We characterized what women with rUTI know, do, and receive in everyday care and identified gaps between patient understanding and guideline-concordant management. Materials and Methods: We conducted a single-center, cross-sectional survey of consecutive adult women presenting with rUTI to a urology clinic in Poland. A structured questionnaire captured demographics, knowledge, symptoms and triggers, diagnostics, treatments and prevention, and satisfaction. Responses were standardized a priori; descriptive statistics and exploratory comparisons were performed (N = 36). Results: The mean age was 53.0 years (SD: 14.8). Only 36.1% identified the correct rUTI definition, while 83.3% recognized bacteria as the common cause. The symptom profile was dominated by frequency and dysuria (each 88.9%); 27.8% reported intercourse as a precipitant, and this was more frequent among sexually active women (43.5% vs. 7.7%; p = 0.031). Over half (55.6%) perceived no seasonality. The median number of episodes in the prior year was five (IQR 4–6). Urine culture was obtained before treatment in 38.9% and after treatment in 13.9%. The overall satisfaction with care was low to moderate (13.9% were very satisfied, 61.1% were moderately satisfied, and 25.0% were dissatisfied). Prior antibiotic exposure included ciprofloxacin (55.6%), furazidin (75.0%), and fosfomycin (47.2%). The uptake of preventive options was uneven: immunoactive vaccines accounted for 19.4%, methenamine hippurate for 16.7%, pelvic floor physiotherapy for 33.3%, and vaginal estrogen for 5.6% overall (9.5% among women ≥ 50 years). Conclusions: In this clinic-referred cohort, rUTI was frequent and disruptive, factual knowledge was limited, urine culture use was inconsistent, and fluoroquinolone exposure remained common. Preventive care was misaligned with guidelines, with underuse of vaginal estrogen and variable adoption of non-antibiotic strategies. Targeted education, stewardship, and structured access to evidence-based prevention may improve outcomes. Full article

Osteoporosis is a prevalent metabolic bone disorder characterized by reduced bone mass, compromised microarchitecture, and increased fracture risk. Its pathogenesis extends beyond simple bone mineral density (BMD) loss and reflects complex disruptions in bone remodeling governed by osteoblast–osteoclast coupling and systemic metabolic factors. This review lays particular emphasis on diabetes mellitus-related osteoporosis (DOP) and estrogen deficiency-induced osteoporosis (EDOP), discussing bone remodeling between osteoclastogenesis and osteoblast differentiation regulated by key signaling pathways, including the RANKL/RANK/OPG, Wnt/β-catenin, BMP–Smad, Hedgehog, and inflammatory cytokine networks. This review then explores how chronic hyperglycemia, insulin deficiency or resistance, oxidative stress, ferroptosis, advanced glycation end products, and low-grade inflammation disrupt bone homeostasis in diabetes, resulting in impaired bone quality and elevated fracture risk, particularly in type 2 diabetes. In parallel, we discuss the genomic and non-genomic actions of estrogen in maintaining skeletal integrity and elucidate how estrogen deficiency accelerates bone resorption and suppresses bone formation through altered cytokine signaling, oxidative stress, and impaired mechanotransduction. Advances in diagnostic strategies beyond BMD, including trabecular bone score, high-resolution peripheral quantitative computed tomography, and emerging biomarkers, are reviewed. Finally, this review summarizes current and emerging therapeutic approaches tailored to DOP and EDOP, emphasizing the need for mechanism-based, individualized management. A deeper understanding of these shared and distinct pathways may facilitate improved risk stratification and the development of targeted interventions for osteoporosis. Full article

Zearalenone (ZEA) is a common estrogenic mycotoxin in rabbit breeding that causes various toxic effects. Selenomethionine (SeMet) is a feed additive with potent anti-inflammatory and antioxidant properties. To evaluate the protective role and action mechanism of SeMet against ZEA-induced liver injury, 90-day-old rabbits were randomized into five groups: control, ZEA-alone, and SeMet pretreatment at 0.2, 0.35, and 0.5 mg/kg. SeMet was administered for 21 days, followed by continuous intragastric ZEA (1.2 mg/kg B.W.) for 7 days starting on day 15. As a result, ZEA exposure significantly elevated liver function parameters, disrupted lobular architecture, and impaired glycogen synthesis. It also induced liver oxidative stress, thus upregulating expressions of Bax, Cyt C, Caspase-3, and Caspase-9, triggering hepatocyte apoptosis, mitochondrial damage, and mitophagy. SeMet pretreatment activated SIRT1, reduced the acetylated FOXO1/P53 levels, and enhanced CAT and SOD2 expression, mitigating ZEA-induced oxidative stress, apoptosis, and mitophagy. Based on the above findings, SeMet’s alleviating effect might be mediated via the SIRT1-FOXO1/P53 pathway, with 0.35 mg/kg of SeMet exerting the optimal efficacy, highlighting its therapeutic potential for mitigating ZEA-induced hepatotoxicity in rabbits. Full article