NLR and PLR could reflect inflammatory response and disease activity in SLE patients.

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress that initiates the unfolded protein response (UPR). UPR activates both adaptive and apoptotic pathways, which contribute differently to disease pathogenesis. To further understand the functional mechanisms of UPR, we identified 12 commonly UPR-upregulated genes by expression microarray analysis. Here, we describe characterization of Armet/MANF, one of the 12 genes whose function was not clear. We demonstrated that the Armet/MANF protein was upregulated by various forms of ER stress in several cell lines as well as by cerebral ischemia of rat. Armet/MANF was localized in the ER and Golgi and was also a secreted protein. Silencing Armet/MANF by siRNA oligos in HeLa cells rendered cells more susceptible to ER stress-induced death, but surprisingly increased cell proliferation and reduced cell size. Overexpression of Armet/MANF inhibited cell proliferation and improved cell viability under glucose-free conditions and tunicamycin treatment. Based on its inhibitory properties for both proliferation and cell death we have demonstrated, Armet is, thus, a novel secreted mediator of the adaptive pathway of UPR.

IntroductionThe evidence from published studies on the association between obesity and rheumatoid arthritis has been contradictory. To clarify the association between obesity and rheumatoid arthritis, we conducted a systematic review and dose-response meta-analysis to assess the relationship between body mass index and rheumatoid arthritis risk.MethodsA systematic literature search of PubMed and Embase (up to 12 July 2014) was performed to identify all eligible published reports. The pooled relative risk results with corresponding 95% confidence intervals of rheumatoid arthritis development were estimated using a random-effects model.ResultsEleven eligible related citations fulfilled the inclusion criteria and were included in the study. Compared with individuals with a body mass index under 30, obese individuals showed an association with a significantly increased risk of rheumatoid arthritis (relative risk = 1.25, 95% confidence interval: 1.07 to 1.45, Pheterogeneity <0.01, I2 = 63%). Compared to normal weight subjects, the pooled relative risks for rheumatoid arthritis were 1.31 (1.12 to 1.53) and 1.15 (1.03 to 1.29) for the categories of obese and overweight, respectively. In the dose-response analysis, there was evidence of a nonlinear association (Pnonlinear = 0.005) and the estimated summary relative risk for a 5-unit increment was 1.03 (95% confidence interval: 1.01 to 1.05, Pheterogeneity = 0.001, I2 = 70.0%).ConclusionsAn increase in body mass index can contribute to a higher risk for rheumatoid arthritis development. However, the finding also highlights the need for research on the association between body mass index and rheumatoid arthritis risk with adjustment for more confounding factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0601-x) contains supplementary material, which is available to authorized users.

The present metaanalysis indicates that PM and DM are significantly associated with increased risks of overall malignancy and most site-specific malignancies. The number of studies on association between PM or DM and some malignancies is too small to draw a firm conclusion. Accordingly, more research is needed for these malignancies.

This study was aimed to evaluate levels of neutrophil- (NLR), monocyte- (MLR), eosinophil- (ELR), and basophil-lymphocyte ratio (BLR) and their association with inflammatory markers in systemic autoimmune rheumatic diseases (SARDs). A total of 1139 SARD patients and 170 healthy individuals were enrolled. Clinical and laboratory data were extracted. NLR and MLR were significantly increased, but BLR decreased in most SARD patients (p < 0.05). ELR were significantly decreased in systemic lupus erythematosus (SLE) patients, but increased in those with other SARDs (p < 0.001). In SLE patients, C-reactive protein (CRP) showed positive correlation with NLR, MLR, and BLR. IgG negatively correlated with NLR, and did positively with ELR. IgM negatively correlated with NLR and MLR. In those with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and osteoarthritis (OA), NLR and MLR positively correlated with erythrocyte sedimentation rate (ESR) and CRP. In primary Sjögren's syndrome (pSS) patients, ESR showed positive correlation with NLR and MLR. IgA had positive correlation with BLR. In polymyositis/dermatomyositis (PM/DM) patients, ESR and CRP positively correlated with NLR. Additionally, significant correlations were also found between CRP and BLR, IgG and ELR, IgM and ELR. In systemic sclerosis (SSc) patients, clear correlations were only observed between CRP and NLR or MLR. In mixed connective tissue disease (MCTD) patients, NLR positively correlated with ESR and CRP, while NLR and MLR did negatively with IgM. In polymyalgia rheumatic (PMR) patients, MLR positively correlated with CRP, while ELR did negatively with IgG. This study demonstrated increased NLR and MLR and deceased BLR in most SARDs, decreased ELR in SLE and increased ELR in other SARDs. Furthermore, NLR and MLR may be useful tools to reflect inflammatory status of SARDs.

This meta-analysis indicates that pSS is significantly associated with increased risks of overall malignancy, NHL and thyroid cancer. However, it is not yet known whether the apparent increased risk of overall malignancy in patients with pSS is due to the relatively high prevalence of NHL in that group.

Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia. Focal cerebral ischemia in rats was induced by right middle cerebral artery occlusion with a suture; ischemic lesions were assessed by magnetic resonance imaging and histology; neuronal apoptosis was determined by TUNEL staining; the expressions of proteins were measured by immunohistochemistry, immunofluorescent labeling, and Western blotting. ARMET was found to be extensively upregulated in ischemic regions in a time-dependent manner. The expression of ARMET was neuronal in all examined structures in response to the ischemic insult. We also found that ARMET expression is earlier and more sensitive to ischemic stimulation than C/EBP homologous protein (CHOP). ER stress agent tunicamycin induced ARMET and CHOP expressions in the primary cultured neurons. Treatment with recombinant human ARMET promoted neuron proliferation and prevented from neuron apoptosis induced by tunicamycin. These results suggest that cerebral ischemia-induced ARMET expression may be protective to the neurons.

Multiple familial trichoepithelioma (MFT) is an autosomal dominant skin disease characterized by the presence of many small benign tumors with pilar differentiation predominantly on the face. The first locus has been previously mapped to chromosome 9p21, but no gene for MFT has been identified to date. To identify the disease gene in a large Chinese family, we initially performed linkage analysis with microsatellite markers from 9p21, but failed to confirm the linkage to this region. Previous publications showed MFT and familial cylindromatosis (FC) can occur within one family and in a single person. Therefore, we speculated that the cylindromatosis gene (CYLDI gene) responsible for FC may be related to the pathogenesis of MFT. In view of that, we genotyped all available individuals using 11 microsatellite markers spanning the CYLDI gene region at 16q12-q13. We identified the linkage of MFT to this region. Mutation analysis in the CYLDI gene detected a frameshift mutation, designated as c.2355-2358delCAGA. The study firstly identified the cylindromatosis gene responsible for MFT and showed that different mutations of the CYLDI gene can give rise to distinct clinical and histological expression such as FC and MFT.