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摘要： Dear Editor, We are delighted by the interest in our publication “Immunomodulatory soluble HLA-G and HLA-E are associated with rapidly deteriorating CLAD and HCMV viremia after lung transplantation” and want to thank Brugière and colleagues for th...

关键词： Cytokines and Chemokines   Innate immunity   Animal Models  

关键词： biological DMARD   Cytokines and Chemokines  

摘要： Background: Eosinophilic granulomatosis with polyangiitis (EGPA) was first described in 1951 as a form of disseminated necrotizing vasculitis characterized by extravascular granulomas in patients with asthma and tissue hypereosinophilia. Serum anti-neutrophil cytoplasmic antibodies (ANCA), typically directed against myeloperoxidase (MPO), and rheumatoid factor (RF) are frequently detected, strongly suggesting an autoimmune component to the disease. Eosinophilia is a hallmark feature of EGPA, and recently, mepolizumab (MPZ)—a monoclonal antibody targeting interleukin (IL)-5, which regulates eosinophil progenitor cell proliferation and activation—has been approved as a treatment option. While Th2 responses are recognized as central to the pathogenesis of EGPA, the roles of Th1 and Th17 responses remain less well understood. Additionally, cytokines upstream of IL-5, including “alarmins” such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), have gained interest in EGPA research. Objectives: To elucidate the pathogenesis of EGPA through (1) a cross-sectional analysis to quantify multiple humoral factors in the serum of untreated patients with EGPA and explore their interrelationships and (2) a longitudinal analysis to assess the behavior of these factors before and after the initial treatment, as well as after MPZ treatment. Methods: We included 27 patients with EGPA (15 newly diagnosed) diagnosed at the University Hospital between May 2020 and April 2024. For comparison, 26 newly diagnosed patients with SLE or those with exacerbated SLE served as the control group. EGPA cases were classified according to the 1990 American College of Rheumatology (ACR) classification criteria. SLE cases were classified according to the 2019 European Alliance of Associations for Rheumatology/ACR classification criteria. Serum levels of eotaxin, fibroblast growth factor basic, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon gamma

关键词： Propolis alcoholic extract   Osteoblast   Hypoxia   Cell proliferation  

摘要： Numerous studies have demonstrated the significant role of propolis in various biological processes, including inflammation and the repair of endothelial and bone tissues. The cascade of inflammation, proliferation, and tissue remodeling characterizes the injury site. Remarkable progress has been made in the field of alternative medicine with the utilization of propolis. In this study, we specifically investigated the effects of alcoholic extract of propolis on cell adhesion, survival, remodeling, and differentiation pathways in osteoblasts. Our findings revealed the activation of survival proteins such as AKT, ERK, and phosphorylated ERK during the adhesion phase, while interleukins, specifically IL-6 and TNF, exhibited increased expression during cell differentiation. Furthermore, treatment with propolis extract led to enhanced activity of metalloproteinases (MMP9 and MMP2) and HIF-1 alpha, a crucial activator of angiogenesis and bone remodeling. It was observed that the alcoholic propolis extract stimulated cell proliferation, differentiation, and repair, with key molecules involved in these processes including pro-inflammatory factors IL-6 and TNF alpha, as well as HIF-1, MMP2, and BMP7 proteins. Collectively, these factors induced an initial state of proliferation followed by differentiation and repair. Therefore, the alcoholic extract of propolis holds promise as a potential therapeutic agent, particularly in cases involving tissue repair. Nevertheless, further comprehensive in vitro and in vivo studies targeting this area are necessary to advance our understanding.

关键词： psoriasis   keratinocytes   IL-17A   heat shock protein 70  

摘要： Psoriasis, which is characterized by keratinocyte hyperproliferation, presents complex management challenges. The heat shock protein 70 (HSP 70) family, which is essential in protein folding and stress responses, also modulates inflammation, suggesting its therapeutic potential in inflammation-driven diseases. The present study aimed to explore the effects of brevilin A, a natural compound known to alleviate imiquimod-induced psoriasis, on HSP 70 expression and proinflammatory cytokine production in HaCaT cells stimulated with IL-17A. An HSP 70 inhibitor was used to determine its role in cytokine regulation, and the effect of brevilin A on skin pathology in mice was examined via immunohistochemistry and hematoxylin and eosin staining. The results revealed that brevilin A markedly decreased IL-6 and IL-8 levels after IL-17A stimulation at both 9 and 24 h in HaCaT cells, and increased HSP 70 and HSP 90 expression levels. Notably, the brevilin A-induced suppression of cytokine levels was reversed when cells were co-treated with the HSP 70 inhibitor. In vivo, brevilin A enhanced HSP 70 expression and reduced skin hyperproliferation. These findings suggested that brevilin A may modulate HSP 70 expression and dampen the inflammatory response induced by IL-17A, indicating its potential as an innovative treatment for psoriasis.

关键词： Mycobacterium tuberculosis   Tubercular serpiginous–like choroiditis   Molecular mimicry   IL   interleukin   MTB   Mycobacterium tuberculosis   PR   photoreceptor   RHO   rhodopsin   RMSD   root mean square deviation   RPE   retinal pigment epithelium   TB   tuberculosis   TBU   TB uveitis   TLR   Toll-like receptor  

摘要： Purpose: The presentation of posterior ocular tuberculosis (TB) varies greatly along with the need for immunomodulatory therapy to control inflammation. In this study, we explore the potential mechanisms and pathways for autoimmune-related inflammation in ocular TB using molecular mimicry-based mathematical modeling. Design: Computational protein analysis. Methods: Twenty-three TB-related proteins, including ESAT-6 subgroup proteins, and 23 retinal ganglion cells, photoreceptor, and retinal pigment epithelium (RPE) cellular proteins were included in this study. The 3-dimensional structure and sequence of the TB AG proteins were compared to the above-mentioned retinal, photoreceptor, and RPE cellular proteins. All retinal proteins were obtained from the UniProt database. The sequence and 3-dimensional structure of TB-related proteins and retinal proteins were compared with the TM-align server. The interactions of proteins showing significant similarity (template modeling score above 0.5, root mean square deviation [RMSD] value below 5A degrees) with cytokines (interleukin [IL]6, IL10, IL12A, IL12B, TLR2, TLR3, and TLR4) were analyzed. Autoimmune and autoinflammation-related protein-receptor interaction of similar proteins was assessed using the CABS-dock web server. Main Outcome Measures: Template modeling score, structural alignment accuracy using RMSD value, protein-cytokine interaction. Results: We detected a high level of structural similarity between ESAT-6 (EsxA, EsxB) proteins and rhodopsin, HSPA1A, RPE-related BEST-1, ABCC-1, ABCC-4, ABCC-5, SLC47A1, SLC1A5, SLC38A7, SLC6A6, SLC5A6, LAT-1, and SLC16A1 proteins. When we evaluated the likelihood/potential to stimulate an immune response via a cytokine release, TLR-2 (most common), TLR-3, and TLR-4, which are highly susceptible to Mycobacterium tuberculosis ESAT-6 (ESXA and ESXB) proteins, showed a potential receptor-protein interaction with retinal proteins. Moreover, some eye-related proteins had the capacity

关键词： biological DMARD   Disease-modifying Drugs (DMARDs)  

关键词： Arthritis   Biomarkers   Chalcone   Cytokines   Inflammation   Oxidative stress  

摘要： Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and chronic pain due to the degradation of subchondral bone and the loss of cartilage function. The present study was designed to evaluate the activity of 1N,N-dimethyl chalcone (DGCHAL) against RA. A primary 28-day investigation was conducted on adjuvant-induced arthritic rats with DGCHAL (10 mg/kg, 20 mg/kg, and 30 mg/kg) and methotrexate (STDMTX). The therapeutic effect was estimated on the basis of measurements of paw diameter, fluctuations in body weight, oxidative stress biomarkers, and hematological parameters. In addition, the study sought to quantify the expression of key cytokines, including TNF alpha, IL-6, IL-10, IL-1 beta, and NF kappa beta, using qRT-PCR and ELISA techniques. Treatment with DGCHAL significantly restored the paw volume, body weight, arthritis-induced anemia, and leukocyte count. The tested compound remarkably downregulated the expression of COX-2, TNF alpha, IL-6, IL-1 beta, and NF kappa B and upregulated the expression of IL-10. The treatment groups increased the activities of SOD, CAT, and GSH, whereas they reduced the formation of MDA and NO as compared to the arthritic group. These findings provide an evident basis for the anti-arthritic potential of DGCHAL in a chronic arthritis rat model and should be further studied for dosage form design.