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Recent Advances in Understanding Proteins Involved in Lipid Droplet Formation, Growth and Fusion

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Journal of Genetics and Genomics 2014年第5期41卷 251-259页

作者： Jolene S.Y.Tan Colin J.P.Seow Vera J.Goh David L.Silver Signature Research Program in Cardiovascular & metabolic disorders Duke-NUS Graduate Medical School Singapore

Lipid droplets （LDs） were once viewed as simple, inert lipid micelles. However, they are now known to be organelles with a rich proteome involved in a myriad of cellular processes. LDs are heterogeneous in nature with different sizes and compositions of phospholipids, neutral lipids and proteins. This review takes a focused look at the roles of proteins involved in the regulation of LD formation, expansion, and morphology. The related proteins are summarized such as the fat-specific protein （Fsp27）, fat storage-inducing trans- membrane （FIT） proteins, seipin and ADP-ribosylation factor 1-coat protein complex I （Arf-COPI）. Finally, we present important challenges in LD biology for a deeper understanding of this dynamic organelle to be achieved.

关键词： Lipid droplets LD-associated proteins Perilipin Phospholipids

Non-coding RNAs in hepatitis C-induced hepatocellular carcinoma:Dysregulation and implications for early detection,diagnosis and therapy

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World Journal of Gastroenterology 2013年第44期19卷 7836-7845页

作者： Weihong Hou Herbert L Bonkovsky the Liver Digestive and Metabolic Disorders Laboratory and the Liver-Biliary-Pancreatic Center Cannon Research Center Carolinas Medical CenterCharlotte NC 28203 United States

Hepatitis C virus(HCV)infection is one of main causes of hepatocellular carcinoma(HCC)and the prevalence of HCV-associated HCC is on the rise *** is particularly important and helpful to identify potential markers for screening and early diagnosis of HCC among high-risk individuals with chronic hepatitis C,and to identify target molecules for the prevention and treatment of *** noncoding RNAs,mainly microRNAs(miRNAs),and long non-coding RNAs(lncRNAs)with size greater than 200nucleotides,are likely to play important roles in a variety of biological processes,including development and progression of *** the most part their underlying mechanisms of action remain largely *** recent years,with the advance of high-resolution of microarray and application of next generation sequencing techniques,a significant number of non-coding RNAs(ncRNAs)associated with HCC,particularly caused by HCV infection,have been found to be differentially expressed and to be involved in pathogenesis of HCVassociated *** this review,we focus on recent studies of ncRNAs,especially miRNAs and lncRNAs related to HCV-induced *** summarize those ncRNAs aberrantly expressed in HCV-associated HCC and highlight the potential uses of ncRNAs in early detection,diagnosis and therapy of HCV-associated *** also discuss the limitations of recent studies,and suggest future directions for research in the ***,lncRNAs and their target genes may represent new candidate molecules for the prevention,diagnosis and treatment of HCC in patients with HCV *** of the potential uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their infancy.

关键词： MicroRNA Long non-coding RNAs Non-coding RNAs Hepatitis C virus Hepatocellular carcinoma

Non-invasive diagnosis of H pylori infection: Evaluation of serological tests with and without current infection marker CIM

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World Journal of Gastroenterology 2008年第8期14卷 1231-1236页

作者： Sufi HZ Rahman M Golam Azam M Anisur Rahman MS Arfin M Mahbub Alam Tareq M Bhuiyan Nasim Ahmed Motiur Rahman Shamsun Nahar MS Hassan Department of Immunology Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders Dhaka Bangladesh Department of Gastrointestinal Hepatobiliary and Pancreatic Diseases Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders Dhaka Bangladesh Department of Pathology Ibrahim MedicalCollege Dhaka Bangladesh laboratory Sciences Division International Centre for Diarrhoeal Diseases Research Bangladesh Dhaka Bangladesh

AIM:To evaluate the performance of commercially available immunochromatographic (ICT) and immunoblot tests covering the current infection marker CIM and conventional ELISA for the diagnosis of H pylori infection in adult dyspeptic patients. METHODS:Consecutive non-treated dyspeptic patients undergoing diagnostic endoscopy were tested for H pylori infection by culture, rapid urease test, and histology of gastric biopsy specimens. Serum from 61 H pylori infected and 21 non-infected patients were tested for anti-H pylori IgG antibodies by commercial ELISA (AccuBindTM ELISA, Monobind, USA), ICT (Assure H pylori Rapid Test, Genelabs Diagnostics, Singapore), and immunoblot (Helico Blot 2.1, Genelabs Diagnostics, Singapore) assays. ICT and immunoblot kits cover CIM among other parameters and their performance with and without CIM was evaluated separately. RESULTS:Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of ELISA were 96.7%, 42.8%, 83.1%, 81.8%, and 82.9%, of ICT were 90.1%, 80.9%, 93.2%, 73.9%, and 87.8%, of ICT with CIM were 88.5%, 90.4%, 96.4%, 73.0%, and 89.0%, of immunoblot were 98.3%, 80.9%, 93.7%, 94.4%, and 93.9%, and of immunoblot with CIM were 98.3%, 90.4%, 96.7%, 95.0%, and 96.3%, respectively. CONCLUSION:Immunoblot with CIM had the best performance. ICT with CIM was found to be more specific and accurate than the conventional ELISA and may be useful for non-invasive diagnosis of H pylori infection.

关键词： H pylori ELISA Immunochromatographic test Immunoblot Current infection marker

Prediction of metabolic disorders Using NMR-Based Metabolomics:The Shanghai Changfeng Study

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Phenomics 2021年第4期1卷 186-198页

作者： Qi Wu Qing-xia Huang Hai-luan Zeng Shuai Ma Huan-dong Lin Ming-feng Xia Hui-ru Tang Xin Gao Department of Endocrinology and Metabolism Zhongshan HospitalFudan Institute for Metabolic DiseaseHuman Phenome InstituteFudan UniversityShanghai 2000032China State Key laboratory of Genetic Engineering School of Life SciencesMetabonomics and Systems Biology LaboratoryHuman Phenome InstituteFudan UniversityShanghai 201203China

A metabolically healthy status,whether obese or not,is a transient stage with the potential to develop into metabolic disor-ders during the course of *** investigated the incidence of metabolic disorders in 1078 metabolically healthy Chinese adults from the Shanghai Changfeng Study and looked for metabolites that discriminated the participants who would develop metabolic disorders in the *** were divided into metabolically healthy overweight/obesity(MHO)and meta-bolically healthy normal weight(MHNW)groups according to their body mass index(BMI)and metabolic *** serum metabolomic profile was measured using a ^(1)H nuclear magnetic resonance spectrometer(^(1)H-NMR).The prevalence of diabetes,hypertriglyceridemia,hypercholesterolemia and metabolic syndrome was similar between the MHNW and MHO participants at *** a median of 4.2 years of follow-up,more MHO participants became metabolically unhealthy than MHNW ***,a subgroup of MHO participants who remained metabolically healthy(MHO→MHO)had a similar prevalence of metabolic disorders as the MHNW participants at the follow-up examination,despite a signifi-cant reduction in their serum concentrations of high-density lipoprotein(HDL)and an elevation in valine,leucine,alanine and *** correlation analysis indicated that serum intermediate-density lipoprotein(IDL)and very low-density lipoprotein cholesterol(VLDL-CH)might be involved in the transition from metabolically healthy to unhealthy status and could be valuable to identify the MHNW and MHO with increased metabolic risks.

关键词： metabolically healthy normal weight(MHNW) metabolically healthy overweight/obesity(MHO) ^(1)H nuclear magnetic resonance spectrometer(^(1)H-NMR) metabolic disorders Very low-density lipoprotein cholesterol(VLDL-CH) Intermediate-density lipoprotein(IDL)

The Role of Adipose Tissue-derived Exosomes in Chronic metabolic disorders

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Current Medical Science 2024年第3期44卷 463-474页

作者： Rui HE Yong CHEN Division of Endocrinology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China laboratory of Endocrinology & Metabolism Key Laboratory of Vascular Aging of the Ministry of EducationTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Branch of National Clinical Research Center for metabolic Diseases Wuhan430030China

Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body *** are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine ***,the roles of AT Exos in crosstalk with metabolic organs remain to be fully *** this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic ***,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.

关键词： exosome adipose tissue obesity diabetes chronic metabolic disorder miRNA

Nonmuscle myosin Ⅱ regulates migration but not contraction in rat hepatic stellate cells

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World Journal of Hepatology 2011年第7期3卷 184-197页

作者： Cathy C Moore Ashley M Lakner Christopher M Yengo Laura W Schrum Department of Biology University of North Carolina at CharlotteCharlotteNC 28223United States Liver Digestive and Metabolic Disorders LaboratoryCarolinas Medical Center

AIM: To identify and characterize the function of non-mu-scle myosin Ⅱ (NMM Ⅱ) isoforms in primary rat hepatic stellate cells (HSCs).METHODS: Primary HSCs were isolated from male Spra-gue-Dawley rats by pronase/collagenase digestion. Total RNA and protein were harvested from quiescent and culture-activated HSCs. NMM Ⅱ isoform (Ⅱ-A, Ⅱ-B and Ⅱ-C) gene and protein expression were measured by RealTime polymerase chain reaction and Western blot analyses respectively. NMM Ⅱ protein localization was visualized in vitro using immunocytochemical analysis. For in vivo assessment, liver tissue was harvested from bile duct-ligated (BDL) rats and NMM Ⅱisoform expression determined by immunohistochemistry. Using a selective myosin Ⅱ inhibitor and siRNA-mediated knockdown of each isoform, NMM Ⅱ functionality inprimary rat HSCs was determined by contraction and migration ***: NMM Ⅱ-A and Ⅱ-B mRNA expression was increased in culture-activated HSCs (Day 14) with sig-niflicant increases seen in all pairwise comparisons (Ⅱ-A: 12.67 ± 0.99 (quiescent) vs 17.36 ± 0.78 (Day 14), P < 0.05; Ⅱ-B: 4.94 ± 0.62 (quiescent) vs 13.90 ±0.85 (Day 14), P < 0.001). Protein expression exhibited similar expression patterns (Ⅱ-A: 1.87 ± 2.50 (quiescent) vs 58.64 ± 8.76 (Day 14), P < 0.05; Ⅱ-B: 1.17 ± 1.93 (quiescent) vs 103.71 ± 21.73 (Day 14), P < 0.05). No signif icant differences were observed in NMM Ⅱ-C mRNA and protein expression between quiescent and activated HSCs. In culture-activated HSCs, NMM Ⅱ-A and Ⅱ-B merged with F-actin at the cellular periphery and throughout cytoplasm respectively. In vitro stud-ies showed increased expression of NMM Ⅱ-B in HSCs activated by BDL compared to sham-operated animals. There were no apparent increases of NMM Ⅱ-A and Ⅱ-C protein expression in HSCs during hepatic BDL injury. To determine the contribution of NMM Ⅱ-A and Ⅱ-B to migration and contraction, NMM Ⅱ-A and Ⅱ-B expres-sion were downregulated with siRNA. NMM Ⅱ-A and/or Ⅱ-B siRNA inhibited HSC mi

关键词： Hepatic stellate cells Nonmuscle myosin Ⅱ Migration Contraction Blebbistatin Hepatic injury

Heme status affects human hepatic messenger RNA and microRNA expression

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World Journal of Gastroenterology 2013年第10期19卷 1593-1601页

作者： Herbert L Bonkovsky Weihong Hou Nury Steuerwald Qing Tian Ting Li Judy Parsons Alicia Hamilton Sunil Hwang Laura Schrum the Liver Digestive and Metabolic Disorders LaboratoryCannon Research CenterCarolinas Medical Center1542 Garden TerraceCharlotteNC 28203United States the Molecular Core laboratory Cannon Research CenterCarolinas Medical CenterCharlotteNC 28203United States

AIM:To assess effects of heme on messenger RNA(mRNA) and microRNA(miRNA) profiles of liver cells derived from ***:We exposed human hepatoma cell line Huh-7 cells to excess iron protoporphyrin(heme)(10 μmol/L) or induced heme deficiency by addition of 4,6-dioxoheptanoic acid(500 μmol/L),a potent inhibitor of aminolevulinic acid dehydratase,for 6 h or 24 *** harvested total RNA from the cells and performed both mRNA and miRNA array analyses,with use of Affymetrix chips,reagents,and instruments(human genome U133 plus 2.0 and miRNA 2.0 arrays).We assessed changes and their significance and interrelationships with Target Scan,Pathway Studios,and Ingenuity ***:Changes in mRNA levels were most numerous and striking at 6 h after heme treatment but were similar and still numerous at 24 *** 6 h of heme exposure,the increase in heme oxygenase 1 gene expression was 60-fold by mRNA and 88-fold by quantitative reverse transcription-polymerase chain *** found striking changes,especially up-regulation by heme of nuclear erythroid-2 related factor-mediated oxidative stress responses,protein ubiquitination,glucocorticoid signaling,P53 signaling,and changes in RNAs that regulate intermediary *** mRNAs were down-regulated by heme,and the fold decreases were less exuberant than were the *** decreases after 24 h of heme exposure were patatin-like phospholipase domain-containing protein 3(-6.5-fold),neuronal PAS domain protein 2(-1.93-fold),and protoporphyrinogen oxidase(-1.7-fold).CONCLUSION:Heme excess exhibits several toxic effects on liver and kidney,which deserve study in humans and in animal models of the human porphyrias or other disorders.

关键词： Delta-aminolevulinic acid synthase Heme Heat shock proteins Hepatotoxicity Messenger RNA MicroRNA

WTAP:a new player in postnatal BAT development

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Life Metabolism 2022年第3期1卷 201-202页

作者： Lei Sun Cardiovascular and metabolic disorders Program Duke-NUS Medical SchoolSingapore 169857Singapore

Understanding the mechanisms underlying brown fat development and metabolism can provide unique insights into the regulation of energy *** a recent study published in Life Metabolism,Wang et *** Wilms’tumor 1-associating protein(WTAP),a key component in m6A methyltransferase complex,as a new and essential regulator in the postnatal development and maturation of interscapular brown adipose tissue(iBAT).Interscapular brown adipose tissue(iBAT)is the major organ responsible for nonshivering thermogenesis in rodents[1].

关键词： metabolism homeostasis

Effects of Electroacupuncture on metabolic Changes in Motor Cortex and Striatum of 6-Hydroxydopamine-Induced Parkinsonian Rats

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Chinese Journal of Integrative Medicine 2020年第9期26卷 701-708页

作者： LI Min WANG Ke SU Wen-ting JIA Jun WANG Xiao-min Departments of Neurobiology and Physiology Key Laboratory for Neurodegenerative Disorders of the Ministry of EducationBeijing Key Laboratory for Parkinson's DiseaseCapital Medical UniversityBeijing Institute for Brain DisordersBeijing(100069)China

Objective:To explore the possible underlying mechanism by investigating the effect of electroacupuncture(EA)treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine(6-0HDA)induced rat Parkinson's disease(PD)***:Male Sprague-Dawley rats were randomly divided into sham group(n=16),model group(n=14),and EA group(n=14).EA stimulation at Dazhui(GV 14)and Baihui(GV20)was applied to PD rats in the EA group for 4 *** tests were conducted to evaluate the effectiveness of EA *** were detected by 7.0 T proton nuclear magnetic ***:Following 4 weeks of EA treatment in PD model rats,the abnormal behavioral impairment induced by 6-0HDA was *** monitoring changes in metabolic activity,ratios of myoinositol/creatine(Cr)and N-acetyl aspartate(NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats(P=0.024 and 0.020).The ratios of glutamate+glutamine(Glx)/Cr and NAA/Cr in the striatum were higher and lower,respectively,at the injected side than the non-injected side(P=0.046 and 0.008).EA treatment restored the balance of metabolic activity in the primary motor cortex and *** addition,the taurine/Cr ratio and GIx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats(P=0.026 and 0.000).EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio(P=0.001).The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats(P=0.027 and P=0.0007).Conclusions:EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats,which may contribute to its therapeutic effect on motor *** striatal GIx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

关键词： electroacupuncture magnetic resonance spectroscopy motor cortex striatum Parkinson's disease