课程文献中心 更多>>

关键词： Interstitial lung disease   Rheumatoid arthritis   Interleukin-22   High-resolution computed tomography  

摘要： Background Interstitial lung disease (ILD) is a common and severe extra-articular manifestation of rheumatoid arthritis (RA), contributing significantly to patient morbidity and mortality. Recent studies have identified interleukin-22 (IL-22) as a cytokine implicated in immune regulation and fibrotic processes in various organs, including the lungs. However, its specific role in RA-associated ILD (RA-ILD) remains unclear. Understanding this relationship may offer insights into novel biomarkers and therapeutic strategies. Methods A cross-sectional study was conducted on 20 RA patients with ILD, 20 RA patients without ILD, and 20 age and gender-matched healthy controls. ILD was confirmed via high-resolution chest computed tomography (HRCT). Serum IL-22 concentrations were measured using enzyme-linked immunosorbent assay. Disease activity was assessed using the DAS28 score, ESR, CRP, and ILD severity were analyzed. Results IL-22 concentrations were considerably higher in RA-ILD patients (1309;IQR 943.85-1600) in comparison to RA patients without ILD (321;IQR 213.3-449.4) and healthy controls (64.78;IQR 54.3-72.08) (p < 0.001). IL-22 levels correlated positively with disease activity score 28 (DAS28), ESR, and CRP. Elevated IL-22 concentrations were also associated with more severe ILD, as indicated by the Warrick scores (p = 0.022). Receiver operating characteristic(ROC) analysis demonstrated a cut-off value of 651.7 ng/L for IL-22 with 90% specificity and 85% sensitivity (AUC = 0.92). Elevated IL-22 levels and smoking were found to be independent predictors of ILD in RA patients. Conclusions Serum IL-22 levels are significantly increased in RA-ILD patients and are associated with disease activity and ILD severity. Elevated IL-22 and smoking may serve as essential predictors of ILD in RA. IL-22 may also serve as a valuable biomarker for early detection as well as a potential treatment target in RA-ILD.

关键词： Acute toxicity   Anti-inflammatory effect   Ethanol extract   Phytochemistry   Pro-inflammatory cytokines   Salvia argentea L  

摘要： Salvia argentea L. (Lamiaceae) is a medicinal plant originating from the Mediterranean region and has been used since ancient times for the treatment of various diseases. This study aimed to determine the phytochemical composition of S. argentea L. ethanol extract and to evaluate its in vitro and in vivo anti-inflammatory activity and its acute oral toxicity. The chemical constituents of the ethanol extract prepared from the aerial parts of the plant were identified using HPLC. The in vitro anti-inflammatory activity of the extract was evaluated in LPS-stimulated murine macrophage RAW 264.7 cells and the human monocytic cell line THP-1 by measuring the levels of nitric oxide (NO), pro-inflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha). Acute toxicity of the extract was assessed in accordance with OECD guideline no 423. In vivo anti-inflammatory activity was evaluated based on the inhibition of 1% carrageenan-induced paw edema in rats. Serum CRP levels as an inflammatory marker, were measured via ELISA. Histological and immunohistochemical assessments were performed to identify tissue changes in the paw. HPLC profiling revealed that the extract contained rosmarinic acid (11.334 mu g/mg dry extract), and salvigenin (2.74 mu g/mg of dry extract) as major compounds. The extract significantly inhibited the production of NO, IL-1 beta, IL-6, and TNF-alpha without affecting cell viability. In vivo, the extract treatment exhibited a dose-dependent reduction in paw edema and serum CRP levels, along with notable histological improvements. Administration of the extract resulted in dose-dependent decreases of NF-kappa B expressions in the paw tissues. No signs of acute toxicity were observed (oral LD50 > 2000 mg/kg). These findings suggest that S. argentea L. ethanol extract possesses significant anti-inflammatory potential supporting its possible development as a natural therapeutic agent for inflammatory disorders.

关键词： HLH   IL-2   T cell   cytokine complexes   cytotoxicity  

关键词： appendicitis   gene variants   inflammation   polymorphism  

摘要： Objectives Acute appendicitis (AA) is the primary cause of urgent surgery. The goal of this case-control study was to establish the possible associations of tumor necrosis factor (TNF), toll-like receptor-2 (TLR2), and toll-like receptor-4 (TLR4) gene polymorphisms in cases of AA in a Turkish population. Methods This prospective research was performed on 160 AA cases admitted into the Erciyes University Emergency Medicine Department. A total of 197 healthy volunteers were also included as a control group. TNF -308 G>A (rs1800629), TLR2 -196 to -174 del/ins (rs111200466), and TLR4 (Asp299Gly, 896A>G, rs4986790) polymorphisms were analyzed using real-time polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLR) methods. Results The TNF rs1800629 polymorphism had significant increases in the patient group's A allele frequencies and AA genotype (p<0.001). However, for the TLR2 (-196 to -174 del/ins) and TLR4 Asp299Gly polymorphisms (p>0.05), no significant correlations were found in the genotype frequencies. Conclusions This research demonstrated that TNF -308G>A, but not the TLR2 (-196 to -174 del/ins) or TLR4 Asp299Gly variant, is a contributing factor to the susceptibility of AA development in the Turkish population.

摘要： Recently, we described that glyceraldehyde-3-phosphate dehydrogenase from Leishmania major (LmGAPDH) is present in extracellular vesicles and inhibits host TNF-alpha expression during infection via post-transcriptional repression. LmGAPDH binding to AU-rich elements in the 3 '-untranslated region of TNF-alpha mRNA (TNF-alpha ARE) was sufficient for limiting cytokine production, but the TNF-alpha ARE binding residues in LmGAPDH remain unexplored. RNA electrophoretic mobility shift assay (REMSA) and catalytic activity measurements revealed that the inhibition by the TNF-alpha ARE was competitive with respect to the cofactor NAD+ in LmGAPDH. To identify the TNF-alpha ARE binding residues of LmGAPDH, we performed a systematic mutational analysis of its NAD+ binding domain. Catalytic activity measurements indicated that both R13 and N336 amino acids in the NAD+ binding site are absolutely required for activity, whereas other mutants, including I14A, R16A, D39A, and T112A, showed higher K m (lower affinity) values for NAD+ binding and lower catalytic activity. REMSA studies revealed that the replacement of Arg13 with Ala/Lys or Asn336 with Ala resulted in a complete loss of binding to the TNF-alpha ARE. I14A, R16A, D39A, and T112A residues at or near the NAD+ binding site showed lower binding to the TNF-alpha ARE compared to the wild-type protein. Protein-induced fluorescence enhancement (PIFE) studies and in vitro protein translation assays further confirmed the REMSA results. Based on our findings, the NAD+ binding residues in LmGAPDH are important for TNF-alpha ARE binding.

关键词： C*07:1216   HLA-C   new allele  

摘要： Characterisation of the novel HLA-C allele, C*07:1216.

关键词： bidirectional roles   bioinformatics   IL-18   immune infiltration   prostate neoplasm  

摘要： Background In recent years, the incidence and mortality of prostate cancer (PCa) have risen significantly, rendering it a serious health concern for middle-aged and elderly men. Interleukin-18 (IL-18), an important pro-inflammatory cytokine within the interleukin-1 superfamily, has been implicated in various malignancies, yet there is a notable scarcity of comprehensive studies exploring the regulatory role of IL-18 in the onset and progression of PCa. Methods This study employed integrated bioinformatics and immunohistochemical analyses to investigate the expression patterns and potential mechanistic roles of IL-18 and its receptors in PCa. Differential expression analyses were performed on IL-18 mRNA and protein levels in normal prostate (NP), benign prostatic hyperplasia (BPH), and PCa tissues. Correlations between IL-18 expression and clinical features were also assessed. Additionally, immune cell infiltration was analyzed to explore the immunological landscape associated with IL-18 expression. Results A comparative analysis of IL-18 mRNA and protein expression levels between paracancerous and PCa tissues revealed an obvious decrease in IL-18 expression in both benign prostatic hyperplasia (BPH) and PCa tissues compared to normal prostate (NP) tissue (p < 0.05). The expression of IL-18 was found to be significantly elevated in correlation with the progression of pathological T-stage and an increase in the Gleason score among patients with PCa. Immune infiltration analysis, which examined 24 immune cell types, showed that IL-18 was correlated with the infiltration of Th17 cells negatively, while exhibiting positive correlations with other immune cell types. Congo red staining revealed that eosinophils were predominantly localized in the entravascular and perivascular regions of prostate tissues. Notably, Eosinophil infiltration was significantly increased PCa tissues when compared to NP tissues (p < 0.05). Immunohistochemical staining also showed that CD20(+) B c

摘要： Dengue, transmitted by Aedes mosquitoes, represents a significant global health challenge due to its complex host-pathogen interactions and varying disease severity. Genetic factors are known to influence the clinical outcome of dengue infections. This study aimed to investigate the potential role of TNF-α gene polymorphism 308 (rs1800629) and INF-γ +874 (rs62559044) in the progression of dengue virus infection. Conducted in the Central region of Burkina Faso, this study included 246 participants, comprising 117 controls and 129 dengue-positive patients. Genotyping of the TNF-α 308 (rs1800629) and INF-γ +874 A/T (rs62559044) polymorphisms was performed using restriction fragment length polymorphism (RFLP) and Amplification Refractory Mutation System PCR (ARMS-PCR) techniques, respectively.  Our analysis revealed no significant correlation between lymphocyte count and dengue severity (P = 0.95). Although we did not find an association between the alleles of the SNPs TNF-α 308 (rs1800629) and INF-γ +874 (rs6255904) studied with either DF or severe DS, we cannot conclude the same for their respective genotypes Thus, the AA and GG genotypes of TNF-α are associated with the contraction of DF and DS, respectively;the former is even associated with the progression of  DF to the severe form of the disease. For INF-γ  AA genotypes are more associated with progression to severe dengue and the AT heterozygote could be associated with a possibility of preventing progression to DS forms. . The A allele frequencies was higher frequency in DF than in DS pour TNF-α 308  , but this difference lacked statistical significance (P > 0.005). With INF-γ  tTT genotype was more prevalent in DS, whereas the AT genotype frequencies differed between DF (23.96%) and DS (19.35%). Our results reveal through the allelic levels of TNF-α 308 and INF-γ +874;that the latter would not play a significant role in the progression of dengue virus infection to severe forms. However, previous studies through

关键词： Cancer   Immunology   Immunotherapy   Oncology   Radiation therapy  

摘要： The immunosuppressive tumor microenvironment (TME) drives radioresistance, but the role of γδ T cells in regulating radiosensitivity remains incompletely understood. In this study, we found that γδ T cell infiltration in the TME substantially increased after radiotherapy and contributed to radioresistance. Depletion of γδ T cells enhanced radiosensitivity. Single-cell RNA sequencing revealed that γδ T cells in the post-radiotherapy TME were characterized by the expression of Zbtb16, Il23r, and Il17a, and served as the primary source of IL-17A. These γδ T cells promoted radioresistance by recruiting myeloid-derived suppressor cells and suppressing T cell activation. Mechanistically, radiotherapy-induced tumor cell-derived microparticles containing dsDNA activated the cGAS-STING/NF-κB signaling pathway in macrophages, upregulating the expression of the chemokine CCL20, which was critical for γδ T cell recruitment. Targeting γδ T cells and IL-17A enhanced radiosensitivity and improved the efficacy of radiotherapy combined with anti-PD-1 immunotherapy, providing potential therapeutic strategies to overcome radioresistance.