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1.
Nat Med ; 26(2): 193-199, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32042196

RESUMO

Immune checkpoint blockade (ICB) of PD-1 and CTLA-4 to treat metastatic melanoma (MM) has variable therapeutic benefit. To explore this in peripheral samples, we characterized CD8+ T cell gene expression across a cohort of patients with MM receiving anti-PD-1 alone (sICB) or in combination with anti-CTLA-4 (cICB). Whereas CD8+ transcriptional responses to sICB and cICB involve a shared gene set, the magnitude of cICB response is over fourfold greater, with preferential induction of mitosis- and interferon-related genes. Early samples from patients with durable clinical benefit demonstrated overexpression of T cell receptor-encoding genes. By mapping T cell receptor clonality, we find that responding patients have more large clones (those occupying >0.5% of repertoire) post-treatment than non-responding patients or controls, and this correlates with effector memory T cell percentage. Single-cell RNA-sequencing of eight post-treatment samples demonstrates that large clones overexpress genes implicated in cytotoxicity and characteristic of effector memory T cells, including CCL4, GNLY and NKG7. The 6-month clinical response to ICB in patients with MM is associated with the large CD8+ T cell clone count 21 d after treatment and agnostic to clonal specificity, suggesting that post-ICB peripheral CD8+ clonality can provide information regarding long-term treatment response and, potentially, facilitate treatment stratification.

2.
Stem Cell Reports ; 14(2): 210-225, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32004493

RESUMO

The effects of ascorbate on adult cell fate specification remain largely unknown. Using our stepwise and chemically defined system to derive lateral mesoderm progenitors from human pluripotent stem cells (hPSCs), we found that ascorbate increased the expression of mesenchymal stromal cell (MSC) markers, purity of MSCs, the long-term self-renewal and osteochondrogenic capacity of hPSC-MSCs in vitro. Moreover, ascorbate promoted MSC specification in an iron-dependent fashion, but not in a redox-dependent manner. Further studies revealed that iron synergized with ascorbate to regulate hPSC-MSC histone methylation, promote their long-term self-renewal, and increase their osteochondrogenic capacity. We found that one of the histone demethylases affected by ascorbate, KDM4B, was necessary to promote the specification of hPSC-MSCs. This mechanistic understanding led to the metabolic optimization of hPSC-MSCs with an extended lifespan in vitro and the ability to fully repair cartilage defects upon transplantation in vivo. Our results highlight the importance of ascorbate and iron metabolism in adult human cell fate specification.

3.
Analyst ; 145(6): 2191-2196, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32101219

RESUMO

The Au-Hg amalgam anchored on the surface of reduced graphene oxide nanosheets (Au-Hg/rGO) has been synthesized successfully and characterized by various techniques such as transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The Au-Hg/rGO nanocomposites were found to possess excellent peroxidase-like catalytic activity and can quickly catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxTMB in the presence of H2O2. The obvious color change offered accurate determination of the H2O2 concentration by recording the absorbance at 652 nm using a UV-vis spectrophotometer. The linear response range for H2O2 was from 5 µM to 100 µM and the detection limit was 3.25 µM (S/N = 3). Furthermore, a kinetic study indicated that the catalytic behavior of Au-Hg/rGO nanocomposites followed the typical Michaelis-Menten theory and Au-Hg/rGO nanocomposites showed good affinity for H2O2. We envision that the simple and sensitive colorimetric detection system holds great promising applications in clinical diagnostics and food and environment monitoring.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31910027

RESUMO

Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance, and patients with GDM have a higher risk of cardiovascular disease. Multiple microRNAs (miRNAs) are reported to be involved in the regulation of myocardial injury. Moreover, miR-873 was predicted to target insulin-like growth factor binding protein 2 (IGFBP2) through bioinformatic analysis, which was further confirmed using a luciferase assay. Thus, our objective was to assess whether microRNA-873 (miR-873) affects insulin resistance and myocardial injury in an established GDM rat model. The GDM rats were treated with miR-875 mimic or inhibitor, or IGFBP2 siRNA. The effects of miR-875 and IGFBP2 on the cardiac function, insulin resistance, and myocardial injury were evaluated by hemodynamic measurements, determination of biochemical indices of myocardium and serum, and insulin homeostatic model assessment. The results indicated that down-regulation of miR-873 up-regulated the expression of IGFBP2 and promoted the activation of PI3K/AKT/mTOR axis. With down-regulation of miR-873 in GDM rats, the cardiac function was improved, and the myocardial apoptosis was inhibited, coupled with elevated activity of superoxide dismutase, carbon monoxide synthase, and the nitric oxide content. Besides, the inhibition of miR-873 in GDM rats modulated the insulin resistance and reduced myocardial apoptosis. Overall, the data showed that inhibition of miR-873, by targeting IGFBP2, may regulate the insulin resistance and curtail myocardial injury in GDM rats through activating PI3K/AKT/mTOR axis, thus providing a potential means of impeding the progression of GDM.

5.
Toxicon ; 173: 62-67, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759921

RESUMO

Amanita neoovoidea (genus Amanita Pers.) poisoning leads to acute renal failure. Here, we present seven case reports of acute renal failure with acute hepatic failure due to ingestion of A. neoovoidea. Clinical manifestations included gastrointestinal symptoms 1-72 h after ingestion; elevation of renal parameters and blood uric acid, blood urea nitrogen, and creatinine levels; a few abnormal hepatic parameters, primarily albumin decrease and alanine aminotransferase increase; and elevation of zymogram parameters such as cholinesterase and lactate dehydrogenase. To determine whether the hepatic/renal lesions were caused by amanitins, we analyzed the blood and urine samples of patients and specimens of poisonous mushrooms. Morphological and molecular biological analyses indicated that the mushroom was A. neoovoidea. However, no amatoxins and phallotoxins were detected in its basidiomata.

6.
J Enzyme Inhib Med Chem ; 35(1): 404-413, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31880473

RESUMO

A urease inhibitor with good in vivo profile is considered as an alternative agent for treating infections caused by urease-producing bacteria such as Helicobacter pylori. Here, we report a series of N-monosubstituted thioureas, which act as effective urease inhibitors with very low cytotoxicity. One compound (b19) was evaluated in detail and shows promising features for further development as an agent to treat H. pylori caused diseases. Excellent values for the inhibition of b19 against both extracted urease and urease in intact cell were observed, which shows IC50 values of 0.16 ± 0.05 and 3.86 ± 0.10 µM, being 170- and 44-fold more potent than the clinically used drug AHA, respectively. Docking simulations suggested that the monosubstituted thiourea moiety penetrates urea binding site. In addition, b19 is a rapid and reversible urease inhibitor, and displays nM affinity to urease with very slow dissociation (koff=1.60 × 10-3 s-1) from the catalytic domain.


Assuntos
Helicobacter pylori/efeitos dos fármacos , Ureia/farmacologia , Urease/antagonistas & inibidores , Antibacterianos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos , Helicobacter pylori/citologia , Helicobacter pylori/enzimologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Ureia/análogos & derivados , Ureia/química , Urease/metabolismo
7.
Onco Targets Ther ; 12: 9309-9318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807011

RESUMO

Background: Dysregulation of long non-coding RNAs (lncRNAs) is closely related with the progression of cancer in humans. The functional and regulatory roles of lncRNAs in colorectal cancer (CRC) are still largely unclear. The purpose of this study is to explore the function of lncRNA STARD13-AS in CRC. Methods: The bioinformatics tool "GEPIA" was used to predict the potential expression of STARD13-AS in CRC. qRT-PCR was used to evaluate the relative expression level of STARD13-AS in CRC cells lines and tissues samples. The functional involvement of STARD13-AS in the CRC cells was assessed using MTT assay, flow cytometry, and Transwell assay. The expression levels of cyclin D, cyclin E, E-cadherin, N-cadherin, and vimentin were assessed using Western blot. Results: Bioinformatics prediction and qRT-PCR results showed that STARD13-AS expression was decreased in CRC tissues. Patients with low STARD13-AS expression exhibited distant and lymphatic metastasis as well as enhancement in tumor size. STARD13-AS expression was downregulated in CRC cell lines compared to normal human colon mucosal epithelial cell line NCM460 and STARD13-AS expression in SW620 and LoVo cell lines was lowest. Moreover, we observed that while STARD13-AS overexpression suppressed the cell cycle, proliferation, migration, and invasion, while promoted apoptosis both in LoVo and SW620 cells. In addition, STARD13-AS overexpression inhibited Cyclin E, Cyclin D, N-cadherin and vimentin expression, and promoted E-cadherin expression both in LoVo and SW620 cells. Conclusion: Expression of STARD13-AS suppresses cell proliferation and metastasis in CRC, suggesting that STARD13-AS might act as a potential target for CRC treatment.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31861922

RESUMO

Objective: With the participation of private hospitals in the health system, improving hospital efficiency becomes more important. This study aimed to evaluate the technical efficiency of public and private hospitals in Beijing, China, and analyze the influencing factors of hospitals' technical efficiency, and thus provide policy implications to improve the efficiency of public and private hospitals. Method: This study used a data set of 154-232 hospitals from "Beijing's Health and Family Planning Statistical Yearbooks" in 2012-2017. The data envelopment analysis (DEA) model was employed to measure technical efficiency. The propensity score matching (PSM) method was used for matching "post-randomization" to directly compare the efficiency of public and private hospitals, and the Tobit regression was conducted to analyze the influencing factors of technical efficiency in public and private hospitals. Results: The technical efficiency, pure technical efficiency and scale efficiency of public hospitals were higher than those of private hospitals during 2012-2017. After matching propensity scores, although the scale efficiency of public hospitals remained higher than that of their private counterparts, the pure technical efficiency of public hospitals was lower than that of private hospitals. Panel Tobit regression indicated that many hospital characteristics such as service type, level, and governance body affected public hospitals' efficiency, while only the geographical location had an impact on private hospitals' efficiency. For public hospitals in Beijing, those with lower average outpatient and inpatient costs per capita had better performance in technical efficiency, and bed occupancy rate, annual visits per doctor, and the ratio of doctors to nurses also showed a positive sign with technical efficiency. For private hospitals, the average length of stay was negatively associated with technical efficiency, but the bed occupancy rate, annual visits per doctor, and average outpatient cost were positively associated with technical efficiency. Conclusions: To improve technical efficiency, public hospitals should focus on improving the management standards, including the rational structure of doctors and nurses as well as appropriate reduction of hospitalization expenses. Private hospitals should expand their scale with proper restructuring, mergers, and acquisitions, and pay special attention to shortening the average length of stay and increasing the bed occupancy rate.

9.
Huan Jing Ke Xue ; 40(8): 3530-3538, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854758

RESUMO

After the construction of the Xiangjiaba Dam, the hydrodynamic conditions, nutrient distributions, and transport conditions of the Jinsha River were changed. Here, the nutrient distribution characteristics and retention effects of Xiangjiaba Reservoir were investigated according to the results of water quality monitoring from 2015 to 2016. Spatial and temporal variations in TN, TP, SiO32-Si, and other nutrients, and retention flux and retention rate were analyzed. The results showed that the nutrient mass concentration of TN, TP, and SiO32--Si was 0.905 mg·L-1, 0.034 mg·L-1, and 7.98 mg·L-1, respectively. The distribution of TN was affected by point sources and the concentration of TN was large in urban areas. This distribution of TP was mainly granular and the mass concentrations decreased along the river path. The mass concentration of SiO32--Si did not significantly vary over time and space. Furthermore, Xiangjiaba Reservoir had a persistent effect on nutrient salts; the average annual retention of TN, TP, and SiO32--Si was 2.30×104 t·a-1, 0.146×104 t·a-1, and -2.4×104 t·a-1, respectively. During different seasons, the retention of TN and SiO32--Si varied between positive or negative; however, TP appeared to be consistent. The average monthly retention efficiency of TN, TP, and SiO32--Si was 17.5%, 32.8%, and -2.14%, respectively. Overall, retention efficiencies were higher during the dry season than that wet season, and phosphorus retention was most pronounced. The retention of TN in the reservoir may be related to denitrification and the input of external load; the flux of SiO32--Si was mainly affected by runoff; and the particle morphology of phosphorus, as well as reservoir period, were the main factors affecting TP retention. There were no clear correlations between nutrient retention and the mass concentrations of TN and SiO32--Si, but the nutrient retention effect of Xiangjiaba Reservoir reduced TP concentrations along the river path and increased TP concentration with vertical depth.

10.
J Sleep Res ; : e12975, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881109

RESUMO

This study examined the changes in sleep duration (total sleep time, night-time sleep and daytime naps) after retirement transitions in China using a panel dataset of the China Health and Retirement Longitudinal Study in 2011, 2013 and 2015 with a total of 48,458 respondents. Linear regression analysis with generalized estimating equations was employed to examine the changes in sleep duration after transitions between different types of employment status. After controlling for the confounders, the results showed that the retired population and the population working in agricultural sectors slept 8.02 (p < .01) and 5.19 (p < .01) minutes longer than the population working in non-agricultural sectors, respectively. Employment transition also had significant effects on sleep duration. Transition from non-agricultural sectors to retirement increased total sleep time by 13.58 (p < .01) minutes and also raised the probability of daytime naps by 18% (OR = 1.18, p < .01). Transition from agricultural employment to retirement did not significantly affect the total sleep time, but significantly increased the probability of daytime naps (OR = 1.12, p = .02). Reentering the non-agricultural sectors for the retirees did not significantly affect night-time sleep, but decreased the probability of daytime naps (OR = 0.73, p < .01) and daytime nap duration (by 5.26 min, p = .01). In conclusion, people in China increased their sleep duration after transitions to retirement, but the magnitudes were much smaller than those in Western countries. Differences may be attributed to an abundant amount of Chinese people working in agricultural sectors, the high volume of retired people reentering the work force and the large proportion of people in China that had daytime naps at baseline.

11.
BMJ Open ; 9(11): e027902, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678935

RESUMO

INTRODUCTION: Obesity is a public health concern that is becoming increasingly more serious worldwide. Effective and sustainable childhood obesity prevention strategies may help to reduce the prevalence of obesity and may have an impact on lifelong health. However, few such strategies have been rigorously evaluated for Chinese children in different regions of China. METHODS AND ANALYSIS: The Diet, ExerCIse and CarDiovascular hEalth-Children is a cluster-randomised controlled trial that aims to assess the effectiveness and sustainability of a school-based, multi-faceted intervention to prevent obesity among Grade 4 primary school students (8-10 years old) in China. Twenty-four schools (approximately 1200 students) from above average, average and below average developed regions in China will be randomised to an intervention (12 schools) or usual practice (12 schools) group. The intervention will last for one school year (9 months) and consists of activities towards students, parents and school environment. A smartphone application will be used to assist in providing information on, monitoring and providing feedback on the behaviours and body weight of the students. Data will be collected at baseline, 4 months, 9 months and 21 months. The primary outcome will be the difference between groups in the change in students' body mass index at 9 months after the baseline investigation. The secondary outcomes will include the differences between groups in the changes in anthropometric measures, diet, physical activity levels and other measures at the follow-up visits. A variety of process evaluation methods will be used to evaluate the implementation process of the complex intervention. ETHICS AND DISSEMINATION: This study was approved by the Peking University Institution Review Board (IRB00001052-18021). The results will be disseminated through publication in peer-reviewed journals, presentations at conferences and in lay summaries provided to school staff and participants. TRIAL REGISTRATION NUMBER: NCT03665857.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31765831

RESUMO

We propose a computational workflow (I3) for intuitive integrative interpretation of complex genetic data mainly building on the self-organising principle. We illustrate the use in interpreting genetics of gene expression and understanding genetic regulators of protein phenotypes, particularly in conjunction with information from human population genetics and/or evolutionary history of human genes. We reveal that loss-of-function intolerant genes tend to be depleted of tissue-sharing genetics of gene expression in brains, and if highly expressed, have broad effects on the protein phenotypes studied. We suggest that this workflow presents a general solution to the challenge of complex genetic data interpretation. I3 is available at http://suprahex.r-forge.r-project.org/I3.html.

13.
ACS Appl Mater Interfaces ; 11(39): 35667-35674, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31502826

RESUMO

Spinel LiNi0.5Mn1.5O4 (LNMO) has been considered as one of the most promising candidate cathode materials for power lithium-ion batteries. However, its cycle performance suffers from the increasing impedance of the LNMO-cathode/electrolyte interface (LNMO-CEI) layer caused by parasitic reactions on the electrode surface at high operating potentials. To address the capacity degradation upon cycling, we present a feasible way to realize electrode modification by electrophoretically deposited graphene ultrathin films on the exterior surface of the LNMO cathodes without decreasing the electrode density. A p-phenylene diamine reduced graphene oxide (pPD-rGO) film with an area density of 20 µg/cm2 not only increases the capacity retention rate of the 1000th cycle at 4.2-5.2 V from 71.7 to 81.7% but also boosts the specific capacity from 110.6 to 122.4 mAh/g. X-ray photoelectron spectroscopy (XPS) spectra reveal that the pPD-rGO film with Lewis-base nature increases the content of LiF and reduces the number of RCFx groups in the cycled electrode, indicating the consumption of high-potential-generated F radicals by the pPD-rGO film. Such consumption favors the formation of a robust interphase between the pPD-rGO film and the electrolyte, which could hinder the sustained production of F radicals, consequently stabilize the LNMO-CEI layer, and improve the cycle performance. An electrophoretically deposited Lewis-acid GO film of 20 µg/cm2 reduces the specific capacity and fails to work as the pPD-rGO film. The chemical process for the formation of interphase on the GO film is similar to that on the bare LNMO electrode.

14.
Drug Des Devel Ther ; 13: 2619-2632, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534311

RESUMO

Objective: The aim was to investigate the role and potential mechanism of geranylgeranylacetone (GGA) in the development of atherosclerosis, and to explore the role of heat shock protein 22 (HSP22) in mediating GGA effect. Methods: Human coronary artery endothelial cell (HCAEC) was used for in vitro study. RNA interference was applied to suppress HSP22 in the cells. Cellular apoptosis and intracellular level of reactive oxygen species (ROS) were detected by flow cytometer, and proteins of HSP22, NF-κB, eNOS, and ICAM-1 were assessed by immunoblotting. HSP22-/-//ApoE-/-, and HSP22+/+//ApoE-/- mice were used to investigate the effect of GGA in the animal model of atherosclerosis. Atherosclerotic lesion of the mice aortas was evaluated by Oil Red O staining and H&E staining. Results: GGA significantly inhibited HCAEC apoptosis in response to oxidized-LDL (ox-LDL), but stimulated HSP22 synthesis in the cells. Transfection of HSP22-siRNA in the cells resulted in complete blockage of the GGA effect on apoptosis. GGA also significantly inhibited ROS, NF-κB, and ICAM-1 in the cells transfected control siRNA, but not in the cells transfected with HSP22-siRNA. Atherosclerotic plaque in the aorta was significantly less in the wild type (WT) animals treated with GGA as stained either by Oil Red O or by H&E staining, but not in the HSP22-KO mice. GGA significantly inhibited expression of NF-κB and ICAM-1 in the WT mice, but not in the HSP22-KO mice. Conclusion: GGA-induced HSP22, and inhibited ox-LDL-induced apoptosis as well as expression of NF-κB and ICAM-1 in the HCAECs. GGA also attenuated formation of atherosclerotic plaques in mice aorta. Suppression of HSP22 by siRNA resulted in blockage of the GGA inhibition on apoptosis or stimulation on NF-κB and ICAM-1. These findings suggested that GGA protects endothelial cells from injury in response to ox-LDL and block atherosclerotic development in mice aorta through induction of HSP22.

16.
Front Pharmacol ; 10: 863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31427972

RESUMO

Scopoletin, a phenolic coumarin derived from many medical or edible plants, is involved in various pharmacological functions. In the present study, we showed that Scopoletin effectively ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through novel regulatory mechanisms involving inhibition of NF-κB activity in dendritic cells (DCs). Scopoletin treatment significantly improved the severity of the disease and prominently decreased inflammation and demyelination of central nervous system (CNS) in EAE mice. Disease alleviation correlated with the downregulation of major histocompatibility complex (MHC) class II, CD80 and CD86, expressed on DCs of CNS or spleens, and the infiltration and polarization of encephalitogenic Th1/Th17 cells. Consistent with the in vivo data, Scopoletin-treated, bone marrow-derived dendritic cells (BM-DCs) exhibited reduced expression of MHC class II and costimulatory molecules (e.g., CD80 and CD86) and reduced NF-κB phosphorylation. These findings, for the first time, demonstrated the ability of Scopoletin to impair DC activation, downregulating pathogenic Th1/Th17 inflammatory cell responses and, eventually, reducing EAE severity. Our study demonstrates new evidence that natural products derived from medical or edible plants, such as Scopoletin, will be valuable in developing a novel therapeutic agent for MS in the future.

17.
Hum Reprod Update ; 25(4): 486-503, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260048

RESUMO

BACKGROUND: Endometriosis is a chronic gynaecological disorder that affects 2-10% of women of reproductive age. The aetiology of endometriosis is largely under-explored, yet abnormalities in the immune system have been suggested to explain the origin of ectopic endometrial tissues, and an association between endometriosis and autoimmune diseases has been proposed. Evaluation of current evidence investigating the association between endometriosis and autoimmune diseases from population-based studies will facilitate our understanding of the causes and consequences of endometriosis and provide a reference for better healthcare practices population-wide. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the literature on population-based studies investigating an association between endometriosis and autoimmune diseases and to conduct a meta-analysis of combinable results to investigate the extent and robustness of evidence. SEARCH METHODS: Four electronic databases were searched (MEDLINE, Embase, Web of Science, and CINAHL) from each database inception date until 7 April 2018. Search terms included a combination of database-specific controlled vocabulary terms and free-text terms relating to 'endometriosis' and 'autoimmune diseases'. Study inclusion criteria focused on peer-reviewed published articles that reported an association between endometriosis and autoimmune diseases, excluding case reports/series, review papers, meta-analyses, organizational guidelines, editorial letters, expert opinions, and conference abstracts. Quality assessment of included studies was performed based on GRADE criteria. Key information of eligible studies was abstracted into a standard form. Meta-analysis was performed for autoimmune diseases with combinable study results from at least three studies investigating an association with endometriosis. For cross-sectional studies and case-control studies, raw data from each study were documented to calculate a Mantel-Haenszel odds ratio with 95% CIs. For cohort studies, an inverse variance probability weighted model was used to pool study results to calculate a rate ratio (a hazard ratio or a standardized incidence rate) with 95% CIs. OUTCOMES: A total of 26 published population-based cross-sectional, case-control, and cohort studies that investigated the association between endometriosis and autoimmune diseases met all eligible criteria and were included in the review. The studies quantified an association between endometriosis and several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), rheumatoid arthritis (RA), autoimmune thyroid disorder, coeliac disease (CLD), multiple sclerosis (MS), inflammatory bowel disease (IBD), and Addison's disease. However, the quality of the evidence was generally poor due to the high risk of bias in the majority of the chosen study designs and statistical analyses. Only 5 of the 26 studies could provide high-quality evidence, and among these, 4 supported a statistically significant association between endometriosis and at least 1 autoimmune disease: SLE, SS, RA, CLD, MS, or IBD. WIDER IMPLICATIONS: The observed associations between endometriosis and autoimmune diseases suggest that clinicians need to be aware of the potential coexistence of endometriosis and autoimmune diseases when either is diagnosed. Scientists interested in research studies on endometriosis or autoimmune diseases should consider the likelihood of comorbidity when studying these two types of health conditions. Well-designed large prospective cohort studies with confounding control and mediation quantification, as well as genetic and biological studies, are needed to generate further insights into whether endometriosis is a risk factor for, or a consequence of, autoimmune diseases, and whether these two types of disorders share pathophysiological mechanisms even if they arise independently. Such insights may offer opportunities for the development of novel non-hormonal medications such as immuno-modulators or repurposing of existing immunomodulatory therapies for endometriosis.

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