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Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation

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Science China(Life Sciences) 2024年第11期67卷 2344-2353页

作者： Qian Hao Jinfeng Li Leng-Siew Yeap Shanghai Institute of Immunology Department of Immunology and MicrobiologyState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of MedicineShanghai 200025China Center for Immune-Related diseases at Shanghai Institute of Immunology Department of Endocrinology and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Antibody diversification is essential for an effective immune response,with somatic hypermutation(SHM)serving as a key molecular process in this ***-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 *** this regard,translesion synthesis(TLS)polymerases contribute to the diversity of mutational outcomes in antibody genes by enabling the bypass of DNA *** review summarizes our current understanding of the distinct molecular mechanisms that generate point mutations and indels during *** these mechanisms is critical for elucidating the development of broadly neutralizing antibodies(bnAbs)and autoantibodies,and has implications for vaccine design and therapeutics.

关键词： somatic hypermutation(SHM) insertions and deletions(indels) AID base excision repair(BER) mismatch repair(MMR) translesion synthesis(TLS)polymerases

disease dependent qualitative and quantitative differences in the inflammatory response to ascites occurring in cirrhotics

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World Journal of Hepatology 2014年第2期6卷 85-91页

作者： Bashar M Attar Magdalena George Nicolae Ion-Nedelcu Guilliano Ramadori David H Van Thiel Division of Gastroenterology and Hepatology John H Stroger Hospital of Cook County Rush University Medical Center Victor Babes Infectious and Tropical disease Clinic Department of Gastroenterology and endocrinology August Georg University

AIM:To assess differing patterns and levels of ascitic fluid cyctokine and growth factors exist between those with a high risk and low risk of spontaneous bacterial peritonitis(SBP). METHODS: A total of 57 consecutive patients with ascites requiring a large volume paracentesis were studied. Their age, gender, specific underlying disease conditions were recorded after a review of their clinical records. Each underwent a routine assessment prior to their paracentesis consisting of a complete blood count, complete metabolic profile and prothrombin time/international normalized ratio(INR) determination. The ascitic fluid was cultured and a complete cellcount and albumin determination was obtained on the fluid. In addition, blood and ascitic fluid was assessed for the levels of interleukin interleukin(IL)-1A, IL-1B, IL-2, IL-4, IL-8, IL-10, monocyte chemotactic protein(MCP)-1, tumor necrosis factor(TNF)-α, interferon(IFN)-γ, vascular endothelial growth factor(VEGF) and epidermal growth factor(EGF) utilizing the Randox Biochip platforms(Boston, MA). A serum-ascites gradient, for each cytokine and growth factor was calculated. The results are reported as mean ± SEM between disease groups with statistical analysis consisting of the student t-test(two tailed) with a P value of 0.05 defining significance. RESULTS: No clinically important demographic or biochemical differences between the 4 groups studied were evident. In contrast, marked difference in the cytokine and growth factors levels and pattern were evident between the 4 disease groups. Individuals with alcoholic cirrhosis had the highest levels of IL-1A, IL-1B, IL-4, IFNγ. Those with malignant disease had the highest levels of IL-2. Those with hepatitis C virus(HCV) associated cirrhosis had the highest value for IL-6, IL-8, IL-10, MCP-1 and VEGF. Those with cardiac disease had the highest level of TNF-α and EGF. The calculated serum- ascites gradients for the cardiac and malignant disease groups had a greater frequenc

关键词： Ascites Cirrhosis Growth factors Inflammation Procalcitonin

Role of Peripheral Regulatory T Lymphocytes in Patients with Thyroid Associated Ophthalmopathy During Systemic Glucocorticoid Treatment:A Prospective Observational Study

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Current Medical Science 2023年第1期43卷 130-138页

作者： Qin-qin XU Xiao-ling ZHANG Ban LUO Tao LI Gang YUAN Shi-ying SHAO Department of endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Branch of the National Clinical Research Center for metabolic diseases Wuhan430030China Depatment of Ophthalmology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital *** study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)*** Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were *** percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC *** activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were *** correlation with the peripheral Tregs was *** There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical *** Treg reduction after systemic GC therapy is indicative of a poor therapeutic ***,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.

关键词： thyroid-associated ophthalmopathy regulatory T cells intravenous methylpred-nisolone glucocorticoids T2 relaxation time

Role of X-Box Binding Protein-1 in Fructose-Induced De Novo Lipogenesis in HepG2 Cells

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Chinese Medical Journal 2018年第19期131卷 2310-2319页

作者： Xian Yu Lu-Ping Ren Chao Wang Ya-Jun Zhu Han-Ying Xing Jing Zhao Guang-Yao Song Department of Internal Medicine Hebei Medical University Shijiazhuang Hebei 050051 China Department of endocrinology Hebei General Hospital Shijiazhuang Hebei 050051 China Hebei Key Laboratory of metabolic disease Hebei General Hospital Shijiazhuang Hebei 050051 China Department of Oncology Hebei General Hospital Shijiazhuang Hebei 050051 China

Background：A high consumption of fructose leads to hepatic *** 20-30% of triglycerides are synthesized via de novo *** studies showed that endoplasmic reticulum stress （ERS） is involved in this process,while others showed that a lipotoxic environment directly influences ER ***,our aim was to investigate the causal relationship between ERS and fatty acid synthesis and the effect of X-box binding protein-1 （XBP-1）,one marker of ERS,on hepatic lipid accumulation stimulated by high ***：HepG2 cells were incubated with different concentrations of *** regulators of de novo lipogenesis （i.e.,carbohydrate response element-binding protein [ChREBP] and sterol regulatory element-binding protein 1 c [SREBP-lc]） were measured by polymerase chain reaction and key lipogenic enzymes （acetyl-CoA carboxylase [ACC],fatty acid synthase [FAS],and stearoyl-CoA desaturase-1 [SCD-1]） by Western *** same lipogenesis-associated factors were then evaluated after exposure of HepG2 cells to high fructose followed by the ERS inhibitor tauroursodeoxycholic acid （TUDCA） or the ERS inducer ***,the same lipogenesis-associated factors were evaluated in HepG2 cells after XBP-1 upregulation or downregulation through cell ***：Exposure to high fructose increased triglyceride levels in a dose-and time-dependent manner and significantly increased mRNA levels of SREBP-1c and ChREBP and protein levels ofFAS,ACC,and SCD-1,concomitant with XBP-1 conversion to an active spliced ***-associated factors induced by high fructose were inhibited by TUDCA and induced by *** level in XBP-l-deficient group decreased significantly compared with high-fructose group （4.41 ± 0.54 μmol/g vs.6.52 ± 0.38 μmol/g,P 〈 0.001）,as mRNA expressions of SREBP-1c （2.92 ± 0.46 vs.5.08 ± 0.41,P 〈 0.01） and protein levels of FAS （0.53 ± 0.06 vs.0.85 ± 0.05,P =0.01）,SCD-1 （0.65 ± 0.06 vs.0.90 ± 0.04,P

关键词： Endoplasmic Reticulum Stress Fatty Liver Lipogenesis X-Box Binding Protein-I

Characteristics of Persistent or Recurrent Differentiated Thyroid Cancer

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Open Journal of Endocrine and metabolic diseases 2020年第1期10卷 1-5页

作者： Annelie Kérékou Hodé Siham El Aziz Alihonou Dédjan Asma Chadli Ahmed Farouqi endocrinology Metabolism and Nutrition Department CNHU-HKM Cotonou Bénin endocrinology Diabetology and Metabolic Diseases Department Ibn Rochd University Hospital Center of CasablancaCasablanca Morocco

Introduction: The differentiated thyroid cancer has generally an excellent prognosis after the treatment. The aim of this study is to describe the characteristics of persistent or recurrent differentiated thyroid cancers. Patients/ Methods: It is about a descriptive and retrospective study conducted from 392 patients followed for differentiated thyroid cancer. The data concerning the persistent or recurrent differentiated thyroid cancer have been collected from 1986 to 2015 in endocrinology service in Ibn Rochd CHU. Results: In total, twenty-four patients have shown the relapse or the persistency of their tumor, corresponding to the prevalence of 6.12 percent. The papillary carcinoma was dominant in 79 percent of cases and the follicular carcinoma in 21 percent of cases. The metastases were cerebral (two cases), lung (3 cases), bones (3 cases, Figure 1), and lymph nodes (9 cases). In our series, eighteen cases of persistent differentiated thyroid cancer have been found against six cases of recurrent differentiated thyroid cancer. Two cases of death at least three years of followed in our series and concerned the two cases of cerebral metastasis. Conclusion: The persistent or recurrent differentiated thyroid cancer rate is low in our series. The discovery of the relapse t is late.

关键词： Differentiated Thyroid Cancer Metastasis

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

Adipose tissues as a target for metabolic diseases

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Adipose tissues as a target for metabolic diseases

Exercise-induced microbial changes in preventing type 2 diabetes

第三届中国生物物理学会代谢生物学分会学术研讨会

作者： Fang Hu metabolic Syndrome Research Center Department of Metabolism and EndocrinologyNational Clinical Research Center for Metabolic Diseasesthe Second Xiangya Hospital of Central South University

＜正＞Both white （WAT） and brown （BAT） adipose tissues are important regulators of energy homeostasis in animals and *** of WAT due to extra energy storage and defects in thermogenic gene expression in BAT are associated with obesity,type 2 diabetes,and other metabolic *** studies have uncovered a subset of cells in WAT that show a"brown-like"or"beige"phenotype when induced by certain environmental or hormonal *** process,

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Science China(Life Sciences) 2024年第5期67卷 892-899页

作者： Ting Yao Hui Wang Kaiqing Lin Ruwen Wang Shanshan Guo Peijie Chen Hao Wu Tiemin Liu Ru Wang School of Exercise and Health Shanghai Frontiers Science Research Base of Exercise and Metabolic HealthShanghai University of SportShanghai 200438China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi’an Jiaotong University School of MedicineXi’an 710061China Shanghai Key Laboratory of metabolic Remodeling and Health Institute of Metabolism&Integrative BiologyFudan UniversityShanghai 200433China State Key Laboratory of Genetic Engineering Human Phenome InstituteFudan Microbiome Centerand Department of Bariatric and Metabolic SurgeryHuashan HospitalFudan UniversityShanghai 201203China State Key Laboratory of Genetic Engineering Department of Endocrinology and MetabolismHuman Phenome Instituteand School of Life SciencesZhongshan HospitalFudan UniversityShanghai 200032China

The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut *** we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and *** found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students *** additionally showed that those microbial changes correlated more with handgrip strength,a simple but valuable biomarker suggestive of the diabetes states,than maximum oxygen intake,one of the key surrogates for endurance ***,the causal relationships among exercise,risks for diabetes,and gut microbiota were explored based on mediation *** propose that the protective roles of exercise against type 2 diabetes are mediated,at least partly,by the gut microbiota.

关键词： gut microbiota body fat diabetes handgrip maximum oxygen intake

Serum Glypican 4 Levels Are Associated with metabolic Syndrome in a Han Population from Guizhou Province, China

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Biomedical and Environmental Sciences 2019年第5期32卷 383-388页

作者： NING Dong Ping XU Ke ZHU Hui Juan SHAN Guang Liang WANG Ding Ming PING Bo YU Yang Wen PAN Hui GONG Feng Ying Key Laboratory of endocrinology of National Health Commission Dept. of EndocrinologyPeking Union Medical College HospitalTranslation Medicine CentreCAMS & PUMCBeijing 100730China Graduate School Hebei North UniversityZhangjiakou 075000HebeiChina Linfen Central Hospital Linfen 041000ShanxiChina Dept. of endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityZhejiang Provincial First Hospital of WenzhouWenzhou 325000ZhejiangChina Dept. of Epidemiology and Health Statistics Institute of Basic Medical SciencesCAMS & PUMCBeijing 100005China Guizhou Provincial Center for disease Control and Prevention Guiyang 550004GuizhouChina Longli Center for disease Control and Prevention Longli 551200GuizhouChina

metabolic syndrome (MetS) is the presence of a battery of cardiovascular risk factors including abdominal obesity, hypertension, dyslipidemia, and disturbed carbohydrate metabolism[1]. MetS affects 20% of adults in the Western world and 33% of adults in China[2] and has become a serious public health problem worldwide. However, the mechanism underlying the occurrence and progression of MetS is still largely unclear. It is now well established that excess fat deposition leads to abdominal obesity, which plays a vital role in the underlying mechanism. Adipose tissue can function as an endocrine organ that secretes various adipokines. The dysregulated expression of adipokines caused by excess adiposity and adipocyte dysfunction, has been linked to the pathogenesis of MetS[3]. Some serum adipokines such as leptin, adiponectin, interleukin 6 (IL-6), and tumour necrosis factor-α(TNF-α), might be potential markers for MetS development.

关键词： Serum Glypican 4 Levels metabolic Syndrome