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关键词： blood-brain barrier   cognitive impairment   Creutzfeldt-jakob disease   epileptic encephalopathy   IL-1 beta   IL-8  

摘要： Inflammatory cytokines play a crucial role in Creutzfeldt-jakob disease (CJD). We examined inflammatory cytokine levels in both blood and CSF in a CJD patient and an epileptic encephalopathy as a control case. Results showed that IL-6, IL-8, IL-1 beta, and TNF-alpha levels were elevated in blood, but only IL-8 and IL-1 beta levels, especially IL-8, were significantly elevated in Cerebrospinal fluid (CSF). This suggests that IL-8 and IL-1 beta are closely related to cognitive impairment and blood-brain barrier (BBB) damage in CJD, and IL-8 might be a key target in early cognitive impairment in CJD.

关键词： allele variant   next-generation sequencing   novel allele  

摘要： Allele variants HLA-A*02:11:01:08 and HLA-A*11:01:01:91 differ from HLA-A*02:11:01:01 and HLA-A*11:01:01:01 by a single nucleotide respectively.

关键词： HLA   next-generation sequencing   novel allele  

摘要： HLA-A*29:01:15 differs from HLA-A*29:01:01:01 by a single nucleotide change in exon 1, 39 C -> G (codon -12.3 CTC -> CTG).

关键词： Interleukin-26   Monoclonal antibodies   T cells   Macrophages   Bacterial infection  

摘要： Interleukin-26 (IL-26) belongs to the IL-10 cytokine family and exerts diverse biological functions in regulating immune responses in vertebrates. Although IL-26 has been extensively studied in mammals, the functions of IL- 26 remain largely unexplored in lower vertebrates. In this study, we determined the tissue and cell sources of IL- 26 using a monoclonal antibody (mAb) generated against grass carp (Ctenopharyngodon idella, Ci) IL-26, and investigated the responses of IL-26 producing cells to bacterial infection. We showed that the CiIL-26 mAb specifically recognized the recombinant CiIL-26 proteins expressed in the Escherichia coli and HEK293 cells. Flow cytometry analysis revealed that the CiIL-26 mAb could detect the intracellular CiIL-26 expressed in the HEK293 cells and CIK cells stimulated with inactivated Aeromonas hydrophila (A. hydrophila). Using confocal microscopy, we analyzed IL-26+ cells in various tissues of grass carp following infection with A. hydrophila. It was shown that the IL-26+ cells were significantly increased in the gills, head kidney, posterior intestine and spleen. Remarkably, for the first time, we observed that most IL-26+ cells were CD3 gamma/delta+ T cells and MCSFR+ monocytes/macrophages, which could be induced by A. hydrophila. Our findings highlight the essential roles of CD3 gamma/delta+/IL-26+ T cells and MCSFR+/IL-26+ macrophages in the immune defense against bacterial infections in fish.

关键词： Tuberculosis   Class I & II MHC epitopes   Cell mediated immunity   Vaccine candidate  

摘要： Tuberculosis (TB) remains a global health challenge as annual mortality rate due to drug resistant TB is increasing exponentially. This is mostly associated with the delayed diagnosis of Multidrug-resistant (MDR) or latent TB. Effective management of TB demands development of novel immunological strategies, such as peptidebased/subunit vaccines that can stimulate specific immune responses. In this context, we evaluated the immunogenic potential of two Major Histocompatibility Complex (MHC) Class I/II-restricted peptides from Mycobacterium tuberculosis (M. tuberculosis): Rv2588c and Rv0148. The peptides were tested on T and monocyte populations from healthy donors and pulmonary TB (PTB) patients. Flow cytometry analysis revealed significant T cell activation in peripheral blood mononuclear cells (PBMC) from both groups. Enzyme-linked immunosorbent assay (ELISA) demonstrated a strong IFN-gamma response, confirming effective T cell activation. Additionally, these peptides induced increased nitric oxide (NO) production in macrophages, indicating their role in activating the innate immune system. Overall, Rv2588c and Rv0148 peptides exhibited robust immunogenicity, stimulating both adaptive and innate immune responses in PBMCs from healthy and PTB individuals. These findings highlight their potential as promising TB vaccine candidates, paving the way for improved TB treatment and prevention strategies.

关键词： Macrophages   Eggs   Schistosoma mansoni   Cloning   Cytokines   Collagens   Fibrosis   Liver fibrosis  

摘要： Tissue damage in Schistosoma mansoni infection results from a granulomatous, T cell-mediated response to parasite eggs, leading to liver fibrosis and portal hypertension. This immune response, initially Th1-dominated, progressively shifts toward a Th2 profile, contributing to hepatic stellate cell (HSC) activation and fibrosis. However, the precise regulatory mechanisms remain unclear. In this study, we analyzed T cell responses to soluble egg antigens (SEA) in 121 T cell clones (Tcc) from S. mansoni-infected patients. All clones produced high levels of IL-13 upon anti-CD3 stimulation;a minority secreted IFN-gamma (n = 33) or IL-10 (n = 38). Notably, 51 clones co-produced IL-22 and IL-13. To investigate IL-22's role, we examined IL-22 receptor (IL-22R) expression on human M0 and M2 macrophages. Both subsets expressed IL-22R, and its engagement triggered phosphorylation of p38, STAT3, and STAT5. IL-22 also downregulated IL-13-induced M2 markers (CD163, CD200R). Furthermore, IL-22 treatment of HSCs inhibited IL-13-driven collagen I/III production and cell proliferation. These results suggest that IL-22-producing T cells modulate Th2 macrophage polarization and directly suppress fibrogenesis in HSCs. IL-22 may thus act as a regulatory cytokine counteracting liver fibrosis during schistosomiasis.

关键词： ovarian cancer   lncRNA   ZNF667-AS1   tumor necrosis factor  

摘要： Ovarian cancer (OC) is the most lethal gynecological malignancy and poses a significant public health burden. The present study explored the function and mechanism of long noncoding RNA (lncRNA) ZNF667-AS1 in OC progression. The present study conducted a multifaceted evaluation, including transcriptomic analyses, to examine the expression and prognostic value of lncRNA ZNF667-AS1 in OC via the Cancer Genome Atlas and Genotype-Tissue Expression data. In vitro experiments on OC cell lines were used to investigate the functional effect of ZNF667-AS1 via cell proliferation, migration and invasion assays and RNA sequencing and western blotting were used to explore the implicated molecular pathways. ZNF667-AS1 was significantly underexpressed in OC tissues and cell lines. Its expression levels were positively associated with improved patient prognosis and affected both tumor behavior and tumor microenvironment interactions. Functional analysis confirmed the tumor-suppressive role of ZNF667-AS1 and revealed a marked decrease in proliferation, migration and invasion in ZNF667-AS1-overexpressing cells. Additionally, ZNF667-AS1 was identified as a key regulator in the tumor necrosis factor signaling pathway, which suggests a strong link between ZNF667-AS1 expression and OC progression. The present study identified ZNF667-AS1 as a potential biomarker for OC prognosis and treatment and illustrated its significant regulatory effects on the TNF pathway and its broader implications in cancer pathobiology.

关键词： HLA-C   new allele   NGS   silent mutation  

摘要： Sequences of the novel HLA-C*02:31:02, -C*12:03:95, -C*12:03:96 and -C*17:03:06 alleles identified in Russian individuals.