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Intricate roles of estrogen and estrogen receptors in digestive system cancers:a systematic review
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作者 Xiaoning Gan Guanqi Dai +2 位作者 Yonghao Li Lin Xu Guolong Liu 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第10期898-915,共18页
Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potentia... Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potential protective role of female steroid hormones,particularly estrogen,in the development of these cancers.Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors(ERs),including the classic(ERαand ERβ)and non-traditional ERs[G protein-coupled estrogen receptor(GPER)].Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers.In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers,including hepatocellular,pancreatic,esophageal,gastric,and colorectal carcinoma.Furthermore,we discuss the potential molecular mechanisms underlying ERα,ERβ,and GPER effects,and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs.The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved.Additionally,deciphering the intricate roles of estrogen,ERs,and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers,eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies. 展开更多
关键词 estrogen estrogen receptor CANCER digestive system cancers gender disparity
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Comprehensive Analysis of Estrogen Receptor 1 Dysregulation in Liver Hepatocellular Carcinoma: Implications for Prognosis and Therapeutic Targeting - A Secondary Publication
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作者 Syed Hussain Raza Yasir Hameed 《Proceedings of Anticancer Research》 2024年第3期51-59,共9页
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
关键词 estrogen receptor 1 liver hepatocellular carcinoma BIOMARKER PROGNOSIS
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Unveiling the effect of estrogen receptors in alcoholic liver disease:A novel outlook
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作者 Sukriti Baweja Ashmit Mittal +3 位作者 Swati Thangariyal P.Debishree Subudhi Shivani Gautam Rashmi Kaul 《Liver Research》 CSCD 2023年第4期333-341,共9页
Alcoholic liver disease(ALD)has a multifaceted development,progressing from alcoholic steatosis to alcoholic hepatitis and ultimately to alcoholic cirrhosis,irreversible liver damage that can even result in hepatocell... Alcoholic liver disease(ALD)has a multifaceted development,progressing from alcoholic steatosis to alcoholic hepatitis and ultimately to alcoholic cirrhosis,irreversible liver damage that can even result in hepatocellular carcinoma.The prevalence of ALD is increasing globally,particularly among middle-aged adults.Gender-based studies have revealed that ALD affects more men;however,disease progression differs between men and women.Despite this,the molecular understanding of alcohol-induced liver injury among genders and its association with changes in sex hormone metabolism,particularly with estrogen and estrogen receptors(ERs)in ALD,remains poor.This review focuses on experimental and human studies describing alcohol and its association with estrogen metabolism and signaling via ERs.Chronic alcohol consumption affects the immune response,and whether estrogen has any contributory effect remains inadequately studied.This review also discusses various therapeutic approaches currently in use and future approaches that can affect the response or progression via estrogen signaling.The role of gender on alcohol consumption and its association with steroid hormones must be elucidated for a better understanding of the pathogenesis of ALD,the development of effective therapeutic approaches,and better disease management in both men and women,as ALD remains a major public health concern. 展开更多
关键词 Alcoholic liver disease(ALD) estrogen estrogen receptors(ERs) INFLAMMATION Immune response Therapeutic target
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Expression of P450 and nuclear receptors in normal and end-stage Chinese livers 被引量:5
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作者 Hong Chen Zhong-Yang Shen +5 位作者 Wang Xu Tie-Yan Fan Jun Li Yuan-Fu Lu Ming-Liang Cheng Jie Liu 《World Journal of Gastroenterology》 SCIE CAS 2014年第26期8681-8690,共10页
AIM: To investigate the expression of P450 enzyme genes by using end-stage liver disease samples and trimmed normal Chinese donor livers.
关键词 Cytochrome P450 Nuclear receptors mRNA expression End-stage livers Chinese donor livers Hepatocellular carcinoma
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Ulcerative colitis: From inflammation to cancer. Do estrogen receptors have a role? 被引量:4
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作者 Mariabeatrice Principi Michele Barone +4 位作者 Maria Pricci Nicola De Tullio Giuseppe Losurdo Enzo Ierardi Alfredo Di Leo 《World Journal of Gastroenterology》 SCIE CAS 2014年第33期11496-11504,共9页
Ulcerative colitis(UC) is a condition at increased risk for colorectal carcinoma(CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in... Ulcerative colitis(UC) is a condition at increased risk for colorectal carcinoma(CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors(extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogenreceptors(ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anticarcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields. 展开更多
关键词 Ulcerative colitis Epithelial dysplasia Colorectal cancer estrogen receptors Chemopreven-tion PHYTOestrogenS Dietary supplementation Inflam-matory bowel disease
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Liver X receptors and epididymal epithelium physiology
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作者 Fabrice Saez Eléore Chabory +4 位作者 Rémi Cadet Patrick Vernet Silvère Baron2 Jean-Marc A. Lobaccaro Joeol R. Drevet 《Asian Journal of Andrology》 SCIE CAS CSCD 2007年第4期574-582,共9页
Aim: To investigate the roles of liver X receptors (LXR) in the lipid composition and gene expression regulation in the murine caput epididymidis. LXR are nuclear receptors for oxysterols, molecules derived from ch... Aim: To investigate the roles of liver X receptors (LXR) in the lipid composition and gene expression regulation in the murine caput epididymidis. LXR are nuclear receptors for oxysterols, molecules derived from cholesterol metabolism that are present in mammals as two isoforms: LXRα, which is more specifically expressed in lipid-metabolising tissues, such as liver, adipose and steroidogenic tissues, and macrophages, whereas LXRβ is ubiquitous. Their importance in reproductive physiology has been sustained by the fact that male mice in which the function of both LXR has been disrupted have fertility disturbances starting at the age of 5 months, leading to complete sterility by the age of 9 months. These defects are associated with epididymal epithelial degeneration in caput segments one and two, and with a sperm midpiece fragility, leading to the presence of isolated sperm heads and flagella when luminal contents are recovered from the cauda epididymidis. Methods: The lipid composition of the caput epididymidis of wild-type and LXR-deficient mice was assessed using oil red O staining on tissue cryosections and lipid extraction followed by high performance liquid chromatography or gas chromatography. Gene expression was checked by quantitative real time polymerase chain reaction. Results: Using LXR-deficient mice, we showed an alteration of the lipid composition of the caput epididymidis as well as a significantly decreased expression of the genes encoding SREBPlc, SCD1 and SCD2, involved in fatty acid metabolism. Conclusion: Altogether, these results show that LXR are important regulators of epididymal function, and play a critical role in the lipid maturation processes occurring during sperm epididymal maturation. (Asian J Androl 2007 July; 9: 574-582) 展开更多
关键词 EPIDIDYMIS liver X receptors nuclear receptors LIPIDS CHOLESTEROL gene expression
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Expression of Progesterone and Estrogen Receptors in Human Renal Cell Carcinoma
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作者 钱立新 眭元庚 +4 位作者 徐正铨 吴宏飞 尤国才 张炜 金雁 《The Journal of Biomedical Research》 CAS 1997年第2期17-21,共5页
Progesterone receptor(PR) and estrogen receptor(ER) were investigated in 29 specimens of renal cell carcinoma (RCC) and its autologous kidneys, 12 samples of control kidnerys with high sensitive and specific enzymelab... Progesterone receptor(PR) and estrogen receptor(ER) were investigated in 29 specimens of renal cell carcinoma (RCC) and its autologous kidneys, 12 samples of control kidnerys with high sensitive and specific enzymelabelled histochemical techniques. The positive expression rates of PR in RCC, its autologous kidneys and control kidneys were 31.0%, 82.8% and 83.3% respectively, while the positive expression rates of ER of those tissues were 58.6%, 79.3% and 83.3%, respectively. It showed that the positive rate and the value of PR and ER in RCC were significantly less than those determined in the autologous kidneys and normal tissues(P<0.05) and no significant differences of PR and ER were found between autologous and normal kidneys(P>0.05). The level and positive rate of PR in stage Ⅰ were higher than those in stage Ⅱ to Ⅳ of RCC tissues (P<0.05). There was no relationship between the status of PR, ER and patient sex(P>0.05). Expression of PR in RCC had correlation to Robson stage closely. The positive rate of PR may be treated as a prognostic factor because it decreased as the stage rose. Our result provided an experimental basis for the application of hormonal therapy in RCC and emphasized that patients who may be benefited from hormonal therapy must have sufficient hormone receptors. 展开更多
关键词 renal neoplasm progesterone receptors estrogen receptors
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Estrogen, estrogen receptors, and hepatocellular carcinoma: Are we there yet? 被引量:11
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作者 Olga A Sukocheva 《World Journal of Gastroenterology》 SCIE CAS 2018年第1期1-4,共4页
A protective role of the sex steroid hormone estrogenin hepatocellular carcinoma(HCC) was suggested a few decades ago according to clinical data showing higher HCC morbidity and mortality among males. Several recent s... A protective role of the sex steroid hormone estrogenin hepatocellular carcinoma(HCC) was suggested a few decades ago according to clinical data showing higher HCC morbidity and mortality among males. Several recent studies further confirmed the anti-cancer effects of estrogen in the liver. However, it remains to be identified how to exploit estrogen signalling within clinical settings for HCC treatment. There are several unresolved issues related to the estrogen pathway in liver cells. The main problems include the absence of a clear understanding of which estrogen receptor(ER) isoform is predominantly expressed in normal and malignant liver cells, the ER isoform expression difference between males and females, and which ER isoform should be targeted when designing HCC therapy. Some of those questions were recently addressed by Iyer and coauthors. The current editorial review critically analyses the study by Iyer et al(WJG, 2017) that investigated the expression of ER subtypes in liver samples collected from patients with a healthy liver, hepatitis C virus cirrhosis, and HCC. ER presence was evaluated in association with gender, intracellular localization, inflammation marker NF-kB, and proliferation-related effector cyclin D1. The study limitations and advantages are discussed in light of recent advances in the HCC and estrogen signalling areas. 展开更多
关键词 HEPATOCELLULAR carcinoma HEPATITIS C virus HEPATITIS estrogen receptors CIRRHOSIS
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Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease 被引量:30
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作者 Vettickattuparambil George Giby Thekkuttuparambil Ananthanarayanan Ajith 《World Journal of Hepatology》 CAS 2014年第8期570-579,共10页
Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabe... Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evi-dence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipo-genesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transform-ing growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription fac-tors, namely peroxisome proliferator-activated receptor(PPAR)-α. Recent studies have proposed downregula-tion of PPAR-α in cases of hepatic steatosis. This re-view discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD. 展开更多
关键词 NONALCOHOLIC FATTY liver disease ADIPOSE tissue Energy HOMEOSTASIS PEROXISOME proliferator activated receptors ADIPOKINES
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Elafibranor:A promising treatment for alcoholic liver disease,metabolic-associated fatty liver disease,and cholestatic liver disease
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作者 Hang Zhang Xuan Dong +1 位作者 Lei Zhu Fu-Shan Tang 《World Journal of Gastroenterology》 SCIE CAS 2024年第40期4393-4398,共6页
Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment ... Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application. 展开更多
关键词 Elafibranor Peroxisome proliferator activated receptor liver fibrosis Alcoholic liver disease Metabolic-associated fatty liver disease Metabolic-associated steatohepatitis Cholestatic liver disease Primary biliary cholangitis liver diseases
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Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease 被引量:21
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作者 Vanessa Souza-Mello 《World Journal of Hepatology》 CAS 2015年第8期1012-1019,共8页
Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcr... Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcription factors that modulate the expression of genes involved in lipid metabolism, energy homeostasis and inflammation, being altered in diet-induced obesity. Experimental evidences show that PPAR-alpha is the master regulator of hepatic beta-oxidation(mitochondrial and peroxisomal)and microsomal omega-oxidation, being markedly decreased by high-fat(HF) intake. PPAR-beta/delta is crucial to the regulation of forkhead box-containing protein O subfamily-1 expression and, hence, the modulation of enzymes that trigger hepatic gluconeogenesis. In addition, PPAR-beta/delta can activate hepatic stellate cells aiming to the hepatic recovery from chronic insult. On the contrary, PPAR-gamma upregulation by HF diets maximizes NAFLD through the induction of lipogenic factors, which are implicated in the fatty acid synthesis. Excessive dietary sugars also upregulate PPAR-gamma, triggering de novo lipogenesis and the consequent lipid droplets deposition within hepatocytes. Targeting PPARs to treat NAFLD seems a fruitful approach as PPAR-alpha agonist elicits expressive decrease in hepatic steatosis by increasing mitochondrial beta-oxidation, besides reduced lipogenesis. PPAR-beta/delta ameliorates hepatic insulin resistance by decreasing hepatic gluconeogenesis at postprandial stage. Total PPAR-gamma activation can exert noxious effects by stimulating hepatic lipogenesis. However, partial PPAR-gamma activation leads to benefits, mainly mediated by increased adiponectin expression and decreased insulin resistance. Further studies are necessary aiming at translational approaches useful to treat NAFLD in humans worldwide by targeting PPARs. 展开更多
关键词 PEROXISOME proliferator-activated receptors Non-alcoholic FATTY liver disease Obesity Treatment Insulin resistance BETA-OXIDATION LIPOGENESIS
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Toll-like receptors in pathophysiology of liver diseases 被引量:28
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作者 Safak Kiziltas 《World Journal of Hepatology》 CAS 2016年第32期1354-1369,共16页
Toll-like receptors(TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated mole... Toll-like receptors(TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated molecular patterns. Given constant exposure to pathogens from gut, strict control of TLR-associated signaling pathways is essential in the liver, which otherwise may lead to inappropriate production of pro-inflammatory cytokines and interferons and may generate a predisposition to several autoimmune and chronic inflammatory diseases. The liver is considered to be a site of tolerance induction rather than immunity induction, with specificity in hepatic cell functions and distribution of TLR. Recent data emphasize significant contribution of TLR signaling in chronic liver diseases via complex immune responses mediating hepatocyte(i.e., hepatocellular injury and regeneration) or hepatic stellate cell(i.e., fibrosis and cirrhosis) inflammatory or immune pathologies. Herein, we review the available data on TLR signaling, hepatic expression of TLRs and associated ligands, as well as the contribution of TLRs to the pathophysiology of hepatic diseases. 展开更多
关键词 Toll-like receptors Innate immunity liver disease PATHOPHYSIOLOGY SIGNALING
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Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma 被引量:11
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作者 FJ Vizoso M Rodriguez +7 位作者 A Altadill ML González-Diéguez A Linares LO González S Junquera F Fresno-Forcelledo MD Corte L Rodrigo 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第23期3221-3227,共7页
AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to asses... AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS: We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specif ic antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitive score based on their intensity, and the percentage of immunostained cells was measured. RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies. 展开更多
关键词 ANDROGEN estrogen Progesterone and Apolipoprotein D receptors Hepatocellular carcinoma Tissue micro-arrays
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Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease 被引量:34
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作者 Eric R Kallwitz Alan McLachlan Scott J Cotler 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第1期22-28,共7页
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of ... Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH. 展开更多
关键词 Non-alcoholic fatty liver disease Peroxisome proliferators-activated receptors Insulin resiatance Metabolic syndrome Pharmacologic ligands
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Effect of liver regeneration after partial hepatectomy and ischemia-reperfusion on expression of growth factor receptors 被引量:9
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作者 P Baier G Wolf-Vorbeck +2 位作者 S Hempel UT Hopt E von Dobschuetz 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第24期3835-3840,共6页
AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. T... AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration. METHODS: For partial hepatectomy (PH) 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion (I/R) were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression (24 h). RESULTS: In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control. CONCLUSION: At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liverregeneration 24 h after the damage might be not successful. 展开更多
关键词 Partial hepatectomy liver ischemia Growthfactor receptors
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Critical role of estrogen in the progression of chronic liver diseases 被引量:6
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作者 Devaraj Ezhilarasan 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2020年第5期429-434,共6页
Background:Estrogens regulate sexual function and also have a significant role in various pathophysiological processes.Estrogens have a non-reproductive role as the modulators of the immune system,growth,neuronal func... Background:Estrogens regulate sexual function and also have a significant role in various pathophysiological processes.Estrogens have a non-reproductive role as the modulators of the immune system,growth,neuronal function,and metabolism.Estrogen receptors are expressed in the liver and their impaired expression and function are implicated with obesity and liver associated metabolic dysfunctions.The purpose of the current review is to discuss the disparity role of estrogens on several forms of liver diseases.Data sources:A comprehensive search in PubMed and EMBASE was conducted using the keywords“estrogens and liver diseases”,“estradiol and liver diseases”,“hormones and liver diseases”,“endocrine function in liver diseases”,and“female hormones in liver diseases”.Relevant papers published before September 30,2019 were included.Results:The present review confirms the imperative role of estrogen in various forms of chronic liver diseases.Estrogens play a key role in maintaining homeostasis and make the liver less susceptible to several forms of chronic liver diseases in healthy premenopausal individuals.In contrast,clinical studies also showed increased estrogen levels with chronic liver diseases.Conclusions:Several studies reported the protective role of estrogens in chronic liver diseases and this has been widely accepted and confirmed in experimental studies using ovariectomized rat models.However,in a few clinical studies,increased estrogen levels are also implicated in chronic liver diseases.Therefore,further studies are warranted at molecular level to explore the role of estrogen in various forms of chronic liver diseases. 展开更多
关键词 estrogen Hepatic fibrosis Chronic liver diseases Hepatic stellate cells
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Lack of estrogen receptors expression in malignant and pre-malignant colorectal lesions in Egyptian patients 被引量:2
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作者 Mohamed Said Marwa Khairy +4 位作者 Aly El-Hendawy Osama A. Khalf Mohamed S. Abdelbary Yasmin Saadi Ayman Yosry 《Open Journal of Gastroenterology》 2013年第2期155-163,共9页
Background: incidence of Colorectal cancer (CRC) is increasing globally. In Egypt, CRC ranks the sixth most common cancer in males and the fifth in females. Aim: To assess the expression of estrogen receptors (alpha a... Background: incidence of Colorectal cancer (CRC) is increasing globally. In Egypt, CRC ranks the sixth most common cancer in males and the fifth in females. Aim: To assess the expression of estrogen receptors (alpha and beta) in pre-malignant (adenomatous polyps and IBD), malignant colorectal lesions and normal colonic mucosa in group of Egyptian patients. Methods: This prospective study was done on 45 patients presenting with colonic symptoms, patients were divided into four groups;15 CRC patients, 10 patients with adenomatous polyps, 10 IBD patients and 10 patients in the control group. Patients subjected to: Stool analysis, FOBT, CBC, CEA, Abdominal ultrasound & colonoscopy and biopsy (number = 80), Pathological, immunohistochemistry and RT- PCR quantification of ERα and ERβ were done. Results: Mean age: 39.2 (12 - 73), gender: M/F: 28/17. Bleeding per rectum was the commonest presentation;29/45 (64.4%). CEA was significantly elevated in the CRC group compared with other studied groups (1692 mg/L vs. 4.0, 4.0 and 4.4 mg/L). Ultrasonography of the studied patients showed that metastatic CRC: 3/15 (20%);Colonic wall thickening: 5/15 (33.3%), 1/10 showed colonic polypoidal lesions in adenomatous polyps groups, in IBD group: 4/10 (40%) showed colonic and ileocecal thicknening. All the studied patients showed negative results for estrogen receptors (alpha and beta) by the use of immunohistochemistry staining and RT-PCR technique. Conclusion: Role of estrogen receptors in the colonic mucosa, precancerous and colorectal cancer is doubtful, contradictory results with some literature data could be due to racial and genetic difference in the studied population. 展开更多
关键词 COLORECTAL Cancer PREMALIGNANT Lesions estrogen receptors
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G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment 被引量:3
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作者 Ming Yang Chun-Ye Zhang 《World Journal of Gastroenterology》 SCIE CAS 2021年第8期677-691,共15页
Nonalcoholic fatty liver disease(NAFLD)is a broad-spectrum disease,ranging from simple hepatic steatosis to nonalcoholic steatohepatitis,which can progress to cirrhosis and liver cancer.Abnormal hepatic lipid accumula... Nonalcoholic fatty liver disease(NAFLD)is a broad-spectrum disease,ranging from simple hepatic steatosis to nonalcoholic steatohepatitis,which can progress to cirrhosis and liver cancer.Abnormal hepatic lipid accumulation is the major manifestation of this disease,and lipotoxicity promotes NAFLD progression.In addition,intermediate metabolites such as succinate can stimulate the activation of hepatic stellate cells to produce extracellular matrix proteins,resulting in progression of NAFLD to fibrosis and even cirrhosis.G protein-coupled receptors(GPCRs)have been shown to play essential roles in metabolic disorders,such as NAFLD and obesity,through their function as receptors for bile acids and free fatty acids.In addition,GPCRs link gut microbiota-mediated connections in a variety of diseases,such as intestinal diseases,hepatic steatosis,diabetes,and cardiovascular diseases.The latest findings show that gut microbiota-derived acetate contributes to liver lipogenesis by converting dietary fructose into hepatic acetyl-CoA and fatty acids.GPCR agonists,including peptides and natural products like docosahexaenoic acid,have been applied to investigate their role in liver diseases.Therapies such as probiotics and GPCR agonists may be applied to modulate GPCR function to ameliorate liver metabolism syndrome.This review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated treatment.Overall,understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD. 展开更多
关键词 Nonalcoholic fatty liver disease G protein-coupled receptors METABOLISM Bile acids Short-chain fatty acids Gut microbiota
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Interrelationship between Toll-like receptors and infection after orthotopic liver transplantation 被引量:5
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作者 Mahmoud El-Bendary Mustafa Naemattalah +4 位作者 Ahmed Yassen Naser Mousa Dina Elhammady Ahmed M Sultan Mohamed Abdel-Wahab 《World Journal of Transplantation》 2020年第6期162-172,共11页
Early microbial recognition by the innate immune system is accomplished by Toll-like receptors(TLRs),with resultant initiation of a pro-inflammatory response against infecting organisms.In spite of presence of an abun... Early microbial recognition by the innate immune system is accomplished by Toll-like receptors(TLRs),with resultant initiation of a pro-inflammatory response against infecting organisms.In spite of presence of an abundance of Toll-like receptors on the surface of the liver,gut bacteria does not elicit an inflammatory reaction in healthy individuals due to tolerance to these TLRs,suggesting that the inflammatory responses seen in the liver are the result of breakdown of this tolerance.While orthotopic liver transplantation is often life saving in many instances,death following this procedure is most commonly due to infection that occurs in up to 80%of transplant recipients,most commonly due to microbial causes in up to 70%of cases and viral infections in 20%,while fungal infections affect only 8%of cases.The probability of acquiring infection following hepatic transplantation is heightened due to affection of the innate immune defense mechanisms of the host following this procedure.Single nucleotide polymorphisms of TLRs have been associated with increased likelihood of either development of post-transplant infection or eradication of infecting organism.However,conflicting reports from other studies reveal that prevalence of this single nucleotide polymorphism is not increased in infected patients. 展开更多
关键词 Toll like receptors INFECTION liver transplantation CIRRHOSIS IMMUNITY ORTHOTOPIC
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Bile acid receptors and nonalcoholic fatty liver disease 被引量:17
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作者 Liyun Yuan Kiran Bambha 《World Journal of Hepatology》 CAS 2015年第28期2811-2818,共8页
With the high prevalence of obesity, diabetes, and otherfeatures of the metabolic syndrome in United States, nonalcoholic fatty liver disease(NAFLD) has inevitably become a very prevalent chronic liver disease and is ... With the high prevalence of obesity, diabetes, and otherfeatures of the metabolic syndrome in United States, nonalcoholic fatty liver disease(NAFLD) has inevitably become a very prevalent chronic liver disease and is now emerging as one of the leading indications for liver transplantation. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrogenesis, are essential pathways in the development of the more clinically significant form of NAFLD, known as nonalcoholic steatohepatitis(NASH). Recent advances in the functional characterization of bile acid receptors, such as farnesoid X receptor(FXR) and transmembrane G protein-coupled receptor(TGR) 5, have provided further insight in the pathophysiology of NASH and have led to the development of potential therapeutic targets for NAFLD and NASH. Beyond maintaining bile acid metabolism, FXR and TGR5 also regulate lipid metabolism, maintain glucose homeostasis, increase energy expenditure, and ameliorate hepatic inflammation. These intriguing features have been exploited to develop bile acid analogues to target pathways in NAFLD and NASH pathogenesis. This review provides a brief overview of the pathogenesis of NAFLD and NASH, and then delves into the biological functions of bile acid receptors, particularly with respect to NASH pathogenesis, with a description of the associated experimental data, and, finally, we discuss the prospects of bile acid analogues in the treatment of NAFLD and NASH. 展开更多
关键词 BILE acids BILE acid receptors Nonalcoholicsteatohepatitis Farnesoid X RECEPTOR TransmembraneG protein-coupled RECEPTOR 5 NONALCOHOLIC fatty liverdisease Hepatic STEATOSIS
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