Journal of Interferon and Cytokine Research最新文献

Hirudin, a polypeptide extracted from medicinal leeches, has demonstrated potential in treating renal fibrosis. This study aimed to explore the underlying mechanisms by which Hirudin alleviates renal fibrosis. Renal fibrosis models were established using unilateral ureteral obstruction (UUO) surgery in rats and transforming growth factor-β (TGF-β)-induced HK-2 cells, followed by treatment with different concentrations of Hirudin. Renal function indicators were detected using an automatic analyzer. Renal pathology was observed using hematoxylin-eosin and Masson staining, and α-smooth muscle actin (α-SMA) (a fibrosis marker) expression was detected by immunohistochemistry. Cell viability was tested using cell counting kit-8 assay. Western blot was utilized to detect α-SMA, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), cleaved caspase-1, phosphorylated mammalian target of rapamycin (p-mTOR), mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF-1α) levels. Interleukin (IL)-1β and IL-18 levels were measured using enzyme-linked immunosorbent assay (ELISA). UUO rats exhibited impaired renal function and severe renal fibrosis, accompanied by increased NLRP3, GSDMD, cleaved caspase-1, IL-1β, IL-18, p-mTOR/mTOR, and HIF-1α levels. Hirudin alleviated renal fibrosis, reduced pyroptosis, and inhibited mTOR/HIF-1α pathway in UUO rats. TGF-β stimulation decreased cell viability, increased α-SMA expression and pyroptosis, and activated mTOR/HIF-1α pathway in HK-2 cells. These changes were reversed by Hirudin. However, the mTOR agonist MHY1485 altered the effects of Hirudin. In conclusion, Hirudin reduces pyroptosis to alleviate renal fibrosis, potentially by suppressing mTOR/HIF-1α pathway.

C-X-C chemokine receptor 4 (CXCR4) is a chemokine receptor. Paired box protein 5 (PAX5) is a nuclear transcription factor. Octamer-binding protein 2 (OCT2) is a B-cell-restricted transcription factor. This study aimed to evaluate the protein expression of CXCR4, PAX5, and OCT2, as well as the gene expression of long noncoding RNA (lncRNA) X-inactive specific transcript (XIST)/miR-34/PAX5, in diffuse large B-cell lymphoma (DLBCL). The study included 67 patients with DLBCL and 15 lymphoid tissue samples from reactive lymph nodes. Immunohistochemical (IHC) methods were used to evaluate protein expression. Gene expression was measured by real-time polymerase chain reaction. Correlation analysis showed significant negative correlations between miR-34 expression and each of the XIST expression (r = -0.41, P < 0.001) and PAX5 expression (r = -0.43, P < 0.001). At the same time, there was a strong positive correlation between XIST expression and PAX5 expression (r = 0.92, P < 0.001). In conclusion, our findings indicate that CXCR4, OCT2, and PAX5 IHC expressions can be considered diagnostic markers in DLBCL. In addition, the XIST/miR-34/PAX5 axis may serve as a potential diagnostic marker in DLBCL. Moreover, CXCR4 and XIST/miR-34/PAX5 expressions may be potential prognostic markers in DLBCL.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. The genomic database for NSCLC is expanding rapidly, highlighting the importance of characterizing subpopulations from diverse regions. This study aims to identify and correlate genomic variants in patients with non-squamous NSCLC from two cities in Paraná, Brazil, and compare these findings with data from The Cancer Genome Atlas (TCGA) and the broader Brazilian population. We conducted a retrospective study sequencing tumor sample from 133 patients. An in silico analysis was performed for gene functional analysis. Additional data on tumor mutational burden (TMB), microsatellite status, and clinicopathological characteristics were also collected. The mutational load in the studied population was comparable to that of the TCGA cohort. However, gene expression profiles differed significantly, particularly for the EGFR, TP53, KRAS-NRAS, STK11-KEAP1, MTAP-CDKN2A/B, and PDL-1 genes. The gene expression profile in this study also showed marked differences from the general Brazilian population, with notably higher expression rates of EGFR and PDL-1. Specifically, considering the PDL-1 expression levels, 14% were classified as hyper-expressors, 33% as hypo-expressors, and 52% as non-expressors. These proportions were statistically distinct from global literature but aligned with the Brazilian profile. The genomic profile of patients with NSCLC in Paraná reveals a regional signature, characterized by a higher frequency of EGFR and TP53 mutations, along with elevated PDL-1 expression. These findings highlight the potential for regional variations in NSCLC, which could inform personalized treatment strategies for this population.

We aimed to measure serum concentrations of interleukin (IL) 8, tumor necrosis factor-α (TNF-α), IL-6, IL-1β, and human neutrophil gelatinase-associated lipocalin (N-gal) in children with Shiga toxin-producing Escherichia coli (STEC) infection to determine the inflammatory cytokine profile and the role of these molecules in hemolytic uremic syndrome (HUS) development and severity. Three groups of patients with evidence of STEC infection were incorporated: bloody diarrhea (BD), patients with HUS requiring dialysis (HUSD), and patients with HUS and no dialysis requirement (HUSND). Serum samples were assayed for cytokines and N-gal using immunoassays. Thirty-six children were enrolled: 13 with BD, 10 with HUSND, and 13 with HUSD. We found significantly higher levels of IL-8, TNF-α, IL-6, and N-gal in patients with HUSD compared to patients with BD. Only TNF-α levels were significantly higher in patients with HUSND than in patients with BD. Higher IL-8 and N-gal levels were evidenced in HUSD than in patients with HUSND at the initial stages of disease. Principal component analysis revealed that children with HUSD exhibited an immune profile different from the other study groups. These results suggest a possible involvement of IL-8 in disease severity in patients with STEC-HUS. Furthermore, our results indicate a potential role of N-gal in HUS development. [Figure: see text].

Background: The pro-apoptotic and pro-inflammatory effects of FK506 binding protein 5 (FKBP5) in sepsis-induced acute kidney injury have been previously reported. However, its biological functions and underlying mechanisms in regulating sepsis-induced intestinal injury remain elusive. Therefore, this study aimed to explore the effects of FKBP5 on sepsis-induced intestinal injury. Methods: A mouse model of sepsis was established by cecal ligation and puncture (CLP). A cell model was established by treating Caco-2 cells with lipopolysaccharide (LPS). The impacts of FKBP5 knockdown on apoptosis, barrier integrity, inflammation, and the nuclear factor kappa B (NF-κB) signaling were evaluated in ileal tissue and Caco-2 cells. Results: FKBP5 expression was elevated in the ileal tissue in response to CLP and LPS treatments. In mice with sepsis, FKBP5 knockdown reduced cell apoptosis and regulated Bax, Bcl-2, and cleaved PARP levels. FKBP5 knockdown also reduced the levels of D-lactic acid, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1β, improved intestinal histopathological damage, and enhanced the expression of zonula occludens-1 and occludin. FKBP5 knockdown also displayed protective effects in LPS-stimulated cells. FKBP5 knockdown inhibited the NF-κB signaling in CLP and LPS groups. Conclusion: Inhibition of FKBP5 alleviates inflammation and intestinal barrier dysfunction in sepsis, partially by inhibiting the NF-κB signaling.

This prospective study investigated the utility of baseline CXCL13 levels in predicting methotrexate response and monitoring disease activity in 50 treatment-naive early rheumatoid arthritis (RA) patients (2010 American College of Rheumatology/European League Against Rheumatism criteria) treated with methotrexate. Participants were categorized into methotrexate responders (MTX-R, n = 29) and nonresponders (MTX-NR, n = 21) at 12 weeks. Baseline CXCL13 levels were significantly higher in MTX-R compared with MTX-NR (P = 0.035). Receiver operating characteristic curve analysis identified a baseline CXCL13 cutoff of >100 pg/mL for predicting methotrexate response, with 69% sensitivity, 52% specificity, and 62% accuracy. Posttreatment, CXCL13 levels decreased significantly in MTX-R (P < 0.001) but remained unchanged in MTX-NR. Disease activity parameters (eg, DAS-28) correlated with CXCL13 dynamics, though specific coefficients were not detailed. The study highlights CXCL13 as a potential biomarker for stratifying methotrexate therapy, with higher baseline levels favoring therapeutic response and posttreatment reductions reflecting clinical improvement. While moderate diagnostic accuracy limits standalone use, CXCL13 may complement existing tools to guide early personalized treatment. Further validation in larger cohorts is warranted to confirm its role in optimizing RA management.

Listeriosis is a foodborne disease caused by Listeria monocytogenes (Lm) that usually leads to serious adverse outcomes in pregnant women. Interleukin (IL)-33/serum stimulation (ST)2 axis has an important impact on infectious diseases, but its role in listeriosis is rarely studied. Here, the immunomodulatory effects of IL-33/ST2 axis during perinatal Lm infection were investigated. In our study, the perinatal Lm infection model was constructed by injecting Lm into the tail vein of C57BL/6J mice. IL-33/ST2 axis was blocked by intraperitoneal injection of anti-IL-33Rα/ST2 antibody. In vitro, mouse cytotoxic T lymphocyte cell line (CTLL)-2 cells were activated by using CD3/CD28 antibodies. Perinatal Lm infection caused massive necrosis of liver tissue. Blocking IL-33/ST2 axis in pregnant mice inhibited the infiltration of CD8⁺ T lymphocytes into the site of infection and further aggravated liver damage. We also found that IL-33 promotes mitochondrial autophagy in activated CTLL-2 cells in vitro. Mitochondrial autophagy was beneficial to the clearance of damaged mitochondria and reduced the production of reactive oxygen species. IL-33/ST2 axis affects the immune function of CD8⁺ T lymphocytes by regulating mitophagy, which plays a very important role in the occurrence and development of perinatal Lm infection. Immunomodulation targeting IL-33/ST2 axis may be an effective way to adjuvant treatment of perinatal Lm infection.

Kawasaki disease (KD) is an acute childhood vasculitis, commonly seen in children under the age of five. Despite extensive research over the past five decades, the pathogenesis of KD remains elusive. The objective of this epigenetic reanalysis study is to delineate common pathways involved in KD using a bioinformatics approach. Array datasets from the Gene Expression Omnibus repository were extracted and subjected to analysis using the Chip Analysis Methylation Pipeline in the R statistical tool for the identification of differential methylation probes and differential methylation regions. Adaptive immune genes CD8B, RAG1, IL-7R, STAT1, and CCR7 were significantly hypermethylated in acute KD as compared to healthy controls. Gene enrichment analysis showed that genes involved in T-cell receptor activation and differentiation, antigen processing and presentation of MHC class I were hypermethylated, whereas neutrophil degranulation was hypomethylated in the acute phase of KD as compared to healthy controls. The proportion of neutrophils significantly increased, while the proportions of CD4 T-cells and CD8 T-cells decreased in the peripheral blood of children with acute KD as compared to healthy controls. Reduced proportions of CD4 T cells and CD8 T cells, as well as hypermethylation of their genes, have been observed in the peripheral blood of patients with acute KD.

The association between local oral inflammation and cardiovascular risk has been extensively studied, with results indicating a bidirectional relationship. The aim of the present study was to investigate the associations between blood cells and a large number of salivary cytokines, chemokines, and growth factors. The study consisted of 165 individuals who were referred to the Oral and Maxillofacial Surgery clinic at Falun County hospital, Sweden, for surgical removal of impacted lower third molar. The study subjects did not have any known inflammatory disorders. Complete blood cell counts were analyzed using the routine laboratory at Falun Hospital, Falun, Sweden. Proteomic analysis of 92 inflammation-related protein biomarkers in saliva was performed using a multiplex proximity extension assay. After adjustment for multiplicity testing using the false discovery rate approach, there remained significant association between several saliva cytokines, chemokines, and growth factors and white blood cell counts (n = 19), neutrophil counts (n = 18), erythrocyte counts (n = 13), hemoglobin concentrations (n = 20), erythrocyte volume fractions (n = 22), and platelet counts (n = 12). There are several significant associations between local inflammatory cytokines in the oral cavity and blood cell parameters indicating a relationship between local and systemic inflammatory activity.

The expansion of social media has fundamentally transformed biomedical research dissemination and collaboration, particularly within the interferon and cytokine research community. This paper explores recent trends (2024-2025) that have amplified the role of platforms such as Twitter (now "X"), LinkedIn, Mastodon, Threads, and Bluesky. These tools have facilitated rapid knowledge exchange, democratized access to scientific discourse, enabled diverse voices to participate meaningfully, and fostered cross-disciplinary and global collaborations. Additionally, the integration of preprint repositories like bioRxiv and medRxiv, along with the evolution of open access publishing, further accelerates the accessibility and immediacy of scientific communication. Despite evident benefits, the rapid dissemination facilitated by social media also poses ethical challenges, including concerns about misinformation, premature dissemination of preliminary data, and privacy considerations. Practical strategies for researchers and institutions to effectively navigate these platforms responsibly are presented, aiming to optimize the impact of social media on scientific discovery and public engagement.