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关键词： Biomarkers   Cytokines and Chemokines  

关键词： Randomised controlled trial   Clinical Trial   Rare/orphan diseases   biological DMARD  

关键词： allergy   anti-inflammatory cytokine   eczema   parthenium dermatitis   sunshine vitamin  

摘要： Introduction The imbalance between pro- and anti-inflammatory mediators was suggested to be a contributory factor to the manifestations of allergic parthenium dermatitis. Inadequate circulating vitamin D and IL-10 levels can significantly influence the course of this allergic dermatitis. Objective The objective was to study the association between circulating IL-10 levels and vitamin D status in patients with parthenium dermatitis. Materials and methods Patients attending the dermatitis clinic were screened for eligibility, and 88 individuals were recruited. A total of 101 unrelated healthy volunteers were included as controls. Circulating IL-10 cytokine and vitamin D levels were determined in both groups and compared. Results A higher prevalence of vitamin D deficiency (79.5% vs. 59.4%, P = 0.000315) and lower IL-10 levels (6.84 vs. 9.04 pg/ml, P < 0.0001) were observed in the patient group compared to healthy controls. The vitamin D-deficient patients were also found to have significantly lower IL-10 levels. A significant positive correlation between vitamin D and IL-10 levels was observed among individuals with allergic dermatitis. Lower vitamin D and IL-10 levels were associated with higher Dermatology Life Quality Index (DLQI) scores. Conclusion Lower circulating vitamin D and IL-10 levels, observed in patients with parthenium dermatitis, significantly impacted their quality of life. Assessing plasma IL-10 levels could be a potential biomarker for evaluating disease severity and treatment efficacy. Correcting vitamin D deficiency may improve IL-10 levels and enhance treatment outcomes.

关键词： HLA-DQB1*03   new alleles   next-generation sequencing  

摘要： Genomic sequences of the HLA-DQB1*03:01:01:70, -DQB1*03:01:01:77, -DQB1*03:02:01:28, -DQB1*03:02:01:29, and -DQB1*03:03:02:19 alleles.

关键词： TNF   Metabolic disorders   Liver diseases   Inflammatory response   Therapeutic implication  

摘要： Tumor necrosis factor (TNF) is identified as a pro-inflammatory cytokine critical to the pathology of liver disease. In the carbohydrate metabolism, TNF has been demonstrated to impede the insulin signaling pathway, thereby precipitating glucose intolerance and insulin resistance. In lipid metabolism, TNF upregulates genes implicated in fatty acid synthesis, resulting in increased lipid accumulation within the liver. In amino acid metabolism, TNF has shown to promote the gene expression for amino acid catabolism, leading to decreased protein synthesis. Additionally, TNF stimulates the production of other chemokines and inflammatory cytokines that can further exacerbate liver injury. Overall, TNF is crucial in developing liver diseases by disrupting various metabolic pathways in the liver, causing insulin resistance, lipid accumulation, and decreased protein synthesis. This review summarizes the present understanding of TNF's role in the regulation of carbohydrate, lipid and amino acid metabolism in liver disease together with its potential therapeutic implications.

关键词： Pancreatic Cancer   Macrophages   Tumor Immune Microenvironment   TREM2   Single-Cell RNA-Sequencing   Genetically Engineered Mouse Models  

摘要： BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) has a complex tumor microenvironment enriched with tumor-associated macrophages. Triggering receptor expressed on myeloid cells 2 (TREM2) is highly expressed by a subset of macrophages in PDAC. However, the functional role of TREM2 in PDAC progression remains elusive. METHODS: We generated a novel transgenic mouse model (KPPC;Trem2-/-) that enables the genetic depletion of TREM2 in the context of spontaneous PDAC development. Single-cell RNA-sequencing analysis was used to identify changes in the tumor immune microenvironment on TREM2 depletion. We evaluated the impacts of TREM2 depletion on the tumor immune microenvironment to elucidate the functions of TREM2 in macrophages and PDAC development. RESULTS: Unexpectedly, genetic depletion of TREM2 significantly accelerated spontaneous PDAC progression and shortened the survival of KPPC;Trem2-/- mice. Single-cell analysis revealed that TREM2 depletion enhanced proinflammatory macrophages and exacerbated pathogenic inflammation in PDAC. Specifically, TREM2 functions as a key braking mechanism for the NLRP3/nuclear factor-kB/ interleukin (IL)-1,6 inflammasome pathway, opposing to microbial lipopolysaccharide as the key activator of this pathway. TREM2 deficiency orchestrated with microbial lipopolysaccharide to trigger IL-1,6 upregulation and pathogenic inflammation, thereby fueling PDAC development. Notably, IL-1,6 inhibition or microbiome ablation not only reversed the accelerated PDAC progression caused by TREM2 depletion, but also further inhibited PDAC progression in the TREM2-depleted context. CONCLUSIONS: TREM2 depletion accelerates tumor progression by enhancing proinflammatory macrophages and IL-1,6-medi-ated pathogenic inflammation in PDAC. The accelerated tumor progression by TREM2 depletion can be reversed by blocking IL-1,6-associated pathogenic inflammation.

关键词： Disease-modifying drugs (DMARDs)   Descriptive studies   Infection   Biological DMARD  

关键词： Interdisciplinary research   Rare/orphan diseases  

关键词： Interleukin-22   Inflammatory bowel diseases   Pharmacotherapy   Biologics   Intestinal barrier function  

摘要： Background IL-22 facilitates mucosal healing by directly inducing epithelial regeneration and barrier integrity, which is essential for achieving remission and thereby treating inflammatory bowel disease. Aims Here, we evaluated efficacy of a novel lipidated IL-22 alone and in combination with immunomodulatory agents in addressing chronic dextran sodium sulfate (DSS)-induced colitis in mice and demonstrated action of IL-22 on mucosal healing. Methods Mice were treated with DSS, followed by various doses of lipidated IL-22, anti-TNF antibody, fingolimod, or anti-mouse alpha 4 beta 7 integrin antibody. Additionally, gene expression was determined in colonic biopsies from ulcerative colitis patients to assess effects of IL-22 stimulation. Results Lipidated IL-22 significantly improved all aspects of chronic DSS-induced colitis in mice, with dose-dependent efficacy. Combinations of a range of immunomodulatory agents with lipidated IL-22 showed further additive reductions in disease activity, significantly greater than those of monotherapies. Immunohistochemistry revealed that lipidated IL-22 increased epithelial cell proliferation and reduced CD3+ T-cell infiltration, indicating enhanced mucosal healing. This was further supported gene expression data from colonic biopsies from ulcerative colitis patients after IL-22 stimulation. Conclusions Given the challenges in achieving long-term remission in IBD due to inflammation and mucosal damage, lipidated IL-22 presents a promising treatment option that directly promotes mucosal healing, unlike traditional immunomodulatory therapies.

关键词： Cytokines and Chemokines   Autoantibodies