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Fibroblast growth factor 21:a novel metabolic regulator from pharmacology to physiology

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Frontiers of Medicine 2013年第1期7卷 25-30页

作者： Huating Li Jing Zhang Weiping Jia Department of endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes InstituteShanghai Clinical Center of DiabetesShanghai 200233China

Fibroblast growth factor 21(FGF21)is a member of the fibroblast growth factor *** actually functions as endocrine hormones but does not regulate cell growth and *** is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism,including enhancing insulin sensitivity,decreasing triglyceride concentrations,causing weight loss,ameliorating obesity-associated hyperglycemia and ***,FGF21 also plays important roles in some physiological processes,such as fasting and feeding,growth hormone axis and thermogenic function of brown adipose *** relevance of FGF21 in humans is still unclear,and the basis and consequences of increased FGF21 in metabolic disease remain to be *** the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease,but some questions remain to be *** article concentrates on recent advances in our understanding of FGF21.

关键词： FGF21 metabolism pharmacology physiology clinical relevance

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial

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Frontiers of Medicine 2021年第3期15卷 460-471,F0004页

作者： Lingli Cai Jun Yin Xiaojing Ma Yifei Mo Cheng Li Wei Lu Yuqian Bao Jian Zhou Weiping Jia Department of endocrinology and Metabolism Shanghai Clinical Center for DiabetesShanghai Diabetes InstituteShanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China

Lifestyle interventions,including dietary adjustments and exercise,are important for obesity *** study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet(LCD)or exercise is more effective in metabolism ***-five eligible subjects were randomly divided into an LCD group(n=22)and an exercise group(EX,n=23).The subjects either adopted LCD(carbohydrate intake<50 g/day)or performed moderate-to-vigorous exercise(≥30 min/day)for 3 *** the interventions,LCD led to a larger weight loss than EX(−3.56±0.37 kg vs.−1.24±0.39 kg,P<0.001),as well as a larger reduction in fat mass(−2.10±0.18 kg vs.−1.25±0.24 kg,P=0.007)and waist circumference(−5.25±0.52 cm vs.−3.45±0.38 cm,P=0.008).Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin *** decreased in both two groups,whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX *** glycemic parameters,including serum glycated albumin,mean sensor glucose,coefficient of variability(CV),and largest amplitude of glycemic excursions,substantially declined in the LCD *** CV slightly decreased after *** pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin *** with exercise,LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.

关键词： low-carbohydrate diet obesity nonalcoholic fatty liver disease continuous glucose monitoring mean sensor glucose

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Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life Sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang Ting Guo Wenqing Ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250021China State Key Laboratory of Reproductive Medicine and Offspring Health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China Department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of *** represents a significant detriment to female ***,the known POI-causative genes currently account for only a fraction of *** elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in *** a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 *** variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 ***,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling *** analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and *** further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian ***,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse *** conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

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Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer

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Cancer Biology & Medicine 2024年第1期21卷 83-103页

作者： Yumei Wang Haiyan Wang Wei Shao Yuhui Chen Yu Gui Chao Hu Xiaohong Yi Lijun Huang Shasha Li Dong Wang School of Basic Medical Sciences State Key Laboratory of Southwestern Chinese Medicine ResourcesChengdu University of Traditional Chinese MedicineChengdu 611137China Department of Pathology School of MedicineQinghai UniversityXining 810001China Omics Biosciences Inc Beijing 100871China Laboratory of Integrative Medicine Clinical Research Center for BreastState Key Laboratory of BiotherapyWest China HospitalSichuan University and Collaborative Innovation CenterChengdu 610041China State Key Laboratory of Southwestern Chinese Medicine Resources School of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China Department of endocrinology and Metabolism Guangdong Provincial Key Laboratory of Diabetology&Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity ResearchMedical Center for Comprehensive Weight ControlThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain *** is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic ***:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic ***,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast ***:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific *** discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and ***,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene ***,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast ***:Our work deciphered the extensive regulation among hundreds of epigenetic *** identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

关键词： Epigenetic regulators breast cancer regulatory network HTS^(2)

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Preimplantation genetic testing for aneuploidy could not improve cumulative live birth rate among 1003 couples with recurrent pregnancy loss

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中华医学杂志(英文版) 2024年第17期137卷 2134-2136页

作者： Zhao Shaotong Lyu Chunzi Liu Yingbo Wang Xiyao Zhang Zhaowen Lv Hong Ni Tianxiang Yan Junhao center for Reproductive Medicine Shandong University Jinan Shandong China Key Laboratory of Reproductive endocrinology of Ministry of Education Shandong University Jinan Shandong China Shandong Key Laboratory of Reproductive Medicine Jinan Shandong China Shandong Provincial Clinical Research center for Reproductive Health Jinan Shandong China Shandong Technology Innovation center for Reproductive Health Jinan Shandong China National Research center for Assisted Reproductive Technology and Reproductive Genetics Shandong University Jinan Shandong China

Mediating role of social support in dysphoria,despondency,and quality of life in patients undergoing maintenance hemodialysis

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World Journal of Psychiatry 2024年第3期14卷 409-420页

作者： Xiang Zhou Hong Jiang Yi-Peng Zhou Xiao-Yu Wang Hai-Yan Ren Xue-Fei Tian Qing-Qing Zhang Department of Nephrology People’s Hospital of Xinjiang Uygur Autonomous RegionXinjiang Clinical Research Center for Kidney DiseaseUrumqi 832000Xinjiang Uygur Autonomous RegionChina Department of endocrinology and Metabolism People’s Hospital of Xinjiang Uygur Autonomous RegionUrumqi 832000Xinjiang Uygur Autonomous RegionChina Section of Nephrology Department of Internal MedicineYale University School of MedicineNew HavenCT 06510United States

BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can significantly improve the physical and mental well-being of patients undergoing ***,there is limited research on how social support mediates the relationship between dysphoria,despondency,and overall QOL in patients undergoing *** is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD,ultimately enhancing their overall *** To investigate the mediating role of social support in relationships between dysphoria,despondency,and QOL among patients undergoing *** Participants comprised 289 patients undergoing MHD,who were selected using a random sampling *** Social Support Rating Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and QOL Scale were *** analysis was performed to examine the associations between social support,dysphoria,despondency,and QOL in patients undergoing *** assess the mediating impact of social support on dysphoria,despondency,and QOL in patients undergoing MHD,a bootstrap method was *** Significant correlations among social support,dysphoria,despondency,and quality in patients undergoing MHD were observed(all P<0.01).Dysphoria and despondency negatively correlated with social support and QOL(P<0.01).Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD(P<0.05).The direct effect of dysphoria on QOL was statistically significant(P<0.05).Social support mediated the relationship between dysphoria and QOL,and this mediating effect was significant(P<0.05).Similarly,the direct effect of despondency on QOL was significant(P<0.05).Moreover,social support played a mediating role between despondency and QOL,with a significant mediating effect(P<0.05).CONCLUSION These find

关键词： Maintenance hemodialysis Social support Dysphoria Despondency Quality of life Mediating effect

Clinical and molecular characterization of 10 Chinese children with congenital adrenal hyperplasia due to 11beta‑hydroxylase deficiency

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World Journal of Pediatrics 2024年第4期20卷 422-433页

作者： Wen‑Li Lu Xiao‑Yu Ma Jiao Zhang Jun‑Qi Wang Ting‑Ting Zhang Lei Ye Yuan Xiao Zhi‑Ya Dong Wei Wang Shou‑Yue Sun Chuan‑Yin Li Rong‑Gui Hu Guang Ning Li‑Dan Zhang Department of Pediatrics Ruijin HospitalShanghai Jiao Tong University School of MedicineNo.197Ruijin 2nd RdHuangpu DistrictShanghai 200025China Department of Pediatric Genetic and Metabolic endocrinology West China Second University HospitalSichuan UniversityNo.20Section 3Renmin South RoadSichuan 610041China Department of Endocrine and Metabolic Diseases Shanghai Clinical Center for Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Cancer center School of MedicineShanghai Tenth People’s HospitalTongji UniversityYanchang Zhong Lu 301St RdJing’an DistrictShanghai 200031China

Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase *** this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal *** Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively *** examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of *** We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were *** patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 *** most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>*** mutations lead to spatial conformational changes that affect protein *** Our study found that there was no significant correlation between each specific mutation and the severity of clinical *** patients with the same gene pathogenic variant may have mild or severe clinical *** correlation between genotype and phenotype needs further ***-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.

关键词： 11β-hydroxylase deficiency CYP11B1 Enzymatic activity Phenotype-genotype correlation Threedimensional protein simulations

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第6期30卷 565-578页

作者： Wen-Peng Wang Dan Shi Duo Yun Jun Hu Jie-Fu Wang Jia Liu Yan-Peng Yang Ming-Rui Li Jun-FengWang Da-Lu Kong Department of Colorectal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Gastrointestinal Surgery Tianjin Nan Kai HospitalTianjin Medical UniversityTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM RepairInstitute of Integrative Medicine for Acute Abdominal DiseasesTianjin 300100China Department of Oncology The First Hospital of HohhotHohhot 010000Inner Mongolia Autonomous RegionChina Department of endocrinology Dazhou Central HospitalDazhou 635000Sichuan ProvinceChina

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment ***(DUBs)have been confirmed to play a crucial role in the development of malignant ***2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in *** To investigate the impact of JOSD2 on the progression of *** Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in *** transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor *** analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal ***2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ***,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these *** vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ***,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling *** spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and *** JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

关键词： Esophageal squamous cell carcinoma JOSD2 Ubiquitination Biomarker Targeted therapy Drug resistance

What is artificial endocrine pancreas? Mechanism and history

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World Journal of Gastroenterology 2009年第33期15卷 4105-4110页

作者： Kenro Nishida Seiya Shimoda Kenshi Ichinose Eiichi Araki Motoaki Shichiri Division of diabetes and endocrinology Minamata City Hospital and Medical Center Department of Metabolic Medicine Graduate School of Medical SciencesKumamoto University

The artificial endocrine pancreas is a feedback control instrument that regulates insulin delivery on a minute-by-minute basis according to measured blood glucose levels. Only one type of bedsidetype artificial endocrine pancreas is now available in Japan: STG-22 (Nikkiso Co. Ltd., Japan). In the insulin infusion algorithm, insulin is infused on the basis ofits proportional and derivative actions, to blood glucose concentrations with a constant time delay. The bedside-type artificial endocrine pancreas has been proven to be useful not only as a therapeutic tool for diabetes mellitus, but also as an elegant research tool for investigating the pathophysiology of the disease, by using the euglycemic hyperinsulinemic glucose clamp technique. The wearable type of closed-loop system has been developed recently. The breakthrough is the establishment of a needle-type glucose sensor. The development of closed-loop glycemic control systems that enable long-term physiological regulation has focused on implantable devices. Much effort has been expended to realize these devices.

关键词： diabetes mellitus Artificial pancreas Blood glucose Insulin Infusion