The preclinical study established the safety and efficacy of haMSCs. Intra-articular injections of haMSCs were safe and improved pain, function and cartilage volume of the knee joint, rendering them a promising novel treatment for knee osteoarthritis. The dosage of 5 × 10 haMSCs exhibited the highest improvement (ClinicalTrials.gov Identifier: NCT01809769).

Results indicate that T-614 therapy 50 mg/day is effective and well tolerated, and represents a new option for the treatment of patients with active RA.

SummaryBackground Although some features of dermatomyositis (DM) and polymyositis (PM) have been reported as possible prognostic indicators for cancer development, previous studies were small in size and were unable to establish a definitive relationship between neoplasms and DM and PM. Objectives To evaluate risk factors for developing malignancies in patients with DM and PM. Methods Meta-analysis of the studies reported in the literature was performed to unveil risk factors for developing cancer among patients with DM and PM. The included studies were either cohort or retrospective case-control studies with information on cancer status. Risk for malignancy was determined as the odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (CI), determined by fixed and random effects models. Stata 10.0 software was used to identify possible publication bias. Results Twenty studies with 380 patients and 1575 controls were included in the analysis. The factors that may increase the risk of cancer in patients with DM and PM were older age (WMD 11Á41, 95% CI 9Á84-12Á98), male sex (OR 1Á92, 95% CI 1Á49-2Á48), cutaneous necrosis (OR 5Á52, 95% CI 3Á49-8Á74) and dysphagia (OR 2Á41, 95% CI 1Á50-3Á86), whereas those that may provide protection against cancer included arthritis (OR 0Á38, 95% CI 0Á24-0Á61) and interstitial lung disease (OR 0Á32, 95% CI 0Á20-0Á51). Conclusions Our data suggest that age, sex, cutaneous necrosis, dysphagia, arthritis and lung complications may influence susceptibility to cancer in patients with DM and PM.

Objective Anti-Ro52 antibody often co-occurs with anti-Jo1 antibody in antisynthetase syndrome and their co-occurrence correlates with a more aggressive clinical phenotype and poorer prognosis. The strong association of anti-Ro52 antibody with anti-melanoma differentiation-associated protein-5 (anti-MDA5) antibody has been indicated in juvenile myositis. The aim of this study was to assess the clinical significance of anti-Ro52 antibody in a cohort of adult patients with anti-MDA5-positive clinically amyopathic dermatomyositis with interstitial lung disease (CADM-ILD). Methods We assessed a cohort of 83 consecutive patients with anti-MDA5-positive CADM-ILD. Anti-MDA5 antibodies and anti-Ro52 antibodies were detected in immunoblotting and semi-quantitatively analysed by densitometry. Clinical features and the 24 month survival were compared between anti-MDA5-positive patients with and without anti-Ro52 antibodies. Results Anti-Ro52 antibodies were found in 74.7% of anti-MDA5-positive CADM-ILD patients and were associated with an increased frequency of rapidly progressive interstitial lung disease (RP-ILD; 54.8% vs 23.8%; P = 0.014) and cutaneous ulcerations (27.4% vs 4.8%; P = 0.033). The cumulative 24 month survival rate tended to be lower in patients with anti-Ro52 antibodies than patients without (59.9% vs 85.7%; P = 0.051). The combination of anti-Ro52 antibody status and anti-MDA5 antibody levels further stratified patients’ survival rates, showing that the survival rate of patients who were dual positive for anti-MDA5 antibody and anti-Ro52 antibody was significantly lower than patients with mild positive anti-MDA5 antibody alone (59.9% vs 100%; P = 0.019). Conclusion Anti-Ro52 antibody is highly prevalent in anti-MDA5-positive CADM-ILD patients and their coexistence correlates with a subgroup of patients with more aggressive phenotypes. The combination of anti-MDA5 antibody levels and anti-Ro52 antibody status could help to predict patients’ prognosis and guide risk-based therapy.

Introduction T-614 is a novel oral antirheumatic agent for the treatment of rheumatoid arthritis. Whether it has immunomodulatory or disease-modifying properties and its mechanism of action are largely undetermined.

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Objective Over proliferation of synovium is a key event of invasive pannus formation and cartilage damage in the progression of rheumatoid arthritis (RA) disease. At the same time, ferroptosis may play a pivotal role in maintaining the balance of proliferation and death of synovium. In this study, we firstly evaluated the ferroptosis level in RA fibroblast-like synoviocytes (FLS) and then explored the role of glycine in ferroptosis. Methods Ferroptosis was evaluated in RA synovium and FLS. The therapeutic effect of glycine on RA was evaluated by clinical and histopathological score and cytokine level in a collagen-induced arthritis (CIA) mouse model. The influence of glycine on ferroptosis was evaluated by mitochondrial morphology observation and membrane potential assay in RA FLS. Methylase expression was detected to explore the mechanism behind the effect of glycine on glutathione peroxidase 4 (GPX4) methylation. Results Compared with healthy controls (HC), ferroptosis decreased in the RA synovium and FLS, with a decrease in Acyl Coenzyme A Synthetase Long Chain 4 (ACSL4) and an increase in Ferritin heavy chain 1(FTH1), GPX4, and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Although both oxidation and antioxidation levels of lipids were higher in RA FLS than in HC, the increase in antioxidation was slightly higher than oxidation. RNA-Seq and verification showed that glycine regulated the ferroptosis pathway through increase S-adenosylmethionine (SAM) concentration and decrease the expression of GPX4 and FTH1 by promoting SAM-mediated GPX4 promoter methylation and reducing FTH1 expression in RA FLS. Conclusions In summary, we confirmed a decline in ferroptosis in RA and explored that glycine enhanced ferroptosis via SAM-mediated GPX4 promoter methylation and ferritin decrease.

IntroductionGlucocorticoid (GC) therapy remains important in improving the prognosis of patients with systemic lupus erythematosus (SLE). However, some patients do not achieve an effective response with GC treatment, creating an obstacle to the remission of SLE. Identification of the underlying mechanisms responsible for steroid resistance can be significant. Macrophage migration inhibitory factor (MIF) arouses our interest because of its reciprocal relationship with GCs. In the present study, we investigated for the first time whether MIF correlated with steroid resistance in SLE and explored potential mechanisms of action.MethodsSixty-two patients with SLE (40 steroid sensitive and 22 steroid resistant) and 21 normal controls were recruited. Serum levels of MIF were measured by ELISA. Cytosolic MIF and IκB expression in peripheral blood mononuclear cells (PBMCs) were determined by western blotting. The electrophoretic mobility shift assay was assessed by NF-κB in nuclear aliquots. Gene silencing was applied to reduce expression of MIF in PBMCs in steroid-resistant patients. PBMCs obtained from steroid-sensitive patients were treated with recombinant human MIF of different concentrations.ResultsMIF levels in serum and PBMCs were higher in steroid-resistant patients compared with steroid-sensitive patients and controls. In contrast to the steroid-sensitive group, NF-κB levels were significantly higher and IκB levels lower in steroid-resistant patients. After MIF gene silencing, IκB levels in cells from steroid-resistant patients were increased. In steroid-sensitive patients, a decrease in IκB levels and an increase in NF-κB expression from baseline were detected in PBMCs treated with a higher concentration of recombinant human MIF. Treatment with recombinant human MIF did not regulate expression of IκB and NF-κB in PBMCs from patients treated with an anti-MIF monoclonal antibody.ConclusionsOur results indicated that MIF may play a role in the formation of steroid resistance in SLE by affecting the NF-κB/IκB signaling cascade. As a regulator of glucocorticoid sensitivity, MIF may be a potential target for steroid sparing.