Background Systemic lupus erythematosus (SLE) patients exhibit T-cell dysfunction which can be regulated through the mitochondrial transmembrane potential (Δψm) and mammalian target of rapamycin (mTOR) by glutathione. Therefore, the safety, tolerance, and efficacy of glutathione-precursor N-acetylcysteine (NAC) were examined in this randomized double-blind placebo-controlled study. Methods 36 SLE patients received daily placebo or 1.2 g, 2.4 g or 4.8 g of NAC. Disease activity was monthly evaluated by BILAG, SLEDAI and fatigue assessment scale (FAS) before, during, and after 3-month treatment. Δψm and mTOR were assessed by flow cytometry. 42 healthy subjects matched for patients’ age, gender, and ethnicity were studied as controls. Results NAC was tolerated by all patients up to 2.4 g/day while 33% of those receiving 4.8 g/day had reversible nausea. Placebo or 1.2 g/day NAC did not influence disease activity. Considered together, 2.4 g and 4.8 g NAC reduced: 1) SLEDAI after 1 month (p=0.0007), 2 months (p=0.0009), 3 months (p=0.0030) and 4 months (p=0.0046); 2) BILAG after 1 month (p=0.029) and 3 months (p=0.0009); and 3) FAS after 2 months (p=0.002) and 3 months (p=0.004). NAC increased Δψm (p=0.0001) in all T cells, it profoundly reduced mTOR activity (p=0.0001), enhanced apoptosis (p=0.0004) and reversed expansion of CD4−/CD8− T cells (1.35 ± 0.12-fold; p=0.008), stimulated Foxp3 expression in CD4+/CD25+ T cells (p=0.045), and reduced anti-DNA production (p=0.049). Conclusions This pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes.

Pfizer, the National Institutes of Health, and the Central New York Community Foundation.

Background:Nonalcoholic fatty liver disease (NAFLD) is emerging as a public health issue worldwide and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). However, there was a great disparity across studies in the estimated prevalence of NAFLD in T2DM patients. This meta-analysis, therefore, aimed to estimate the pooled prevalence of NAFLD in T2DM patients.Methods:Electronic databases of PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, and Wanfang were searched using MeSH terms to identify relevant studies. Eligibility assessment and data extraction were conducted independently by 2 investigators and a meta-analysis was performed to synthesize the data. Heterogeneity was evaluated using the Cochran Q test and quantified using the I2 statistic. Publication bias was assessed using both the Begg and Egger tests. Subgroup analyses were performed to identify the possible sources of heterogeneity.Results:Twenty-four studies involving 35,599 T2DM patients were included in this meta-analysis, of which 20,264 were identified with NAFLD. A high degree of heterogeneity (I2 = 99.0%, P < .001) was observed among the eligible studies, with the reported prevalence ranging from 29.6% to 87.1%. The pooled prevalence of NAFLD in T2DM patients, by a random-effects model, was 59.67% (95% confidence interval: 54.31–64.92%). Sensitivity was low and both the Begg test and Egger test showed low possibility of publication bias. Subgroup analyses indicated that the prevalence of NAFLD in T2DM patients differed by gender, obesity, hypertension, dyslipidemia, coronary heart disease, and chronic kidney disease.Conclusions:The high pooled prevalence of NAFLD in T2DM patients found in this study significantly underscores the need for early assessment of NAFLD and the importance of strengthening the management of NAFLD in T2DM patients.

BackgroundPost-traumatic stress disorder (PTSD) is a common psychological disorder caused by unusual threats or catastrophic events. Little is known about the combined incidence of PTSD after earthquakes. This study aimed at evaluating the combined incidence of PTSD among survivors after earthquakes using systematic review and meta-analysis.MethodsThe electronic databases of PubMed, Embase, Web of Science and PsycARTICLES were searched for relevant articles in this study. Loney criteria were used to assess the quality of eligible articles. The combined incidence of PTSD was estimated by using the Freeman-Tukey double arcsine transformation method. Subgroup analyses were conducted using the following variables: the time of PTSD assessment, gender, educational level, marital status, damage to one’s house, bereavement, injury of body and witnessing death.ResultsForty-six eligible articles containing 76,101 earthquake survivors met the inclusion criteria, of which 17,706 were diagnosed as having PTSD. Using a random effects model, the combined incidence of PTSD after earthquakes was 23.66 %. Moreover, the combined incidence of PTSD among survivors who were diagnosed at not more than 9 months after earthquake was 28.76 %, while for survivors who were diagnosed at over nine months after earthquake the combined incidence was 19.48 %. A high degree of heterogeneity (I2 = 99.5 %, p<0.001) was observed in the results, with incidence ranging from 1.20 to 82.64 %. The subgroup analyses showed that the incidence of PTSD after earthquake varied significantly across studies in relation to the time of PTSD assessment, gender, educational level, damage to one’s house, bereavement, injury of body and witnessing death. However, stratified analyses could not entirely explain the heterogeneity in the results.ConclusionsGiven the high heterogeneity observed in this study, future studies should aim at exploring more possible risk factors for PTSD after earthquakes, especially genetic factors. In spite of that, the results of this study suggest that nearly 1 in 4 earthquake survivors are diagnosed as having PTSD. Therefore, the local government should plan effective psychological interventions for earthquake survivors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-0891-9) contains supplementary material, which is available to authorized users.

The mechanistic target of rapamycin (mTOR) is recognized as a sensor of mitochondrial dysfunction and effector of T-cell lineage development, however, its role in autoimmunity, including systemic lupus erythematosus, remains unclear. Here, we prospectively evaluated mitochondrial dysfunction and mTOR activation in PBL relative to SLE disease activity index (SLEDAI) during 274 visits of 59 patients and 54 matched healthy subjects. Partial least square-discriminant analysis identified 15 of 212 parameters that accounted for 70.2% of the total variance and discriminated lupus and control samples (p<0.0005); increased mitochondrial mass of CD3+/CD4−/CD8− double-negative (DN) T cells (p=1.1×10−22) and FoxP3 depletion in CD4+/CD25+ T cells were top contributors (p=6.7×10−7). Prominent necrosis and mTOR activation were noted in DN T cells during 15 visits characterized by flares (SLEDAI increase ≥4) relative to 61 visits of remission (SLEDAI decrease ≥4). mTOR activation in DN T cells was also noted at pre-flare visits of SLE patients relative to those of stable disease or healthy controls. DN lupus T cells showed increased production of IL-4, which correlated with depletion of CD25+/CD19+B cells. Rapamycin treatment in vivo blocked the IL-4 production and necrosis of DN T cells, increased the expression of FoxP3 in CD25+/CD4+T cells, and expanded CD25+/CD19+ B cells. These results identify mTOR activation to be a trigger of IL-4 production and necrotic death of DN T cells in patients with SLE.