P38β MAPK mediates ULK1-dependent induction of autophagy in skeletal muscle of tumor-bearing mice –

Exosomes have generated significant interest in the last few decades owing to their important roles in a diverse range of biological pathways. They are nano-sized lipid bilayer membrane vesicles of endosomal origin, and are produced by a vast number of cell types. They are released into the extracellular environment and are found in most biological fluids. Exosomes can contain proteins, lipids and nucleic acids. The cargo of exosomes allows them to play roles in cell communication, antigen presentation, as biomarkers and in immune regulation. Substantial efforts have been made to understand their biology and potential clinical use in various diseases, including autoimmune connective tissue diseases (ACTD). In this review, we highlight the known functions of exosomes and detail recent advances made in the elucidation of the roles of exosomes in ACTDs with an emphasis on their potential use as a biomarker for disease diagnosis and as a therapeutic target.

Bullous pemphigoid (BP) is a chronic autoimmune blistering disorder that has a predilection for the elderly. It is characterized by a poor prognosis due to its high mortality rate and the tendency to relapse. The relapse rate of BP ranges from 27.87% to 53% after disease remission, while the majority of relapses occur early (within 6 months) during remission. Clinical interventions aimed to prevent early relapses could reduce potential complications from first-line treatment and make follow-up care easier for clinicians in practice, thus improving the prognosis of BP and the quality of patients' lives. In this article, we attempt to review previous studies from the medical literature concerning relapse and risk factors related to relapse in BP patients. Treatments found to be able to reduce or increase relapse rate were also discussed. We propose that clinicians be aware of these risk factors and manage proper treatment accordingly. Key Messages • The relapse rate of bullous pemphigoid ranges from 27.87% to 53% after disease remission, while the majority of relapses occur early (within 6 months) during remission. • Ageing, disease severity, neurological disorder, serum ECP, BAFF, IL-17, IL-23, CXCL10 and anti-BP180 antibody levels have been shown to be related to relapse, while confirmation studies are needed before using them for guidance for relapse prevention. • Longer usage of corticosteroid with a low dose, combination of immunosuppressants and intravenous immunoglobulin are helpful in lowering relapse rate.

Aim: Bullous pemphigoid (BP) is an organ-specific autoimmune bullous disease characterized by autoantibodies that target the cellular adhesion molecules BP180 and BP230. Both immunoglobulin (Ig)G and IgE are involved in the induction of subepidermal blisters. Specifically, IgE autoantibodies are presumed to be responsible for the pruritic and erythematous features of BP. Histologically, eosinophil infiltration is a prominent feature in BP. Eosinophils and IgE are mostly associated with the Th2 immune response. Th2 cytokines, particularly interleukin (IL)-4 and IL-13, are presumed to contribute to the pathology of BP. The aim of this review is to discuss the role of IL-4/13 in the pathogenesis of BP and the potential of using IL-4/13 antagonists for treatment.Methods: After searching in PubMed and Web of Science databases using ‘bullous pemphigoid’, ‘interleukin-4/13’, and ‘dupilumab’ as keywords, studies related was compiled and examined.Results: Overall, IgE, eosinophils, IL-4, and IL-13 may interact with each other in the pathogenesis of BP; these potential interactions provide clues concerning targets for molecular treatment.Conclusion: Anti-IL-4/13 treatment has been experimentally used in patients with BP, with satisfactory outcomes and few side effects. However, before this novel therapy can be approved for regular usage, further studies are needed concerning the long-term safety and systemic usage of IL-4/13 monoclonal antibody treatment in BP.

Background: ADCK2 is a member of the AarF domain-containing kinase family, which consists of five members, and has been shown to play a role in CoQ metabolism. However, ADCKs have also been connected to cancer cell survival, proliferation and motility. In this study, we investigated the role of ADCK2 in melanoma. Methods: The effect of ADCK2 on melanoma cell motility was evaluated by a scratch assay and a transwell invasion assay upon siRNA-mediated knockdown or stable overexpression of ADCK2. Results: We found that high levels of intratumoral ADCK2 and MYL6 are associated with a higher survival rate in melanoma patients. Knocking down ADCK2 resulted in enhanced cell migration of melanoma cells. Moreover, ADCK2-knockdown cells adopted a more dedifferentiated phenotype. A gene expression array revealed that the expression of ADCK2 correlated with the expressions of MYL6 and RAB2A. Knocking down MYL6 in ADCK2-overexpressing cells could abrogate the effect of ADCK2 overexpression and thus confirm the functional connection between ADCK2 and MYL6. Conclusion: ADCK2 affects melanoma cell motility, most probably via MYL6. Our results allow the conclusion that ADCK2 could act as a tumor suppressor in melanoma.

Objective: Current evidence has revealed a significant association between bullous pemphigoid (BP) and neurological diseases (ND), including stroke, but the incidence of BP autoantibodies in patients with stroke has not previously been investigated. Our study aimed to assess BP antigen-specific antibodies in stroke patients. Design: One hundred patients with stroke and 100 matched healthy controls were randomly selected for measurement of anti-BP180/BP230 IgG autoantibodies by enzyme-linked immunosorbent assay (ELISA), salt-split indirect immunofluorescence (IIF), and immunoblotting against human cutaneous BP180 and BP180-NC16A. Results: Anti-BP180 autoantibodies were found in 14 (14.0%) patients with stroke and 5 (5.0%) of controls by ELISA (p < 0.05). Sera from 13 (13.0%) patients with stroke and 3 (3.0%) controls reacted with 180-kDa proteins from human epidermal extract (p < 0.05). 11 (11.0%) of stroke and 2 (2.0%) of control sera recognized the human recombinant full length BP180 and NC16A (p < 0.05). The anti-BP180-positive patients were significantly younger than the negative patients at the time of stroke (p < 0.001). Conclusion: Development of anti-BP180 autoantibodies occurs at a higher frequency after stroke, suggesting BP180 as a relatively common autoantigen after stroke and providing novel insights into BP pathogenesis in aging.