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Early-life famine exposure,adulthood obesity patterns,and risk of low-energy fracture

Frontiers of Medicine 2024年第1期18卷 192-203页

作者： Hongyan Qi Chunyan Hu Jie Zhang Lin Lin Shuangyuan Wang Hong Lin Xiaojing Jia Yuanyue Zhu Yi Zhang Xueyan Wu Mian Li Min Xu Yu Xu Tiange Wang Zhiyun Zhao Weiqing Wang Yufang Bi Meng Dai Yuhong Chen Jieli Lu department of Endocrine and metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for Endocrine and metabolic diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People’s Republic of ChinaShanghai National Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains *** study included 5323 community-dwelling subjects aged⩾40 years from ***-life famine exposure was identified based on the participants’birth *** obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or *** to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in *** interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

关键词： famine obesity body mass index waist-to-hip ratio low-energy fracture

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Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2581-2597页

作者： Hongliang Qiu Sihui Huang Yuting Liu Libo Liu Fengming Guo Yingying Guo Dan Li Xianfeng Cen Yajie Chen Meng Zhang Yan Che Man Xu Qizhu Tang department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China Hubei Key Laboratory of metabolic and Chronic diseases Wuhan 430060China

Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively *** was recently identified as a major mechanism of DOX-induced ***,a novel ferroptosis inhibitor,is a well-described clinical drug widely ***,its role and pathological mechanism in DOX-induced cardiotoxicity are still *** this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced *** results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in *** and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by ***,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of *** could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with *** results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination *** conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.

关键词： Idebenone DOX-induced cardiotoxicity Ferroptosis FSP1 Ubiquitination Lipid peroxidation Iron overload Clinical translation

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Multi-omics analyses of G6PD deficiency variants in Chinese population

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Journal of Genetics and Genomics 2024年第1期51卷 100-104页

作者： He Ji Jiahuan Chen Peide Huang Zhimin Feng Weining Hu Mengyao Dai Xiaohui Sun Xiao Jin Guangquan Chen Guang Ning Lin Li Weiqing Wang Yanan Cao department of Endocrine and metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesNational Clinical Research Centre for Metabolic DiseasesState Key Laboratory of Medical GenomicsResearch Unit of Clinical and Basic Research on Metabolic Diseases of Chinese Academy of Medical SciencesRuijin Yangtze River Delta Health InstituteWuxi Branch of Ruijin HospitalRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China National Research Center for Translational Medicine National Key Scientific Infrastructure for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China SJTU-BGI Innovation Research Center Shanghai 200240China BGI-ShenZhen ShenzhenGuangdong 518083China

Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).

关键词： al. G6PD epidemiology

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Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

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World Journal of Diabetes 2024年第4期15卷 735-757页

作者： Jing Gao Ying Zou Xiao-Yu Lv Li Chen Xin-Guo Hou department of Endocrinology Qilu Hospital of Shandong UniversityCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina Institute of Endocrine and metabolic diseases Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Endocrine and metabolic diseases Shandong Province Medicine&HealthJinan 250012Shandong ProvinceChina department of Endocrinology Jinan Clinical Research Center for Endocrine and Metabolic DiseaseJinan 250012Shandong ProvinceChina

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully ***-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the *** To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive *** To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database *** identify T2DM module genes,we used Weighted Gene Co-Expression Network *** the genes were subject to Gene Set Enrichment ***-protein interaction network construction and machine learning were utilized to identify three hub *** cell infiltration analysis was *** three hub genes were validated in GSE152539 via receiver operating characteristic curve *** experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in *** identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using *** taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were ***,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune *** three hub genes were validated in *** experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics ***,11 potential drugs associated with RAC3 and TFRC were identified based on the *** Immune-related genes that differ in expression in the hippocampus are closely linked to microgli

关键词： Bioinformatics analysis Type 2 diabetes mellitus Cognitive impairment Hippocampus Immune Microglia

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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

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Male and Female Hypogonadisms: Etiological, metabolic and Osteodensitometric Aspects

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Open Journal of Endocrine and metabolic diseases 2024年第2期14卷 39-52页

作者： Nestor Ghislain Andzouana Mbamognoua Ikram Damoune Sana Doubi Asmae Lahlou Farida Ajdi department of metabolic and Endocrine diseases Brazzaville University Hospital Brazzaville Republic of the Congo Faculty of Health Sciences Marien Ngouabi University Brazzaville Republic of Congo department of Endocrinology Metabolic Diseases Hassan II University Hospital of Fez Fez Morocco

Introduction: Studies showed a high prevalence of metabolic abnormalities including dyslipidemia, type 2 diabetes in cases of low testosterone in men and which are associated with increased cardiovascular risk. Hypogonadism represents the second cause of endocrine osteoporosis. Objectives: The objectives of our work were: to determine the main causes of hypogonadism in women and men;to assess the frequency of metabolic and osteosdensitometric abnormalities in the hypogonadal population. Patients and methods: A retrospective descriptive study was carried out over 7 years on 120 patients, hospitalized in the Endocrinology department of the Hassan II University Hospital of Fez-Morocco for hypogonadism. The patients selected were those who had symptoms of hypogonadism confirmed in men by: low total testosterone for Tanner stage in adolescents, ng/ml or lower limit of normal for adults;in women, hypoestrogenia 30 pg/l. Gonadotropin dosage, karyotype, pelvic or testicular ultrasound and pituitary MRI, for etiological diagnosis, were performed. Bone densitometry was performed for bone impact and lipid profile for metabolic profile. Results: Out of 120 patients, there were 77 women and 43 men. The average age was 31.51 years. In men, the main causes were central hypogonadism in 67.4% and primary testicular failure in 32.6%. In women, central hypogonadism was also the most common cause noted in 63.7% and premature ovarian failure was observed in 36.4%. HypoHDL was significantly more frequent p (0.005) in women, osteopenia and osteoporosis were significantly more frequent in women than in men p (0.046). Conclusion: Central causes represent the most common etiology of hypogonadism in both sexes;abnormalities of bone mineralization and metabolic disorders were predominant in women.

关键词： Hypogonadism Etiological metabolic Osteodensitometric Fez

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Transient diabetes mellitus with ABCC8 variant successfully treated with sulfonylurea:Two case reports and review of literature

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World Journal of Diabetes 2024年第8期15卷 1811-1819页

作者： Ling-Hua Shen Yan Cui Dong-Xia Fu Wei Yang Sheng-Nan Wu Hui-Zhen Wang Hai-Hua Yang Yong-Xing Chen Hai-Yan Wei department of Endocrinology and Metabolism Henan Key Laboratory of Children's Genetics and Metabolic DiseasesChildren's Hospital Affiliated to Zhengzhou UniversityHenan Children's Hospital Zhengzhou Children's HospitalZhengzhou 450018Henan ProvinceChina

BACKGROUND Transient neonatal diabetes mellitus(TNDM)is a rare form of diabetes mellitus that usually presents within the first 6 mo of *** often enter remission within several months,although relapse can occur later in *** in the ABCC8 gene,which encodes the sulfonylurea receptor 1 of the ATP-sensitive potassium channel in pancreatic beta cells,are associated with TNDM and permanent neonatal *** study describes a novel de novo c.3880C>T heterozygous ABCC8 variant that causes TNDM and can be treated with sulfonylurea *** SUMMARY We retrospectively analyzed 2 Chinese patients with TNDM who were diagnosed,treated,or referred for follow-up between September 2017 and September *** patients were tested for mutations using targeted next-generation *** with neonatal diabetes mellitus caused by a c.3880C>T heterozygous missense variant in the ABCC8 gene have not been reported *** children had an onset of post-infectious diabetic ketoacidosis,which is worth *** a follow-up visit after discontinuing insulin injection,oral glyburide was found to be effective with no adverse *** Early genetic testing of neonatal diabetes mellitus aids in accurate diagnosis and treatment and helps avoid daily insulin injections that may cause pain.

关键词： Neonatal diabetes mellitus ABCC8 Sulfonylurea receptors 1 KATP channels Sulfonylurea Glyburide Insulinulin Case report

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Analysis of an adult diabetes mellitus caused by a rare mutation of the gene:A case report

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World Journal of Clinical Cases 2024年第19期12卷 3942-3949页

作者： Wen-Xuan Li Li-Li Xu Chuan-Feng Liu Bing-Zi Dong Yun-Yang Wang department of Endocrine and metabolic diseases The Affiliated Hospital of Qingdao UniversityQingdao 266003Shandong ProvinceChina

BACKGROUND This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence,featuring a unique mutation in the peroxisome proliferator-activated receptor gamma(PPARG)*** Access Statement:Research data supporting this publication are available from the NN repository at ***/download/.CASE SUMMARY The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family ***,high-throughput sequencing was conducted to analyze the PPARG genes of the patient,her siblings,and their *** results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy,accompanied by insulin resistance and ***,these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation *** results from the gene detection process demonstrated a heterozygous mutation of guanine(G)at position 284 in the coding region of exon 2 of PPARG,which replaced the base adenine(A)(exon2c.284A>***95Cys).This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated ***,both of her siblings harbored a nucleotide heterozygous variation at the same site,and both were diagnosed with *** The PPARG gene mutation,particularly the ***95Cys mutation,may represent a newly identified subtype of maturity-onset diabetes of the *** subtype is characterized by insulin resistance and lipid metabolism disorders.

关键词： Diabetes Gene mutation Maturity-onset diabetes of the young Peroxisome proliferator-activated receptor gamma Lipid metabolism

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Large-scale manufacturing of functional single-atom ink for convenient glucose sensing

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Nano Research 2024年第8期17卷 7256-7263页

作者： Muyu Yan Xiaofei Zhu Can Xiong Xiao Han Zhenggang Xue Yuen Wu department of Endocrinology Institute of Endocrine and Metabolic DiseasesThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Deep Space Exploration Laboratory University of Science and Technology of ChinaHefei 230026China NEST Laboratory Department of PhysicsDepartment of ChemistryCollege of ScienceShanghai UniversityShanghai 200444China Center of Advanced Nanocatalysis(CAN) Department of Applied ChemistryUniversity of Science and Technology of ChinaHefei 230026China

Printing techniques hold great potential in the manufacture of electronics such as sensors,micro-supercapacitors,and flexible ***,developing large-scale functional conductive inks with appropriate rheological properties and active components still remains a ***,through optimizing the formulations of ink,iron single sites supported N-doped carbon black(Fe_(1)-NC)inks can serve as both conductive electrodes and high-reactive catalysts to realize convenient glucose detection,which pronouncedly reduces the dosage of enzyme and simplifies the sensors *** detail,utilizing in-situ pyrolysis method,Fe_(1)-NC single-atom catalysts(SACs)are prepared in bulk(dekagram-level).The batched Fe_(1)-NC SACs materials can be uniformly mixed with modulated ink to realize the screen printing with high resolution and ***,the whole scalable preparation and ink-functional process can be extended to various metals(including Co,Ni,Cu,and Mn).The introduction of highly active Fe_(1)-NC sites reduces the amount of enzyme used in glucose detection by at least 50%,contributing to the cost reduction of *** strategy in harnessing the SACs onto the carbon inks thus provides a broad prospect for the low-cost and large-scale printing of sensitive sensing devices.

关键词： large-scale manufacturing single-atom inks screen printing glucose sensing low enzyme dosage

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Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation

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Science China Life Sciences 2024年

作者： Qian Hao Jinfeng Li Leng-Siew Yeap Shanghai Institute of Immunology Department of Immunology and Microbiology State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine Center for Immune-Related diseases at Shanghai Institute of Immunology Department of Endocrinology and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Antibody diversification is essential for an effective immune response, with somatic hypermutation(SHM) serving as a key molecular process in this adaptation. Activation-induced cytidine deaminase(AID) initiates SHM by inducing DNA lesions, which are ultimately resolved into point mutations, as well as small insertions and deletions(indels). These mutational outcomes contribute to antibody affinity *** mechanisms responsible for generating point mutations and indels involve the base excision repair(BER) and mismatch repair(MMR)pathways, which are well coordinated to maintain genomic integrity while allowing for beneficial mutations to occur. In this regard,translesion synthesis(TLS) polymerases contribute to the diversity of mutational outcomes in antibody genes by enabling the bypass of DNA lesions. This review summarizes our current understanding of the distinct molecular mechanisms that generate point mutations and indels during SHM. Understanding these mechanisms is critical for elucidating the development of broadly neutralizing antibodies(bnAbs) and autoantibodies, and has implications for vaccine design and therapeutics.

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