Bisphenol A(BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins.Inevitably, general populat...Bisphenol A(BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins.Inevitably, general population has been widely exposed to BPA due to extensive use of BPAcontaining products. BPA has similar chemical structure with the natural estrogen and has been shown to induce a variety of estrogen-like endocrine effects on organism in vivo or in vitro. High doses of BPA tend to act as antagonist of estrogen receptors(ERs) by directly regulating the genomic transcription. However, BPA at environmentally relevant low-dose always disrupt the biological function via a non-genomic manner mediated by membrane receptors, rather than ERs. Although some studies had investigated the non-genomic effects of low-dose BPA, the exact molecular mechanism still remains unclear. Recently, we found that membrane G protein-coupled estrogen receptor 1 and integrin αvβ3 and its relative signal pathways participate in the induction of male germ cell proliferation and thyroid transcription disruption by the low-dose BPA. A profound understanding for the mechanism of action of the environmentally relevant BPA exposure not only contributes to objectively evaluate and predict the potential influence to human health, but also provides theoretical basis and methodological support for assessing health effects trigged by other estrogen-like environmental endocrine disruptors. Based mainly on our recent findings, this review outlines the research progress of molecular mechanism on endocrine disrupting effects of environmental low-dose BPA, existing problems and some consideration for future studies.展开更多
OBJECTIVE:To investigate the mechanism underlying the anticancer effect of Artemisia species through the inhibition of cell growth and induction of apoptosis in breast carcinoma cells.METHODS:To evaluate the anticance...OBJECTIVE:To investigate the mechanism underlying the anticancer effect of Artemisia species through the inhibition of cell growth and induction of apoptosis in breast carcinoma cells.METHODS:To evaluate the anticancer activity of methanol extracts of eight Artemisia species(Artemisia stolonifera,Artemisia selengensis,Artemisia japonica,Artemisia Montana,Artemisia capillaris,Artemisia sylvatica,Artemisia keiskeana,and Artemisia scoparia),we first investigated the proliferation of estrogen receptor(ER)-positive MCF-7breast carcinoma cells exposed to 5 or 200 g/mL for72 h.Apoptosis induction was assessed by an Annexin V binding assay in cells exposed to extracts at a high concentration(200 g/mL).To verify the mechanism of apoptosis,ER expression and its related signaling was investigated using an immunoblot assay under the same conditions.RESULTS:MCF-7 cells showed the strongest antiproliferative response to the tested extracts.Howev-er,a biphasic effect was observed:the extracts inhibited proliferation at high concentrations whereas they stimulated it at low ones.ER expression was similarly modulated by the extracts.However,all of the extracts induced apoptosis at a high concentration(200 g/mL).Compared to the control level,exposure to the extracts resulted in a remarkable increase in the shift of cell populations.CONCLUSION:The present study suggests that the tested Artemisia species exerted their anticancer effects through the induction of apoptosis via an ER-related pathway.展开更多
The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2...The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.展开更多
Background： Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1 （ESR 1）. The polymorp...Background： Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1 （ESR 1）. The polymorphisms ofESR 1 were involved in recurrent spontaneous abortion （RSA）; however, the association between ESRI polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESRI Pvull （-397C/T, rs2234693） and Xbal （-351 A/G, rs9340799） polymorphisms and the risk of RSA. Methods： All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3,2018. Data were processed in the Stata 12.0 software. The odds ratios （ORs） and 95% confidence intervals （95% Cls） were calculated using fixed-effects models （FEM）/random-effects models （REM）. Results： Seven case-control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR 1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model （OR = 2.40, 95% CI = 1.05-5.50, P = 0.039）. Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model （OR = 0.53, 95% CI = 0.33-0.85, P = 0.009） and the dominant genetic model （OR=0.55, 95% CI = 0.30 0.98, P = 0.042）. Conclusions： Generally. there was no significant association between the polymorphisms of ESRI and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.展开更多
Objective:To elucidate the active compounds and the molecular mechanism of Cyathula Off/c/na//s as a drug treatment for rheumatoid arthritis(RA).Methods:The target genes of active ingredients from Cyathula Officinalis...Objective:To elucidate the active compounds and the molecular mechanism of Cyathula Off/c/na//s as a drug treatment for rheumatoid arthritis(RA).Methods:The target genes of active ingredients from Cyathula Officinalis were obtained from bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine.The protein-protein interaction between the target genes were analyzed using STRING and Genemania.The transcriptome of RA patients compared to healthy people(GSE121894)were analyzed using R program package Limma.The relative expression of the target genes was obtained from the RNA-seq datasets.The molecular docking analyses were processed based on the molecular model of estrogen receptor 1(ESR1)binding with estradiol(PDB ID:1A52).The binding details were analyzed by SYBYL.Results:Inokosterone,ecdysterone,and cyaterone were the 3 active ingredients from Cyathula Officinalis that bind to target genes.Of all the significantly changed genes from RA patients,ESR1,ADORA1,and ANXA1 were significantly increased in mRNA samples of RA patients.Conclusion:ESR1,the transcription factor that binds inokosterone in the molecular binding analysis,is the target protein of Cyathula Officinalis.展开更多
基金supported by Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDB01020300)the National Natural Science Foundation of China (Nos.21377158,21577149,21477139,21237005,21621064 and 21321004)
文摘Bisphenol A(BPA) is one of the highest volume industrial products worldwide and has been widely used to make various products as the intermediates of polycarbonate plastics and epoxy resins.Inevitably, general population has been widely exposed to BPA due to extensive use of BPAcontaining products. BPA has similar chemical structure with the natural estrogen and has been shown to induce a variety of estrogen-like endocrine effects on organism in vivo or in vitro. High doses of BPA tend to act as antagonist of estrogen receptors(ERs) by directly regulating the genomic transcription. However, BPA at environmentally relevant low-dose always disrupt the biological function via a non-genomic manner mediated by membrane receptors, rather than ERs. Although some studies had investigated the non-genomic effects of low-dose BPA, the exact molecular mechanism still remains unclear. Recently, we found that membrane G protein-coupled estrogen receptor 1 and integrin αvβ3 and its relative signal pathways participate in the induction of male germ cell proliferation and thyroid transcription disruption by the low-dose BPA. A profound understanding for the mechanism of action of the environmentally relevant BPA exposure not only contributes to objectively evaluate and predict the potential influence to human health, but also provides theoretical basis and methodological support for assessing health effects trigged by other estrogen-like environmental endocrine disruptors. Based mainly on our recent findings, this review outlines the research progress of molecular mechanism on endocrine disrupting effects of environmental low-dose BPA, existing problems and some consideration for future studies.
基金Supported by Priority Research Centers Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(NRF-2009-0094017 and NRF-2011-0017017)
文摘OBJECTIVE:To investigate the mechanism underlying the anticancer effect of Artemisia species through the inhibition of cell growth and induction of apoptosis in breast carcinoma cells.METHODS:To evaluate the anticancer activity of methanol extracts of eight Artemisia species(Artemisia stolonifera,Artemisia selengensis,Artemisia japonica,Artemisia Montana,Artemisia capillaris,Artemisia sylvatica,Artemisia keiskeana,and Artemisia scoparia),we first investigated the proliferation of estrogen receptor(ER)-positive MCF-7breast carcinoma cells exposed to 5 or 200 g/mL for72 h.Apoptosis induction was assessed by an Annexin V binding assay in cells exposed to extracts at a high concentration(200 g/mL).To verify the mechanism of apoptosis,ER expression and its related signaling was investigated using an immunoblot assay under the same conditions.RESULTS:MCF-7 cells showed the strongest antiproliferative response to the tested extracts.Howev-er,a biphasic effect was observed:the extracts inhibited proliferation at high concentrations whereas they stimulated it at low ones.ER expression was similarly modulated by the extracts.However,all of the extracts induced apoptosis at a high concentration(200 g/mL).Compared to the control level,exposure to the extracts resulted in a remarkable increase in the shift of cell populations.CONCLUSION:The present study suggests that the tested Artemisia species exerted their anticancer effects through the induction of apoptosis via an ER-related pathway.
文摘The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.
基金This work was supported by the Natural Science Foundation of China （No. 81373670, No. 81673981, and No. 81601442）, the Primary Research and Development Plan of Shandong Province （No. 2016GSF202016, No. 2017GSF19118, 2017G006018, and No. 2017GSF218013）, the Project of Transformation in High-tech Achievements （No. 2013ZHZX2A0405）, the Science and Technology Development Grant of the State Administration of traditional Chinese medicine of Shandong Province （No. 2013-2016 and No. 2017-174）, the Family Planning Committee of Shandong Province （No. [2014] 14）, the Project for Shandong Medical and Health Science and Technology Plan （No. 2015WS0191）, the Project of Science and Technology of Shandong Academy of Medical Sciences （No. 2016-34, No. 2016-35, and No. 2017-15）, and the Innovation Project of Shandong Academy of Medical Sciences.
文摘Background： Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1 （ESR 1）. The polymorphisms ofESR 1 were involved in recurrent spontaneous abortion （RSA）; however, the association between ESRI polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESRI Pvull （-397C/T, rs2234693） and Xbal （-351 A/G, rs9340799） polymorphisms and the risk of RSA. Methods： All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3,2018. Data were processed in the Stata 12.0 software. The odds ratios （ORs） and 95% confidence intervals （95% Cls） were calculated using fixed-effects models （FEM）/random-effects models （REM）. Results： Seven case-control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR 1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model （OR = 2.40, 95% CI = 1.05-5.50, P = 0.039）. Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model （OR = 0.53, 95% CI = 0.33-0.85, P = 0.009） and the dominant genetic model （OR=0.55, 95% CI = 0.30 0.98, P = 0.042）. Conclusions： Generally. there was no significant association between the polymorphisms of ESRI and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.
文摘Objective:To elucidate the active compounds and the molecular mechanism of Cyathula Off/c/na//s as a drug treatment for rheumatoid arthritis(RA).Methods:The target genes of active ingredients from Cyathula Officinalis were obtained from bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine.The protein-protein interaction between the target genes were analyzed using STRING and Genemania.The transcriptome of RA patients compared to healthy people(GSE121894)were analyzed using R program package Limma.The relative expression of the target genes was obtained from the RNA-seq datasets.The molecular docking analyses were processed based on the molecular model of estrogen receptor 1(ESR1)binding with estradiol(PDB ID:1A52).The binding details were analyzed by SYBYL.Results:Inokosterone,ecdysterone,and cyaterone were the 3 active ingredients from Cyathula Officinalis that bind to target genes.Of all the significantly changed genes from RA patients,ESR1,ADORA1,and ANXA1 were significantly increased in mRNA samples of RA patients.Conclusion:ESR1,the transcription factor that binds inokosterone in the molecular binding analysis,is the target protein of Cyathula Officinalis.
