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European Journal of Pharmacology Jun 2024Given estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate...
AIM
Given estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate the underlying metabolic regulations.
METHODS
Female mice underwent ovary removal surgery, followed by carbon tetrachloride (CCl) administration to induce liver injury. Biochemical index analysis and histopathological examination were then conducted. The expression levels of alpha-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and collagen type 1 alpha 1 chain (COL1A1) were assessed using western blotting to further elucidate the extent of liver injury. Finally, metabolite extraction and metabolomic analysis were performed to evaluate metabolic changes.
RESULTS
Ovary removal exacerbated CCl-induced liver damage, while estrogen supplementation provided protection against hepatic changes resulting from OVX. Furthermore, estrogen mitigated liver injury induced by CCl treatment in vivo. Estrogen supplementation significantly restored liver damage induced by OVX and CCl. Comparative analysis revealed significant alterations in pathways including aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism, lysine degradation, and taurine and hypotaurine metabolism in estrogen treatment.
CONCLUSION
Estrogen supplementation alleviates liver injury induced by OVX and CCl, highlighting its protective effects against fibrosis and associated metabolic alterations.
PubMed: 38936452
DOI: 10.1016/j.ejphar.2024.176774 -
Biochemical and Biophysical Research... Jun 2024With the aging of the global demographic, the prevention and treatment of osteoporosis are becoming crucial issues. The gradual loss of self-renewal and osteogenic...
With the aging of the global demographic, the prevention and treatment of osteoporosis are becoming crucial issues. The gradual loss of self-renewal and osteogenic differentiation capabilities in bone marrow stromal cells (BMSCs) is one of the key factors contributing to osteoporosis. To explore the regulatory mechanisms of BMSCs differentiation, we collected bone marrow cells of femoral heads from patients undergoing total hip arthroplasty for single-cell RNA sequencing analysis. Single-cell RNA sequencing revealed significantly reduced CRIP1 (Cysteine-Rich Intestinal Protein 1) expression and osteogenic capacity in the BMSCs of osteoporosis patients compared to non-osteoporosis group. CRIP1 is a gene that encodes a member of the LIM/double zinc finger protein family, which is involved in the regulation of various cellular processes including cell growth, development, and differentiation. CRIP1 knockdown resulted in decreased alkaline phosphatase activity, mineralization and expression of osteogenic markers, indicating impaired osteogenic differentiation. Conversely, CRIP1 overexpression, both in vitro and in vivo, enhanced osteogenic differentiation and rescued bone mass reduction in ovariectomy-induced osteoporosis mice model. The study further established CRIP1's modulation of osteogenesis through the Wnt signaling pathway, suggesting that targeting CRIP1 could offer a novel approach for osteoporosis treatment by promoting bone formation and preventing bone loss.
PubMed: 38936225
DOI: 10.1016/j.bbrc.2024.150277 -
Journal of Biological Physics Jun 2024Bone is a complex tissue that fulfills the role of a resistance structure. This quality is most commonly assessed by bone densitometry, but bone strength may not only be...
Bone is a complex tissue that fulfills the role of a resistance structure. This quality is most commonly assessed by bone densitometry, but bone strength may not only be related to bone mineral density but also to the preservation of bone cytoarchitectonics. The study included two groups of rats, ovariectomized and non-ovariectomized. Each group was divided into three batches: control, simvastatin-treated, and fenofibrate-treated. In the ovariectomized group, hypolipidemic treatment was instituted at 12 weeks post ovariectomy. One rat from each of the 6 batches was sacrificed 8 weeks after the start of treatment in the group. The experimental study was performed using a Bruker Minispec mq 20 spectrometer operating at a frequency of 20 MHz, subsequently also performed by H T-T molecular exchange maps. The results were represented by T-T molecular exchange maps that showed, comparatively, both pore size and their interconnectivity at the level of the femoral epiphysis, being able to evaluate both the effect of estrogen on bone tissue biology and the effect of the lipid-lowering medication, simvastatin, and fenofibrate, in both the presence and absence of estrogen. T-T molecular exchange maps showed that the absence of estrogen results in an increase in bone tissue pore size and interconnectivity. In the presence of estrogen, lipid-lowering medication, both simvastatin and fenofibrate alter bone tissue cytoarchitectonics by reducing pore interconnectivity. In the absence of estrogen, fenofibrate improves bone tissue cytoarchitectonics, the T-T molecular exchange map being similar to that of non-osteoporotic bone tissue.
PubMed: 38935192
DOI: 10.1007/s10867-024-09658-2 -
Amino Acids Jun 2024Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine...
Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.
Topics: Animals; Mice; Osteoclasts; Osteogenesis; Rats; Humans; Cell Differentiation; Eflornithine; Female; Polyamines; Osteoblasts; RAW 264.7 Cells; Ovariectomy; Rats, Sprague-Dawley; Spermidine
PubMed: 38935136
DOI: 10.1007/s00726-024-03403-8 -
Molecular Nutrition & Food Research Jun 2024The decline in estrogen during menopause contributes to a variety of menopausal symptoms, for which hormone replacement therapy (HRT) has been extensively applied....
SCOPE
The decline in estrogen during menopause contributes to a variety of menopausal symptoms, for which hormone replacement therapy (HRT) has been extensively applied. Regarding side effects and limited effectiveness of HRT for specific individuals, there is a growing interest in safe alternatives such as phytoestrogens which are structurally analogous to estrogens. This study aims to investigate the efficacy of yam and gromwell extracts, rich in bioactive compounds, and the synergistic effect of extracts on symptoms induced by estrogen deficiency in ovariectomized (OVX) mice.
METHODS AND RESULTS
OVX mice receive dietary intervention of either yam, gromwell extract, or their mixture for 14 weeks. Sham-operated mice and E2-injected OVX mice serve as positive controls. Following 14 weeks of oral administration, blood, adipose tissue, vagina, uterus, femurs, and tibias are harvested for further investigation. Consequently, yam and gromwell extracts ameliorate menopausal conditions such as weight gain, glucose intolerance, dyslipidemia, and osteoporosis in estrogen-deficient OVX mice. In addition, the mixture of yam and gromwell extracts synergistically aids in the relief of the indications.
CONCLUSION
These results indicate the potential use of yam and gromwell extracts, as well as their mixture, for the development of healthy functional foods to modulate menopausal symptoms.
PubMed: 38934532
DOI: 10.1002/mnfr.202400158 -
Current Opinion in Obstetrics &... Aug 2024Hysterectomy is the most common gynecologic surgical procedure performed on women in the United States. While there are data supporting that hysterectomy for benign... (Review)
Review
PURPOSE OF REVIEW
Hysterectomy is the most common gynecologic surgical procedure performed on women in the United States. While there are data supporting that hysterectomy for benign indication often does not reduce sexual function and may in fact improve sexual function as fibroids and endometriosis are resected, it remains unclear if there are factors within the perioperative period that affect sexual function in the years following surgery. To date, there is no consensus on what factors can optimize patients' sexual function after hysterectomy.
RECENT FINDINGS
We present the current literature that assesses factors which may contribute to sexual function after hysterectomy. Preoperative demographic factors, including increasing age, pelvic pain, and preoperative sexual dysfunction, play a large role in postoperative sexual function. Perioperatively, there is a growing amount of data suggesting that premenopausal salpingo-oophorectomy at the time of hysterectomy may increase the risk of sexual dysfunction after hysterectomy, and no conclusive evidence that subtotal hysterectomy improves sexual function. The route of hysterectomy and technique of cuff closure can impact sexual function after hysterectomy due to the risk of shortening the vaginal length.
SUMMARY
There is a lack of high-quality evidence that can provide a consensus on factors to optimize sexual function after hysterectomy. A growing area of research in the excision of endometriosis procedures is the consideration of nerve-sparing surgery. Considering the many variables that exist when counseling a patient on benign hysterectomy and its effects on sexual function, it is critical to understand the current research that exists with regards to these factors.
Topics: Humans; Female; Hysterectomy; Sexual Dysfunction, Physiological; Risk Factors; Endometriosis; Postoperative Complications; Pelvic Pain; Salpingo-oophorectomy
PubMed: 38934105
DOI: 10.1097/GCO.0000000000000959 -
Medicina (Kaunas, Lithuania) May 2024The ongoing concern of the medical profession regarding chronic medication is related to increasing patient adherence and compliance to treatment and reducing...
The ongoing concern of the medical profession regarding chronic medication is related to increasing patient adherence and compliance to treatment and reducing medication side effects. In this respect, drugs represented by fixed-dose combinations of active substances within the same tablet have emerged. Such a principle can be extrapolated by following the potential beneficial effects that a chronic medication can have on chronic pathologies affecting different systems. The study included 48 female Albino Wistar rats, aged 16-18 months, which were divided into two groups: ovariectomized and non-ovariectomized rats. One batch of 12 non-ovariectomized rats received no treatment, becoming a control batch (NOVX-M). The ovariectomized (OVX) group was divided into 3 batches of 12 rats each: no treatment, control (OVX-M), fenofibrate-treated (OVX-F) and statin-treated (OVX-S) rats. At 12 weeks after ovariectomy, a femoral fracture occurred in the right hind limb of all animals included in the experiment To reveal the changes, at intervals of 2, 4, 6 and 8 weeks post-fracture, the proximal part of the femur was evaluated by NMR diffusiometry, which allows random motion of proton molecules expressed by self-diffusion coefficients, , thus allowing analysis of the size and complexity of microscopic order cavities within biological structures, such as pores inside bones. The effects of hypolipidemic medication in the absence of estrogen were evidenced, proving the beneficial effect that fenofibrate can have in preserving healthy tissue exposed to osteoporotic risk during the menopausal period. The effects of lipid-lowering medication are also influenced by the duration of administration. Osteoporosis and heart disease are two chronic pathologies that affect mainly female population in the second half of life, and proving the dual therapeutic potential of lipid-lowering medication may also have positive effects by increasing adherence and compliance to treatment.
Topics: Animals; Rats, Wistar; Female; Rats; Ovariectomy; Hypolipidemic Agents; Magnetic Resonance Spectroscopy; Fenofibrate; Disease Models, Animal; Femur; Bone and Bones
PubMed: 38929535
DOI: 10.3390/medicina60060918 -
Animals : An Open Access Journal From... Jun 2024The ovariectomy (OVE) procedure can trigger somatosensory and visceral peritoneal nociception. Sacrococcygeal epidural (ScE) anesthesia may complement or replace...
The ovariectomy (OVE) procedure can trigger somatosensory and visceral peritoneal nociception. Sacrococcygeal epidural (ScE) anesthesia may complement or replace systemic analgesia used for feline OVE, reducing opioid consumption and their related undesirable adverse effects and consequently reducing or completely blocking the sympathetic nervous system activation during this procedure. The present study aimed to evaluate the activation of the sympathetic nervous system resulting from adding an ScE injection of bupivacaine 0.25% (0.3 mL kg) in feline OVE and identify whether this translates to hemodynamic variables stability. A Parasympathetic Tone Activity (PTA) monitor was applied given that it performs analysis of heart rate variability (HRV) detecting changes in sympathetic and parasympathetic tone, making it a good tool for detecting activation of the sympathetic nervous system during the study. Two groups of animals were evaluated in five perioperative times, namely, the control group (CG) (n = 18) with systemic analgesia alone and the sacrococcygeal epidural group (ScEG) (n = 20) with 0.25% bupivacaine combined with systemic analgesia. Thirty-eight female cats were selected. All animals assigned to CG and ScEG were premedicated with dexmedetomidine (20 μg kg IM) and methadone (0.2 mg kg IM). General anesthesia was induced with propofol IV ad effectum and maintained with isoflurane in 100% oxygen. Heart rate, non-invasive systolic and median blood pressure, respiratory rate, and instantaneous parasympathetic tone activity were recorded. Compared to systemic analgesia alone (CG), sacrococcygeal epidural (ScEG) reduced the rise of common hemodynamic variables but did not prevent sympathetic nervous system activation.
PubMed: 38929350
DOI: 10.3390/ani14121732 -
Antioxidants (Basel, Switzerland) May 2024Menopause brings about profound physiological changes, including the acceleration of insulin resistance and other abnormalities, in which adipose tissue can play a...
Menopause brings about profound physiological changes, including the acceleration of insulin resistance and other abnormalities, in which adipose tissue can play a significant role. This study analyzed the effect of ovariectomy and estradiol substitution on the metabolic parameters and transcriptomic profile of adipose tissue in prediabetic females of hereditary hypertriglyceridemic rats (HHTgs). The HHTgs underwent ovariectomy (OVX) or sham surgery (SHAM), and half of the OVX group received 17β-estradiol (OVX+E2) post-surgery. Ovariectomy resulted in weight gain, an impaired glucose tolerance, ectopic triglyceride (TG) deposition, and insulin resistance exemplified by impaired glycogenesis and lipogenesis. Estradiol alleviated some of the disorders associated with ovariectomy; in particular, it improved insulin sensitivity and reduced TG deposition. A transcriptomic analysis of perimetrial adipose tissue revealed 809 differentially expressed transcripts in the OVX vs. SHAM groups, mostly pertaining to the regulation of lipid and glucose metabolism, and oxidative stress. Estradiol substitution affected 1049 transcripts with overrepresentation in the signaling pathways of lipid metabolism. The principal component and hierarchical clustering analyses of transcriptome shifts corroborated the metabolic data, showing a closer resemblance between the OVX+E2 and SHAM groups compared to the OVX group. Changes in the adipose tissue transcriptome may contribute to metabolic abnormalities accompanying ovariectomy-induced menopause in HHTg females. Estradiol substitution may partially mitigate some of these disorders.
PubMed: 38929066
DOI: 10.3390/antiox13060627 -
International Journal of Molecular... Jun 2024Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables,...
Onion ( L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells.
Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis.
Topics: Animals; Osteoblasts; RANK Ligand; Osteoporosis; Flavonoids; Mice; Onions; Cell Differentiation; Plant Extracts; Rats; Cell Proliferation; RAW 264.7 Cells; Osteogenesis; Humans; Female; Osteoclasts; Bone Density; Ovariectomy; Rats, Sprague-Dawley; Osteoprotegerin
PubMed: 38928460
DOI: 10.3390/ijms25126754