Search Results (301)

Background: The vaginal microbiota plays a crucial role in maintaining urogenital health, and its disruption may contribute to adverse surgical outcomes. Transobturator tape (TOT) procedures are widely used in the treatment of stress urinary incontinence (SUI), yet factors influencing postoperative complications remain incompletely understood. This study aimed to evaluate the association between preoperative vaginal microbiota and postoperative complications following TOT surgery. Methods: This pilot observational study included 24 women diagnosed with SUI who underwent TOT surgery between February and December 2023. Prior to surgery, all patients received standardized preoperative preparation, including local estrogen therapy and antimicrobial treatment. Vaginal swabs were collected and analyzed using quantitative culture methods to assess microbial composition. Clinical, microbiological, and surgical data were analyzed. Associations between microbiota profiles and postoperative complications were evaluated using univariate and multivariable statistical analyses. Results: Postoperative complications occurred in 5 patients (20.8%). Patients with complications had significantly higher body mass index (BMI) (33.8 ± 5.0 vs. 27.9 ± 5.1 kg/m²; p = 0.028) and a higher prevalence of previous surgeries (80% vs. 42%; p = 0.048). Microbiological analysis revealed that Lactobacillus spp. deficiency was more frequent in patients with complications (60% vs. 21%; p = 0.048), as was the presence of mixed microbial flora indicative of dysbiosis (100% vs. 47%; p = 0.041). Multivariable logistic regression identified BMI (OR = 1.16; p = 0.031), previous surgeries (OR = 3.9; p = 0.049), Lactobacillus spp. deficiency (OR = 4.8; p = 0.038), and mixed flora (OR = 6.2; p = 0.027) as independent factors associated with postoperative complications. Conclusions: Preoperative vaginal microbiota may significantly influence outcomes following TOT surgery. Vaginal dysbiosis, particularly Lactobacillus spp. deficiency and mixed microbial flora, appears to be associated with an increased risk of postoperative complications. These findings suggest that microbiota assessment could be considered in preoperative evaluation. Further large-scale studies using advanced microbiome analysis are warranted to confirm these results. Full article

Aim: Increasing female participation in elite sports has highlighted the need to better understand how intensive training affects reproductive health and sexual function. The aim of this cross-sectional study was to assess the prevalence of libido loss and sexual dysfunction in female climbers and to explore potential associations with low energy availability within the “relative energy deficiency in sports” framework. Methods: This is a cross-sectional multinational cohort study of female climbers as well as non-athletic controls from Switzerland, Germany, Austria, and Italy, to investigate female sexual function in athletes compared to a non-athletic control group from the general population through specific questionnaires, e.g., eating disorder screening (EDE-QS), sexual function (FSFI-d), low energy availability (LEAF-Q), and estrogen deficiency symptoms (MRS-II). A nonparametric procedure was used to check whether distribution differences between the groups were detectable. Where distributional differences were statistically detectable, selected parameters were considered as covariates in an analysis of covariance (ANCOVA). This has been carried out with the following covariates: LEAF- Q, MRS-II-score, age, BMI, and subjective satisfaction. Only participants without the signs of an eating disorder (normal EDE-QS scores) were included in this study. Results: A total of 173 women were included (elite: n = 31, amateur: n = 55, controls: n = 87). No significant differences in overall sexual function (FSFI-d total score) (p = 0.518) and libido (p = 0.610) were observed between groups in unadjusted analyses. However, after adjustment for relevant covariates, including MRS-II score and subjective sexual satisfaction, elite climbers demonstrated significantly lower FSFI-d scores compared to controls (p = 0.018). Notably, elite climbers reported higher subjective sexual satisfaction than controls (p = 0.002). Conclusions: While overall sexual function did not differ in unadjusted analyses, adjusted comparisons suggest that elite climbers may experience subtle differences in sexual function. Full article

Background/Objectives: Obesity and menopause are major determinants of skeletal deterioration; however, their combined effects on bone remodeling and associated cellular bioenergetics remain incompletely understood. This study aimed to determine whether obesity induces osteoporotic alterations under both estrogen-replete and estrogen-deficient conditions and to evaluate the therapeutic potential of dental tissue-derived mesenchymal stem cells (D-MSCs). Methods: Female mice were subjected to ovariectomy (OVX) and/or high-fat diet (HFD) feeding for 16 weeks to establish obesity-associated osteoporosis models. D-MSCs were administered intraperitoneally at defined intervals. Body weight and serum leptin levels were measured to assess metabolic status. Femoral tissues were analyzed by quantitative real-time PCR for estrogen receptors (ERα, ERβ), inflammatory markers (Il-1β, Tnf-α), mitochondrial regulators (Pgc1α, Pgc1β), and the OPG/RANKL ratio. Histological analysis was performed to evaluate bone marrow adiposity. Results: HFD significantly increased body weight and serum leptin levels in both intact and OVX mice. Obesity was associated with reduced expression of ERα and ERβ, decreased Pgc1α levels, and a lower OPG/RANKL ratio, accompanied by increased Il-1β, Tnf-α, and Pgc1β expression. D-MSC administration attenuated body weight gain and reduced leptin levels, particularly in OVX mice. In femoral tissue, D-MSC treatment restored estrogen receptor expression, increased Pgc1α, decreased Pgc1β, and normalized the OPG/RANKL ratio. In addition, inflammatory marker expression and bone marrow adiposity were reduced following MSC administration. Conclusions: Obesity induces bone remodeling dysregulation under both intact and estrogen-deficient conditions, characterized by altered estrogen signaling, inflammatory activation, and mitochondrial imbalance. D-MSC administration was associated with partial restoration of these alterations, suggesting a potential role in modulating metabolic and skeletal homeostasis in obesity-associated bone loss. Full article

Background: Estrogen deficiency negatively affects alveolar bone by disrupting key regulators of bone remodeling. Humic acids (HAs) are natural compounds with recognized antioxidant and anti-inflammatory properties that may attenuate bone resorption. This study investigated the effects of HAs on alveolar bone in an experimental model of estrogen depletion. Methods: Female C57BL/6 mice were randomly assigned to four groups: Sham, Sham + HA, ovariectomized (OVX), and OVX + HA. Estrogen deficiency was induced by bilateral ovariectomy. HAs derived from vermicomposted biomass were administered daily by oral gavage (80 mg/kg) for 28 days. At the end of the experimental period, mandibles were collected for structural, mineral, and histological analyses. Bone elemental composition was assessed using scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM/EDS). Alveolar bone loss was evaluated by histomorphometry, while RANKL and osteoprotegerin (OPG) expression were assessed by immunohistochemistry. Osteoclasts were quantified by tartrate-resistant acid phosphatase (TRAP) staining. Data were analyzed using two-way ANOVA followed by Bonferroni’s post hoc test. Results: Ovariectomy resulted in reduced calcium and phosphorus content, increased alveolar bone loss, elevated RANKL immunolabeling, increased osteoclast numbers, and a higher RANKL/OPG ratio (p < 0.05). HA treatment increased calcium and phosphorus content and attenuated alveolar bone loss in OVX animals (p < 0.05). Additionally, HA treatment partially increased OPG expression and reduced the RANKL/OPG ratio (p < 0.05), without significantly affecting RANKL immunolabeling or osteoclast numbers. Conclusions: HA therapy attenuated alveolar bone resorption in a model of estrogen depletion, possibly associated with modulation of the RANKL/OPG balance. Full article

Background/Objectives: Postmenopausal osteoporosis is associated with systemic metabolic alterations related to estrogen deficiency. This exploratory study investigated the early metabolic, oxidative, and histomorphological effects of alendronate, a standardized hop extract, and their combination in ovariectomized (OV) rats. Methods: Female Wistar rats (n = 70) were randomly allocated to seven groups: six OV groups or a sham-operated control (n = 10 per group). Following a 30-day postoperative period for model development, animals received daily treatment for 2 weeks with vehicle (placebo), low- or high-dose alendronate (1 and 2 mg/kg, respectively), standardized hop extract (60 mg/kg), or both. Oxidative stress markers, liver and perigonadal adipose tissue histology, and tissue metabolism were assessed. Results: No evidence of adverse hepatic, renal, or systemic effects was observed. Oxidative damage markers remained largely unchanged, although ovariectomy was associated with reduced hepatic catalase activity, which was increased by high-dose alendronate. Treatment-related morphological changes in adipose tissue were observed. Serum triglyceride levels were unaffected, whereas total cholesterol was significantly increased in animals receiving hop extract. Hepatic triglyceride levels were influenced by alendronate treatment, modified by hop extract. MALDI-TOF MS suggested no OV-related alterations in amino acid, lipid, steroid, and redox-related metabolism in liver and adipose tissue. The subsequent treatments, especially in the high-dose alendronate group and hop-extract group, partially modified these metabolic signatures; however, these findings remain provisional pending MS/MS validation. Conclusions: Most outcomes were not significantly altered by OV. Alendronate and hop extract exert distinct short-term effects on selected metabolic and oxidative parameters in this exploratory model. Further studies are needed to investigate translational potential. Full article

Background: We previously reported that knocking down the ubiquitin E3 ligase LNX2 in bone marrow monocytes by shRNAs attenuated osteoclastogenesis in vitro. However, the role of LNX2 in the regulation of osteoclasts and bone homeostasis in vivo remains unknown. Methods: In this study, we generated myeloid Lnx2 conditional knockout mice by crossing Lnx2-flox mice with LysM-Cre mice. The role of LNX2 was verified through in vitro osteoclast induction experiments using mononuclear macrophages and experiments on estrogen-deficient osteoporosis models. Results: Micro-CT and histological analysis unveiled that loss of Lnx2 in osteoclast precursor cells decreased osteoclast numbers and increased trabecular bone mass in mice. Moreover, Lnx2 deficiency prevented bone loss in an ovariectomized mouse model of postmenopausal osteoporosis. In vitro mechanistic studies identified that the loss of Lnx2 had little effect on cell proliferation but significantly inhibited the formation of osteoclasts and bone resorption. Furthermore, the deletion of Lnx2 decreased the expression of NOTCH2 and its downstream HES1 via enhancing the level of the NOTCH2 inhibitor, NUMB. Conclusions: Our findings elucidate an important role of Lnx2 in the regulation of osteoclasts and bone metabolism and indicate that Lnx2 is a potential therapeutic target for the treatment of osteoporosis. Full article

Background: Estrogen deficiency and glucocorticoid exposure are major contributors to osteoporosis. Although menaquinone-7 (MK-7) exhibits osteoprotective effects, whether low-dose supplementation is comparable to high-dose treatment remains unclear. Methods: Female Sprague–Dawley rats were assigned to sham control (SC), ovariectomy plus dexamethasone (OVX+Dex), and OVX+Dex treated with low-dose MK-7 (100 μg/kg) or high-dose MK-7 (20 mg/kg). Bone microarchitecture, histopathology, and serum bone turnover markers were evaluated. Results: OVX+Dex induced marked deterioration of trabecular bone microarchitecture, characterized by reduced bone volume and structural disruption. These changes were accompanied by increased osteoclast activity (cathepsin K), decreased osteogenic and extracellular matrix–related markers (cbfa-1, osteonectin, and biglycan), and downregulation of osteoprotegerin, indicating a pronounced imbalance in bone remodeling. Serum analysis further revealed reduced estradiol levels and alterations in circulating bone turnover markers, consistent with a dysregulated high-turnover state. Both low- and high-dose MK-7 significantly improved bone microarchitecture, restored remodeling-related protein expression, and partially normalized serum calcium-regulating hormones and bone turnover markers (all p < 0.05), with no significant differences observed between doses. Conclusions: MK-7 attenuates osteoporosis by restoring the balance between bone resorption and formation. Notably, low-dose MK-7 provides protective effects comparable to high-dose treatment, supporting its potential clinical utility. Full article

Poor bone quality in osteoporotic patients remains a major challenge for achieving predictable osseointegration. This study serves as a mechanistic complement to previously reported structural data, aiming to investigate the molecular pathways underlying the synergy between nanostructured surfaces and autologous blood concentrates in compromised bone. Ninety-six Wistar rats were divided into healthy (SHAM) and osteoporotic (OVX) groups. Implants with nanostructured hydroxyapatite (NanoHA) or dual acid-etched (DAE) surfaces were installed in the tibiae, associated or not with leukocyte- and platelet-rich fibrin (L-PRF). Gene expression (RT-qPCR) for Runx2, Alpl, Bglap, Spp1, Tnfrsf11, and Tnfrsf11b was assessed at 7 and 30 days. In compromised systemic conditions (OVX), the NanoHA + L-PRF association promoted a robust “molecular rescue” of bone metabolism. At 30 days, this synergistic group exhibited a significant upregulation of Alpl (mean: 11.69 ± 1.65) and Runx2 (mean: 4.49 ± 0.82) compared to DAE controls (p < 0.05). Crucially, the therapy orchestrated a protective remodeling environment by significantly inducing Tnfrsf11b expression (5.50 ± 0.88), effectively balancing the Tnfrsf11/Tnfrsf11b ratio. Late-stage maturation markers (Bglap and Spp1) were also significantly elevated, effectively mimicking healthy physiological levels observed in the SHAM group. NanoHA biofunctionalization, synergistically with L-PRF, triggers a transcriptional reprogramming of the peri-implant microenvironment, mitigating the catabolic effects of estrogen deficiency. These findings provide a biological foundation for enhanced clinical predictability in high-risk patients, suggesting that local interfacial modifications can overcome systemic bone compromise. Full article

Women are twice as likely to suffer from major depressive disorder (MDD). The underlying mechanism between estrogen and depression is still unknown. We used ovariectomized rats to simulate menopausal status and established a depression model of chronic and acute stress. The therapeutic effects of estrogen were systematically studied through behavioral testing, Western blotting, ELISA, LC-MS, and cell experiments. In chronic stress, OVX rats showed depressive-like behaviors, and elevated hippocampal ER, BDNF, IL-1β/IL-18, and body weight. ERT reduced depression-like behavior by 64% to 76% in the behavioral test. ERT also reversed the molecules without affecting GPR30. In acute stress, ERT reduced depression-like behavior by 20% to 58% in the behavioral test. OVX decreased ER, BDNF, P2X7, IL-1β/IL-18, spine density, and microglia and increased the expression of GPR30. ERT reversed all the above. ERT normalized metabolic abnormalities caused by CUMS. Our study demonstrates that estrogen deficiency contributes to the onset and progression of depression in a rat model of menopause-like estrogen deficiency. Estrogen replacement therapy appears to alleviate depressive-like behaviors by reducing brain inflammation and supporting the brain’s adaptive capacities through ER. Furthermore, the dual function positions GPR30 as a promising potential target for future treatments of menopausal depression, and GPR30 regulates neuroinflammation and neuroplasticity through the NLRP3/P2X7/IL-1β pathway. Full article

Background: Aging, especially after menopause, reduces the quantity and function of adult stem cells. Estrogen deficiency impairs proliferation, differentiation, and regenerative capacity. This study evaluated whether estrogen enhances endothelial differentiation of adipose-derived stromal cells (ADSCs) and improves therapeutic efficacy in critical limb ischemia (CLI). Methods: Male-derived ADSCs were assessed in vitro for endothelial differentiation using flow cytometry, biochemical assays, and angiogenesis analyses. Therapeutic effects were tested in a rat CLI model using endothelial-differentiated ADSCs (ED-ADSCs) with or without 17β-estradiol (E2). An ovariectomized (OVX) model examined estrogen deficiency and supplementation in vivo. Results: E2 promoted endothelial differentiation, increasing ERα/ERβ expression and activating PI3K/Akt/eNOS and MAPK signaling. This led to elevated VEGF expression, enhanced tube formation, and increased CD34⁺, KDR⁺, and CD31⁺ cell populations. In vivo, E2-pretreated ED-ADSCs significantly improved blood flow recovery. Estrogen deficiency reduced endothelial progenitor populations, which were restored by E2 supplementation. Conclusions: Estrogen modulates endothelial-associated characteristics and angiogenesis-related responses of ADSCs via ER-associated signaling, and may contribute to improved functional outcomes in ischemic conditions. E2 preconditioning may represent a potential strategy for stem cell-based therapy in estrogen-deficient settings. Full article

Background: Osteoporosis is a major skeletal disorder, particularly affecting postmenopausal women. Young ovariectomized rat models are commonly used to investigate estrogen deficiency-related skeletal changes, although they do not fully reproduce osteoporosis in a mature postmenopausal skeleton. Established pharmacological therapies remain the cornerstone of osteoporosis management, while nutritional factors continue to be investigated for their potential supportive role in bone metabolism. Menaquinone-7 (MK-7), a form of vitamin K2, has been investigated for potential skeletal effects through vitamin k-dependent mechanisms, particularly osteocalcin carboxylation. The aim of this study was to evaluate the dose-dependent effects of MK-7 on bone turnover markers, femoral mechanical resistance, qualitative histological findings, and hepatic safety in a young ovariectomized rat model. Methods: Forty female Wistar rats that were 8 weeks old, and thus still undergoing skeletal maturation, were assigned to four groups: sham-operated controls, ovariectomized controls, ovariectomized rats treated with low-dose MK-7, and ovariectomized rats treated with high-dose MK-7. Treatment was administered every 48 h for 12 weeks. At study completion, 35 rats survived; standardized analysis included eight animals per group. Plasma bone turnover markers (BTMs) and alanine aminotransferase were measured, femoral strength was assessed by the three-point bending test, and bone and liver histology was analyzed. Results: Biomechanical testing showed that high-dose MK-7 was associated with greater femoral mechanical resistance compared with untreated ovariectomized rats, while qualitative histology suggested differences in cortical architecture among groups. Biochemically, MK-7 treatment reduced undercarboxylated osteocalcin, suggesting vitamin K-dependent target engagement, whereas conventional turnover markers showed discordant findings. Overall, hepatic architecture was preserved, although mild hepatocellular apoptosis was observed. Conclusions: In this young OVX rat model, high-dose MK-7 was associated with improved femoral mechanical resistance compared with untreated OVX controls. However, because ovariectomy was performed during skeletal maturation, these findings should be interpreted as preliminary and cannot be directly extrapolated to established postmenopausal osteoporosis in a mature skeleton, and further studies are needed to clarify its activity pathways and safety profile. Full article

Background: Current post-treatment surveillance strategies for endometrial cancer rely predominantly on clinical stage and histological grade, without integration of molecular tumor biology. Molecular classification has revealed profound biological heterogeneity across endometrial cancer subtypes, including differences in recurrence patterns, prognosis, and treatment responsiveness, yet surveillance strategies have not been systematically adapted to reflect this heterogeneity. Objective: To propose a biology-driven surveillance framework for endometrial cancer that integrates molecular subtype, clinicopathological risk factors, and recurrence phenotype. Methods: This narrative review and conceptual framework synthesizes evidence from cohort studies, molecular classification analyses, international guidelines, and the literature addressing recurrence patterns and treatment responsiveness across molecular subtypes of endometrial cancer. Results: We propose a three-tier surveillance model stratifying patients into low-, intermediate-, and high-risk groups. The framework integrates molecular subtype with clinicopathological modifiers and expected recurrence phenotype. Within the no specific molecular profile (NSMP) subtype, CTNNB1 mutation status is incorporated as a primary modifier, assigning CTNNB1-mutated tumors to the intermediate-risk group regardless of estrogen receptor (ER) status. In CTNNB1 wild-type NSMP tumors, ER expression functions as a secondary modifier, allowing identification of a biologically low-risk subgroup. L1CAM expression is considered a high-risk modifier within NSMP. The framework also accounts for differences in the therapeutic modifiability of recurrence, including the role of immunotherapy in mismatch repair-deficient tumors. Conclusions: Uniform post-treatment surveillance does not reflect the biological diversity of endometrial cancer. The proposed framework provides a biologically grounded approach to surveillance that aligns follow-up intensity with recurrence phenotype and therapeutic opportunities. This model may serve as a conceptual basis for prospective studies evaluating personalized surveillance strategies in endometrial cancer. Full article

Background: Postmenopausal osteoporosis (PMOP) is a common metabolic bone disorder characterized by disrupted bone remodeling due to estrogen deficiency. Erxian Decoction (EXD), a traditional Chinese medicine formula, has shown clinical efficacy against PMOP, but its bioactive constituents and molecular mechanisms remain elusive. Methods: The therapeutic effects of EXD were evaluated in ovariectomized (OVX) mice using micro-CT and bone histomorphometry. Absorbed constituents of EXD were identified by UHPLC-Q analysis. Network pharmacology and quantitative proteomics were integrated to predict the key pathways and targets. The candidate target was validated by in vivo assays, including Western blot, glutathione (GSH) levels, glutathione S-transferases (GSTs) activity, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) levels. Molecular docking was performed to assess the binding affinity between bioactive components and the target protein. Results: EXD treatment significantly ameliorated bone microarchitecture deterioration and restored bone remodeling balance in OVX mice. A total of 137 core absorbed constituents of EXD were identified. Integrated network pharmacology and proteomics analyses revealed that EXD primarily modulates the glutathione metabolism pathway to counteract oxidative stress. Glutathione S-transferase A1 (GSTA1) was pinpointed as a potential target. In vivo experiments confirmed that EXD upregulated GSTA1 expression, restored total GSTs activity, replenished GSH reserves, and reduced MDA and 4-HNE levels. Molecular docking demonstrated stable protein–ligand interactions between bioactive components of EXD and GSTA1. Conclusions: EXD alleviates PMOP by activating GSTA1-mediated glutathione metabolism and suppressing oxidative stress. These findings provide a mechanistic basis for the clinical application of EXD in treating PMOP. Full article

Premature ovarian insufficiency (POI) is a clinical condition characterized by loss of ovarian function indicated by amenorrhea or irregular menstrual cycles for at least 4 months and elevated gonadotrophins (FSH > 25 IU/L, measured on one occasion) and low estrogen serum levels in women under the age of 40. Premature ovarian insufficiency can be non-iatrogenic or spontaneous (idiopathic or due to genetic, autoimmune, or metabolic reasons, or infections) and iatrogenic (a consequence of oophorectomy, chemotherapy, radiotherapy, or uterine artery embolization). Women with POI are faced not only with estrogen deficiency but also with infertility and psychological implications. Hormonal replacement therapy is effective in treating the symptoms of premature ovarian insufficiency as well as in lowering the health risk of long-term consequences of premature ovarian insufficiency. Currently, oocyte donation is the standard treatment for patients with POI desiring pregnancy. Recently developed methods for the regeneration of ovarian tissue, such as stem cell therapy, platelet-reach plasma therapy and in vitro activation of ovarian tissue, are still under research and further adequate multicentric clinical studies are needed to develop standardized effective and safe protocols for the infertility treatment of patients with premature ovarian insufficiency. Full article

Background/Objectives: Vasomotor symptoms (hot flashes) affect 70–80% of menopausal women, significantly impairing quality of life. Current treatments include hormone therapy, which is contraindicated for many patients, and non-hormonal alternatives with limited efficacy or adverse effects. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential therapeutic candidate due to its interaction with the endocannabinoid system. This study aimed to investigate whether a standardized Cannabis sativa extract containing isolated CBD attenuates heat dissipation in ovariectomized rats, a preclinical model of estrogen deficiency. Methods: Female Wistar rats were randomly assigned to sham-operated vehicle-treated (SHAM-V), ovariectomized vehicle-treated (OVX-V), or ovariectomized CBD-treated (OVX-CBD; 10 mg/kg/day, oral gavage) groups. Treatment began on postoperative day 2 and continued for 21 days. Tail-skin temperature, a surrogate marker of heat dissipation, was assessed by infrared thermography on day 14. Energy metabolism was evaluated by indirect calorimetry on day 21. Uterine weight was measured as a biomarker of estrogen depletion. Results: Ovariectomy significantly increased tail temperature compared to SHAM-V. CBD treatment completely prevented this effect, with OVX-CBD animals exhibiting thermographic profiles similar to SHAM-V. Uterine atrophy was not reversed by CBD. No differences in the calorimetry parameter were observed among groups. Conclusions: This study provides novel preclinical evidence that cannabidiol attenuates ovariectomy-induced heat dissipation in rats, without detectable effects on uterine weight or metabolic parameters. These findings suggest that CBD may represent a potential non-hormonal approach for the management of menopausal vasomotor symptoms; however, further studies are required to elucidate the underlying mechanisms and to determine its translational and clinical relevance. Full article