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1.
Front Endocrinol (Lausanne) ; 14: 1242050, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37867519

RESUMO

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age and can cause metabolic disorder, infertility, and increased anxiety and depression; as a result, it can seriously affect the physical and mental health of fertile women. PCOS is a highly clinically heterogeneous disease with unclear etiology and pathogenesis, which increases the difficulty of treatment. The thyroid gland has complex regulatory effects on metabolism, reproduction, and emotion, and produces hormones that act on almost all cells of the human body. The clinical manifestations of PCOS are similar to some thyroid diseases. Furthermore, some thyroid diseases, such as subclinical hypothyroidism (SCH), not only increase the incidence rate of PCOS, but also exacerbate its associated metabolic abnormalities and reproductive disorders. Interestingly, PCOS also increases the incidence of some thyroid diseases. However, the role of the thyroid in PCOS remains unclear. This review is intended to thoroughly explore the critical role of the thyroid in PCOS by summarizing the comorbidity of PCOS and thyroid diseases and their combined role in metabolic disorders, related metabolic diseases, and reproductive disorders; and by analyzing the potential mechanism through which the thyroid influences the development and progression of PCOS and its symptoms. We hope this review will provide a valuable reference for the role of the thyroid in PCOS.


Assuntos
Hipotireoidismo , Infertilidade , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/diagnóstico , Hipotireoidismo/epidemiologia , Comorbidade , Infertilidade/epidemiologia
2.
Front Endocrinol (Lausanne) ; 14: 1229900, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745707

RESUMO

Introduction: Observational studies have reported an association between polycystic ovary syndrome (PCOS) and COVID-19, but a definitive causal relationship has not been established. This study aimed to assess this association using two-way two-sample Mendelian randomization (MR). Methods: A summary of PCOS characteristics was compiled using the PCOS summary statistics from the Apollo University of Cambridge Repository. COVID-19 susceptibility and severity statistics, including hospitalization and extremely severe disease, were obtained from genome-wide association studies from the COVID-19 Host Genetics Initiative. The primary analysis used the inverse variance-weighted method, supplemented by the weighted median, MR-Egger, and MR-PRESSO methods. Results: The forward MR analysis showed no significant impact of PCOS on COVID-19 susceptibility, hospitalization, or severity (OR = 0.983, 1.011, 1.014; 95% CI = 0.958-1.008, 0.958-1.068, 0.934-1.101; and p = 0.173, 0.68, 0.733; respectively). Similarly, reverse MR analysis found no evidence supporting COVID-19 phenotypes as risk or protective factors for PCOS (OR = 1.041, 0.995, 0.944; 95% CI = 0.657-1.649, 0.85-1.164, 0.843-1.058; and p = 0.864, 0.945, 0.323; respectively). Consequently, no significant association between any COVID-19 phenotype and PCOS was established. Conclusion: This MR study suggested that PCOS is not a causal risk factor for the susceptibility and severity of COVID-19. The associations identified in previous observational studies might be attributable to the presence of comorbidities in the patients.


Assuntos
COVID-19 , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/genética , Causalidade
3.
Am J Physiol Endocrinol Metab ; 325(4): E346-E362, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37584608

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disorder related to psychological distress. However, the mechanism underlying increased prevalence of depression in PCOS remained unclear. This study aimed to explore the unique transcriptional landscape of ovary and offered a platform to explore the mechanism of PCOS, as well as the influences caused by depression. The PCOS rat model was established by letrozole whereas PCOS rat model with depression was established by letrozole combined with chronic unpredicted mild stress (CUMS). Then single-cell RNA sequencing (scRNA-Seq) was applied to analyze the transcriptional features of rat ovaries. Granulosa cells (GCs) and fibroblasts (Fibros) accounted for the top two clusters of total 12 cell types. There were nine clusters in GCs, related to inflammatory response, endoplasmic reticulum (ER) stress, and steroidogenesis. The expression of differentially expressed genes (DEG) Hes1 was higher in PCOS and PCOS + CUMS groups, exhibiting enhanced expression by pseudotime and positively related to inflammation. Pseudotemporal analysis revealed that inflammation contributed to the different GCs distributions. Moreover, analysis of DEGs and gene ontology (GO) function enrichment revealed CUMS aggravated inflammation in PCOS GCs possibly via interferon signaling pathway. In theca cells (TCs), nine clusters were observed and some of them were relevant to inflammation, ER stress, and lipid metabolism. DEGs Ass1, Insl3, and Ifi27 were positively related to Cyp17a1, and Ces1d might contribute to the different trajectory of TCs. Subsequent scRNA-seq revealed a signature profile of endothelial cells (ECs) and Fibros, which suggest that inflammation-induced damage of ECs and Fibro, further exacerbated by CUMS. Finally, analysis of T cells and mononuclear phagocytes (MPs) revealed the existence of immune dysfunction, among which interferon signaling played a critical role. These findings provided more knowledge for a better understanding PCOS from the view of inflammation and identified new biomarkers and targets for the treatment of PCOS with psychological diseases.NEW & NOTEWORTHY In this study, we mapped the landscape of polycystic ovary syndrome (PCOS) ovary with rat model induced by letrozole and provided a novel insight into the molecular mechanism of PCOS accompanied by chronic unpredicted mild stress (CUMS) at single-cell transcriptomic level. These observations highlight the importance of inflammation in the pathogenesis of PCOS, which might also be the bridge between PCOS and psychological diseases.


Assuntos
Síndrome do Ovário Policístico , Humanos , Feminino , Ratos , Animais , Síndrome do Ovário Policístico/metabolismo , Letrozol/efeitos adversos , Letrozol/metabolismo , Células Endoteliais/metabolismo , Células da Granulosa/metabolismo , Inflamação/genética , Inflamação/metabolismo , Interferons/efeitos adversos , Interferons/metabolismo
4.
PLoS One ; 18(2): e0279633, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36827330

RESUMO

Ovarian age assessment is an important indicator to evaluate the ovarian reserve function and reproductive potential of women. At present, the application of ovarian age prediction model in China needs further improvement and optimization to make it more suitable for the actual situation of women in China. In this study, we collected subjects and their data in three ways: firstly, we collected clinical data from a number of women go to local hospital, including healthy women and women with DOR or PCOS; secondly, we obtained data by recruited healthy women through CRO companies for a fee; thirdly, we collected data from a number of healthy women using WeChat applet. Using the data collected by CRO company and WeChat applet, we applied the generalized linear model to optimize the ovarian age prediction model. The optimized formula is: OvAge = exp (3.5254-0.0001*PRL-0.0231*AMH), where P = 0.8195 for PRL and P = 0.0003 for AMH. Applying the formula to the hospital population data set for testing, it showed that the predicted ovarian age in the healthy women was comparable to their actual age, with a root mean squared error (RMSE) = 5.6324. The prediction accuracy was high. These data suggest that our modification of the ovarian age prediction model is feasible and that the formula is currently a more appropriate model for ovarian age assessment in healthy Chinese women. This study explored a new way to collect clinical data, namely, an online ovarian age calculator developed based on a WeChat applet, which can collect data from a large number of subjects in a short period of time and is more economical, efficient, and convenient. In addition, this study introduced real data to optimize the model, which could provide insights for model localization and improvement.


Assuntos
Modelos Estatísticos , Reserva Ovariana , Feminino , Humanos , Prognóstico , Ovário , Reprodução , Hormônio Antimülleriano
5.
Purinergic Signal ; 19(1): 145-153, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35235139

RESUMO

Atractylenolide I (Atr-I) was found to sensitize a variety of human cancer cells in previous studies. Purinergic P2X7R plays important role in different cancers. However, whether Atr-I could generate antitumor activity in human cervical cancer cells and P2X7R get involved in this effect remain unclear. In this study, Hela (HPV 18 +) and SiHa (HPV 16 +) cells were treated with different doses of Atr-I. The results indicated that agonist and antagonist of P2X7 receptors, BzATP and JNJ-47965567 (JNJ), could suppress the proliferation of Hela and SiHa cells. Atr-I demonstrated a considerable antitumor effect in both human cervical cancer cells in vitro. Atr-I combined with P2X7R agonist, BzATP, restored Atr-I-induced growth inhibition in Hela cells but not in SiHa cells. However, the combinatorial treatment of P2X7R antagonist JNJ and Atr-I has an additive effect on cell growth inhibition in SiHa cells rather than in Hela cells. It implied that P2X7R would get involved in the anti-human cervical cancer cells effect of Atr-I.


Assuntos
Receptores Purinérgicos P2X7 , Neoplasias do Colo do Útero , Feminino , Humanos , Proliferação de Células , Células HeLa , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antineoplásicos/uso terapêutico
6.
Comput Intell Neurosci ; 2022: 6833078, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268143

RESUMO

Background: The prognostic role of CRP (C-reactive protein) in gynecological tumors has been previously reported in individual studies, but whether CRP can be used as a separate potential prognostic factor has not been systematically reviewed. The purpose of this research is to determine if there is a link between CRP levels and the prognosis of gynecological cancer patients. Methods: A systematic search was carried out to find the literature evaluating the predictive role of CRP in the prognosis of gynecological cancer patients. For the purpose of determining the relationship between CRP and clinicopathological characteristics, the pooled odds ratio (OR) was calculated. A hazard ratio (HR) with a 95% confidence interval (CI) was used to determine differences in overall survival (OS), disease-free survival (DFS), or progression-free survival (PFS) between patients with low and high CRP levels. Results: A total of 19 studies, including 4062 patients, were analyzed retrospectively. The FIGO stage was related to the CRP level (OR = 0.43, 95% CI: 0.19-1.00). Age, lymph node metastasis, and histological grade were not associated with CRP level (OR = 0.93, 95% CI: 0.69-1.25; OR = 0.91, 95% CI: 0.65-1.28; OR = 0.74, 95% CI: 0.52-1.05). Worse OS (HR = 1.40, 95% CI: 1.23-1.57), DFS (HR = 1.20, 95% CI: 1.12-1.28), and PFS (HR = 1.57, 95%CI: 1.23-1.91) were associated with elevated CRP levels, as shown by the pooled results. Subgroup analysis was performed according to cancer type (endometrial cancer: HR = 1.15, 95% CI: 1.02-1.28; ovarian cancer: HR = 1.67, 95% CI: 1.03-2.31; cervical cancer: HR = 1.42, 95% CI: 1.19-1.64), multivariate value (HR = 1.22, 95% CI: 1.10-1.33), and age (HR = 1.50, 95% CI: 1.28-1.72). Significant correlations were observed between CRP and OS. Conclusions: CRP may be utilized as a prognostic indicator for a variety of gynecologic malignancies, including cervical cancer, ovarian cancer, endometrial cancer, and vulvar cancer.


Assuntos
Proteína C-Reativa , Neoplasias dos Genitais Femininos , Humanos , Feminino , Proteína C-Reativa/metabolismo , Estudos Retrospectivos , Prognóstico , Neoplasias dos Genitais Femininos/diagnóstico , Biomarcadores
7.
Front Microbiol ; 13: 979087, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36188003

RESUMO

Human papillomavirus (HPV) oncogenes E6 and E7 are essential for HPV-related cancer development. Here, we developed a cell line model using lentiviruses for transfection of the HPV16 oncogenes E6 and E7 and investigated the differences in mRNA expression during cell adhesion and chemokine secretion. Subsequently, RNA sequencing (RNA-seq) analysis was performed to explore the differences in mRNA expression. Compared to levels in the control group, 2,905 differentially expressed mRNAs (1,261 downregulated and 1,644 upregulated) were identified in the HaCaT-HPV16E6E7 cell line. To predict the functions of these differentially expressed genes (DEGs) the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used. Protein-protein interactions were established, and the hub gene was identified based on this network. Real-time quantitative-PCR (RT-qPCR) was conducted to confirm the levels of 14 hub genes, which were consistent with the RNA-seq data. According to this, we found that these DEGs participate in the extracellular matrix (ECM), cell adhesion, immune control, and cancer-related signaling pathways. Currently, an increasing number of clinicians depend on E6/E7mRNA results to make a comprehensive judgment of cervical precancerous lesions. In this study, 14 hub genes closely related to the expression of cell adhesion ability and chemokines were analyzed in HPV16E6E7-stably expressing cell lines, which will open up new research ideas for targeting E6E7 in the treatment of HPV-related cancers.

8.
Cancer Cell Int ; 22(1): 126, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305641

RESUMO

Colorectal cancer (CRC) is one of the most lethal and prevalent solid malignancies worldwide. There is a great need of accelerating the development and diagnosis of CRC. Long noncoding RNAs (lncRNA) as transcribed RNA molecules play an important role in every level of gene expression. Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) is a highly conserved nucleus-restricted lncRNA that regulates genes at the transcriptional and post-transcriptional levels. High expression of MALAT1 is closely related to numerous human cancers. It is generally believed that MALAT1 expression is associated with CRC cell proliferation, tumorigenicity, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) plays a pivotal role in CRC pathogenesis. Therefore, MALAT1 can be a potent gene for cancer prediction and diagnosis. In this review, we will demonstrate signaling pathways associated with MALAT1 in CRC.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35198031

RESUMO

BACKGROUND: Although the Bushen Huoxue (BSHX) recipe is commonly used for the effective treatment of the prethrombotic state of recurrent abortions, its mechanism of action is unclear. In this article, we investigated the therapeutic effects of BSHX on anti-cardiolipin antibody (ACA) positive recurrent miscarriage mice and the molecular mechanism involved in the treatment of the prethrombotic state of ACA-positive recurrent miscarriages based on the PI3K-Akt signaling pathway, to provide a scientific basis for clinical practice. METHODS: An ACA-positive recurrent miscarriage mouse model and normal pregnancy mouse model were adopted in this experiment. Seventy CBA/J female mice were induced to establish the ACA-positive recurrent model; the mice were mated with DBA/2 male mice. Of these mice, 50 became pregnant, which were randomly divided into a BSHX high-dose group (BH, 2.52 g/kg), BSHX medium-dose group (BM, 1.26 g/kg), BSHX low-dose group (BL, 0.63 g/kg), model group (M, distilled water), and an aspirin enteric-coated tablet group; each group had 10 mice. In addition, 16 CBA/J female mice were induced to establish the normal pregnant mouse model; the mice were mated with BALB/C male mice. Of these mice, 10 became pregnant, which were used as the blank control group (C) and received distilled water by gavage. Stillbirth and abortion rates were recorded for each group, and the uterine tissue, urine, and serum were collected. The serum expression levels of ACA, interleukin-6 (IL-6), progesterone ,estradiol, and endometrial histological changes were compared between the groups. Metabolomics was performed on the urine and uterine tissues of both groups using UHPLC-QTOF/MS, and the expression levels of PI3K, p-PI3K, AKT, and p-AKT proteins in the uterine tissues were detected using Western blot. RESULTS: Compared with the model pregnancy group, the BSHX high-dose group, BSHX medium-dose group, and BSHX low-dose group all had a lower absorption rate of mouse embryos, improved uterine histopathological morphology, significantly reduced serum levels of ACA and IL-6, increased serum levels of progesterone and estradiol, and significantly upregulated uterine levels of p-AKT, PI3K, and p-PI3K proteins. The metabolomic results showed that the metabolic levels in the urine and uterine tissues were significantly altered in the mouse model of ACA-positive recurrent abortion. The results also suggested that the pathogenesis of ACA-positive recurrent abortion may be associated with metabolic pathways, such as pentose, glucuronide, lysine degradation, and steroid hormone biosynthesis. CONCLUSION: The BSHX recipe improved the uterine histopathological morphology of pregnant mice and promoted vascular formation in uterine tissues. The mechanisms involved the reduction in serum ACA and IL-6 levels, the increment in serumprogesterone and estradiol levels, the upregulation of the levels of p-AKT, PI3K, and p-PI3K proteins, and the activation of the PI3K-Akt signaling pathway. These data will be useful for effective drug research and development.

10.
Curr Opin Pharmacol ; 61: 83-90, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34649216

RESUMO

The different Lactobacillus strains of probiotics have been applied to the treatment and prevention of bacterial vaginosis and vulvovaginal candidiasis. The experimental data demonstrated that it works well via reducing the number of harmful bacteria, maintaining the acidic microenvironment, inhibiting the immune response, and so on, to restore the vaginal microecology. However, the clinical data indicated that it is not sufficient to support the use of probiotics in the intervention of vulvovaginal candidiasis rather than bacterial vaginosis. Hunting for novel probiotic strains and uncovering the precise mechanism of probiotics, especially with the new concept gut-vagina axis, to maintain the homeostasis of vaginal microbiota should be a great challenge in the future.


Assuntos
Candidíase Vulvovaginal , Probióticos , Vaginose Bacteriana , Candidíase Vulvovaginal/tratamento farmacológico , Feminino , Humanos , Lactobacillus , Probióticos/uso terapêutico , Vaginose Bacteriana/tratamento farmacológico
11.
Contrast Media Mol Imaging ; 2021: 5175072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629993

RESUMO

To explore the diagnostic value of MRI image features based on convolutional neural network for tubal unobstructed infertility, 30 infertile female patients were first selected as the research objects, who admitted to the hospital from May 2018 to January 2020. They all underwent routine MRI examinations and CNN-based MR-hysteron-salpingography (HSG) examinations, in order to discuss the diagnostic accuracy of the two examinations. In the research, it was necessary to observe the patients' imaging results, calculate the diagnosis rate of the two examination results, and analyze the application effect of the CNN algorithm, thereby selecting the best reconstruction method. In this study, the analysis was conducted on the basis of no statistical difference in the baseline data of the included patients. The results of undersampling reconstruction at 2-fold, 4-fold, and 6-fold showed that CNN for data consistency layer (CNN_DC) had a better effect, and its peak signal-to-noise ratio (PSNR) was lower sharply than that of the other two reconstruction methods, while the normalized mean square error (NMSE) and structural similarity index measure (SSIM) were higher markedly than the values of the other two reconstruction methods. The diagnostic rate of routine MRI examination of the fallopian tube and other parts of the uterus was lower than or equal to that of MR-HSG examination by CNN. Routine MRI examinations of fallopian tube imaging artifacts were large, and the definition was reduced, which increased the difficulty of identification. However, MR-HSG examination by CNN indicated that the imaging artifacts were low, the clarity was high, and the influence of noise was small, which was conducive to clinical diagnosis and identification. For endometriosis, the accuracy of MR-HSG was 33.33% and the accuracy of MRI was 46.67%. CNN MR-HSG inspection method was significantly better than the conventional MRI inspection method (P < 0.05). Therefore, the results of this study revealed that MR-HSG examination by CNN had a clear imaging effect and obvious inhibition effect on background signals and rapid image generation without the need for reconstruction with the same spatial resolution, which improved the imaging quality and could provide a reference value for clinical diagnosis and subsequent related studies.


Assuntos
Tubas Uterinas/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Infertilidade Feminina/diagnóstico , Imageamento por Ressonância Magnética , Adulto , Tubas Uterinas/patologia , Feminino , Humanos , Histerossalpingografia/métodos , Infertilidade Feminina/diagnóstico por imagem , Infertilidade Feminina/patologia , Redes Neurais de Computação , Adulto Jovem
12.
Bioengineered ; 12(1): 3159-3176, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34187307

RESUMO

N6-methyladenosine (m6A) RNA methylation regulators play a regulatory role in tumor pathogenesis and development. However, the role of m6A regulator genes in ovarian cancer (OC) has not been fully elucidated. This study aims to investigate the mRNA expressions, clinicopathological features, and prognostic values of m6A regulators in OC. Here, we demonstrate that the 17 m6A RNA methylation regulators are differentially expressed in ovarian cancer and normal tissues. By using consensus clustering, all ovarian cancer patients can be divided into two subgroups (cluster 1 and 2) based on the expression of 17 m6A RNA methylation regulators. Using Gene Set Enrichment Analysis, we identified that cluster 1 was most connected to oxidative phosphorylation pathways. Regression models identified that prognosis is associated with HNRNPA2B1, KIAA1429, and WTAP. qRT-PCR result show that the expression trends of HNRNPA2B1 and KIAA1429 are consistent with the predicted results. Multivariate Cox regression analysis results show that the risk score was an independent predictive factor in OV. The overall survival of high-risk patients was significantly shorter than that of low-risk patients. ROC curve analysis showed that the prognostic signature precisely predicted the 5-year survival of OV patients. A nomogram was developed to predict each patient's survival probability and well calibrated and showed a satisfactory discrimination. Dendritic fraction, macrophage fraction, and neutrophil fraction showed higher fraction in high-risk patients. In conclusion, m6A RNA methylation regulators are vital participants in ovarian cancer pathology, and three-gene mRNA levels are valuable factors for prognosis predictions.


Assuntos
Adenosina/análogos & derivados , Neoplasias Ovarianas , RNA/metabolismo , Adenosina/genética , Adenosina/metabolismo , Bases de Dados Genéticas , Feminino , Redes Reguladoras de Genes/genética , Humanos , Metilação , Invasividade Neoplásica/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , RNA/genética , Transcriptoma/genética
13.
BMC Womens Health ; 20(1): 69, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252736

RESUMO

BACKGROUND: Vitamin E, which is critically important in the whole process of reproduction, can antagonize the oxidative stress caused by the oxygen free radicals and antioxidant imbalance and regulate normal physiological function of the reproductive system. The effect of short-term supplementation of vitamin E on outcomes of infertile women with polycystic ovary syndrome (PCOS) when they underwent ovulation induction with clomiphene citrate (CC) and human menopausal gonadotropin (HMG) remains unknown. METHODS: This was a retrospective cohort clinical trial from October 2015 to April 2017. A total of 321 PCOS cases underwent ovulation induction with CC and HMG. Patients in group A (n = 110) did not receive vitamin E while patients in group B (n = 105) and group C (n = 106) received oral treatment of vitamin E at 100 mg/day during follicular phase and luteal phase, respectively. RESULTS: It was observed no significant differences of ovulation rate, clinical pregnancy rate, and ongoing pregnancy rate among the three groups. It was interesting that dosage of HMG were significant lower in group B compared with those in group A and group C (P<0.05). CONCLUSIONS: A short-term supplementation of vitamin E can improve oxidative stress, and reduce exogenous HMG dosage to lower the economic cost with a similar pregnancy rate in the ovulation induction cycle. However, the supplementation does not alter the pregnancy rate in the ovulation induction cycle. TRIAL REGISTRATION: ChiCTR-OOC-14005389, 2014.


Assuntos
Clomifeno/uso terapêutico , Suplementos Nutricionais/efeitos adversos , Fármacos para a Fertilidade Feminina/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Síndrome do Ovário Policístico/complicações , Vitamina E/uso terapêutico , Adulto , Feminino , Humanos , Indução da Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Gravidez , Estudos Retrospectivos , Vitamina E/efeitos adversos
14.
Ann Endocrinol (Paris) ; 81(1): 18-27, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32127169

RESUMO

BACKGROUND: We aimed to identify key genes and microRNAs (miRNAs) associated with the development of polycystic ovary syndrome (PCOS). METHODS: GSE84376 mRNA microarray data (15 PCOS granulosa cells and 13 control granulosa cells) and GSE34526 mRNA microarray data (7 PCOS granulosa cells and 3 control granulosa cells) were downloaded from the Gene Expression Omnibus (GEO) database. First, differentially expressed gene (DEG) analysis, gene set enrichment analysis (GSEA) for differentially expressed mRNAs, and protein-protein interaction (PPI) network analysis were conducted. Next, miRNA-target genes were analyzed and functions predicted, and a competing endogenous RNA (ceRNA) network was constructed. Finally, the relationship between miR-486-5p and PRELID2 was experimentally validated. RESULTS: Spleen tyrosine kinase (SYK), major histocompatibility complex, class II, DR alpha (HLA-DRA), and interleukin 10 (IL-10) were important nodes in the PPI network. Interestingly, HLA-DRA was significantly enriched in phagosomes mediated by Staphylococcus aureus infection, and in IL-10 enriched during S. aureus infection. One miRNA (miR-486-5p) and a single target gene (PRELID2) were obtained from the ceRNA network. Further experiments showed that miR-486-5p is upregulated and PRELID2 is downregulated in PCOS patient granulosa cells, and that miR-486-5p targets the PRELID2 3'UTR. Topological property analysis showed that hsa-miR-4687-5p downregulation and hsa-miR-4651 upregulation determined the levels of most mRNAs. Levels of the hsa-miR-4651 target gene were significantly enriched in the leukocyte transendothelial migration pathway. CONCLUSIONS: Our results suggest that HLA-DRA and IL-10 may contribute to PCOS progression via phagosome enriched by S. aureus infection, while miR-486-5p may be implicated in follicular development in PCOS by targeting PRELID2. Besides, miR-4651 may be involved in inflammation via leukocyte transendothelial migration, by regulating its target gene. These findings may indicate new directions and constitute a breakthrough in studying the pathophysiology of PCOS.


Assuntos
MicroRNAs/genética , Síndrome do Ovário Policístico/genética , RNA Mensageiro/genética , Adulto , Estudos de Casos e Controles , Células Cultivadas , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Estudos de Associação Genética , Predisposição Genética para Doença , Células da Granulosa/metabolismo , Humanos , MicroRNAs/metabolismo , Análise em Microsséries , Síndrome do Ovário Policístico/patologia , RNA Mensageiro/metabolismo
15.
Aging (Albany NY) ; 11(10): 3094-3116, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31097679

RESUMO

Many infertile women suffered from poor ovarian response, and increased reactive oxygen species with age might mediate the poor ovarian response to FSH. In this study, we collected follicular fluids and isolated granulosa cells from female patients. Increased levels of peroxynitrite, tyrosine nitrations of FSH receptor (FSHR) and apoptosis were obviously detectable with decreased FSHR protein expressions in granulosa cells of the poor ovarian responders. In KGN (a human ovarian granulosa cell line) cells, exogenous peroxynitrite could sequester FSHR in the cytoplasm, and these dislocated FSHR might suffer from proteasome-mediated degradations. Here, we identified four peroxynitrite-mediated nitrated tyrosine residues of FSHR. Site-directed mutagenesis of FSHR revealed that Y626 was pivotal for intracellular trafficking of FSHR to the cell surface. Akt-induced inactivation of FoxO3a was required for the repression of FSH on granulosa cell apoptosis. However, peroxynitrite impaired FSH-induced Akt-FoxO3a signaling, while FSHR-Y626A mutant took similar effects. In addition, FoxO3a knockdown indeed impaired FSH-mediated cell survival, while FoxO3a-S253A mutant reversed that significantly.


Assuntos
Células da Granulosa/metabolismo , Estresse Oxidativo , Receptores do FSH/metabolismo , Adulto , Linhagem Celular , Feminino , Hormônio Foliculoestimulante , Proteína Forkhead Box O3/metabolismo , Humanos , Mutagênese Sítio-Dirigida , Ácido Peroxinitroso , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores do FSH/genética , Tirosina/metabolismo
16.
J Cell Biochem ; 120(8): 13076-13084, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30937963

RESUMO

OBJECTIVE: Clinical trials comparing the efficacy of different interventions for endometriosis are limited and controversial. The aim of the present study is to perform a network meta-analysis on the efficacy of various interventions for endometriosis. METHODS: We searched PubMed and Ovid EMBASE through 1 June, 2018, for trials reporting the pain score and 1-year pregnancy rate of patients including at least one pair of direct control group. The mean difference of pain score, odds ratio of 1-year pregnancy rate, and their associated 95% credible intervals (CrI) were used to describe efficacy. The surface under the cumulative ranking curve (SUCRA) was calculated to illustrate the rank probability of various treatments for different outcomes, on the basis of network meta-analysis. RESULTS: Our meta-analysis enrolled six studies for the evaluation of reducing pain and 10 studies for the 1-year pregnancy rate. All involved trials were sufficiently powered with a low risk of bias. Expectant management (EM), progesterone (PR), and gonadotropin-releasing hormone (GnRH)-agonist (GN) were significantly effective to reduce pain when compared with the placebo; EM ranked the highest on the SUCRA curve. For the 1-year pregnancy rate, no significant difference between the interventions was evident. Ablation ranked the highest with a SUCRA value of 0.6328. The rank of EM was acceptable with a SUCRA value of 0.4452. Our experimental results need to be verified by more high-quality randomized controlled trial articles. CONCLUSION: Limited available evidence showed that EM, PR, and GN were significantly effective to reduce pain when compared with the placebo. Due to a lack of convincing evidence favoring surgery or medication, we recommend considering EM.


Assuntos
Endometriose/terapia , Hormônio Liberador de Gonadotropina/agonistas , Dor/prevenção & controle , Progesterona/uso terapêutico , Conduta Expectante/métodos , Endometriose/complicações , Feminino , Humanos , Metanálise em Rede , Dor/complicações , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 41(6): 653-6, 2016 Jun 28.
Artigo em Chinês | MEDLINE | ID: mdl-27374452

RESUMO

The diagnosis and treatment of a patient with Mullerian duct cyst torsion combined with bladder cancer were retrospectively analyzed. The patient received an open abdominal operation with right accessory resection plus pelvic adhesion release, and conducted microscopic examination for the bladder under general anesthesia. The results of histopathological examination confirmed the diagnosis of Mullerian duct cyst and papillary urothelial carcinoma at low level. After surgery, the patient received chemotherapy and follow-up observation, and all the indices for the patient were normal and no obvious discomfort. Although the final diagnosis of Mullerian duct cysts is based on histopathological examination, ultrasonography, CT scan and MRI can also detect it. Most of the Mullerian duct cysts are benign, and surgical excision is safe and effective.


Assuntos
Ductos Paramesonéfricos , Neoplasias da Bexiga Urinária , Carcinoma Papilar , Cistos , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
18.
Tumour Biol ; 37(4): 4493-500, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26501422

RESUMO

It has been reported that nuclear factor of activated T cells (NFATC1) was up-regulated in cancers mediating malignant behaviors. However, the role of NFATC1 in ovarian cancer has not been elucidated. In the present study, we undertook to explore the clinicopathological significance of NFATC1 expression and the mechanism by which NFATC1 works in ovarian cancer. Expression status of NFATC1 was examined using immunohistochemistry. Both knockdown and re-expression of NFATC1 on ovarian cancer cells were employed to observe the effect overgrowth. It was found that NFATC1 was significantly overexpressed in ovarian cancer tissues in comparison with paired normal control tissues and that overexpression of NFATC1 was significantly associated with metastasis and poor prognosis on clinical tissue level. In in vitro ovarian cancer cell lines, we found that NFATC1 can promote proliferation up-regulating c-myc through activation of ERK1/2/p38/MAPK signal pathway. Together, the results we obtained demonstrated that NFATC1 played oncogenic role in ovarian cancer. Mechanistically, NFATC1 promoted growth of ovarian cancer cells up-regulating c-myc through activation of ERK1/2/p38/MAPK signal pathway, suggesting that NFATC1 might be used as a therapeutic target for ovarian cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição NFATC/fisiologia , Neoplasias Císticas, Mucinosas e Serosas/genética , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/metabolismo , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ativação Transcricional , Carga Tumoral , Regulação para Cima
19.
Acta Crystallogr C Struct Chem ; 71(Pt 2): 116-21, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25652278

RESUMO

A potentially pentadentate hydrazone ligand, N'-[1-(pyrazin-2-yl)ethylidene]nicotinohydrazide (HL), was prepared from the condensation reaction of nicotinohydrazide and acetylpyrazine. Reactions of HL with MnCl2, Mn(CH3COO)2 and Cd(CH3COO)2 afforded three metal complexes, namely dichlorido{N'-[1-(pyrazin-2-yl-κN(1))ethylidene]nicotinohydrazide-κ(2)N',O}manganese(II), [MnCl2(C12H11N5O)], (I), bis{N'-[1-(pyrazin-2-yl-κN(1))ethylidene]nicotinohydrazidato-κ(2)N',O]manganese(II), [Mn(C12H10N5O)2], (II), and poly[[(acetato-κ(2)O,O'){µ3-N'-[1-(pyrazin-2-yl-κ(2)N(1):N(4))ethylidene]nicotinohydrazidato-κ(3)N',O:N(1)}cadmium(II)] chloroform disolvate], {[Cd(C12H10N5O)(CH3COO)]·2CHCl3}n, (III), respectively. Complex (I) has a mononuclear structure, the Mn(II) centre adopting a distorted square-pyramidal coordination. Complex (II) also has a mononuclear structure, with the Mn(II) centre occupying a special position (C2 symmetry) and adopting a distorted octahedral coordination environment, which is defined by two O atoms and four N atoms from two N'-[1-(pyrazin-2-yl)ethylidene]nicotinohydrazidate (L(-)) ligands related via a crystallographic twofold axis. Complex (III) features a unique three-dimensional network with rectangular channels, and the L(-) ligand also serves as a counter-anion. The coordination geometry of the Cd(II) centre is pentagonal bipyramidal. This study demonstrates that HL, which can act as either a neutral or a mono-anionic ligand, is useful in the construction of interesting metal-organic compounds.

20.
Acta Chim Slov ; 61(1): 170-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24664341

RESUMO

A series of dinuclear paddle-wheel like transition metal complexes based on 2-phenylquinoline-4-carboxylic derivative L have been synthesized and characterized by IR, elemental analysis, and X-ray diffraction single crystal analysis. The biological activities of L and its complexes were evaluated as assayed antibacterial activities, including Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. The results indicated that these complexes showed better antibacterial activities than the free ligand or metal salts alone. Among them, the Zn(II) and Cd(II) complexes with IC50 of 0.57 µg/mL and 0.51 µg/mL, respectively, showed excellent antibacterial activity against Staphylococcus aureus.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Quinolinas/química , Antibacterianos/química , Bactérias/efeitos dos fármacos , Técnicas de Química Sintética , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/química
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