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1.
J Ethnopharmacol ; 301: 115835, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36252878

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Er-Xian decoction (EXD) is a traditional Chinese medicine (TCM) formula used to treat osteoporosis (OP). However, the anti-OP mechanism of EXD has not yet been fully elucidated. AIM OF THE STUDY: The study aimed to verify the anti-OP effect of EXD and to explore its underlying mechanism. METHODS: The anti-OP targets and mechanisms of EXD were predicted by network pharmacological analysis. Then, an ovariectomized (OVX) rat model was established to validate the key anti-OP mechanism of EXD. Firstly, the therapeutic effect of EXD on OP was confirmed using micro-CT bone analysis, pathological observation, and ELISA detection. Secondly, serum metabolites related to key biological processes were detected using an automatic biochemical analyzer and GC-MS. Finally, ELISA, qRT-PCR, and western blot were utilized to further explore the potential key anti-OP pathway of EXD. RESULTS: A total of 159 anti-OP targets of EXD were identified. Functional annotation revealed that OP treatment using EXD was associated with lipid metabolism, fatty acid (FA) metabolism, and PI3K/AKT signaling pathway. Experimental studies confirmed that EXD ameliorated ovariectomy-induced bone loss and bone microstructure deterioration. EXD treatment also upregulated the level of serum estrogen and downregulated the level of OC, PⅠNP, CTX-1, TC, and LDL-C. Besides, principal component analysis (PCA) and heat map of serum FAs distinguished OVX rats from the SHAM and EXD groups. Serum concentrations of important n-3 FAs, including C20:3N3, C20:5N3, and C22:5N3, were significantly increased in the EXD group. The increased stearoyl-CoA desaturase 1 (SCD1) index 1 and index 2 in the OVX group were reversed by EXD administration. Additionally, EXD reversed the decreased serum IGF1 level and tibia IGF1R, PI3K, and AKT expression in OVX rats. CONCLUSION: EXD ameliorated ovariectomy-induced bone loss by modulating lipid metabolism, FA metabolism, and IGF1/PI3K/AKT pathway.


Assuntos
Medicamentos de Ervas Chinesas , Osteoporose , Humanos , Feminino , Ratos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ovariectomia/efeitos adversos , Transdução de Sinais , Metabolismo dos Lipídeos , Ácidos Graxos/uso terapêutico , Fator de Crescimento Insulin-Like I/metabolismo
2.
Biomolecules ; 12(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36358952

RESUMO

Osteoporosis and osteoporotic fractures comprise a substantial health and socioeconomic burden. The leading cause of osteoporosis is an imbalance in bone formation and bone resorption caused by hyperactive osteoclasts. Therefore, a new strategy to suppress osteoclastogenesis is needed. Parkin is likely closely associated with bone metabolism, although its role in osteoclastogenesis is unclear. In this study, the Parkin protein inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, osteoclast-specific gene expression, F-actin ring formation, and bone resorption pit formation in vitro. Moreover, depletion of Parkin enhanced RANKL-induced osteoclast formation, osteoclast-specific gene expression, F-actin ring formation, and bone resorption pit formation. Reactive oxygen species (ROS) activity was suppressed, while autophagy was upregulated with the presence of the Parkin protein. ROS activity was upregulated and autophagy was decreased due to Parkin knockdown. In addition, intravenous administration of Parkin rescued ovariectomy-induced bone loss and reduced osteoclastogenesis in vivo. Collectively, Parkin has therapeutic potential for diseases associated with overactive osteoclasts.


Assuntos
Reabsorção Óssea , Osteoporose , Humanos , Feminino , Animais , Camundongos , Ligante RANK/farmacologia , Osteogênese , Espécies Reativas de Oxigênio/metabolismo , Actinas/metabolismo , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/genética , Ovariectomia/efeitos adversos , Ubiquitina-Proteína Ligases/genética , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Diferenciação Celular , NF-kappa B/metabolismo , Camundongos Endogâmicos C57BL
3.
Front Endocrinol (Lausanne) ; 13: 994642, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339416

RESUMO

Background: Yin Huo Tang (YHT), a traditional Chinese herbal formula, is effectively used for the clinical treatment of menopause-like symptoms in China. This study aimed to investigate its efficacy on menopause-like symptoms in mice using behavioral tests and histopathological assessment, and to determine its possible mechanism of action based on network pharmacology. Methods: Liquid chromatography-mass spectrometry (LC-MS) technology was used to identify the potential active ingredients of YHT. In mice, menopause-like symptoms were induced by combination of bilateral ovariectomy and empty bottle stimulation. The mice were then treated with the YHT aqueous extract for three weeks. Behavior, sleep state, body weight, organ index, and histomorphology were analyzed separately. Additionally, network pharmacology and molecular docking were used to predict the mechanisms underlying the action of YHT. Finally, serum estradiol was quantified to preliminarily verify the results of network pharmacology. Results: YHT not only improved the behavior of mice (attack and explore behavior reduced; modify behavior increased) but also ameliorated the sleep state (sleep time increased and incubation time reduced). YHT reduced body weight, increased uterine weight, and improved the histomorphology of some organs. Network pharmacology and molecular docking analyses revealed that the estrogen signaling pathway might play a key role in attenuating menopause-like symptoms. Furthermore, YHT treatment reversed the reduction in serum estradiol levels. Conclusions: YHT alleviates menopause-like symptoms in a mouse model, providing a rationale for using it as a potential therapeutic strategy.


Assuntos
Estrogênios , Menopausa , Humanos , Feminino , Animais , Camundongos , Simulação de Acoplamento Molecular , Ovariectomia/efeitos adversos , Estrogênios/farmacologia , Estradiol
4.
BMC Womens Health ; 22(1): 441, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36369055

RESUMO

BACKGROUND: The mean incidence of ovarian metastases (OM) in patients with colorectal cancer (CRC) is 3.4%. The 5-year survival of these patients, even when operated with curative intent, is remarkably low. The lifetime risk of ovarian cancer is approximately 1.3%. Prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries and fallopian tubes) could reduce the number of CRC patients that develop OM after removal of the primary tumor, as well as preventing the occurrence of primary ovarian cancer. Recently, the care pathway for CRC has been changed in several hospitals in line with the updated Dutch guideline. The possibility of PSO is now discussed with postmenopausal CRC patients in these hospitals. The aims of the current study are firstly to estimate the incidence of OM and primary ovarian cancer in postmenopausal patients with CRC, and secondly to evaluate the effect of PSO in these patients. METHODS: An information bulletin and decision guide on this topic was implemented in several Dutch hospitals in 2020. Post-decision outcomes will be collected prospectively. The study population consists of postmenopausal (≥ 60 years of age) patients that are operated with curative intent for CRC. Based on their own preference, patients will be divided into two groups: those who choose to undergo PSO and those who do not. The main study parameters are the reduction in incidence of ovarian malignancies (metastatic or primary) following PSO, and the number needed to treat (NNT) by PSO to prevent one case of ovarian malignancy. DISCUSSION: This will be the first study to evaluate the effect of PSO in postmenopausal CRC patients that is facilitated by an altered CRC care pathway. The results of this study are expected to provide relevant information on whether PSO adds significant value to postmenopausal patients with CRC. TRIAL REGISTRATION: International Clinical Trials Registry Platform, NL7870. Registered on 2019 July 12. URL of trial registry record: https://trialsearch.who.int/Trial2.aspx?TrialID=NL7870 . PROTOCOL VERSION: 1.0, date 2021 June 8.


Assuntos
Neoplasias Colorretais , Neoplasias Ovarianas , Humanos , Feminino , Salpingo-Ooforectomia , Pós-Menopausa , Ovariectomia , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/epidemiologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia
5.
J Orthop Surg (Hong Kong) ; 30(3): 10225536221130824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36369661

RESUMO

OBJECTIVE: Osteoporosis (OP) is a widespread disease that causes risks of spine and hip fractures. Morinda officinalis polysaccharide (MOP) shows therapeutic potential in OP. This article intended to understand the mechanism by which MOP impacts bone mineral density (BMD) and serum trace elements in OP rats. METHODS: OP rat models were established by bilateral ovariectomy (OVX). Rats were intragastrically administered with MOP or ZLN005 [the activator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)] since the first day after operation for 8 weeks. Microstructural changes in OP rats were analyzed using micro-computed tomography system. Contents of serum Zn, Cu, Fe, and Mg in rats were measured. Levels of serum superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), GSH, and malondialdehyde (MDA) in rats were determined by Enzyme-linked immunosorbent assay. Protein levels of PGC-1α and peroxisome proliferator-activated receptor γ (PPARγ) in cartilage tissues of rats were determined via Western blotting. RESULTS: MOP enhanced BMD, bone volume per trabecular volume (BV/TV), Tb.N, and Tb.Th and reduced Tb.Sp in the distal femur of OVX rats, elevated levels of serum Cu, Fe, and Mg and contents of SOD, GSH, and GSH-PX and decreased MDA content. Moreover, MOP suppressed the PGC-1α/PPARγ pathway. Activation of PGC-1α partially abolished the action of MOP on ameliorating OP in OVX rats and strengthening anti-oxidation ability. CONCLUSION: MOP mitigated OP in OVX rats by inhibiting the PGC-1α/PPARγ pathway.


Assuntos
Morinda , Osteoporose , Animais , Feminino , Humanos , Ratos , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Ovariectomia , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , PPAR gama/metabolismo , Superóxido Dismutase/metabolismo , Microtomografia por Raio-X
6.
Pharm Biol ; 60(1): 2219-2228, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36382865

RESUMO

CONTEXT: Isoorientin has many biological activities, including antioxidant, anti-inflammatory, antitumor. However, the effect of isoorientin on postmenopausal osteoporosis remains unclear. OBJECTIVE: To evaluate the effect of isoorientin on postmenopausal osteoporosis. MATERIALS AND METHODS: Sprague-Dawley rats were divided into five groups (n = 5): sham, model, 17-ß-oestradiol (E2, 10 µg/kg/day), low-dose isoorientin (L-Iso, 50 mg/kg), and high-dose isoorientin (H-Iso, 100 mg/kg). The rats were ovariectomized, treated by gavage daily for 12 weeks, and serum and femur samples were collected. Bone mineral density, bone metabolism, and oxidative stress were assessed. H&E staining, immunohistochemistry, and western blotting were employed. RESULTS: Isoorientin improved the bone mineral density of the lumbar vertebrae (2.01 ± 0.05 g/cm3 in H-Iso group vs. 1.74 ± 0.07 g/cm3 in model group) and femur (1.46 ± 0.06 g/cm3 vs. 1.19 ± 0.03 g/cm3), increased the trabecular bone number (1.97 ± 0.03 vs. 1.18 ± 0.13) and thickness (0.27 ± 0.02 vs. 0.16 ± 0.03 mm). Isoorientin decreased the separation degree of trabecular bone, ameliorated bone histomorphology changes, and significantly improved the mechanical properties. Isoorientin diminished MDA (by 60%) and increased SOD (by 49.2%), and GSH-Px (by 159%) activity. Furthermore, osteoprotegerin (OPG), nuclear factor erythroid 2-like 2 (Nrf2), haem oxygenase (HO-1), NAD(P)H quinone dehydrogenase 1(NQO1), and oestrogen receptor 1(ESR1) protein expression increased, while receptor activator of nuclear factor-κB ligand (RANKL) protein expression decreased after treatment. CONCLUSIONS: Isoorientin ameliorates osteoporosis via upregulating OPG and Nrf2/ARE signalling, suggesting isoorientin maybe a potential therapeutic drug for PMOP.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Ratos , Animais , Osteoporose Pós-Menopausa/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Pós-Menopausa , Ratos Sprague-Dawley , Ovariectomia , Osteoprotegerina/metabolismo , Osteoprotegerina/farmacologia , Osteoporose/metabolismo , Ligante RANK/metabolismo , Ligante RANK/farmacologia , Densidade Óssea , Estresse Oxidativo
7.
NPJ Prim Care Respir Med ; 32(1): 52, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36376327

RESUMO

There is increasing evidence that sex hormones may impact the development of obstructive lung disease (OLD). Therefore, we studied the effect of bilateral oophorectomy (oophorectomy) on the development of OLD. Women were identified from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2. Data were collected using the Rochester Epidemiology Project records-linkage system. A total of 1653 women who underwent oophorectomy and 1653 referent women of similar age were assessed for OLD using diagnostic codes and medical record abstraction. Women who underwent oophorectomy had an overall higher risk of all OLD, all chronic obstructive pulmonary disease (COPD), emphysema, and chronic bronchitis but not of all asthma, confirmed asthma, or confirmed COPD. The association with all OLD was stronger in women who were age ≤45 years at oophorectomy, never smokers, non-obese, and in women with benign indications; however, the interactions were not statistically significant. There was an increased risk of all asthma in women age ≤45 years at oophorectomy who took estrogen therapy. Never smokers of all ages had a stronger association of oophorectomy with all asthma and all COPD, whereas smokers had a stronger association of oophorectomy with emphysema and chronic bronchitis. Non-obese women of all ages had a stronger association of oophorectomy with all COPD, emphysema, and chronic bronchitis. The results of this study combined with the increased risk of several chronic diseases reported in previous studies suggest that oophorectomy in premenopausal women should be avoided unless there is clear evidence of a high genetic risk of ovarian cancer.


Assuntos
Asma , Bronquite Crônica , Enfisema , Doença Pulmonar Obstrutiva Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Bronquite Crônica/etiologia , Ovariectomia/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Fatores de Risco , Asma/epidemiologia , Asma/etiologia , Enfisema/etiologia
9.
Nutrients ; 14(20)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36297038

RESUMO

Bone is a dynamic tissue that maintains homeostasis with a balance of osteoclasts for bone resorption and osteoblasts for bone formation. Women are deficient in estrogen after menopause, which promotes bone resorption due to excessive activity of osteoclasts, leading to osteoporosis. TH (also known as dandelion) is native to warm regions and has traditionally been used to treat gynecological diseases and inflammation. Menopause is a major cause of osteoporosis as it causes abnormal activity of osteoclasts, and various studies have shown that anti-inflammatory drugs have the potential to treat osteoporosis. We analyzed the effect of TH on osteoclast differentiation and the relevant mechanisms using RANKL. After administration of TH in a menopause-like rat model in which ovariectomy of the was rats carried out, changes in bone microstructure were analyzed via micro-CT, and the antiosteoporosis effect of TH was verified by a histological analysis. In addition, the pharmacological effects of TH in an animal model of osteoporosis were compared and analyzed with osteoporosis medications (17ß-estradiol (E2) and alendronate (ALN)). TH significantly inhibited the initial osteoclast differentiation via the NFATc1/c-Fos mechanism. In addition, bone density in the femur of osteoporotic rats was increased, and the expression of osteoclast-related factors in the serum and tissues was controlled. The results of this study provide objective evidence of the inhibitory effect of TH on osteoclastogenesis and OVX-induced bone loss.


Assuntos
Reabsorção Óssea , Osteoporose , Feminino , Humanos , Ratos , Animais , Osteoclastos , Alendronato/farmacologia , Ligante RANK/metabolismo , Reabsorção Óssea/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/patologia , Ovariectomia/efeitos adversos , Osteogênese , Anti-Inflamatórios/farmacologia , Estrogênios/farmacologia , Estradiol/farmacologia , Diferenciação Celular
10.
Front Endocrinol (Lausanne) ; 13: 985424, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36303870

RESUMO

Alzheimer's disease is the most common type of dementia, being highly prevalent in elderly women. The advanced progression may be due to decreased hormone synthesis during post-menopause as estradiol and progesterone both have neuroprotective potentials. We aimed to confirm that female hormone depletion aggravates the progression of dementia in a triple transgenic mouse model of Alzheimer's disease (3xTg-AD). As pathological hallmarks are known to appear in 6-month-old animals, we expected to see disease-like changes in the 4-month-old 3xTg-AD mice only after hormone depletion. Three-month-old female 3xTg-AD mice were compared with their age-matched controls. As a menopause model, ovaries were removed (OVX or Sham surgery). After 1-month recovery, the body composition of the animals was measured by an MRI scan. The cognitive and anxiety parameters were evaluated by different behavioral tests, modeling different aspects (Y-maze, Morris water maze, open-field, social discrimination, elevated plus maze, light-dark box, fox odor, operant conditioning, and conditioned fear test). At the end of the experiment, uterus was collected, amyloid-ß accumulation, and the cholinergic system in the brain was examined by immunohistochemistry. The uterus weight decreased, and the body weight increased significantly in the OVX animals. The MRI data showed that the body weight change can be due to fat accumulation. Moreover, OVX increased anxiety in control, but decreased in 3xTg-AD animals, the later genotype being more anxious by default based on the anxiety z-score. In general, 3xTg-AD mice moved less. In relation to cognition, neither the 3xTg-AD genotype nor OVX surgery impaired learning and memory in general. Despite no progression of dementia-like behavior after OVX, at the histological level, OVX aggravated the amyloid-ß plaque deposition in the basolateral amygdala and induced early cholinergic neuronal fiber loss in the somatosensory cortex of the transgenic animals. We confirmed that OVX induced menopausal symptoms. Removal of the sexual steroids aggravated the appearance of AD-related alterations in the brain without significantly affecting the behavior. Thus, the OVX in young, 3-month-old 3xTg-AD mice might be a suitable model for testing the effect of new treatment options on structural changes; however, to reveal any beneficial effect on behavior, a later time point might be needed.


Assuntos
Doença de Alzheimer , Complexo Nuclear Basolateral da Amígdala , Animais , Camundongos , Feminino , Humanos , Doença de Alzheimer/patologia , Camundongos Transgênicos , Complexo Nuclear Basolateral da Amígdala/patologia , Modelos Animais de Doenças , Fibras Colinérgicas/patologia , Sintomas Comportamentais , Hormônios , Ovariectomia , Peso Corporal , Colinérgicos
11.
J Neuroendocrinol ; 34(10): e13188, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36306200

RESUMO

Postmenopausal hot flushes are caused by lack of estradiol (E2) but their neuroendocrine basis is still poorly understood. Here, we investigated the interrelationship between norepinephrine and hypothalamic neurons, with emphasis on kisspeptin neurons in the arcuate nucleus (ARC), as a regulatory pathway in the vasomotor effects of E2. Ovariectomized (OVX) rats displayed increased tail skin temperature (TST), and this increase was prevented in OVX rats treated with E2 (OVX + E2). Expression of Fos in the hypothalamus and the number of ARC kisspeptin neurons coexpressing Fos were increased in OVX rats. Likewise, brainstem norepinephrine neurons of OVX rats displayed higher Fos immunoreactivity associated with the increase in TST. In the ARC, the density of dopamine-ß-hydroxylase (DBH)-immunoreactive (ir) fibers was not altered by E2 but, importantly, DBH-ir terminals were found in close apposition to kisspeptin cells, revealing norepinephrine inputs to ARC kisspeptin neurons. Intracerebroventricular injection of the α2-adrenergic agonist clonidine (CLO) was used to reduce central norepinephrine release, confirmed by the decreased 3-methoxy-4-hydroxyphenylglycol/norepinephrine ratio in the preoptic area and ARC. Accordingly, CLO treatment in OVX rats reduced ARC Kiss1 mRNA levels and TST to the values of OVX + E2 rats. Conversely, CLO stimulated Kiss1 expression in the anteroventral periventricular nucleus (AVPV) and increased luteinizing hormone secretion. These findings provide evidence that augmented heat dissipation in OVX rats involves the increase in central norepinephrine that modulates hypothalamic areas related to thermoregulation, including ARC kisspeptin neurons. This neuronal network is suppressed by E2 and its imbalance may be implicated in the vasomotor symptoms of postmenopausal hot flushes.


Assuntos
Kisspeptinas , Hormônio Luteinizante , Ratos , Feminino , Animais , Humanos , Kisspeptinas/metabolismo , Hormônio Luteinizante/metabolismo , Norepinefrina/farmacologia , Temperatura Alta , Núcleo Arqueado do Hipotálamo/metabolismo , Estrogênios/metabolismo , Estradiol , Regulação da Temperatura Corporal , Ovariectomia
12.
Gen Physiol Biophys ; 41(5): 431-446, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36222341

RESUMO

This study aimed to investigate the effect of cerium oxide nanoparticles (CeO2-NPs) on non-alcoholic fatty liver disease in postmenopausal obesity and the underlying mechanisms.64 adult female rats were allocated into Sham, ovariectomized (OVX), high-fat high-fructose dietfed- OVX (HFHF-OVX), and HFHF-OVX-CeO2-NPs-treated (CeO2-HFHF-OVX) groups. OVX and HFHF-OVX rats presented a significant increase in overall and visceral obesity, dyslipidemia, liver enzymes, serum malondialdehyde, liver TNF-α, TGF-ß1 and free fatty acids, liver X receptor (LXR) expression associated with decreased serum total antioxidant capacity and liver short heterodimer partner (SHP) expression vs. Sham group. Also, histomorphometric studies displayed a significant higher scores of liver steatosis, inflammation and fibrosis. All these parameters were significantly improved by CeO2-NPs treatment in CeO2-HFHF-OVX vs. HFHF-OVX rats. Thus, CeO2-NPs treatment ameliorates liver steatosis, steatohepatitis, and fibrosis in postmenopausal obese rats via alleviation of obesity, dyslipidemia, modulating liver genes involved in lipid metabolism (LXR and SHP), decreasing liver lipogenesis besides its antioxidant and anti-inflammatory effects.


Assuntos
Dislipidemias , Nanopartículas , Hepatopatia Gordurosa não Alcoólica , Animais , Feminino , Humanos , Ratos , Anti-Inflamatórios , Antioxidantes/metabolismo , Cério , Dislipidemias/complicações , Dislipidemias/metabolismo , Dislipidemias/patologia , Ácidos Graxos não Esterificados/metabolismo , Fibrose , Frutose/metabolismo , Fígado/metabolismo , Receptores X do Fígado/metabolismo , Malondialdeído/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Ovariectomia , Pós-Menopausa , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(5): 815-820, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36224683

RESUMO

Objective: To analyze the effects of bone marrow mesenchyml stem cells (BMSCs) on bone alkaline phosphatase (BALP)/C-terminal telopeptide of type-Ⅰ collagen (CTX-1) expression and mechanical dynamics in rats with osteoporotic (OP) vertebral fracture. Methods: A total of 60 female Sprague-Dawley rats were evenly divided into three groups, a control group that received sham operation (sham group), a group consisting of rats with OP vertebral fracture (OP group), and the last group consisting of OP vertebral fracture rats given BMSCs treatment (BMSCs group). Comparison of the three groups of animals was made in terms of bone dynamic change, bone quantitative broadband ultrasound attenuation (BUA) measurement, and bone mineral density (BMD). HE staining was done to examine the bone histological morphological parameters of the vertebral body. Serum CTX-1 and BALP levels were determined by ELISA. Results: Mechanical comparison showed that there were significant differences in mechanical changes of L 5 vertebra body and right femur among the three experimental groups ( P<0.05). The elastic modulus and maximum load of the OP group significantly decreased compared with those of the sham group ( P<0.05). After the intervention, the maximum load and elastic modulus of the BMSCs group were significantly higher than those of the OP group ( P<0.05). Compared with the sham group, BUA and BMD values in the OP group were significantly downregulated ( P<0.05). After intervention, BUA and BMD of the BMSCs group were significantly higher than those of the OP group and were comparable to those of the sham group ( P<0.05). Compared with the sham group, the number of trabeculae in the OP group was significantly fewer, and the distribution of trabeculae was disorderly and lacked regularity. Compared with the OP group, there were more trabeculae in the BMSCs group, and their distribution was more regular. Compared with sham group, bone histological morphological parameters of the vertebral body of rats in the OP group were significantly changed--mean trabecular plate thickness (MTPT) and trabecular bone volume (TBV) parameters were significantly decreased, while mineral apposition rate (MAR) and trabecula bone surface (TRS) parameters were significantly upregulated (all P<0.05). After the experimental intervention, bone histological morphological parameters of the vertebral body in the BMSCs group showed significant improvement compared with those of the OP group ( P<0.05). Compared with the sham group, serum BALP content in the OP group was greatly decreased, while the CTX-1 level was upregulated ( P<0.05). After the intervention, the BMSCs group had higher serum BALP content than that of the OP group and substantially lower CTX-1 content than that of the OP group ( P<0.05). Conclusion: BMSCs can improve the mechanical changes in rats with OP vertebral fracture, and can increase the maximum load and elastic modulus of bone tissue. In addition, BMSCs can upregulate the expression of BALP in serum and downregulate the expression of CTX-1, thus helping rats with OP vertebral fracture heal early.


Assuntos
Colágeno Tipo I , Células-Tronco Mesenquimais , Fragmentos de Peptídeos , Fraturas da Coluna Vertebral , Animais , Feminino , Ratos , Fosfatase Alcalina , Densidade Óssea , Colágeno Tipo I/metabolismo , Ovariectomia , Fragmentos de Peptídeos/metabolismo , Ratos Sprague-Dawley , Coluna Vertebral
14.
Eur J Obstet Gynecol Reprod Biol ; 278: 166-171, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36208522

RESUMO

OBJECTIVE: Germline mutations in the BRCA gene account for most hereditary ovarian and breast cancer. Management of healthy carriers aims to prevent and allow early detection of breast and ovarian cancer. This study compares six different hereditary ovarian cancer management guidelines, highlighting areas of controversy between different societies. We aim to compare international and national guidelines regarding BRCA carriers' management. STUDY DESIGN: A comparative study. We retrieved, reviewed, and compared the most recent guidelines of BRCA mutation carriers from the specializing societies NCCN (National Comprehensive National network) and ESMO (European society of medical oncology), and national societies of the United States (American College of Obstetricians and Gynecologists), England (the Royal College of Obstetricians and Gynecologists), Canada (the Society of Obstetricians and Gynaecologists of Canada) and Spain (Sociedad Española de Oncología Médica). RESULTS: There is a broad consensus regarding the limited role of screening for early ovarian cancer detection (4 out of 6) (4/6) and regarding the recommendation for implementation of Risk-reducing salpingo-oophorectomy (RRSO) (6/6), some variations exist for age at RRSO. It is widely accepted that risk reducing salpingectomy should be performed only as part of research (5/6), and that the addition of risk-reducing hysterectomy should be individualized (3/6). Not all guidelines address fertility issues, and controversy exists regarding hormone replacement therapy (HRT) recommendations in unaffected young BRCA-mutation carriers following RRSO. CONCLUSION: BRCA carrier's management guidelines consist of well-agreed topics such as the ineffective screening for early detection of ovarian cancer and the recommendation of RRSO. HRT remains controversial. Conforming unified recommendations is needed for providing evidence-based recommendations.


Assuntos
Genes BRCA2 , Neoplasias Ovarianas , Feminino , Humanos , Carcinoma Epitelial do Ovário/genética , Mutação , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Ovariectomia , Fatores de Risco
15.
JAMA Netw Open ; 5(10): e2238663, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36287560

RESUMO

Importance: The association of premenopausal bilateral oophorectomy with parkinsonism and Parkinson disease (PD) remains controversial. Objective: To assess whether women who underwent premenopausal bilateral oophorectomy were at increased risk of parkinsonism and PD and whether the associations varied by age at oophorectomy and by receipt of estrogen replacement therapy. Design, Setting, and Participants: This cohort study used data from a combination of 2 independent cohort studies, the Mayo Clinic Cohort Study of Oophorectomy and Aging 1 and 2, which were based on the Rochester Epidemiology Project medical records-linkage system. A population-based sample of 5499 women from Olmsted County, Minnesota, were included; of those, 2750 women underwent bilateral oophorectomy for a benign indication before spontaneous menopause between January 1, 1950, and December 31, 2007 (oophorectomy cohort), and 2749 age-matched women who did not undergo bilateral oophorectomy were randomly sampled from the general population (reference cohort). Data were analyzed from March 1 to April 30, 2022. The date of oophorectomy was considered the index date for both groups. Exposures: Medical record documentation of bilateral oophorectomy abstracted from a medical records-linkage system (Rochester Epidemiology Project). Main Outcomes and Measures: Incidence and risk of parkinsonism or PD, with diagnoses confirmed by in-person examination or medical record review. Results: Among 5499 participants (median [IQR] age, 45.0 [40.0-48.0] years; 5312 [96.6%] White), 2750 women (2679 White [97.4%]) underwent bilateral oophorectomy at a median age of 45.0 years (IQR, 40.0-48.0 years), and 2749 women (2633 White [95.8%]) with a median age of 45.0 years (IQR, 40.0-48.0 years) at the index date were included in the reference cohort. Bilateral oophorectomy was associated with an increased risk of parkinsonism overall (hazard ratio [HR], 1.59; 95% CI, 1.02-2.46) and in women younger than 43 years at oophorectomy (HR, 7.67; 95% CI, 1.77-33.27). There was a pattern of increasing risk with younger age at the time of oophorectomy using 4 age strata (≥50 years: HR, 1.43 [95% CI, 0.50-4.15]; 46-49 years: HR, 1.55 [95% CI, 0.79-3.07]; 40-45 years: HR, 1.36 [95% CI, 0.64-2.89]; <40 years: HR, 8.82 [95% CI, 1.08-72.00]; P = .02 for trend). The number needed to harm was 53 women overall and 27 women younger than 43 years at the time of oophorectomy. Bilateral oophorectomy was also associated with an increased risk of PD in women younger than 43 years at oophorectomy (HR, 5.00; 95% CI, 1.10-22.70), with a number needed to harm of 48 women. Among women who underwent oophorectomy at 45 years and younger, the risk was lower in women who received estrogen after the procedure and through age 50 years compared with women who did not. For parkinsonism, the HRs were 1.72 (95% CI, 0.54-5.53) vs 2.05 (95% CI, 0.80-5.23); for PD, the HRs were 1.53 (95% CI, 0.29-8.23) vs 2.75 (95% CI, 0.84-9.04). However, the differences were not significant. Conclusions and Relevance: In this study, premenopausal women who underwent bilateral oophorectomy before age 43 years had an increased risk of parkinsonism and PD compared with women who did not undergo bilateral oophorectomy. These findings suggest that a reduction in the practice of prophylactic bilateral oophorectomy in premenopausal women at average risk of ovarian cancer may have substantial benefit for reducing the risk of parkinsonism and PD.


Assuntos
Doença de Parkinson , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Doença de Parkinson/epidemiologia , Fatores Etários , Fatores de Risco , Ovariectomia/efeitos adversos , Estrogênios
16.
Biol Pharm Bull ; 45(10): 1438-1443, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36184501

RESUMO

Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17ß-estradiol (E2) but not with HE. Thus, the phytoestrogens in HE may hardly activate ERα. Estrogen receptor beta (ERß) is expressed in the brain, and activation of ERß ameliorates menopausal depressive symptoms. Notably, depressive-like behavior in OVX rats evaluated in forced swim test was reduced by administration of not only E2 but also HE for 92 d. Long-term activation of ERα increases the risk of breast and uterine cancers. HE, therefore, may be effective in treating menopausal depression without the risk of carcinogenesis caused by ERα activation.


Assuntos
Agaricales , Fármacos Neuroprotetores , Animais , Estradiol/farmacologia , Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Feminino , Genisteína , Hericium , Humanos , Metanol , Ovariectomia , Fitoestrógenos , Ratos , Aumento de Peso
17.
Life Sci ; 309: 121020, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36191680

RESUMO

AIMS: Postmenopausal osteoporosis is one of the world's biggest yet unnoticed health issues. After ovariectomy, declined estrogen level significantly contributes to the elevation of bone marrow adiposity and bone loss leading to osteoporosis. Therapeutics to prevent osteoporosis addressing various aspects are now in short supply. In this study we made an approach to synthesize nanoparticles of naturally occurring PPAR-γ inhibitor, betulinic acid (BA/NPs) and tested the same in altered bone metabolisms developed after ovariectomy. MAIN METHODS: The osteogenic efficacy of BA/NPs was established in human and rat primary osteoblast cells using qRT-PCR and immunoblot analysis. Furthermore, lineage allocations of multipotent bone marrow stromal cells were evaluated. Various aspects of altered bone metabolism after ovariectomy such as bone marrow adiposity and pathological bone loss were evaluated using µCT and histological assessments. KEY FINDINGS: BA/NPs exert potential osteogenic efficacy by modulating key osteogenic markers such as RUNX2 and BMP2. Mechanistically BA/NPs regulate osteoblastogenesis through Wnt/ß-catenin signaling. Further, BA/NPs showed the potential to inhibit the differentiation of multipotent BMSCs towards adipogenesis while favouring the osteogenic lineage via Wnt/ß-catenin pathway. In the in vivo study, increased bone marrow adiposity was reduced in ovariectomized rats after BA/NPs treatment as assessed by histology and µCT analysis. Loss of bone mineral density as a hallmark of pathological bone loss was also abrogated by BA/NPs. Furthermore, increased obesity after OVX was also prevented in BA/NPs treated animals. SIGNIFICANCE: Our findings imply that BA/NPs could be used further as a viable drug lead to counteract various pathophysiological challenges after menopause.


Assuntos
Nanopartículas , Osteoporose , Feminino , Ratos , Humanos , Animais , beta Catenina/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Medula Óssea/metabolismo , Adiposidade , PPAR gama/metabolismo , Via de Sinalização Wnt , Osteogênese , Diferenciação Celular , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/metabolismo , Ovariectomia , Estrogênios/uso terapêutico , Obesidade
18.
Biochem Biophys Res Commun ; 634: 168-174, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36244115

RESUMO

Classical histological methods such as hematoxylin-eosin staining, have been, and in some areas still are, an important benchmark for the evaluation of biological tissues. However, the current method of assessment is primarily a qualitative assessment of the tissue under investigation. The aim of this paper is to contribute to the improvement of classical histological methods, by applying physical techniques that allow objective, quantitative data to be added to qualitative assessments, especially in areas where conflicting results are available. To this end, the effect of hypolipidemic medication on the callus formation process of normal bone and pathological osteoporotic bone was investigated. The study allowed us to associate UV-VIS spectroscopy wave number with specific hematoxylin-eosin staining of different types of bone tissue structures, the evolving structures in the callus formation process. This association allowed the quantitative assessment of the callusing process in ovariectomized (associated with pathological, osteoporotic bone) and non-ovariectomized (associated with normal bone) rats, with three groups - the control group, simvastatin-treated group, and fenofibrate-treated group. The study showed that in the non-ovariectomized groups both treatments delayed callus formation. In the ovariectomized groups, simvastatin delayed and fenofibrate promoted callus formation.


Assuntos
Fraturas do Fêmur , Fenofibrato , Osteoporose , Feminino , Humanos , Ratos , Animais , Ratos Wistar , Consolidação da Fratura , Fenofibrato/farmacologia , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Ratos Sprague-Dawley , Ovariectomia , Calo Ósseo/patologia , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/patologia , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Fêmur/patologia , Análise Espectral , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico
19.
Steroids ; 188: 109132, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36273542

RESUMO

Several studies have demonstrated that the underlying mechanism of insulin resistance (IR) is linked with developing diseases like diabetes mellitus, hypertension, metabolic syndrome, and polycystic ovary syndrome. In turn, the dysfunction of female gonadal hormones (especially 17ß-estradiol) may be related to the development of IR complications since different studies have shown that 17ß-estradiol has a cardioprotector and vasorelaxant effect. This study aimed was to determine the effect of the 17ß-estradiol administration in insulin-resistant rats and its effects on cardiovascular responses in pithed rats. Thus, the vasopressor responses are induced by sympathetic stimulation or i.v. bolus injections of noradrenaline (α1/2), methoxamine (α1), and UK 14,304 (α2) adrenergic agonist were determined in female pithed rats with fructose-induced insulin resistance or control rats treated with: 1) 17ß-estradiol or 2) its vehicle (oil) for 5 weeks. Thus, 17ß-estradiol decreased heart rate, prevented the increase of blood pressure induced by ovariectomy, but with the opposite effect on sham-operated rats; and decreased vasopressor responses induced by i.v. bolus injections of noradrenaline on sham-operated (control and fructose group) and ovariectomized (control) rats, and those induced by i.v. bolus injections of methoxamine (α1 adrenergic agonist). Overall, these results suggest 17ß-estradiol has a cardioprotective effect, and its effect on vasopressor responses could be mediated mainly by the α1 adrenergic receptor. In contrast, IR with ovariectomy 17ß-estradiol decreases or loses its cardioprotector effect, this could suggest a possible link between the adrenergic receptors and the insulin pathway.


Assuntos
Resistência à Insulina , Ratos , Feminino , Animais , Humanos , Metoxamina/farmacologia , Ratos Wistar , Vasoconstritores/farmacologia , Sistema Nervoso Simpático/fisiologia , Norepinefrina/farmacologia , Estradiol/farmacologia , Insulina , Ovariectomia , Frutose/farmacologia , Agonistas Adrenérgicos/farmacologia
20.
Can Vet J ; 63(10): 1022-1026, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36185791

RESUMO

Two unrelated queens were presented for persistent signs of estrus despite a history of ovariohysterectomy. Uterine unicornis was suspected based on historical surgical findings. Anti-Müllerian hormone testing was consistent with the presence of ovarian tissue in both queens. Based on the ultrasonographic confirmation of unilateral abnormal structures in the ovarian region and ipsilateral absence of the kidney, a laparoscopic surgical approach was performed on each queen to remove remnant ovarian tissue. Laparoscopy confirmed the absence of a kidney ipsilateral to the remnant ovarian tissue. Both cats recovered from surgery and displayed no further signs of estrus. Key clinical message: To our knowledge, these are the first reported cases of feline uterine unicornis treated with a laparoscopic surgical approach. This minimally invasive approach, preceded by a thorough diagnostic work-up, may be of benefit to future queens with uterine unicornis. In addition, anti-Müllerian hormone testing has not been well-described in the literature when used in cats with remnant ovarian tissue. These cases may be of value to clinicians discovering the absence of a uterine horn when performing an ovariohysterectomy on queens.


Résumé ­ Ovariectomie laparoscopique chez deux chattes avec un utérus unicorne. Deux chattes non apparentées ont été présentées pour des signes persistants d'oestrus malgré des antécédents d'ovariohystérectomie. Un utérus unicorne a été suspecté sur la base des résultats chirurgicaux antérieurs. Un test d'hormone anti-müllérienne était compatible avec la présence de tissu ovarien chez les deux chattes. Sur la base de la confirmation échographique des structures anormales unilatérales dans la région ovarienne et de l'absence ipsilatérale du rein, une approche chirurgicale laparoscopique a été réalisée sur chaque chatte pour retirer le tissu ovarien restant. La laparoscopie a confirmé l'absence d'un rein ipsilatéral au tissu ovarien résiduel. Les deux chattes se sont remises de la chirurgie et n'ont montré aucun autre signe d'oestrus.Message clinique clé:À notre connaissance, ce sont les premiers cas rapportés d'utérus unicorne félin traités par une approche chirurgicale laparoscopique. Cette approche peu invasive, précédée d'un bilan diagnostique approfondi, peut être bénéfique pour les futures chattes atteintes d'utérus unicorne. De plus, le test d'hormone anti-müllérienne n'a pas été bien décrit dans la littérature lorsqu'il est utilisé chez des chats avec du tissu ovarien résiduel. Ces cas peuvent être utiles aux cliniciens qui découvrent l'absence de corne utérine lors de la réalisation d'une ovariohystérectomie sur des chattes.(Traduit par Dr Serge Messier).


Assuntos
Hormônio Antimülleriano , Laparoscopia , Animais , Gatos , Feminino , Laparoscopia/veterinária , Ovariectomia/veterinária , Anormalidades Urogenitais , Útero/anormalidades , Útero/diagnóstico por imagem , Útero/cirurgia
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