检索结果-南通市图书馆

Bile acids inhibit ferroptosis sensitivity through activating farnesoid x receptor in gastric cancer cells

World Journal of Gastroenterology 2024年第5期30卷 485-498页

作者： Chu-xuan Liu Ying Gao xiu-Fang xu xin Jin Yun Zhang Qian xu Huan-xin Ding Bing-Jun Li Fang-Ke Du Lin-Chuan Li Ming-Wei Zhong Jian-Kang Zhu Guang-Yong Zhang Department of General Surgery Shandong Provincial Qianfoshan HospitalShandong UniversityJinan 250014Shandong ProvinceChina Department of General Surgery Linyi People's HospitalLinyi 276034Shandong ProvinceChina Department of Nursing Huantai TCM HospitalZibo 256400Shandong ProvinceChina Center for Translational medical Research The First Affiliated Hospital of Shandong First Medical UniversityJinan 250014Shandong ProvinceChina Department of General Surgery The First Affiliated Hospital of Shandong First Medical UniversityJinan 250014Shandong ProvinceChina

BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid x receptor(FxR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPx4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FxR,which markedly increased the expression of GSH synthetase and GPx4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FxR.Finally,our results suggested that FxR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FxR-BACH1-GSHGPx4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

关键词： Gastric cancer Ferroptosis Bile acids Chenodeoxycholic acid farnesoid x receptor Glutathione

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

A combined nanotherapeutic approach targeting farnesoid x receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

引用

Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu Pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin Wu Jiabao Zhang Chunlin Zhuang Chunquan Sheng Jiajun xu Ying Lu Pei Wang The Center for Basic Research and Innovation of Medicine and Pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration Center for Experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric Medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid x receptor(FxR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)treatment.However,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback.Ferroptosis,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of NASH.Nitric oxide(NO)is a versatile biological molecule that can degrade extracellular matrix.In this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH model.Compared with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis.ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota dysbiosis.These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FxR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy farnesoid x receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

farnesoid x receptor regulators from natural products and their biological function

引用

Journal of Traditional Chinese Medicine 2023年第3期43卷 618-626页

作者： PENG Wan NI Hengfan GUO Dale DENG Yun DAI Manyun Institute of Rare Diseases West China HospitalSichuan UniversityChengdu 610065China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610041China School of Pharmacy Chengdu University of Traditional Chinese MedicineState Key Laboratory of Southwestern Chinese Medicine ResourcesChengdu 611137China School of Medicine Ningbo UniversityNingbo 315000China

Metabolic syndrome(Met S)has been a growing public health concern worldwide without specific medicine.Through summarizing the chemical structure type and effect mechanisms of natural products targeted on farnesoid x receptor(FxR),to provide the research basis for exploring the treatment of Met S.The following databases were searched for natural products which targeting FxR:Pub Med,Embase,the Cochrane Library,Web of Science,China National Knowledge Infrastructure Database,Wanfang Database,China Science and Technology Journal Database,and Chinese Biomedical Literature Database.Totally 120 natural products were summarized,including terpenoids(51 compounds),steroidal saponins(27 compounds),phenylpropanolds(19 compounds),flavonoids(13 compounds),alkaloids(3 compounds)and others(7 compounds),most researches focus on terpenoids and part of synthetic FxR regulators were based on the structure of terpenoids.FxR regulators could improve cholestasis and liver injury,hyperlipidemia,diabetes and atherosclerosis.FxR is a potential target of treating Met S.Natural products are characteristics with unique novel structures and special biological activity,and they are important sources of bioactive precursor compounds and drug discovery.Exploring the effects and mechanism of natural products and its derivative on Met S by targeting FxR may be a new way to develop the new drugs of treating Met S.

关键词： farnesoid x receptor metabolic syndrome biological products molecular docking simulation biological activity

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine,liver and kidney of rats through activation of farnesoid x receptor by cholate and bilirubin

引用

Acta Pharmaceutica Sinica B 2023年第1期13卷 227-245页

作者： Shijin Hong Shuai Li xiaoyan Meng Ping Li xun Wang Mengxiang Su xiaodong Liu Li Liu Center of Drug Metabolism and Pharmacokinetics School of PharmacyChina Pharmaceutical UniversityNanjing 210098China Tianjin Institutes of Pharmaceutical Research Tianjin 300301China Departments of Pharmaceutical Analysis School of PharmacyChina Pharmaceutical UniversityNanjing 210098China

Body is equipped with organic cation transporters(OCTs).These OCTs mediate drug transport and are also involved in some disease process.We aimed to investigate whether liver failure alters intestinal,hepatic and renal Oct expressions using bile duct ligation(BDL)rats.Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure,associated with decreased intestinal absorption and increased urinary excretion.Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2.In vitro cell experiments show that chenodeoxycholic acid(CDCA),bilirubin and farnesoid x receptor(FxR)agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1,which are remarkably attenuated by glycine-β-muricholic acid and silencing FxR.Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL,which are confirmed using CDCA-treated and bilirubin-treated rats.A disease-based physiologically based pharmacokinetic model characterizing intestinal,hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats.In conclusion,BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats,finally,decreasing plasma exposure and impairing hypoglycemic effects of metformin.BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.

关键词： Bilirubin Chenodeoxycholic acid farnesoid x receptor Liver failure Organic cation transporters Bile duct ligation Physiologically based pharmacokinetic model

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Moxibustion improves experimental colitis in rats with Crohn's disease by regulating bile acid enterohepatic circulation and intestinal farnesoid x receptor

引用

Journal of Integrative Medicine 2023年第2期21卷 194-204页

作者： Jia-cheng Shen Qin Qi Dong Han Yuan Lu Rong Huang Yi Zhu Lin-shan Zhang xiu-di Qin Fang Zhang Huan-gan Wu Hui-rong Liu Key Laboratory of Acupuncture and Immunological Effects Shanghai University of Traditional Chinese MedicineShanghai 200030China Shanghai Research Institute of Acupuncture and Meridian Shanghai 200030China

Objective:This study was conducted to explore the mechanism of intestinal inflammation and barrier repair in Crohn’s disease(CD)regulated by moxibustion through bile acid(BA)enterohepatic circulation and intestinal farnesoid x receptor(FxR).Methods:Sprague-Dawley rats were randomly divided into control group,CD model group,mild moxibustion group and herb-partitioned moxibustion group.CD model rats induced by 2,4,6-trinitrobenzene sulfonic acid were treated with mild moxibustion or herb-partitioned moxibustion at Tianshu(ST25)and Qihai(CV6).The changes in CD symptoms were rated according to the disease activity index score,the serum and colon tissues of rats were collected,and the pathological changes in colon tissues were observed via histopathology.Western blot,immunohistochemistry(IHC)and immunofluorescence were used to evaluate the improvement of moxibustion on intestinal inflammation and mucosal barrier in CD by the BA-FxR pathway.Results:Mild moxibustion and herb-partitioned moxibustion improved the symptoms of CD,inhibited inflammation and repaired mucosal damage to the colon in CD rats.Meanwhile,moxibustion could improve the abnormal expression of BA in the colon,liver and serum,downregulate the expression of interferon-γand upregulate the expression of FxR mRNA,and inhibit Toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)mRNA.The IHC results showed that moxibustion could upregulate the expression of FxR and mucin2 and inhibit TLR4 expression.Western blot showed that moxibustion inhibited the protein expression of TLR4 and MyD88 and upregulated the expression of FxR.Immunofluorescence image analysis showed that moxibustion increased the colocalization sites and intensity of FxR with TLR4 or nuclear factor-κB p65.In particular,herb-partitioned moxibustion has more advantages in improving BA and upregulating FxR and TLR4 in the colon.Conclusion:Mild moxibustion and herb-partitioned moxibustion can improve CD by regulating the enterohepatic circulation stability of BA,activating colonic F

关键词： Crohn’s disease Moxibustion Bile acid farnesoid x receptor Colitis Intestinal mucosal barrier

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Duodenal-jejunal bypass reduces serum ceramides via inhibiting intestinal bile acid-farnesoid x receptor pathway

引用

World Journal of Gastroenterology 2022年第31期28卷 4328-4337页

作者： Zhi-Qiang Cheng Tong-Ming Liu Peng-Fei Ren Chang Chen Yan-Lei Wang Yong Dai xiang Zhang Department of General Surgery Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Department of Colorectal and Anal Surgery Feicheng Hospital Affiliated to Shandong First Medical UniversityFeicheng 271600Shandong ProvinceChina Department of General Surgery Lincheng People’s HospitalDezhou 253500Shandong ProvinceChina

BACKGROUND Bile acids play an important role in the amelioration of type 2 diabetes following duodenal-jejunal bypass(DJB).Serum bile acids are elevated postoperatively.However,the clinical relevance is not known.Bile acids in the peripheral circulation reflect the amount of bile acids in the gut.Therefore,a further investigation of luminal bile acids following DJB is of great significance.AIM To investigate changes of luminal bile acids following DJB.METHODS Salicylhydroxamic acid(SHAM),DJB,and DJB with oral chenodeoxycholic acid(CDCA)supplementation were performed in a high-fat-diet/streptozotocininduced diabetic rat model.Body weight,energy intake,oral glucose tolerance test,luminal bile acids,serum ceramides and intestinal ceramide synthesis were analyzed at week 12 postoperatively.RESULTS Compared to SHAM,DJB achieved rapid and durable improvement in glucose tolerance and led to increased total luminal bile acid concentrations with preferentially increased proportion of farnesoid x receptor(FxR)-inhibitory bile acids within the common limb.Intestinal ceramide synthesis was repressed with decreased serum ceramides,and this phenomenon could be partially antagonized by luminal supplementation of FxR activating bile acid CDCA.CONCLUSION DJB significantly changes luminal bile acid composition with increased proportion FxR-inhibitory bile acids and reduces serum ceramide levels.There observations suggest a novel mechanism of bile acids in metabolic regulation after DJB.

关键词： Bariatric surgery Duodenal-jejunal bypass farnesoid x receptor Ceramide Bile acids Liver fat accumulation

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

farnesoid x receptor in the study of fibrosis and its treatments

引用

Chinese Medical Journal 2013年第19期126卷 3775-3781页

作者： ZHAO Cong CONG Yu-ling xU Yi-jun YIN Yan-ru Department of Physiology Southern Medical University Guangzhou Guangdong 510515 China Joint Surgery Central Hospital of Shengli Oil Field Dongying Shandong 257034 China

In the pathogenesis of various organs,fibrosis is often considered as a hardly irreversible progress,treatment of which has already become one of the most important prognostic indicators.Different mechanisms and many factors are involved in the process of organ fibrosis.With the development of relative researches,it is discovered that farnesoid x receptor （FxR;NR1H4） may play a significant role in this process.In addition,synthetic FxR agonists may make it possible for FxR to be the potential therapeutic target in curing fibrosis of organs.

关键词： farnesoid x receptor fibrosis mechanism therapeutic target

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

farnesoid x receptor,the bile acid sensing nuclear receptor,in liver regeneration

引用

Acta Pharmaceutica Sinica B 2015年第2期5卷 93-98页

作者： Guodong Li Grace L.Guo Department of General Surgery the Fourth Hospital of Harbin Medical University Division of Biobank Research Department of General Surgery the Fourth Hospital of Harbin Medical University Department of Pharmacology and Toxicology Ernest Mario School of Pharmacy Rutgers the State University of New Jersey

The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy(PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids(BAs) are ligands of farnesoid x receptor(FxR), a nuclear receptor of ligand-activated transcription factor. FxR has been shown to be highly involved in liver regeneration. BAs and FxR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FxR also contributes to liver regeneration significantly. These novel findings suggest that FxR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FxR as an important pharmaceutical target for potentialuse of FxR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FxR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.

关键词： farnesoid x receptor Liver regeneration Bile acids Fibroblast growth factor 15 Liver-intestine croass talk Transmembrane G protein coupled receptor 5

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Expressions of farnesoid x receptor and myeloid cell leukemia sequence 1 protein are associated with poor prognosis in patients with gallbladder cancer

引用

Chinese Medical Journal 2014年第14期127卷 2637-2642页

作者： Wang Wei Yin xiaobin Li Guiping Yi Jing Wang Jian Shanghai Jiao Tong Univ Dept Biliary Pancreat Surg Ren Ji Hosp Sch Med Shanghai 200127 Peoples R China Shanghai Jiao Tong Univ Dept Biochem & Mol Cell Biol Shanghai Key Lab Tumor Microenvironm & Inflammat Inst Med SciSch Med Shanghai 200025 Peoples R China

Background farnesoid x receptor （FxR） regulates tumorigenesis, but its clinical significance in gallbladder cancer （GBC） remains unclear. This study investigated its clinical and prognostic significance in GBC patients, as well as its association with the anti-apoptotic protein, myeloid cell leukemia sequence 1 （MCL1） protein. Methods FxR and MCL1 expression in 42 primary GBC and 15 normal gallbladder tissues were analyzed by immunohistochemistry. The patients and samples were collected from Ren Ji Hospital from January 2005 to December 2010. Their association with clinicopathologic factors and prognosis, as well as the correlation between FxR and MCL1 protein expression were analyzed by statistical analyses. Results Compared with normal gallbladder tissues, FxR expression was decreased and MCL1 expression was increased in GBC, during progression of tumor node metastasis （TNM） stage. The Kaplan-Meier survival analysis showed that FxR low-expression and MCL1 over-expression were significantly associated with overall poor survival. Furthermore, multivariate analysis showed that FxR and MCL1 are both prognostic factors for GBC patients. FxR low-expression was significantly correlated with MCL1 over-expression. Conclusion FxR might be a new molecular marker to predict the prognosis of patients with GBC and a novel therapeutic target. Chin Med J 2014;127 （14）： 2637-2642

关键词： farnesoid x receptor myeloid cell leukemia sequence 1 protein gallbladder neoplasms prognosis

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Effect of simvastatin on the expression of farnesoid x receptor in diabetic animal models of altered glucose homeostasis

引用

Chinese Medical Journal 2014年第2期127卷 218-224页

作者： Wang Lulu Huang xianping Hu Su Ma xiaoli Wang Shaolian Pang Shuguang Department of Endocrinology Jinan Central Hospital Affiliated to Shandong University Jinan Shandong 250013 China

Background Statin therapy has affected glucose homoeostasis of type 2 diabetes patients,which could be related with bile acids metabolism.Whether bile acid metabolism and the expression of farnesoid x receptor （FxR）,liver x receptor-α （LxR-α） and sterol regulatory element-binding protein （Srebp）-1c is regulated by hyperglycemia,or whether simvastatin therapy led to higher glucose is related with down-regulated expression of FxR in diabetic rats remained unclear.Methods Forty male Wistar rats were randomly divided into four groups：normal control rats,insulin resistance rats,diabetic model rats,and the late simvastatin induced diabetic rats.Normal control rats were fed with standard diet,others were fed with high-fat diet.Diabetic model rats were induced by a single intraperitoneal injection of streptozotocin （STZ）.The late simvastatin induced diabetic rats started simvastatin administration after STZ induced diabetic model rats.Characteristics of fasting blood glucose （FPG）,lipid files and total bile acids （TBAs） were measured and the oral glucose tolerance test （OGTT） was performed after overnight fasting at the eighth weekend.RNA and protein levels of FxR,LxR-α and Srebp-1c were tested by Western blotting and reverse transcription polymerase chain reaction （RT-PCR）.Results The insulin resistance rats showed higher glucose,lipid files and lower expression of FxR compared with normal control rats （P ＞0.05）.The diabetic model rats showed significantly higher glucose,lipid files,TBA and lower expression of FxR compared with insulin resistance rats （P ＜0.05）.The late simvastatin induced diabetic rats displayed higher glucose and TBA and lower expression of FxR compared with diabetic model rats （P ＜0.05）.Conclusions Changes in bile acid homeostasis,including the alterations of bile acid levels and bile acid receptors,are either a cause or a consequence of the metabolic disturbances observed during diabetic models.Statin therapy induced hyperglycemia may be related with FxR,SHP,LxR-α and Srebp-1 pathways.

关键词： farnesoid x receptor diabetes mellitus glucose metabolism liver x receptor sterol regulatory element binding protein 1c simvastatin

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：