Search Results (467)

Estrogen deficiency is associated with endothelial dysfunction, vascular inflammation, increased lipoprotein oxidation, accumulation of lipid-rich material, and platelet activation. The absence of estrogen causes physiological, metabolic, and biochemical changes that increase the risk of cardiometabolic disease development caused by a deregulation in metabolic processes such as lipid metabolism and plasma lipoprotein levels. High-density lipoprotein (HDL) has cardioprotective properties related to the quality and the quantity of its components that can be modified by some nutritional factors. Guava (Psidium guajava L.), a widely cultivated fruit in Mexico, is notable for its high polyunsaturated fatty acid and dietary fiber content in its seeds, but its effect on health is understudied. This study aimed to evaluate the effect of guava-seed supplementation on body weight, blood pressure, lipid profile, HDL composition, and paraoxonase-1 (PON1) activity in an ovariectomized rat model (OVX). Four groups with six adult female Wistar rats each were classified as a SHAM group: rats with simulated ovariectomy; OVX group: rats with ovariectomy; OVX + GS group: ovariectomized rats supplemented with 6 g of guava seeds; OVX + DGS group: ovariectomized rats supplemented with 6 g of defatted guava seeds. Biochemical parameters, size, and lipid concentration of HDL subclasses, apolipoproteins, and PON1 activity were determined. A decrease in body weight gain, systolic blood pressure, mean arterial pressure, and triglycerides in plasma was observed at the end of the experiment in the supplemented groups. The supplementation of 6 g of guava seeds for 30 days decreased biochemical parameters in ovariectomized rats; these results could be attributed to the seed composition, suggesting a protective effect against the risk of developing diseases in menopausal states. Full article

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for degenerative diseases due to their ability to modulate disease progression through paracrine mechanisms. Among various MSC sources, placenta-derived MSCs (PD-MSCs) offer significant advantages, including high proliferation capacity, reduced senescence, and low immunogenicity, making them ideal for allogeneic applications. In this study, we investigated the therapeutic effects of PD-MSC transplantation in an estrogen-deficiency-induced osteoporosis mouse model. Mice were divided into three groups: a normal control group, a non-transplanted osteoporosis group, and a PD-MSC-transplanted group. Our findings demonstrated that PD-MSC transplantation significantly improved osteoporosis-related parameters, including increased femur weight, bone volume, bone mineral density, and calcium deposition. Additionally, estrogen levels were elevated, bone formation markers were upregulated, and bone resorption markers were downregulated. PD-MSCs also reduced inflammatory cytokine levels while enhancing anti-inflammatory factors. Notably, the BMP/SMAD signaling pathway, crucial for bone formation, was significantly upregulated. These results suggest that PD-MSC transplantation effectively restores bone homeostasis by inhibiting osteoclast activity, promoting osteogenesis, and modulating inflammation. This study provides strong evidence supporting the potential of PD-MSCs as a novel therapeutic strategy for osteoporosis, offering a regenerative and anti-inflammatory approach to bone disease management. Full article

Lepidium meyenii Walp. (black maca, BM) is a traditional Andean crop increasingly studied for its bioactive potential. This work characterized the phytochemical profile and evaluated the antioxidant, antinociceptive, and neuroprotective properties of a lyophilized aqueous extract of BM hypocotyls. UHPLC-ESI-QTOF-MS/MS identified twelve major compounds, including macamides, imidazole alkaloids, sterols, and fatty acid amides. BM showed a moderate total phenolic content but strong electron transfer-based antioxidant activity in CUPRAC and FRAP assays, together with moderate radical scavenging capacity in ABTS and DPPH systems. In ovariectomized rats, BM significantly reduced brain malondialdehyde levels, mitigated oxidative stress, and improved spatial learning during acquisition in the Morris water maze, confirming its neuroprotective effect. Antinociceptive assays (hot plate, cold plate, and tail immersion) further revealed a rapid but transient increase in nociceptive thresholds. This study provides experimental evidence supporting the analgesic effect of black maca. Molecular docking highlighted lepidiline B and campesterol as key metabolites with strong interactions with redox enzymes, the μ-opioid receptor, and the FAAH enzyme, supporting their role in the observed bioactivities. ADMET predictions indicated favorable oral bioavailability, CNS penetration, systemic clearance, and acceptable safety profiles. These results substantiate the role of black maca as a neuroprotective nutraceutical and highlight its promise as a novel source of rapidly acting natural analgesic compounds. Full article

Background: An artificial ovary has emerged as a novel alternative approach to prevent the reintroduction of cancerous cells after ovarian tissue autotransplantation. This study evaluates the ability of decellularized Wharton’s jelly (dWJ) to facilitate human ovarian follicle growth in a xenotransplantation model. Materials and Methods: Two transplanted groups were established; one consisted of a decellularized Wharton’s jelly/alginate (dWJ/Alg) composite, and an alginate (Alg) group was used as the control group. Each artificial ovary received approximately 20 partially isolated viable human ovarian follicles, subsequently undergoing xenotransplantation into ovariectomized, non-immunodeficient NMRI mice. Grafts were extracted at 1, 2, 4, or 5 weeks for comprehensive histological and immunohistochemical evaluations. Additionally, mouse blood serum was collected for hormonal analysis. Results: H&E staining confirmed granulosa cell proliferation and follicle growth in dWJ/Alg after 1 week of grafting. While human ovarian-like structures and cell proliferation were visible in other grafts, follicles were not observed. Conversely, immunohistochemical staining for Vimentin, Ki67, and CD45 confirmed the presence of human cells, proliferative cells, and inflammatory cells, respectively. However, hormonal assays revealed no significant difference in estrogen or progesterone levels between the experimental groups. Conclusions: It seems that Wharton’s jelly/alginate hydrogel can be used as an artificial niche for simulating the ovarian environment, effectively supporting the growth of xenotransplants of isolated human follicles. Full article

Osteoporosis is a common skeletal disease characterized by decreased bone density, leading to bone fragility and fractures, especially in menopausal women. The purpose of this study is to confirm the anti-osteoporosis activity of stem cell extracellular vesicles (EVs) as a material of regenerative medicine. Mesenchymal stem cells have a potential to differentiate into osteocytes, so directly reconstruct bone tissue or facilitate bone regeneration via paracrine effects. Paracrine effects are mediated by functional molecules delivered in EVs released from stem cells. EVs containing high concentrations of growth factors (GFs) and neurotrophic factors (NFs) were attained via hypoxia culture of human amniotic membrane stem cells (AMSCs). From the EVs with a mean diameter of 77 nm, 751 proteins and 15 species of lipids were identified. Sprague-Dawley rats were ovariectomized, and eight weeks later, intravenously injected with EVs at doses of 1 × 10⁸, 3 × 10⁸ or 1 × 10⁹ particles/100 μL/body, weekly for eight weeks. One week after the final administration, the serum and bone parameters related to bone density were analyzed. Serum 17β-estradiol, alkaline phosphatase, and calcium levels that decreased in ovariectomized rats were restored by EVs in a dose-dependent manner. Bone parameters such as bone mineral density, bone mineral content, bone volume/tissue volume ratio, trabecular number, trabecular space, and bending strength were also improved by treatment with EVs. Such effects were confirmed by morphological findings of micro-computed tomography. Taken together, it is suggested that AMSC-EVs containing high concentrations of GFs and NFs preserve bone soundness by promoting bone regeneration and inhibiting bone resorption. Full article

Background/Objectives: With the aging of the population, the number of patients with osteoporosis is increasing worldwide. Osteoporosis results from an imbalance in bone remodeling by osteoblasts and osteoclasts. This study investigated the effects of sake lees and rice koji, traditional Japanese rice-fermented products, on bone metabolism. Methods: Both sake lees extract and rice koji extract increased alkaline phosphatase (ALP) activity, extracellular collagen accumulation, and mineralization of MC3T3-E1 cells. In addition, the intracellular protein levels of Hsp47 and Sec23IP, which are required for collagen maturation and secretion, respectively, were increased during the differentiation. On the other hand, both extracts significantly inhibited osteoclastic differentiation. Furthermore, the effects of freeze-dried sake lees or rice koji extract on osteoporotic bones were examined using twelve-week-old female C3H/HeJ ovariectomized (OVX) mice. Results: The groups of mice fed 20% or 40% freeze-dried sake lees showed significant suppression of the loss in bone volume fraction (BV/TV) and trabecular volume (Tb.V) compared with those fed a normal diet as well as the 40% freeze-dried sake lees-fed group reduced in the loss of trabecular thickness (Tb.Th). Similarly, the rice koji extract-treated mice showed significant inhibition of the loss in BV/TV, Tb.V, and even trabecular number (Tb.N.). Folic acid and S-adenosylmethionine (SAM), which have been reported to be present in sake lees, promoted extracellular collagen production by osteoblasts. Conclusions: In OVX mice, the intake of freeze-dried sake lees or rice koji extract was associated with the attenuation of trabecular bone loss, suggesting potential beneficial effects on bone metabolism. Full article

No studies have induced maternal behavior in goats through hormonal treatment. We evaluated whether ovariectomized goats treated with estradiol benzoate (EB2; n = 7 nulliparous and 10 multiparous goats) or progesterone + estradiol benzoate (P4 + EB2; n = 7 nulliparous and 7 multiparous goats), before or after vagino-cervical stimulation (VCS), displayed maternal behavior. When all goats were measured within treatments, in the EB2 group, low-pitch bleats were more frequent, and the time spent cleaning the kids was longer after VCS (p < 0.01), while location changes were more frequent before VCS. In nulliparous goats, those in the EB2 group emitted more low-pitch bleats after VCS than before (p = 0.04). The frequency of location changes was higher before VCS than after (p = 0.05). In multiparous goats, the frequency of smelling the kids and aggression toward the kids before VCS was higher in the EB2 group than in the P4 + EB2 group (p < 0.01). Within treatments, the EB2 group emitted more low-pitch bleats after VCS than before (p = 0.01), and the duration of cleaning the kids was longer after VCS than before (p = 0.028). Within the P4 + EB2 group, the kids were smelled more frequently after VCS than before (p = 0.03). The maternal index after vagino-cervical stimulation was higher in goats with EB2 (p = 0.002). Nulliparous goats treated with P4 + EB2 had a higher maternal index compared with those treated with EB2 alone (p = 0.04). In conclusion, regardless of parity, maternal behavior induced with the EB2 treatment was better when VCS was applied. Likewise, maternal experience altered the response. In multiparous females, any of the treatments were better after VCS, while in nulliparous females, this was only evident with the EB2 treatment. Full article

Postmenopausal osteoporosis is characterized by progressive bone loss and deterioration of trabecular microarchitecture, yet safe and effective nutritional interventions remain limited. This study investigated the skeletal effects of whole sericin compared to isolated L-serine and calcium-only formulations in an ovariectomized (OVX) rat model. Forty female Sprague–Dawley rats underwent either sham surgery or OVX, followed by 8 weeks of daily oral administration with vehicle (calcium + vitamin D, NS), sericin formulation (S55), or L-serine. Sham and untreated OVX groups served as controls. Serum D-serine concentrations and femoral trabecular microarchitecture were assessed using fluorometric assays and micro-computed tomography (μCT), respectively. OVX significantly decreased bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number, while increasing trabecular separation. Sericin supplementation markedly improved BV/TV, BMD, trabecular thickness, and trabecular number, and reduced trabecular separation compared to both vehicle and untreated OVX controls. Sericin improved multiple trabecular parameters compared with L-serine. Serum D-serine levels were significantly elevated in the sericin group relative to calcium-only controls, though comparable to sham. These findings suggest that whole sericin exerts skeletal benefits beyond those attributable to its primary amino acid component, supporting its potential as a functional food ingredient for enhancing postmenopausal bone health. Full article

Background/Objectives: Postmenopausal osteoporosis disrupts magnesium homeostasis and hematological balance, contributing to systemic inflammation and metabolic alterations. This study aimed to assess the effects of dietary interventions—tempeh, daidzein, probiotics, and their combinations—on magnesium status and hematological ratios in a postmenopausal osteoporotic Wistar rat model. Methods: Sixty-four rats were divided into one sham group (n = 8) and seven ovariectomized (OVX) groups (n = 56), with different modified diets administered for six weeks. In addition, one of the groups received alendronate bisphosphonate as a pharmacological reference to benchmark the dietary interventions against standard anti-osteoporotic therapy. Magnesium levels in the tissues and feces, along with blood hematological ratios (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and triglyceride-to-glucose index (TyG)), were evaluated. Results: The results revealed that a combination of tempeh and probiotics (OTL) significantly increased magnesium levels in the feces, spleen, and hair, while reducing liver magnesium levels. Compared to the standard groups (S and O), the hematological analysis revealed that the daidzein group (OD) had the highest MLR, while the OTL group exhibited the lowest TyG index. The alendronate bisphosphonate (OB) intervention showed no significant effect on tissue magnesium levels, feces magnesium levels, or hematological ratios. Correlation analysis revealed a strong negative association between spleen magnesium levels and the PLR (r = −0.626) and a positive relationship between liver magnesium levels and TyG (r = 0.422). Conclusions: The authors of this study concludes that while ovariectomy significantly altered magnesium status and hematological ratios, the dietary combination of tempeh, daidzein, and probiotics did not demonstrate an apparent beneficial effect on magnesium status or inflammatory ratios in a postmenopausal osteoporotic rat model. However, the findings highlight interesting aspects of magnesium status and its correlations with metabolic and inflammatory parameters, warranting further investigation. Full article

Excessive osteoclast activity in bone remodeling can lead to an imbalance between bone resorption and formation, a common occurrence in abnormal bone metabolic diseases. This research investigates the effect of Coptidis rhizoma water extract (CRW) on osteoclastogenesis provoked by RANKL in vitro and bone destruction mediated by ovariectomy (OVX) in vivo. CRW, prepared from dried Coptidis rhizoma (CR), was analyzed for its active compounds—coptisine and berberine—using HPLC analysis. CRW markedly decreased the size and number of TRAP-positive multinucleated cells (TRAP⁺ MNCs), suppressed F-actin ring formation, and diminished bone resorption in RANKL-treated cultures. In the early phase of differentiation, CRW suppressed the phosphorylation of MAPKs p38, JNK, and ERK, as well as NF-κB p65, Iκ-Bα, and Akt. CRW also down-regulated RANKL-mediated induction of c-Fos and NFATc1 and attenuated the activation of NFATc1- dependent genes, such as OSCAR, ATP6V0D2, ACP5 (TRAP), OC-STAMP, DC-STAMP, CTSK (cathepsin K), CALCR (calcitonin receptor), and MMP-9. In ovariectomized rats, micro-CT and histological analyses showed that CRW alleviated femoral bone destruction. These findings indicate that CRW restrains osteoclast differentiation and function and may have therapeutic potential for disorders driven by excessive osteoclast activity. Full article

Despite the rising incidence of osteoporosis (the most common bone disorder) as life expectancy increases worldwide, the genetic and metabolic factors contributing to this multifactorial disease are still poorly understood. This study investigated the role of arginine metabolism in bone formation and its potential for preventing bone loss in postmenopausal osteoporosis. The osteogenic effects of arginine were evaluated in vitro by determining calcium mineral deposition and the expression of marker genes in the human osteoblastic cell line Saos-2. In vivo analyses were conducted in ovariectomized mice treated with arginine, focusing on femoral bone microarchitecture, marker gene expression and serum metabolite profiles. Arginine treatment enhanced calcium deposition and osteoblastic differentiation in vitro. In contrast, however, this treatment had a deleterious effect in vivo, exacerbating trabecular bone loss. These results are particularly relevant given the wide availability of arginine as a dietary supplement, and our findings underscore the necessity of verifying the safety of nutritional supplements in different populations and in the presence of disease. Full article

Background: Premenopausal women typically exhibit superior glucose metabolism compared to males, but this metabolic advantage is lost after menopause. The primary cause is the sharp decline in estrogen levels post-menopause. Genistein, a natural compound predominantly derived from leguminous plants, possesses structural similarity to estrogen. This enables specific binding to estrogen receptors, allowing genistein to exert estrogen-mimicking effects under conditions of estrogen deficiency. The aim of this study was to investigate the effects and potential mechanisms of genistein on glucose metabolism in the liver and skeletal muscle of ovariectomized (OVX) mice fed a high-fat diet (HFD). Methods: Animal experiments were performed using 8-week-old mice that were OVX to construct a model of estrogen deficiency and impaired their glucose metabolism by a continuous HFD. Genistein was administered by gavage (50 mg/kg-day) for 10 weeks and 17β-estradiol was administered subcutaneously (50 μg/kg) every 4 days for 10 weeks as a positive control. Results: Genistein significantly improved glucose metabolism (including fasting glucose, postprandial glucose, serum glucose levels, and HOMA-IR index) but did not affect serum estrogen levels and uterine weights in OVX mice. Genistein promoted increased expression and translocation of glucose transporter 4 (GLUT4) in the gastrocnemius muscle, enhanced phosphorylation of the PI3K/AKT pathway, and upregulated expression of the G protein-coupled estrogen receptor (GPER). Concurrently, it stimulates hepatic glycogen accumulation and upregulates GLUT2 expression in the liver. Conclusions: GEN improves glucose metabolism in ovariectomized mice, and this improvement is primarily attributed to increased expression and membrane translocation of GLUT4 in the gastrocnemius muscle mediated by the GPER-PI3K/AKT pathway. Full article

Salivary gland dysfunction is a common but underexplored complication of menopause that contributes to oral dryness, dysphagia, and increased risk of infection. Although ferroptosis, a form of regulated necrotic cell death driven by iron-dependent lipid peroxidation, has recently been implicated in postmenopausal tissue degeneration, its regulatory mechanisms in salivary glands remain unclear. In this study, we investigated the roles of mitochondrial dysfunction and mitophagy in driving ferroptosis-induced salivary gland injury in an ovariectomized (OVX) rat model of estrogen deficiency. OVX rats exhibited elevated markers of oxidative stress, lipid accumulation, and iron overload, and suppression of GPX4 activity in the salivary glands, consistent with ferroptotic activation. These changes were accompanied by impaired mitochondrial dynamics (MFN1 and OPA1), decreased expression of mitochondrial antioxidant regulators (PGC-1α, SOD, and catalase), and upregulation of mitophagy-related genes (PINK1, ULK1, Rab9, and LC3B), as well as LAMP, a lysosomal marker involved in autophagosome–lysosome fusion, while ferritinophagy (NCOA4) remained unchanged. Early administration of ferrostatin-1 effectively suppressed these pathological changes, preserving both glandular structure and function, as evidenced by the restored AQP5 and AMY2A expression. Collectively, our findings reveal that ferroptosis in estrogen-deficient salivary glands is regulated by mitochondrial instability and aberrant mitophagy, and ferrostatin-1 mitigates this cascade through multi-level mitochondrial protection. These results highlight ferrostatin-1 as a promising preventive agent against menopause-associated salivary gland dysfunction, with broader implications for organ-specific ferroptosis modulation. Full article

Background: Ischemia–reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). While the precise mechanisms of AKI are still incompletely defined, extensive evidence highlights tubular cell injury and death as key factors in its development. Necroptosis has recently emerged as a critical pathway in the pathogenesis of ischemia–reperfusion-induced AKI (IR-AKI). Although sex differences in susceptibility to IR-AKI have been reported, it remains unclear whether there are sex differences in necroptosis dynamics and whether these differences underlie the observed sexual dimorphism in kidney IRI. This study aimed to address these questions. Methods: male and female C57BL/6 J mice were subjected to AKI via ischemia induced by bilateral renal pedicle clamping for 18 min at 37 °C. Plasma, urine, and kidney samples were collected at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h post-reperfusion. Kidney injury and function were assessed by measuring plasma creatinine (PCr), blood urea nitrogen (BUN) levels, and histological damage (PAS and cleaved caspase3 staining). Necroptosis activation was assessed by quantifying phosphorylated forms of key markers: p-RIPK1 and p-MLKL. To explore the role of sex hormones in regulating necroptosis dynamics, ovariectomized female mice were subjected to the same IR-AKI protocol, and their kidney injury and functional outcomes were compared with those of intact counterparts. Results: The PCr was 0.35 ± 0.04 and 0.32 ± 0.06 mg/dL for males and females, respectively, at 3 h of IR. The levels exponentially increased to 2.05 ± 0.18 at 48 h post-reperfusion in the males but only gradually to 0.94 ± 0.13 mg/dL in females. Necroptosis activation began as early as 3 h post-IR in males but was delayed until ~6 h in females. Males exhibited stronger and more sustained necroptosis activation than females, showing elevated phosphorylation levels of pRIPK1 and pMLKL in Western blot. Female sex hormone deficiency exacerbated the female response to IR-induced injury, which reduced the sex difference in the dynamic of the necroptotic activation and subsequent kidney injury. To our knowledge, this is the first study to characterize sex differences in the initiation and progression of necroptosis and subsequent injury in a mouse model of IR-AKI. Conclusions: Our findings reveal distinct temporal patterns of programmed cell death between sexes. Necroptosis-targeted therapies require early intervention in males, which can be delayed in females after IR-AKI, highlighting the need for sex-specific therapeutic windows. Full article

Sheep have been widely used as a model for osteoporosis research. This study aimed to characterise changes in microstructure and composition in lumbar vertebrae L1–L7 and the proximal femur after implementation of a bone loss induction protocol (in this species). A sham control and experimental group (glucocorticoid-treated ovariectomized sheep) were used (n = 6/group), with a study duration up to the 24th postoperative week. Through micro-computed tomography, vertebrae and femoral head trabecular bones from the experimental group presented a consistent decrease in bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) and an increase in trabecular separation (Tb.Sp) and total porosity (p > 0.05). The mineral density of the femoral heads from the experimental group showed a statistically significant decrease (p ˂ 0.05). The entire histomorphometric analysis of the vertebrae in the experimental group showed an increase in cortical porosity (Ct.Po) and a decrease in cortical thickness (Ct.Th) (p ˂ 0.0001 and p ˂ 0.001, respectively). Vertebrae L6 and L7 were the most affected, showing a significant increase in Ct.Po (p < 0.05) and a significant decrease in Ct.Th at the L6 level (p < 0.05). Regarding the trabecular bone at the vertebral level, only L4 showed a significant increase in Tb.Sp (p ˂ 0.05). In the femoral heads’ subchondral cortical layer, the Ct.Po increased significantly and Ct.Th decreased (p < 0.01), and at the trabecular level, the BV/TV, Tb.Th, and Tb.N decreased significantly, while Tb.Sp increased (p < 0.05). In conclusion, the L4, L6 and L7 vertebrae seem the most suitable for further preclinical and translational studies of vertebral augmentation or spinal fusion in this animal model. Full article