摘要
ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg-1·d-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg-1·d-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E2）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E2， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.
摘要
Objective To explore the feasibility and operability in identifying the therapeutic dominant stages of traditional Chinese medicine(TCM)based on subdivision model of disease course.Methods The hierarchical Bayesian model was used to differentiate the disease course of 125 cases of premature ovarian failure(POF),and the disease course of POF were divided into the occult stage,diminished ovarian reserve(DOR)stage,premature ovarian insufficiency(POI)stage,and POF stage.An then the paired sample t-test,Pearson correlation analysis and expert in-depth interview were used for the analysis of the therapeutic effects of TCM for POF at various stages.Results(1)Compared with POF stage,DOR and POI stages were frequently intervened by Chinese patent medicine.(2)In DOR(complicated with POI)stage and POF stage,there was significant difference between the degree of TCM intervention and the therapeutic effect(t =-3.70,P＜0.001).(3)The degree of TCM intervention was positively correlated with treatment outcomes in the DOR stage(r = 0.679,P＜0.001),so did in the POF stage(r = 0.432,P＜0.001),but the correlation in the POF stage was slightly lower than that in the DOR stage.(4)The results of in-depth interviews with experts of TCM gynecology showed that in the concealed phase of POF,the prognosis would be most favorable if TCM regulation and intervention were performed.In the DOR stage and POI stage,treatment with Chinese medicine prescriptions usually brought about better curative effect and prognosis.For the patients at POF stage,the therapeutic effect of TCM depended on the patients'compliance and the treatment course,and the effect was relatively not as good as that of the previous stages.Conclusion In the DOR stage and POF stage,the higher the degree of TCM intervention,the better the prognosis will be achieved for the patients treated with western medicine.In the POF stage,the efficacy of TCM intervention is reduced to a certain extent compared with the DOR stage.The results indicated that it is feasible and operable to identify the TCM therapeutic dominant stages based on the subdivision model of disease course.
摘要
Objective To screen the optimal regimen of Chinese medicine combined with hormones for the treatment of premature ovarian failure(POF)using network meta-analysis and to provide an evidence-based basis for the clinical treatment of POF.Methods The randomized controlled trials(RCTs)of Chinese medicine combined with hormones in the treatment of POF were retrieved from thhe domestic and oversea databases of CNKI,VIP,Wanfang,CBM,PubMed,Cochrane,Embase,and Web of Science.The quality of the literature was assessed using the tools for analysis of bias recommended by Cochrane Reviewer's Handbook and by Jadad scale scores.Rstudio and StataSE 15.1 statistical software were used to perform network meta-analysis and graphical presentation of the data.Results A total of 50 RCTs were included,covering 8 intervention methods.The overall risk of bias of the included studies was low,but the quality of the literature was generally low.The results of network meta-analysis showed that,in terms of the effective rate,the intervetion of 7 various Chinese medicines combined with hormone was superior to the conventional treatment(hormone replacement therapy,HRT)in the control group,and Nuangong Qiwei Powder+HRT was superior to the remaining 6 kinds of Chinese medicines combined with HRT;with reference to the values of the surface under the cumulative ranking curve(SUCRA),the efficiencies of the effective rate of the 8 intervention methods in descending order were Nuangong Qiwei Powder+ HRT(SUCRA=81.2),Zishen Yutai Pills + HRT(SUCRA=80.0),modified Zuogui Pills + HRT(SUCRA= 66.1),Ankun Zhongzi Pills + HRT(SUCRA=49.6),Kuntai Capsules + HRT(SUCRA=45.2),modified Erxian Decoction + HRT(SUCRA=39.5),Liuwei Dihuang Pills + HRT(SUCRA=37.4)and HRT(SUCRA=1.0).In terms of improving serum follicle-stimulating hormone(FSH)levels,modified Zuogui Pills + HRT was superior to the remaining 7 intervention methods;with reference to the values of the SUCRA,the efficiencies of the 8 intervention methods in descending order were modified Zuogui Pills + HRT(SUCRA=97.0),HRT(SUCRA= 77.9),Liuwei Dihuang Pills + HRT(SUCRA=76.6),Kuntai Capsules + HRT(SUCRA=46.5),Nuangong Qiwei Powder+HRT(SUCRA=38.9),Ankun Zhongzi Pills + HRT(SUCRA=29.9),modified Erxian Decoction + HRT(SUCRA=18.1),and Zishen Yutai Pills + HRT(SUCRA=15.1).Conclusion All kinds of Chinese medicines combined with HRT exert stronger effect on improving the primary outcome indicators than HRT alone for the treatment of POF.The intervention with Nuangong Qiwei Powder+HRT exerts the highest probability of the optimal regimen for enhancing the efficiency,and the intervention with Zuogui Pills + HRT exerts the highest probability of the optimal regimen for lowering the serum FSH level.However,due to the low quality of the included studies,more rigorously-designed,large sample-size,and high-quality randomized controlled trials need to be conducted in the future to provide conclusive evidence-based evidence.
摘要
ObjectiveTo investigate the effect of Zuoguiwan on the ovarian function in the rat model of cyclophosphamide-induced premature ovarian failure （POF） based on the changes of ferroptosis pathway. MethodForty SD rats were randomized into blank， model， and low- and high-dose （2， 8 g·kg-1， respectively） Zuoguiwan groups， with 10 rats in each group. The rats in the other groups except the normal group were intraperitoneally injected with CTX at a dose of 50 mg·kg-1 on the first day and 8 mg·kg-1 from the second day to the fifteenth day for the modeling of POF. After modeling， the rats were administrated with corresponding drugs or normal saline by gavage for four weeks. Hematoxylin-eosin staining was performed to observe the pathological changes in the ovarian tissue. The mitochondria of the ovarian tissue was observed by electron microscopy. The serum levels of follicle-stimulating hormone （FSH）， estradiol （E2）， luteinizing hormone （LH）， anti-Mullerian hormone （AMH）， malondialdehyde （MDA）， catalase （CAT）， superoxide dismutase （SOD）， and iron ion were measured by biochemical methods and enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， ferritin heavy chain （FTH1）， and acyl-CoA synthetase long chain family member 4 （ACSL4）. ResultCompared with the blank group， the model group showcased significantly increased atretic follicles， atrophied， fragmented， and vacuolated mitochondria， and reduced， loose， and disordered cristae in mitochondria. Compared with the model group， high-dose Zuoguiwan increased mature follicles， the volume of mitochondria in the ovary， alleviated the vacuolation， and improved the number and arrangement of mitochondrial cristae. Compared with the blank group， the modeling elevated the levels of iron， MDA， FSH， and LH， up-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， decreased the activities of SOD and CAT， lowered the levels of E2 and AMH， and down-regulated the expression of ACSL4 （P<0.05， P<0.01）. Compared with the model group， drug interventions lowered the levels of iron， MDA， FSH， and LH， down-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， increased the activity of CAT， elevated the levels of E2 and AMH， and up-regulated the expression of ACSL4 （P<0.05， P<0.01）. ConclusionZuoguiwan may inhibit the occurrence of ferroptosis by regulating the SLC7A11/GPX4 axis， thereby improving the ovarian function of POF rats.
摘要
Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.
Subject(s)
Child , Humans , Female , Primary Ovarian Insufficiency/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Vascular Endothelial Growth Factor A , Medicine, Chinese Traditional , NF-kappa B , Kidney摘要
In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.
Subject(s)
Female , Humans , Mice , Animals , Primary Ovarian Insufficiency/chemically induced , Proteomics , Signal Transduction , Glycosides/adverse effects摘要
Objective:To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT.Methods:Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results:The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions:The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.
摘要
Premature ovarian failure(POF)is a gynecological endocrine disease caused by ovarian dysfunction.Mesenchymal stem cells(MSCs)can effectively treat premature ovarian failure,and play a role in repairing ovarian structure and improving ovarian function.The specific mechanism can be a direct differentiation into granulosa cells or inhibition of their apoptosis through the homing effect of MSCs or differentiate into primordial germ cells.Benefit of MSCs can also be attributed to ovarian angiogenesis promotion,immune regulation,reduce oxidative stress re-sponse and paracrine,all potentially promote recovery of ovarian function,and thus improve the fertility of women of childbearing age.
摘要
Objective To explore the mechanism of Jiawei Bazhen Yimu Capsule on premature ovarian failure rats from the perspective of metabolomics.Methods Female SD rats were randomly divided into sham operation group,model group and Jiawei Bazhen Yimu Capsule low,medium and high dose groups,with 10 rats in each group.The model of premature ovarian failure was replicated by removing bilateral ovaries of rats and administered intragastrically once a day for 21 days.The serum samples of rats in each group were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UPLC-Q-TOF-MS).Combined with multivariate statistical analysis,the effects of Jiawei Bazhen Yimu Capsule on differential metabolites in rats with premature ovarian failure were investigated.The differential metabolites identified by MELIN database or KEGG database were imported into Metaboanalyst 5.0 online platform for metabolic pathway analysis.Results A total of 18 potential differential metabolites were screened and identified.Most of the differential metabolites showed a good callback trend after intragastric administration of Jiawei Bazhen Yimu Capsule.These 18 differential metabolites were enriched into 2 metabolic pathways(Pathway Impact>0.1),which were glycerophospholipid metabolism and arachidonic acid metabolism pathways.Conclusion The therapeutic effect of Jiawei Bazhen Yimu Capsule on premature ovarian failure may be related to improving the level of differential metabolites in serum and restoring normal metabolic activities in rats.
摘要
Objective:The decision tree Chi-square automatic interactive detection (CHAID) algorithm and binary Logistic regression analysis were used to construct the risk prediction model of premature ovarian failure (POF) in patients with uterine fibroids complicated with hypertension after surgery, and the results of the risk prediction model were compared and analyzed.Methods:Patients with uterine fibroids complicated with hypertension admitted to Taizhou Hospital of Zhejiang Province from Jan. 2019 to Sep. 2022 were retrospectively analyzed as the research objects. CHAID algorithm and Logistic regression analysis were used to establish risk prediction models, respectively. The area under the curve (AUC) of receiver operating characteristic curve (ROC) was used to compare and evaluate the prediction effects of the two models.Results:A total of 860 patients were collected, including 56 patients with premature ovarian function failure after operation, and the incidence of premature ovarian function failure was 6.51%. CHAID method and Logistic regression analysis showed that uterine myoma surgery, hypertension, smoking or passive smoking, family history of premature ovarian failure, sleep status, physical exercise and history of induced curettage were important influencing factors of premature ovarian failure. The accuracy of risk prediction of decision tree model was 88.2%, and the fitting effect of the model was good. The Logistic regression model Hosmer-Leme-show goodness of fit test showed that the model fit was good. The AUC of Logistic regression model was 0.893 (95% CI: 0.862-0.899), and the AUC of decision tree model was 0.882 (95% CI: 0.856-0.899). The predictive value of the two models was moderate, and there was no significant difference between them ( Z=0.254, P>0.05) . Conclusions:The combination of decision tree and Logistic regression model can find the influencing factors of premature ovarian function failure in patients with uterine fibroids complicated with hypertension after operation from different levels, and the relationship between the factors can be more fully understood. The establishment of a risk model for premature ovarian function failure in patients with uterine fibroids complicated with hypertension after surgery can provide a reference for postoperative intervention in patients with uterine fibroids complicated with hypertension, and more effectively help patients actively prevent and slow down the occurrence and development of POF.
摘要
In traditional Chinese medicine, premature ovarian failure is attributed to the menstrual diseases such as amenorrhea, infertility, premenopausal and postmenopausal syndromes. The Zhejiang TCM gynecology schools are good at dialectical treatment of the above menstrual diseases similar to premature ovarian failure, especially Gynecology of Xiaoshan Zhulin Temple, Gynecology of Haining Chen Mushan, Gynecology of Ningbo Song's Family and Gynecology of Hangzhou He's Family. This paper summarizes the characteristics and experience of the four Zhejiang TCM gynecology schools in the dialectical treatment of premature ovarian failure, which can be used for reference.
摘要
ObjectiveTo investigate the protective effect of Zuoguiwan against 60Co-γ ray-induced premature aging of rats based on the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway. MethodSixty sexually mature female SD rats were irradiated with 60Co-γ rays （6.0 Gy， LD40） for 24 h at one time. Then they were randomized into model group， Bujiale group （0.18 g·kg-1·d-1）， Bujiale （0.09 g·kg-1·d-1） + high-dose Zuoguiwan group （23.625 g·kg-1·d-1）， high-dose Zuoguiwan group （23.625 g·kg-1·d-1）， medium-dose Zuoguiwan group （9.45 g·kg-1·d-1）， and low-dose Zuoguiwan group （4.725 g·kg-1·d-1）. The administration （once a day） lasted 21 days. Serum indexes ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2）］ of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and morphological changes of ovarian tissues were observed based on hematoxylin and eosin （HE） staining. The apoptosis rate of granulosa cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） and the protein expression of phosphorylated （p）-PI3K， p-Akt， p-mTOR， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in ovarian tissues by Western blot. ResultCompared with normal group， model group demonstrated increase in serum FSH （P<0.01）， decrease in E2 （P<0.05）， and reduction of follicles and luteum in early ovary （P<0.01）. Moreover， the elevation of apoptosis rate of granulosa cells （P<0.01）， down-regulation of p-PI3K， p-Akt， p-mTOR， and Bcl-2 in ovarian tissue， and increase in expression of Bax were also observed in the model group as compared with the normal group （P<0.01）. In comparison with the model group， the administration groups showed rise of the number of early ovarian follicles， decrease in the apoptosis rate of granulosa cells， increase in the expression of p-PI3K， p-Akt， p-mTOR， and Bcl-2， and down-regulation of Bax， particularly the Bujiale + high-dose Zuoguiwan group（P<0.05，P<0.01）. ConclusionZuoguiwan protects radiation-damaged ovary by activating the expression of PI3K/Akt/mTOR protein in ovarian tissue， increasing Bcl-2， and inhibiting the expression of Bax.
摘要
ObjectiveTo investigate the protective effect of Zuoguiwan against 60Co-γ ray-induced premature aging of rats based on the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway. MethodSixty sexually mature female SD rats were irradiated with 60Co-γ rays （6.0 Gy， LD40） for 24 h at one time. Then they were randomized into model group， Bujiale group （0.18 g·kg-1·d-1）， Bujiale （0.09 g·kg-1·d-1） + high-dose Zuoguiwan group （23.625 g·kg-1·d-1）， high-dose Zuoguiwan group （23.625 g·kg-1·d-1）， medium-dose Zuoguiwan group （9.45 g·kg-1·d-1）， and low-dose Zuoguiwan group （4.725 g·kg-1·d-1）. The administration （once a day） lasted 21 days. Serum indexes ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2）］ of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and morphological changes of ovarian tissues were observed based on hematoxylin and eosin （HE） staining. The apoptosis rate of granulosa cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） and the protein expression of phosphorylated （p）-PI3K， p-Akt， p-mTOR， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in ovarian tissues by Western blot. ResultCompared with normal group， model group demonstrated increase in serum FSH （P<0.01）， decrease in E2 （P<0.05）， and reduction of follicles and luteum in early ovary （P<0.01）. Moreover， the elevation of apoptosis rate of granulosa cells （P<0.01）， down-regulation of p-PI3K， p-Akt， p-mTOR， and Bcl-2 in ovarian tissue， and increase in expression of Bax were also observed in the model group as compared with the normal group （P<0.01）. In comparison with the model group， the administration groups showed rise of the number of early ovarian follicles， decrease in the apoptosis rate of granulosa cells， increase in the expression of p-PI3K， p-Akt， p-mTOR， and Bcl-2， and down-regulation of Bax， particularly the Bujiale + high-dose Zuoguiwan group（P<0.05，P<0.01）. ConclusionZuoguiwan protects radiation-damaged ovary by activating the expression of PI3K/Akt/mTOR protein in ovarian tissue， increasing Bcl-2， and inhibiting the expression of Bax.
摘要
ObjectiveTo study the effect of Siwutang （SWT） on intestinal flora in rats with diminished ovarian reserve （DOR） induced by Tripterygium wilfordii polyglycoside （TWP） based on 16S rRNA sequencing. MethodTwenty 8-week-old female SD rats were randomly assigned into four groups： blank group， model group， SWT high-dose group， and SWT low-dose group. Except the blank group， the other three groups were underwent intragastric administration of TWP tablets at a dose of 50 mg·kg-1 for 14 days. On day 15， the high-dose group was administrated at 3 times of the human dosage （40 g/person/day）， the low-dose group at 1.5 times of the human dosage， and the model group and the blank group with the same volume of normal saline for 18 days. Then， feces were collected for 16S rRNA sequencing. One hour after administration， blood was sampled from abdominal aorta after anesthesia for the measurement of hormone levels by radioimmunoassay， and ovaries were sampled， embedded， sliced， and stained with haematoxylin-eosin （HE） for pathological observation. ResultThe model group had higher level of luteinizing hormone （LH， P<0.05） and lower level of estradiol （E2， P<0.05） than the blank group. The SWT high-dose group and low-dose group had lower LH levels （P<0.05） and higher E2 levels than the model group （P<0.05）. SWT reversed the elevation in follicle-stimulating hormone （FSH） and LH levels and the decline in E2 and progesterone （P） levels caused by TWP to some extent. There were a large number of follicles at different developmental stages in the blank group， while atretic follicles increased significantly in the model group. A large number of mature follicles， secondary follicles， and primary follicles were observed in the high-dose SWT group， and primordial follicles， secondary follicles， and increased corpus luteum in the low-dose SWT group. Compared with that in the blank group and the administration group， the abundance of Verrucomicrobia and Epsilonbacteraeota in the model group significantly reduced. Compared with the blank group， the model group had different intestinal flora in phylum， class， order， family， and genus levels. Specifically， the model group had increased proportions of Firmicutes and Bacteroidetes. After TWP modeling， the abundance of Lachnospiraceae decreased significantly while that of Ruminococcaceae UCG-005 increased significantly. SWT groups， blank group， and model group can be clearly distinguished， and SWT groups had a tendency to approach the blank group. ConclusionSWT may improve the ovarian function of rats with TWP-induced DOR by regulating intestinal flora diversity.
摘要
ObjectiveTo investigate the effect of Jiawei Bazhen Yimu capsule on serum sex hormones， sexual organs and estrogen signaling pathway in female rats with premature ovarian failure. MethodThe key target proteins of Jiawei Bazhen Yimu capsule in the treatment of premature ovarian failure were screened out by network pharmacology analysis. Female healthy SD rats were selected, and the rat model of premature ovarian failure was established by ovariectomy. Fifty ovariectomized rats were randomly divided into a model group, an estradiol (E2) valerate group, and Jiawei Bazhen Yimu capsule low, medium, and high-dose groups. Another 10 healthy female rats were set as a sham operation group. The sham operation group and the model group were given distilled water by gavage, and other administration groups were given corresponding doses of drugs by gavage. After 21 d, the serum hormone levels of female rats were measured, including E2, progesterone (P), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Immunofluorescence staining (IF) was used to detect the protein expression levels of estrogen receptor 1 (ESR1), estrogen metabolism P4503A4 enzyme (CYP3A4), and P45019A1 enzyme (CYP19A1) in the uterine tissues of female rats. ResultAs compared with the model group, the serum E2 and P levels of female rats in the Jiawei Bazhen Yimu capsule low, medium, and high-dose groups were significantly increased. Jiawei Bazhen Yimu capsule improved the endometrial status of female rats and increased positive expression of ESR1, CYP3A4, and CYP19A1 in the uterine tissues of female rats (P<0.05). ConclusionThe mechanism of Jiawei Bazhenyimu capsule in the treatment of premature ovarian failure may be related to its hormone-like effect and activation of the estrogen signaling pathway.
摘要
Resumen: el síndrome X frágil es la causa más frecuente de retraso psicomotor vinculado al cromosoma X en niños, con una prevalencia de 1 : 5.000 en hombres y 1 : 4.000 - 8.000 en mujeres. Además, es la causa hereditaria más asociada al síndrome del espectro autista. Esta patología posee como base etiológica la expansión del triplete CGG en el extremo distal del gen FMR1, lo que causa su silenciamiento. Los pacientes afectados con este síndrome suelen padecer de problemas conductuales, neurológicos, cardíacos y ortopédicos. Este síndrome también se relaciona con la insuficiencia ovárica primaria asociada al X frágil, y el síndrome de temblor y ataxia asociado al X frágil que afectan a la madre y al abuelo materno, y que, por su reciente descripción, podrían ser desconocidos por el personal sanitario, lo que retrasa su diagnóstico y tratamiento. El objetivo de este artículo es analizar estas enfermedades, con el fin de describir el conocimiento actual sobre su etiología, las manifestaciones clínicas, el diagnóstico y el tratamiento. Esto se realizó mediante la recopilación de artículos en Pubmed, con algunas contribuciones de las bases de datos Scielo, Redalyc, Europe PMC, Science Direct, Google Académico y Genetics Home Reference. Entre las conclusiones principales se destaca que los fenotipos asociados a la premutación del gen FMR1 contemplan mecanismos fisiopatológicos diferentes al síndrome X frágil, a pesar de estar íntimamente relacionados.
Abstract: fragile X syndrome is the most common cause of X-linked psychomotor retardation in children, with a prevalence of 1 : 5.000 in males and 1 : 4.000 -8.000 in females. It is also the hereditary cause most associated with autism spectrum syndrome. The etiological basis of this pathology is the expansion of the CGG triplet at the distal end of the FMR1 gene, which causes its silencing. Patients affected with this syndrome usually suffer from behavioral, neurological, cardiac and orthopedic problems. This syndrome is also related to Fragile X-associated primary ovarian insufficiency, and Fragile X-associated tremor and ataxia syndrome affecting the mother and maternal grandfather, which, because of their recent description, may be unknown to health care providers, delaying their diagnosis and treatment. The objective of this article is to analyze these diseases, in order to describe the current knowledge about their etiology, clinical manifestations, diagnosis and treatment. This was done by collecting articles in Pubmed, with some contributions from Scielo, Redalyc, Europe PMC, Science Direct, Google Scholar and Genetics Home Reference databases. Among the main conclusions, it is highlighted that the phenotypes associated with FMR1 gene premutation involve different pathophysiological mechanisms to Fragile X syndrome, despite being closely related.
Resumo: a síndrome do X frágil é a causa mais comum de retardo psicomotor ligado ao cromossomo X em crianças, com prevalência de 1 : 5.000 em homens e 1 : 4.000 a 8.000 em mulheres. Além disso, é a causa mais hereditária associada à síndrome do espectro do autismo. Essa patologia tem como base etiológica a expansão do trigêmeo CGG na extremidade distal do gene FMR1, o que causa seu silenciamento. Pacientes com essa síndrome geralmente sofrem de problemas comportamentais, neurológicos, cardíacos e ortopédicos. Essa síndrome também está relacionada à insuficiência ovariana primária associada ao X frágil, à síndrome do tremor e à ataxia associada ao X frágil, que acometem a mãe e o avô materno, e que, devido à sua descrição recente, poderiam ser desconhecidas pelos profissionais de saúde, o que atrasa seu diagnóstico e tratamento. O objetivo deste artigo é analisar essas doenças, a fim de descrever o conhecimento atual sobre sua etiologia, manifestações clínicas, diagnóstico e tratamento. Isso foi feito através da recopilação de artigos no Pubmed, com algumas contribuições das bases de dados Scielo, Redalyc, Europe PMC, Science Direct, Google Academic e Genetics Home Reference. Dentre as principais conclusões, destaca-se que os fenotipos associados à premutação do gene FMR1 incluem outros mecanismos fisiopatológicos além da síndrome do X frágil, apesar de eles estarem intimamente relacionados.
摘要
El objetivo de este manuscrito es realizar una revisión y actualización de la literatura de la insuficiencia ovárica primaria (IOP) en población adolescente, a partir del diagnóstico, manejo y seguimiento de un caso clínico. La insuficiencia ovárica primaria se define como la menopausia en una mujer antes de los 40 años, acompañada de amenorrea, hipogonadismo hipergonadotrópico e infertilidad. Su prevalencia varía entre 1 a 2%, y en mujeres menores de 20 años su prevalencia es un caso de cada 10,000. Aunque se sabe que muchas afecciones pueden llevar a una IOP, la más común es la causa idiopática. La presentación clínica es diversa, y varios trastornos diferentes pueden también, llevar a esta condición. CASO CLÍNICO: Se presenta el caso de una adolescente de 17 años, previamente sana, con historia de amenorrea secundaria, no embarazada, con examen físico general y ginecológico normal. Se solicita estudio analítico complementario resultando con niveles de hormona folículo estimulante (FHS), estradiol (E2) y hormona antimülleriana (AMH) compatibles con una insuficiencia ovárica como la observada en la posmenopausia. Se inicia terapia hormonal (TH) clásica con estradiol y progesterona, siendo posteriormente reemplazada por anticoncepción hormonal combinada (AHC) oral, coincidente con el inicio de vida sexual, con respuesta favorable y sangrados regulares. La IOP tiene graves consecuencias para la salud incluyendo trastornos psicológicos como angustia, síntomas depresivos o depresión, infertilidad, osteoporosis, trastornos autoinmunes, cardiopatía isquémica, y un mayor riesgo de mortalidad. La enfermedad de Hashimoto es el trastorno autoinmune más frecuente asociado a la IOP. Su tratamiento y diagnóstico deben establecerse de forma precoz para evitar consecuencias a largo plazo. La terapia con estrógenos es la base del tratamiento para eliminar los síntomas de la deficiencia de estrógenos, además de evitar las consecuencias futuras del hipogonadismo no tratado. También el manejo debe incluir los siguientes dominios: fertilidad y anticoncepción, salud ósea, problemas cardiovasculares, función psicosexual, psicológica y neurológica, informando a los familiares y a la paciente sobre la dimensión real de la IOP y la necesidad de tratamiento multidisciplinario en muchos casos. CONCLUSIÓN: El caso presentado, pese a ser infrecuente, permite abordar de manera sistematizada el diagnostico de IOP y evaluar alternativas de manejo plausibles para evitar graves consecuencias en la salud, así como conocer respuesta clínica y de satisfacción de la adolescente.
The objective of this manuscript is to review and update the literature on primary ovarian insufficiency (POI) in an adolescent population, based on the diagnosis, management and follow-up of a clinical case. Primary ovarian insufficiency is defined as menopause in a woman before the age of 40, accompanied by amenorrhea, hypergonadotropic hypogonadism, and infertility. Its prevalence varies between 1 to 2%, and in women under 20 years of age its prevalence is one case in every 10,000. Although it is known that many conditions can lead to POI, the most common is the idiopathic cause. The clinical presentation is diverse, and several different disorders can also lead to this condition. CLINICAL CASE: The case of a 17-year-old adolescent, previously healthy, with a history of secondary amenorrhea, not pregnant, with a normal general physical and gynecological examination is presented. A complementary analytical study is requested, resulting in levels of follicle stimulating hormone (FHS), estradiol (E2) and anti-müllerian hormone (AMH) compatible with ovarian insufficiency such as that observed in postmenopause. Classic hormonal therapy (HT) with estradiol and progesterone was started, later being replaced by combined hormonal contraception (CHC), coinciding with the beginning of sexual life, with a favorable response and regular bleeding. POI has serious health consequences including psychological disorders such as distress, depressive symptoms or depression, infertility, osteoporosis, autoimmune disorders, ischemic heart disease, and an increased risk of mortality. Hashimoto's disease is the most common autoimmune disorder associated with POI. Its treatment and diagnosis must be established early to avoid long-term consequences. Estrogen therapy is the mainstay of treatment to eliminate the symptoms of estrogen deficiency, in addition to avoiding the future consequences of untreated hypogonadism. Management should also include the following domains: fertility and contraception, bone health, cardiovascular problems, psychosexual, psychological and neurological function, informing family members and the patient about the real dimension of POI and the need for multidisciplinary treatment in many cases. CONCLUSION: The case, although infrequent, allows a systematic approach to the diagnosis of POI and evaluate plausible management alternatives to avoid serious health consequences, as well as to know the clinical response and satisfaction of the adolescent.
Subject(s)
Humans , Female , Pregnancy , Adolescent , Primary Ovarian Insufficiency/diagnosis , Primary Ovarian Insufficiency/drug therapy , Menopause, Premature , Hormone Replacement Therapy , Estradiol/analysis , Anti-Mullerian Hormone/analysis , Amenorrhea/etiology , Follicle Stimulating Hormone/analysis , Infertility, Female摘要
With the technology development of cancer treatment, the survival rate of patients with cancer has been significantly improved. However, chemotherapy and radiation therapy may lead to premature ovarian failure and infertility in young women with cancer. Cryopreserved ovarian tissue auto-transplantation is an effective method to preserve fertility of such female patients. At present, the biggest challenge of this technique is mass loss of follicles after transplantation. In this article, the influencing factors and improvement methods of survival of cryopreserved ovarian tissue auto-transplantation were reviewed.
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Chitooligosaccharide-zinc (COS·Zn) is a powerful anti-oxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds vitamin C. Therefore, this study was aimed to investigate the protective effects of COS·Zn against premature ovarian failure (POF) and potential mechanisms. Female KM adult mice were divided into the following groups: a treatment group (150 mg·kg
Subject(s)
Animals , Female , Humans , Mice , Chitosan , NF-E2-Related Factor 2/genetics , Nuclear Proteins , Oligosaccharides , Primary Ovarian Insufficiency/drug therapy , Signal Transduction , Zinc摘要
BACKGROUND: Studies have confirmed that anti-zona zona antibodies can accelerate the destruction and depletion of oocytes, thereby causing premature ovarian failure. OBJECTIVE: To investigate the time of establishing autoimmune premature ovarian failure model in BALB/c mice induced by zona pellucida 3 peptides. METHODS: Thirty healthy female BALB/c mice (7-8 weeks) were randomly divided into immune experimental group (20 mice) and the control group (10 mice). In the experimental group, the mice were given immunization injection starting at 0 week, 0.15 mL of immune reagent injected into the soles at both sides and the lower abdomen. The vaginal exfoliated cell smears were observed every morning to observe the changes in the estrous cycle of the mice. After 2 weeks of injection, 0.15 mL of immune enhancement agent was injected subcutaneously into the same site. On the first day of weeks 4 and 6, the immune agent or immune enhancement agent was injected alternatively. Blood samples were collected before each injection and the serum sex hormone level was measured by enzyme-linked immunosorbent assay. Finally, ovarian tissue and uterus morphology were observed. RESULTS AND CONCLUSION: There was no difference in serum follicle stimulating hormone and estrogen levels between the first immunization injection and 2 weeks after the injection. The serum estrogen level in the experimental group was significantly lower than that in the control group at 4 weeks after injection. The serum estrogen level of the experimental group was significantly lower than that of the control group at 6 weeks after injection (P < 0.05), and meanwhile the serum follicle stimulating hormone level was significantly higher than that of the control group (P < 0.01). The degree of ovarian interstitial fibrosis in the experimental group was more obvious than that in the control group. The ovarian volume decreased and the uterus atrophied in the experimental group. The number of primitive follicles, primary follicles and secondary follicles in mice was significantly lower in the experimental group than the control group, and the number of atresia follicles was significantly higher than the control group (P < 0.05). Therefore, 75 μg of zona pellucida 3 peptides can be used to establish an autoimmune premature ovarian failure disease model in BALB/c mice, and a good modelling effect can be achieved at 6 weeks after immunization.