课程文献中心 更多>>

关键词： IL-1   Head and neck squamous cell carcinoma   Databases   SIGIRR  

摘要： Objective: The Interleukin-1 (IL-1) family plays an important regulatory role in the development of tumors, but its function is still unclear in head and neck squamous cell carcinoma (HNSCC). Analyzing the IL-1 family can help to understand the tumor mechanism. Methods: Using GEPIA2, UALCAN, cBioprotocol and HPA databases, the IL-1 family and related genes (IL-1a, IL-1(3, IL1RN, IL1R1, IL1R2, IL1RL1, IL1RL2, IL1RAP, IL1RAPL1, IL1RAPL2, IL1F10, analyzed for their expression and prognostic relevance in HNSCC. The Kaplan-Meier, log-rank test and Spearman correlation were used to analysis. Results: In tumors, IL-1a, IL-1(3, IL1R1, IL1RL1, IL1F10, IL33, CASP1, and AIM2 are highly expressed, while IL1RN, IL1RAPL1, IL1RAPL2, IL18BP, IL18R1 and IL18RAP are poorly expressed. IL-1a, IL1RAP, and IL1RAPL2 were prognostic risk factors in at least two databases, while IL18RAP, IL36A, and SIGIRR were prognostic protective factors. SIGIRR was confirmed in all three databases. Compared to HPV- tumors, IL18RAP and SIGIRR are highly expressed in HPV+ tumors. In addition, IL-1a, IL-1(3, IL1RL2, IL1RAP were negatively correlated with CD8A/B expression, expression.

关键词： DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS   DERMATOLOGY   Pharmacovigilance   ALLERGY AND IMMUNOLOGY   PARASITOLOGY  

摘要： Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but severe drug hypersensitivity reaction with potentially life-threatening consequences. It is characterised by fever, extensive maculopapular exanthema, lymph node enlargement, abnormal blood cell counts, and organ-related complications. Diagnosis can be challenging due to incomplete or non-specific symptoms, and it can sometimes manifest as a purely systemic disease. Discontinuation of the causative drug is essential. Treatment may involve corticosteroids and supportive care. Genetic screening for specific markers, such as human leucocyte antigen (HLA)-A*68, A11:01, and A29:02, can help identify individuals at risk for severe reactions to benznidazole, a drug used to treat Chagas disease. This case report describes the rarity and severity of DRESS syndrome, underscoring the potential benefit of genetic screening to prevent adverse reactions in patients with Chagas disease.

关键词： Tim-3   MHC-II   Ubiquitination   MARCH8   Immune evasion  

摘要： We previously reported that Tim-3, an immune checkpoint inhibitor, inhibits MHC-II expression, but the molecular mechanisms involved and the implications for antiviral immunity remain to be determined. Here, we found that during H1N1 infection, Tim-3 inhibits MHC-II expression in macrophages/microglia in vitro. Tim-3 interacts with MHC-II via its intracellular tail and induces proteasomal dependent degradation of MHC-II. In H1N1 infected macrophages/microglia, Tim-3 promotes the K48-linked ubiquitination of MHC-II via MARCH8, a ubiquitin E3 ligase that can be upregulated by Tim-3. In H1N1 infected mice, specific knockout of Tim-3 in macrophages leads to a decreased viral load, attenuates tissue damage and increases the survival rate. We have thus identified a novel mechanism by which Tim-3 mediates virus immune escape. Manipulating the Tim-3-MHCII signaling pathway may provide a novel treatment for viral infections.

关键词： Chicken   Genetic lines   MHC class I expression   MHC repertoire  

摘要： The Major Histocompatibility Complex (MHC) is a cluster of genes with primarily immune-related functions. The MHC class I genes are responsible for self- versus non-self-recognition and viral antigen presentation to T lymphocytes. The chicken MHC class I protein binds its cognate antigen(s) over a repertoire spectrum ranging from promiscuous (generalist) to fastidious (specialist). The MHC class I protein expression level at the cell surface is inversely related to the promiscuity of its peptide-binding repertoire. In our study, erythrocytes from 6 diverse and highly inbred lines of chickens, a closed broiler line, and a highly advanced intercross line were evaluated for MHC class I antigen expression level by flow cytometry using monoclonal antibodies to chicken MHC class I molecules. In chickens, the B blood group antigens include the MHC class I antigen expressed from the MHC. Thus, the B blood group has historically been used as a genetic marker for Marek's Disease virus response. Erythrocytes of the inbred lines were blood typed by serology. The B21 blood type is widely recognized as relatively resistant to Marek's disease and regarded as an MHC class I generalist with low MHC class I expression. The Spanish line, which types serologically as B21.1 (similar to B21), was the lowest MHC class I expressing line. The two sublines (B5.1 and B15.2) of the Fayoumi breed, which significantly differed in their MHC class I expression, also differ in response to multiple pathogens. These defined genetic lines of chickens, with distinct MHC class I expression levels, provide an excellent platform to further interrogate the hypothesis of high or low MHC class I expression (antigenic specialists or generalists, respectively) determining diverse responses to pathogens.

关键词： MFGE8   ZBTB7A   Gastric cancer   EMT   IL-6/JAK/STAT3 signaling  

摘要： Objective: Gastric cancer is malignant cancer with high morbidity and mortality worldwide. Milk fat globule EGF and factor V/VIII domain containing (MFGE8) was involved in many cancers. Nevertheless, the role of MFGE8 in gastric cancer remained indistinct. To probe the role of MFGE8 in gastric cancer and further explore the regulating mechanism. Methods: GEPIA was employed for analysis of MFGE8 expression and survival of gastric cancer patients. MFGE8 expression in gastric cancer was determined by immunohistochemistry, PCR, and western blot. The effect of MFGE8 on gastric cancer cells were evaluated by a series of cell function experiments. The mechanism of MFGE8 on gastric cancer was analyzed by GSEA and verified by in vitro and in vivo experiments. Results: MFGE8 was over-expressed in gastric cancer. Silence of MFGE8 suppressed cell viability, proliferated ability, migrated and invasive ability, and EMT, but accelerated cell apoptosis. The opposite results were obtained in MFGE8-overexpressed gastric cancer cells. Zinc finger and BTB domain containing 7 A (ZBTB7A) was a transcription factor of MFGE8. ZBTB7A overexpression eliminated the effect of MFGE8 on gastric cancer cells. MFGE8 activated the IL-6/JAK/STAT3 signaling. Inhibition of IL-6/JAK/STAT3 signaling by Stattic (pathway inhibitor) could eliminate the promoting effect of MFGE8 on IL-6/JAK/STAT3 signaling. In addition, MFGE8 shRNA inhibited tumor growth. Conclusion: MFGE8 promoted cell proliferation, EMT progress, and tumor growth of gastric cancer by activating the IL-6/JAK/STAT3 signaling.

关键词： Mucosal barrier   Goblet cell   Tight junction   Intestinal microbiota   Oxidative stress   Apoptosis   Inflammation  

摘要： The potential role of interleukin-34 (IL-34), an important cytokine that regulates intestinal function in mammals, is currently being explored in the context of fish intestinal diseases. In this study, we assessed the preventive potential of recombinant Megalobrama amblycephala IL-34 (rMaIL-34) protein in bacterial enteritis. MaIL-34 exhibited conserved structural and evolutionary features with teleost IL-34 and was found to be involved in the intestinal immune response to Aeromonas hydrophila infection. Furthermore, treatment with rMaIL-34 significantly improved the survival rate of M. amblycephala following A. hydrophila infection and alleviated the symptoms of enteritis in these fish. In vivo, rMaIL-34 enhanced goblet cell proliferation and mucus layer tightness, thereby maintaining mucosal integrity following infection. Additionally, rMaIL-34 attenuated the decrease in ZO-1 expression and inhibited the increase in intestinal permeability caused by A. hydrophila, thereby reducing the concentrations of DAO and D-LAC in the plasma. Furthermore, rMaIL-34 suppressed oxidative stress, apoptosis, and inflammatory responses triggered by A. hydrophila, thereby strengthening the immune barrier. At the microbiological level, rMaIL-34 contributed to improved intestinal microbiota distribution and enhanced the functions of intestinal microbiota in terms of energy metabolism, antibiotic biosynthesis, and oxidative phosphorylation. This study reveals, for the first time, the multiple roles of fish IL-34 in resistance to bacterial enteritis and paves the way for the development of rMaIL-34 as an immunotherapy for bacterial enteritis in fish.

关键词： inflammatory factors   postmenopausal osteoporosis   circulating metabolites   Mendelian randomization   mediation  

摘要： Objectives: This study aimed to explore the relationship between circulating metabolites and postmenopausal osteoporosis (PMOP) and to assess the mediating role of inflammatory factors. Methods: Utilizing summary-level data from genome-wide association studies (GWAS) and employing a Mendelian Randomization approach, a two-sample MR analysis was conducted to assess the relationship between circulating metabolites and PMOP. Additionally, a two-step MR was used to quantify the mediating impact of inflammatory factors on the effect of circulating metabolites on PMOP. Results: The results revealed a significant association between certain metabolites and the risk of PMOP, notably the ratio of free cholesterol to total lipids in very large VLDL particles (OR: 1.399, 95% CI: 1.002-1.954, p = 0.048) and IL-16 (OR: 0.773, 95% CI: 0.608-0.983, p = 0.036). IL-16 was found to partially mediate the impact of circulating metabolites on PMOP, with a mediation effect of 10.4%. Conclusion: This study underscores the crucial role of circulating metabolites and inflammatory factors in PMOP pathogenesis. A causal relationship between circulating metabolites and PMOP was established, with IL-16 mediating some effects. These findings hold promise for clinical applications in early detection, personalized medicine, and the identification of therapeutic targets for PMOP.

关键词： TNF   anti‐TNF therapy   chronic inflammation   humans   immunomodulation   inflammatory disease   melatonin  

摘要： Tumor necrosis factor (TNF) is a biomarker of inflammation whose levels are elevated in patients with several diseases associated with dysregulation of the immune response. The main limitations of currently used anti-TNF therapies are the induction of immunodepression, which in many cases leads to serious adverse effects such as infection and cancer, and the inability to cross the blood-brain barrier in neuroinflammatory conditions. Melatonin, in addition to being a chronobiotic compound, is widely known for its antioxidant and immunomodulatory capacity to control inflammatory processes in different pathological contexts. The aim of the present review is to address human-based studies that describe the effect of melatonin on TNF production. The review includes all the articles published in PubMed databases until April 15, 2024. After depuration, 45 studies were finally included in the review, 23 related to the in vitro action of melatonin in human cells and 22 in vivo studies in humans. Most of the data reviewed support the idea that melatonin has an immunosuppressive effect on TNF levels, which, together with its low toxicity profile, low cost, and ability to cross the blood-brain barrier, points to melatonin as a potential anti-TNF therapy. Therefore, improving our knowledge of the action of melatonin in regulating TNF through appropriate clinical trials would reveal the true potential of this molecule as a possible anti-TNF therapy.

关键词： Type 1 diabetes   beta-cell autoimmunity   SNPs   GWAS   HLA   gene  

摘要： Type 1 diabetes mellitus (T1D) is a complicated illness marked by the death of insulin-producing pancreatic beta cells, which ultimately leads to insulin insufficiency and hyperglycemia. T lymphocytes are considered to destroy pancreatic beta cells in the etiology of T1D as a result of hereditary and environmental factors. Although the latter factors are very important causes of T1D development, this disease is very genetically predisposed, so there is a significant genetic component to T1D susceptibility. Among the T1D-associated gene mutations, those that affect genes that encode the traditional Human Leukocyte Antigens (HLA) entail the highest risk of T1D development. Accordingly, the results of decades of genetic linkage and association studies clearly demonstrate that mutations in the HLA genes are the most associated mutations with T1D. They can, therefore, be used as biomarkers for prediction strategies and may even prove to be of value for personalized treatments. Other immunity-associated genetic loci are also associated with higher T1D risk. Indeed, T1D is considered an autoimmune disease. Its prevalence is rising globally, especially among children and young people. Given the global rise of, and thus interest in, autoimmune diseases, here we present a short overview of the link between immunity, especially HLA, genes and T1D.

关键词： Qu-Shi-Xie-Zhuo decoction   Gouty arthritis   NLRP3   IL-1 beta  

摘要： Background: Gout is a common type of arthritis marked by monosodium urate (MSU) crystal deposition in joints, triggering an inflammatory response. Qu-Shi-Xie-Zhuo (QSXZ), a traditional Chinese medicine (TCM) formula, has been clinically used for the treatment of gouty arthritis (GA). Purpose: The study sought to examine the impact of QSXZ on GA and to delve into the pharmacological mechanisms that underlie its effects. Methods: The chemical constituents of QSXZ were analyzed through UPLC-MS. MSU-induced acute gouty arthritis (AGA) and subcutaneous (SC) air pouch models in mice were employed to evaluate the anti-inflammatory properties of QSXZ and its primary active compound, Cryptotanshinone (CTS). To investigate the therapeutic mechanisms of QSXZ, we used MS-based network pharmacology, transcriptomic analysis, molecular docking and multiscale bioassays. Results: Treatment of QSXZ revealed a significant reduction of inflammatory cell infiltration and the expression of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin -1 beta (IL-1 beta). Based on UPLC/MS/MS results, 49 components were considered the active ingredients of QSXZ. Network pharmacology analysis indicated that QSXZ regulates multiple inflammation-related pathways. Subsequent transcriptomic analysis showed that QSXZ regulates gene expression of S100A8 and S100A9. Our investigation observed an increased expression of S100A8 and S100A9 in monocytes derived from gout patients. Molecular docking and molecular dynamics simulation analysis revealed the binding pattern and interaction between QSXZ active compound CTS and S100A8/A9, and subsequent surface plasmon resonance (SPR) and cell thermal shift assay (CETSA) experiments verified the direct interaction between them. To investigate the mechanisms of action, we conducted RT-PCR, Western blotting, immunohistochemistry, flow cytometry, and measured the inflammatory response. Our findings highlight the pathogenic role of S100A8/A9