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关键词： Colon cancer   Obesity   Interleukin-36   Inflammation   Visceral adipose tissue  

摘要： Dysfunctional adipose tissue (AT) in the context of obesity promotes a chronic inflammatory state, associated with worse cancer progression and prognosis. Interleukin (IL)-36 gamma is a proinflammatory factor increased in obesity. The aim was to analyse the role of IL-36 gamma in colon cancer (CC) development in patients with obesity. Samples obtained from 74 volunteers (27 with normal weight (NW) and 47 with obesity (OB)) were used in a case-control study. Participants were also subclassified according to the presence of CC (45 without and 29 with CC). HT-29 cells were treated with pro-inflammatory factors, adipocyte conditioned media (ACM) and IL-36 gamma to evaluate the expression levels of inflammation- and extracellular matrix (ECM) remodelling-related molecules. Increased gene expression levels of IL36G and IL36R in visceral AT from patients with OB and CC were found. Moreover, mRNA levels of IL36G were significantly associated with the gene expression levels of its receptor and relevant genes involved in AT inflammation (ASC, IL1B and NLRP6). Consistently, IL36G expression was upregulated by hypoxia, inflammation-related factors (LPS, TNF-alpha and leptin) and by the adipocyte secretome from patients with obesity in HT-29 cancer cells. Furthermore, we revealed that IL-36 gamma increased the gene expression levels of inflammation-related genes (IL36G, IL1 A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells. Increased gene expression levels of IL36G in VAT from patients with OB and CC may promote a pro-inflammatory microenvironment favourable for tumour progression and migration.

关键词： bone health   fractures   IL-6 inhibitors   mortality   osteoporosis   rheumatoid arthritis   TNF-alpha inhibitors  

摘要： BackgroundRheumatoid arthritis (RA) significantly impacts bone health, leading to osteoporosis and increased fracture risks. This study aims to compare the effects of TNF-alpha and IL-6 inhibitors on the incidence of fractures, osteoporosis, and mortality among RA *** conducted a retrospective cohort study using the TriNetX database, spanning from January 1, 2015, to December 31, 2022. The adult patients diagnosed with Rheumatoid Arthritis (RA) were identified and divided into two groups of new users of TNF-alpha and IL-6 inhibitors. Patients with prior fractures or who switched treatments post-index were excluded. Patients baseline characteristics were adjusted with propensity score matching (PSM). We compared TNF-alpha and IL-6 inhibitor cohorts in terms of fracture and osteoporosis incidence, and mortality employing Cox proportional hazards models for risk assessment, adjusting for potential *** study included 2158 RA patients each in the TNF-alpha and IL-6 cohorts after PSM. Both cohorts had 71 osteoporosis/fractures during a 1-year follow-up. The adjusted HR (95% CI) was 0.987 (0.711-1.372) comparing TNFi versus IL-6is initiators. Similar results were shown stratified by age, sex, and steroid usage. However, all-cause mortality was significantly lower in the TNF-alpha cohort with an adjusted HR (95% CI) of 0.247 (0.114-0.536). Subgroup analyses showed the TNF-alpha cohort was associated with lower all-cause mortality among patients older than 65, male patients, and steroid ***-alpha and IL-6 inhibitors exhibit comparable effects on the risk of osteoporosis and fractures among RA patients. Notably, TNF-alpha inhibitors may offer advantages in reducing all-cause mortality, warranting further investigation.

关键词： Renal System   Epitranscriptomics   epigenetics   and genetics   Cytokines and Chemokines   Prognostic factors   Biomarkers  

关键词： Innate immunity   Genetics   Biomarkers  

关键词： MHC class I   MHC class II   Salmonid fish   Polymorphisms  

摘要： Oncorhynchus masou formosanus (Formosan landlocked salmon) is a salmonid fish endemic to Taiwan with a critically endangered extant small population in high-altitude mountain streams. To begin to assess the remaining genetic diversity we characterized the single classical MHC class I (UBA) and MHC class II (DAA and DAB) genes of teleost fish in a small cohort of eight randomly collected O. m. formosanus individuals whose relationship is unknown. We focused on the exons encoding the peptide binding regions of these complexes as they are considered the most highly polymorphic regions in vertebrate genomes. Surprisingly, the DAA and DAB genes appeared homozygous and identical among all eight fish indicating that the encoded class II complex is monomorphic. In contrast, three distinct UBA alleles were discovered with one dominant allele present in every single individual. Notably, 75 % were heterozygous indicating a selective advantage of heterozygosity at this locus. Lastly, our MHC alleles differ from those present in the genome of the closely related Japanese O. m. masou, suggesting that the loss of DAA/DAB diversity and the emergence of the dominant UBA allele occurred after their populations were isolated. Together we discovered residual genetic diversity at the classical MHC class I locus in O. m. formosanus and maintaining this allelic variation unlike the homozygous DAA and DAB genes is likely important for its survival in its geographically restricted unique habitat.

关键词： Cytokines and Chemokines   Fibroblasts   Adaptive immunity   Enthesitis  

摘要： Background: The enthesis is a critical target tissue in spondyloarthritis (SpA), characterised by inflammation and post-inflammatory osteogenesis [1]. Multipotential stromal mesenchymal stem cells (MSCs) with multilineage differentiation capacity, including stromal immune regulation, may play a crucial role in immune regulation and tissue repair at the enthesis. Although our prior work demonstrated that entheseal MSCs regulate T cell activation and proliferation via the CD39/CD73 ectonucleotidase pathway [2]. The effect of MSCs on T-cell IL-17 and TNF cytokine regulation, central to SpA pathogenesis, remains unclear. Objectives: To investigate the immunomodulatory effects of MSCs on CD4 + CD25 − T cells, focusing on their influence on IL-17A, IL-17F, TNF and other cytokines production under co-culture conditions. Methods: MSCs were isolated from healthy soft tissue enthesis (spinous processes and interspinous ligament regions) and bone marrow aspirates (BM-MSCs). Cells were expanded to passages 3–5 and co-cultured with CD4 + CD25 − T cells stimulated with CD3/CD28 beads at a 1:1 ratio for 5 days (n=5). T cell proliferation was assessed via CFSE staining, while IL-17A and IL-17F levels were quantified using intracellular staining and ELISA (n=7). TNF-α, IFN-γ, and IL-22 cytokines were measured using LegendPlex. RNA-seq was performed on stromal MSCs post-co-culture to identify differentially expressed genes and pathways (n=3). Additional RNA-seq experiments analysed MSCs exposed to IL-17A + TNF versus TNF alone for 48 hours (n=3). Results: MSC co-culture suppressed T cell proliferation by 80% (P < 0.0001), demonstrating their strong immunosuppressive capacity. This suppression was accompanied by significant reductions in TNF-α, IFN-γ, and IL-22 levels (P < 0.001). However, a paradoxical effect was observed, with IL-17A production significantly upregulated in co-cultured T cells (P < 0.0001), while IL-17F levels were markedly reduced (P = 0.0014). Flow cytometry reveal

关键词： Biomarkers   biological DMARD   omics  

关键词： Biomarkers   Gastrointestinal tract   biological DMARD  

关键词： MDS   IL-1 beta   Exosomes   Macrophage   Progression  

摘要： Background: Exosomes are extracellular vesicles with a membrane structure that play important roles in intercellular communication, material transport and cellular *** previous study found that exosomes can affect the biological functions of MDS cell lines, but the mechanism of action has not been *** are one of the major innate immune cells that produce a variety of inflammatory cytokines and perform multiple biological functions in the tumor microenvironment (TME).The role of tumor cell-derived exosomes on macrophages and in the progression of MDS is rarely reported,therefore, the aim of our study was to investigate the effect of exosomes on macrophages and the effect of cytokines secreted by macrophages on MDS cells, with a view to exploring the role and mechanisms of exosomes and macrophages in the progression of MDS. Methods: Changes in cytokine content in peripheral blood of MDS patients were detected. The cytokine concentration in the growth environment of MDS cell lines was changed to observe the changes in the biological functions of MDS cell *** induction of human monocyte cell line (THP-1) into THP-1-M phi macrophages with Phorbol 12-myristate 13-acetate (PMA), the macrophages (M phi) were then co-cultured with MDS cell line exosomes extracted by ultrafiltration with THP-1-M phi to observe macrophage (M phi) *** cytometry was used to detect the changes in cytokine content released by macrophages before and after the addition of exosome inhibitors, and the changes in the biological function of MDS cell lines during this *** and protein levels of significantly changed cytokine-related signaling pathways were detected using Q-PCR and WB. Results: IL-1 beta levels were significantly higher in the peripheral blood of MDS patients compared to *** exosomes extracted by ultrafiltration can be taken up by macrophages, which can promote the release of IL-1 beta from THP-1-M phi cells, and promot

关键词： Adaptive immunity   Biomarkers   Cytokines and Chemokines