Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population

AIM:To study the prevalence and clinical biochemical,blood cell and metabolic features of lean-non-alcoholic fatty liver disease(lean-NAFLD)and its association with other diseases.METHODS:Demographic,biochemical and blood examinations were conducted in all the subjects in this study.We classified the subjects into four groups according to their weight and NAFLD status:lean-control,lean-NAFLD[body mass index(BMI)<24 kg/m2],overweight-obese control and overweight-obese NAFLD.One-way analysis of variance(ANOVA)was used to compare the means of continuous variables(age,BMI,blood pressure,glucose,lipid,insulin,liver enzymes and blood cell counts)and theχ2 test was used to compare the differences in frequency of categorical variables(sex,education,physical activity,smoking,alcohol consumption and prevalence of hypertension,hyperlipidemia,diabetes,metabolic syndrome central obesity and obesity).Both univariate and multivariate logistic regression models were adopted to calculate odds ratios(ORs)and predict hyperlipidemia,hypertension,diabetes and metabolic syndrome when we respectively set all controls,lean-control and overweightobese-control as references.In multivariate logistic regression models,we adjusted potential confounding factors,including age,sex,smoking,alcohol consumption and physical activity.RESULTS:The prevalence of NAFLD was very high in China.NAFLD patients were older,had a higher BMI,waist circumference,blood pressure,fasting blood glucose,insulin,blood lipid,liver enzymes and uric acid than the controls.Although lean-NAFLD patients had lower BMI and waist circumstance,they had significantly higher visceral adiposity index than overweightobese controls.Lean-NAFLD patients had comparable triglyceride,cholesterin and low-density lipoprotein cholesterin to overweight-obese NAFLD patients.In blood cell examination,both lean and overweightobese NAFLD was companied by higher white blood cell count,red blood cell count,hemoglobin and hematocrit value.All NAFLD patients were at risk of hyperlipidemia,hypertension,diabetes and metabolic syndrome(Met S).Lean-NAFLD was more strongly associated with diabetes(OR=2.47,95%CI:1.14-5.35),hypertension(OR=1.72,95%CI:1.00-2.96)and Met S(OR=3.19,95%CI:1.17-4.05)than overweight-obese-NAFLD(only OR for Met S was meaningful:OR=1.89,95%CI:1.29-2.77).NAFLD patients were more likely to have central obesity(OR=1.97,95%CI:1.38-2.80),especially in lean groups(OR=2.17,95%CI:1.17-4.05).CONCLUSION:Lean-NAFLD has unique results in demographic,biochemical and blood examinations,and adds significant risk for diabetes,hypertension and Met S in lean individuals.

In vitro inhibition of proliferation,migration and epithelial-mesenchymal transition of human lens epithelial cells by fasudil

AIM： To study the potential role of fasudil as a treatment for posterior capsular opacification（PCO） of the human crystalline lens.METHODS： Human lens epithelial cells（HLECs; line SRA01/04） was exposed to transforming growth factor-β2（TGF-β2） to induce the process of epithelial-mesenchymal transition（EMT）. Fasudil was applied to the cell samples. Its effect on overall HLECs proliferation and migration was studied, as was its influence on EMT induction by TGF-β2 using cell migration assay, MTT colorimetric assay and Western blot assay.RESULTS： Fasudil inhibited the proliferation of SRA01/04. Its effect was time-and concentration-dependent. The migration of SRA01/04 cells was significantly reduced 24-72 h after fasudil treatment, and the half maximal inhibitory concentration（IC50） was 22.37 μmol/mL at 72 h. Reversal of the elongated, fibroblast-like shape changes induced by TGF-β2 in SRA01/04 cells was observed. Fasudil up-regulated the expression of Connexin43 protein and down-regulated the expression of α-SMA protein compared with the cells treated with TGF-β2. Furthermore, when exposed to fasudil, the phosphorylation of Rhoassociated protein kinase（Rock） and myosin light chain（MLC） could not be activated in the cell preparations.CONCLUSION： Fasudil suppresses the proliferation and migration of SRA01/04 cells, and inhibits the process of EMT induced by TGF-β2. These results suggest that fasudil may serve as a therapeutic agent for PCO.

Baseline Naive CD4＋ T-cell Level Predicting Immune Reconstitution in Treated HIV-infected Late Presenters

Background：Among HlV-infected patients initiating antiretroviral therapy （ART）,early changes in CD4＋ T-cell subsets are well described.However,HIV-infected late presenters initiating treatment present with a suboptimal CD4＋ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events.Therefore,factors associated with CD4＋ T-cell reconstitution need to be determined in this population,which will allow designing effective immunotherapeutic strategies.Methods：Thirty-one adult patients with baseline CD4＋ T-cell count 〈350 cells/mm^3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing,China,from October 2002 to September 2013.Changes in T-cell subsets and associated determinants were measured.Results：Median baseline CD4＋ T-cell count was 70 cells/mm3.We found a biphasic reconstitution ofT-cell subsets and immune activation：a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years.Baseline CD4＋ T-cell count 〉200 cells/ mm3 in comparison to CD4＋ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution （77.8% vs.27.3% respectively;P =0.017） and normalized CD4/CD8 ratio.We showed that the baseline percentage of naive CD4＋ T-cell was a predictive marker for complete immune reconstitution （area under receiver operating characteristic curve 0.907）,and 12.4% as cutoffvalue had a sensitivity of 84.6% and a specificity of 88.2%.Conclusions：Baseline naive CD4＋ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy.Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.

Recent advances in the chemical synthesis and semi-synthesis of poly-ubiquitin-based proteins and probes

Ubiquitination, a key and extensive posttranslational modification of proteins, has profound effects on a variety of physiological and pathological processes. The inherent complexity of ubiquitin conjugates makes it highly challenging to study the functional and structural mechanisms of ubiquitination. To address these challenges, accesses to sufficient poly-ubiquitin chains or ubiquitinated proteins are urgently needed. Over the last decade, synthetic protein chemists have developed several novel peptide ligation methods for the preparation of ubiquitin conjugates with precise control over the atomic structure. In this review, we summarize the recent breakthroughs and potential challenges in the chemical synthesis and semi-synthesis of ubiquitin conjugates with respect to the preparation of poly-ubiquitin-based proteins and ubiquitin-based probes.