Anti-MDA5 antibody dermatomyositis-associated rapidly progressive interstitial lung disease patient complicated with mixed connective tissue disease: A case report.

Anti-MDA5 antibody dermatomyositis (DM) is a special type of myositis, which can potentially cause rapidly progressive interstitial lung disease (RP-ILD). Mixed connective tissue disease (MCTD) is a complex disease with different characteristics of autoimmune connective tissue disease, associated with ILD. Both are rare diseases, and few patients with both diseases have been reported. A 71-year-old woman complained of palpitations, with a 2 months history of rash around her hands, extensor surface of right elbow, and the nape of her neck. Subsequently, the patient had acute exacerbation of dyspnea and tachypnea. Anti-Ro52, U1 RNP and MDA5 antibodies were positive; the presenting evidence was suggestive of anti-MDA5+ DM-RP-ILD complicated with MCTD. Our patient deteriorated rapidly and had a fatal outcome, despite "triple therapy" for RP-ILD. This case illustrates that patients with coexisting anti-MDA5+ DM and MCTD have the former's typical clinical manifestations, and may develop ILD quickly rather than slowly as in MCTD, especially with the coexistence of anti-Ro52 antibodies.

From the Cover: Activation of NF-κB-Autophagy Axis by 2-Hydroxyethyl Methacrylate Commits Dental Mesenchymal Cells to Apoptosis.

2-hydroxyethyl methacrylate (HEMA) is the major resin monomer that is released from incomplete polymerized dental restorative and adhesive biomaterials during dental therapy. Autophagy and apoptosis are biologically connected and the relationship between autophagy and apoptosis is complex under various circumstances. This study aimed to determine whether autophagy is activated by HEMA and further explore the function of autophagy during the HEMA-induced apoptosis of dental mesenchymal cells (DMCs). We exposed DMCs to different concentrations of HEMA. Cell viability showed a time- and concentration-dependent decrease when exposed to HEMA. We showed that HEMA exposure increased autophagic vacuoles and the expression of autophagic biomarkers (Beclin1, Atg5 and LC3). Pre-incubated with autophagy inhibitors (3-methyladenine and chloroquine) significantly prevented HEMA-induced apoptosis. Interestingly, HEMA initiated nuclear factor-κB (NF-κB) expression and nuclear translocation, whereas the NF-κB inhibitor (Bay 11-7082) markedly suppressed HEMA-induced autophagic activation and apoptosis. As is consistent with the in vitro results, HEMA treatment resulted in dental pulp tissue toxicity and activation of typical autophagic vacuoles in the tooth slice organ culture model ex vivo. In summary, we demonstrated that NF-κB signaling functioned upstream of HEMA-inducecd autophagy in DMCs and that the activation of NF-κB-autophagy axis was responsible for HEMA-induced apoptosis. Our findings provide novel insights into the mechanisms of resin monomer-mediated dental pulp damage during dental treatment, highlighting the activation of NF-κB-autophagy axis as an important mechanism of HEMA-mediated apoptosis.