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关键词： Biomarkers   Cytokines and Chemokines   Innate immunity  

摘要： Background: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related autoimmune diseases that often occur together. PMR and GCA may form a spectrum encompassing musculoskeletal and arterial inflammation, respectively. Glucocorticoids remain the mainstay treatment. IL-6 receptor targeting therapies have recently emerged as glucocorticoid-sparing agents in PMR and GCA, thereby highlighting the central role of IL-6 in PMR/GCA. We previously identified fibroblasts as potent sources of IL-6 [1, 2]. However, the mechanisms underlying this aberrant IL-6 production are not fully understood. Galectins, which are glycan-binding proteins, appear to be central regulators in the immune system, with galectin 3 playing a prominent pro-inflammatory role in various autoimmune diseases. While galectin 3 shows little effect on macrophages [3], it may induce expression of IL-6 by fibroblasts [4]. To date, it is unknown whether galectin 3 could contribute to the pathogenic IL-6 response in PMR/GCA. Objectives: 1) To determine serum levels of galectin 3 in patients with PMR or GCA. 2) To investigate the expression of galectin 3 in PMR- and GCA-affected tissues. 3) To examine the effects of galectin 3 on the production of IL-6 by human fibroblasts. Methods: Serum levels of galectin 3 were measured by quantitative enzyme-linked immunosorbent assay (ELISA) in patients with newly diagnosed, treatment-naive PMR (n=28) or GCA (n=29), as well as in age- and sex-matched healthy controls (n=25). Ultrasound-guided biopsies were obtained from the subacromial bursa of patients with active PMR (n=9). Temporal artery biopsies (n=9) and aortic aneurysm tissues (n=10) were obtained from patients with GCA, either at diagnosis or during aortic replacement surgery, respectively. Immunohistochemistry staining was performed for galectin 3 and scored quantitatively. Opal triple immunofluorescence staining for CD68, CD3, and galectin 3 was performed to identify the cellular source of gal

关键词： Glioblastoma   Synergism   Curcumin   2-deoxyglucose   Glial stem cells   Potentiate  

摘要： Glioblastoma is the most lethal brain tumor;despite available multimodal therapies. This poor survival is an outcome of many contributing factors the major is resistance due to inflammation and the presence of a subset of cells called glial stem-cells (GSCs). A rationale combination of drugs which act by targeting multiple mechanisms to inhibit cancer cells and GSCs would be more potent in abrogating chemoresistance. In this study, we aimed to target cancer hallmarks using a natural polyphenol in combination with 2-deoxyglucose, a glycolytic inhibitor on the heterogeneous human U-87 Glioblastoma model. The U-87 glioblastoma cells were treated with curcumin, 2-deoxyglucose and combination of both. Cell proliferation was determined by MTT assay and combination index was analyzed. Cell cycle inhibition and apoptosis were assessed by flow cytometry. The tumorigenicity of the cells was evaluated by clonogenic and soft agar assay. Migration efficacy of the cells was assessed by wound healing assay while the inflammation trigger Il-6 was assessed by ELISA. The changes in expression of molecular marker of stemness were analyzed by immuno-cytochemistry. Curcumin enhanced the cytotoxic effect of 2-deoxyglucose in GB cancer cells. The combination of CUR (20 mu M) and 2-DG (4mM) showed a synergistic effect in reducing cell viability with a combination index of less than 0.9. The polyphenol induced apoptosis, arrested the cells in S and G2/M phase of the cell cycle, inhibited anchorage dependent, anchorage independent clone forming efficacy, cell migration capacity as well as stemness while 2-DG downregulated IL-6 expression potently. Our novel combination exhibited the potential to reduce glio-oncogenesis trigger Il-6 and inhibit GSCs responsible for relapse and resistance. The study suggests that our tailor-made combination using established drugs can target multiple cancer signaling molecules to yield optimal therapeutic outcome and is the right approach to address stemness a

关键词： biological DMARD   Gastrointestinal tract   Cytokines and Chemokines   Animal Models   Comorbidities  

关键词： HLA   HLA-B*18:247   new methods   NGS   novel allele  

摘要： HLA-B*18:247 differs from the HLA-B*18:01:01:01 allele by one nucleotide substitution in codon 193 in exon 4.

关键词： Jujube polysaccharides   Ulcerative colitis   Interleukin-33   Tumorigenicity 2 suppression   MYD88  

摘要： Jujube is a medicinal herb and daily food. Polysaccharides extracted from jujube possesses immune regulatory activity. In this study, we investigated whether jujube polysaccharides (JP) could ameliorate ulcerative colitis (UC), an inflammatory disease, and explore the potential mechanism of UC. We first extracted and characterized the structure JP, using dextran sulfate sodium-induced UC mice model to verify the pharmacological function. Research proved that JP treatment could ease UC mice symptoms and pathological injury. According to transcriptomics analysis, majority genes were enriched to cytokines-cytokines receptors signal pathway. Results showed that the increasing proinflammatory cytokines in UC mice colon were declined after JP intervention. Meanwhile, the receptor of interleukin-33 (IL-33), tumorigenicity 2 suppression (ST2) and downstream protein MYD88 expression in UC mice colon were corrected by JP intervention. As a result, according to immunohistochemistry detection, JP downregulated UC mice colon T cells expression (labeled by CD3+). We further employed flow cytometry to validate that JP could suppress CD4+ high expression on Jurkat cell stimulated by IL-33. In conclusion, JP could ameliorate UC mice symptoms, the mechanism of which was related to the regulation of IL-33/ST2 axis.

关键词： Alpha-toxin   Staphylococcus aureus   Hla toxoids   Red blood cells   Vaccines   Pore-forming toxin   HS-AFM  

摘要： Alpha-toxin (Hla) variants, such as the toxoids HlaH35A, HlaH35L, and HlaH35LH48L, have been shown to lack hemolytic activity and present promising antigen sources for vaccine development against S. aureus. The His35 site is critical in the oligomerization process of Hla during transmembrane pore formation, leading to cell lysis. This study employed high-speed atomic force microscopy (HS-AFM) to image the structures of HlaH35A, HlaH35L, and HlaH35LH48L proteins on POPC/Chol lipid membranes. Single-site His35 mutations (HlaH35A, HlaH35L) could form oligomer structures, whereas the double-site HlaH35LH48L mutation resulted in the monomer state. These HS-AFM findings confirm that the region between His35 and His48 is crucial for protomerprotomer interactions essential for oligomerization and pore formation. Hemolytic activity of wild-type Hla on red blood cells (RBCs) was significantly reduced when mixed with HlaH35A, HlaH35L, or HlaH35LH48L at weight ratios 1:5 (HlaWT:toxoid) or higher. However, these toxoids exhibited weak neutralization activities at lower mixing ratios with HlaWT. The increased anti-Hla antibodies (IgG) in mice treated with these Hla toxoids have emerged as a potential treatment avenue to neutralize the hemolytic activity of the HlaWT toxin on RBCs. Serum analysis from mice injected with HlaH35A, HlaH35L, and HlaH35LH48L toxoids showed that these sera could neutralize the hemolytic activity of the HlaWT toxin. Thus, these Hla variants are promising candidates for developing supportive treatments for S. aureus infections.

关键词： Innate immunity   Registries   Descriptive Studies   biological DMAP  

关键词： HLA   HLA-DPB1*29:01:02   new methods   NGS   novel allele  

摘要： HLA-DPB1*29:01:02 differs from HLA-DPB1*29:01:01 by a single synonymous substitution in exon 2.

关键词： Disease-modifying Drugs (DMARDs)   Randomised controlled trial   Biological DMARD   Clinical Trial