Journal of Interferon and Cytokine Research最新文献

Neonatal sepsis remains a major cause of morbidity and mortality, with diagnosis complicated by nonspecific clinical signs and limited reliability of conventional laboratory tests. This study aimed to evaluate and compare the diagnostic efficacy of biomarkers tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and procalcitonin (PCT) with traditional sepsis screening parameters in neonates. This hospital-based case-control study was conducted in the neonatal intensive care unit of a North Indian tertiary care medical university between September 2023 and March 2025. A total of 300 neonates were screened, of which 100 were diagnosed with sepsis (cases) and the remaining 200 served as controls. Sepsis screening, TNF-α, IL-6, PCT, and blood culture were performed to diagnose neonatal sepsis. Results of this study showed significantly higher levels of all tested biomarkers and sepsis parameters in cases compared with controls. Among biomarkers, TNF-α demonstrated the highest accuracy [area under the curve of the receiver operating characteristic (AUROC) 0.99, sensitivity 94%, specificity 100%], followed by PCT (AUROC 0.82, sensitivity 80%, specificity 82.5%) and IL-6 (AUROC 0.79, sensitivity 86%, specificity 74.5%). The study concludes that TNF-α is the most reliable biomarker for diagnosing neonatal sepsis, although a multimodal approach integrating conventional parameters with cytokines and PCT offers the best diagnostic yield. Combining early biomarkers with standard screening may improve early recognition, reduce unnecessary antibiotic exposure, and strengthen antimicrobial stewardship.

TGF-β1 plays a significant role in pregnancy outcomes. This research sought to investigate whether TGF-β1 is involved in the bleeding mechanism after medication abortion (MA) in early pregnancy. The MA rat model was established in vivo using mifepristone and misoprostol, and trophoblasts HTR8/SVneo were treated with lipopolysaccharide in vitro. Changes in uterine morphology, weight, and bleeding were assessed. tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), estradiol, and progesterone levels were detected by ELISA. HE staining was employed to analyze uterine pathological changes. Apoptosis was assessed by TUNEL staining. Inflammatory cytokine expression was assessed by ELISA and qRT-PCR. Related protein levels were analyzed by Western blot. MA induction led to abnormal uterine morphology, reduced uterine weight, and heavier bleeding. MA rats showed higher tPA, uPA, IL-6, and TNF-α levels, and lower estradiol and progesterone levels compared to controls. Moreover, trophoblast tissue damage with excessive apoptosis was observed in MA rats. TGF-β1, p53, and PAI-1 levels were markedly decreased after MA induction. In HTR8/SVneo cells, lipopolysaccharide treatment significantly inhibited cellular functions, reduced TGF-β1, p53, and PAI-1 levels, and increased IL-6 and TNF-α levels. Notably, these changes were partially reversed by overexpression of TGFB1. In conclusion, TGF-β1 protects trophoblasts and alleviates MA-induced uterine bleeding by upregulating the p53/PAI-1 pathway.

Signal transducer and activator of transcription 1 (STAT1) mutations are associated with diverse pathologies. Loss-of-function (LOF) heterozygous mutations impair interferon (IFN) signaling, predisposing to Mendelian susceptibility to mycobacterial diseases (MSMDs). This study characterizes a novel STAT1 LOF mutation in a patient with multisystem manifestations. A patient presenting with mycobacterial infection, skeletal abnormalities, and systemic inflammation underwent whole-exome sequencing. The identified STAT1 variant was analyzed via computational tools (PolyPhen-2/SIFT). Molecular biological validation included IFN-α/γ-induced STAT1 phosphorylation assays and fluorescence microscopy for subcellular localization. Clinical features included mycobacterial osteomyelitis, severe rash, dwarfism, hepatosplenomegaly, and elevated inflammatory markers (C-reactive protein/erythrocyte sedimentation rate). A heterozygous STAT1 mutation (NM_007315.4:c.2120T>C; p.Ile707Thr) was identified and predicted as pathogenic. Mutant cells showed reduced STAT1 phosphorylation (64% versus wild-type, P < 0.05) and impaired nuclear translocation post-IFN-α/γ stimulation. Antibiotic therapy achieved clinical resolution without complications. These findings indicated that the STAT1 I707T mutation disrupts IFN-α/γ immunity, expanding the MSMD genotypic spectrum. Genetic screening for STAT1 defects is critical in patients with mycobacterial infections involving skin. Molecular biological studies corroborate mutation pathogenicity, guiding therapeutic decisions.

Psoriasis is an immune-mediated chronic inflammatory disease characterized by keratinocyte hyperproliferation and inflammatory cell infiltration. While noncoding RNAs are implicated in its progression, research remains limited. Integrating lncRNA microarray data with LncRNASNP2-based predictions identified the long noncoding RNA (lncRNA) HSFY2-10:1 as a potential functional lncRNA contributing to psoriasis pathogenesis. This study aimed to investigate the role of lnc-HSFY2-10:1/miR-145-5p/fibronectin (FN1) axis in psoriasis. We found that HSFY2-10:1 was significantly upregulated in psoriatic tissues. In a psoriasis cell model established by stimulating NHEKs and HaCaT cells with the M5 cytokine cocktail (IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α), lnc-HSFY2-10:1 promoted keratinocyte hyperproliferation and CCL20 secretion. Mechanistically, HSFY2-10:1 functioned as a competitive endogenous RNA for miR-145-5p, thereby regulating FN1 expression. Overexpression of miR-145-5p markedly reversed the HSFY2-10:1-induced upregulation of FN1, keratinocyte proliferation, and CCL20 secretion. These findings indicate that the lnc-HSFY2-10:1/miR-145-5p/FN1 axis plays a crucial role in psoriasis pathogenesis and serves as a potential therapeutic target. [Figure: see text].

This study was conducted to investigate the protective effect of platelet-rich plasma-derived exosomes (PRP-Exos) in diabetic wound healing, as well as the involved molecular mechanism. Exosomes collected from PRP were extracted and identified, then the promoting effect on diabetic wound healing was tested in high glucose and lipopolysaccharide (HL)-induced RAW264.7 cells and excisional wound models constructed in streptozotocin-induced diabetic SD rats. PRP-Exos showed the best capacity for accelerating wound healing in the diabetic rat model. Cell proliferation of RAW264.7 cells was effectively facilitated after HL treatment, while PRP-Exos implemented could obviously eliminate the HL effect on RAW264.7 cells. The protein expression levels of PINK1, parkin, and LC3I/LC3II were both obviously diminished, and the expression of kininogen-1 (KNG1) was obviously increased in HL-induced RAW264.7 cells, while the opposite results were observed after PRP-Exos treatment. HL treatment could remarkably suppress the protein expression levels of p-PI3K/PI3K and p-AKT/AKT in RAW264.7 cells, while PRP-Exos administration could reverse this trend. Interestingly, KNG1 upregulation could effectively reverse the effect of PRP-Exos on the tumor necrosis factor-alpha and high mobility histone 1 levels, protein expression of p-PI3K/PI3K and p-AKT/AKT, and mitophagy-related markers in HL-induced RAW264.7 cells. In conclusion, PRP-Exos facilitated macrophage mitophagy in diabetic wound healing by targeting KNG1 via PI3K-AKT pathway.

This study aims to screen liquid-liquid phase separation (LLPS)-related genes modulating ubiquitination for diagnosing patients with diabetic nephropathy (DN). After performing differential gene expression analysis, ssGSEA, and immune infiltration analysis, LLPS-related genes modulating ubiquitination, key immune cells, and immune-related pathways were acquired. The correlations between LLPS-related genes and ubiquitination, key immune-related pathways were explored, respectively. The diagnostic genes were identified by four machine learning algorithms, followed by evaluation to predict the performance of the machine learning models on ubiquitination using receiver operating characteristic curves and a confusion matrix. In vitro experiments were applied to explore the function of signal transducer and activator of transcription 1 (STAT1) in DN. Totally, 513 differentially expressed genes were screened between the DN and control groups. The activity of the ubiquitin-mediated proteolysis pathway exhibited a significant difference between the DN and control samples. The fraction of a total of 10 immune cells exhibited a significant difference between the lower and higher ubiquitination groups. Totally, nine LLPS-related genes modulating ubiquitination were acquired, and these genes modulating ubiquitination were enriched in ubiquitin pathways and significantly positively correlated with the complement, IFN-α, and IFN-γ pathways. Two diagnostic genes were obtained, namely dual specificity tyrosine phosphorylation regulated kinase 2 (DYRK2) and STAT1. Notably, downregulation of STAT1 effectively alleviated IFN-γ, IFN-α, IL-1β, and TNF-α levels in D-glucose-treated HK-2 cells, as well as the protein level of FK2. LLPS-related STAT1 modulating ubiquitination accelerates the inflammatory response in DN.

Bushen Huoxue Acupuncture shows potential in treating neurodegenerative diseases, but its mechanisms remain incompletely understood. Using the senescence-accelerated mouse-prone 8 (SAMP8) mouse model, we assessed cognitive function via the Morris water maze test, hippocampal neuronal apoptosis with terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and microglial activation through immunohistochemistry. Serum levels of inflammatory cytokines [tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6] were quantified by enzyme-linked immunosorbent assay. The expression of SIRT2 pathway-related proteins, along with Aβ deposition, was analyzed using Western blotting, immunohistochemistry, and immunofluorescence. The results demonstrated that Bushen Huoxue Acupuncture improved cognitive function in SAMP8 mice, reducing hippocampal neuronal apoptosis and decreasing serum levels of pro-inflammatory cytokines. Additionally, it reduced the levels of Aβ42, a more aggregation-prone and toxic Aβ subtype, in both hippocampal tissues and serum, as well as the number of CD68-positive cells in hippocampal tissues, suggesting the inhibition of amyloid pathology and neuroinflammatory. The treatment also downregulated SIRT2, BACE1, and APP-CTF while increasing RTN4B expression. Notably, Bushen Huoxue Acupuncture outperformed non-acupoint acupuncture in enhancing cognitive function and reducing inflammation. Our findings indicate that Bushen Huoxue Acupuncture alleviates cognitive deficits and neuroinflammation by suppressing the SIRT2-mediated RTN4B/BACE1 pathway, highlighting acupuncture as a promising therapy for neurodegenerative diseases.

Myocardial infarction (MI) triggers a systemic inflammatory response that influences cardiac recovery. Pharmacological therapies, including aspirin, β-blockers, Angiotensin-Converting Enzyme (ACE) inhibitors, statins, and P2Y12 inhibitors such as Ticagrelor, may have additional immunomodulatory effects beyond their primary cardiovascular benefits. This study evaluates the impact of different treatment regimens on inflammatory markers, immune cell phenotyping, and cardiac biomarkers in MI patients. A total of 78 MI patients were divided into three treatment groups: standard therapy (aspirin + β-blockers), enhanced therapy (aspirin, β-blockers, ACE inhibitors, and statins), and experimental therapy (Ticagrelor + standard therapy). Inflammatory cytokines (Interleukin (IL)-4, IL-6, IL-10, IL-17, Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α, Transforming Growth Factor (TGF)-β), cardiac biomarkers [Troponin, B-type natriuretic peptide (BNP)], and immune cell profiles (Th1/Th2 balance) were assessed using Enzyme-Linked Immunosorbent Assay (ELISA), qPCR (Polymerase Chain Reaction), and flow cytometry before and after treatment. Pro-inflammatory markers (IL-6, TNF-α, IFN-γ, IL-17) significantly decreased, while anti-inflammatory cytokines (IL-4, IL-10, TGF-β) increased post-treatment (P < 0.0001). Th1 cell proportions declined, with a concurrent rise in Th2 cells, particularly in enhanced and experimental therapy groups. Troponin and BNP levels decreased, indicating reduced myocardial stress. Pharmacological therapies effectively modulate immune responses, suppress inflammation, and promote myocardial recovery. Ticagrelor demonstrated additional anti-inflammatory benefits, suggesting potential for improved post-MI outcomes. Future studies should explore long-term clinical implications of immune-targeted cardiovascular therapy.