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关键词： HLA-E   HLA-G   cancer   immune checkpoint   microchimerism   pregnancy   pseudogene  

摘要：

关键词： nase (RAS/MAPK) pathways. IL-15 influences various immune cells  

摘要： Oncolytic herpes simplex virus type 1 (HSV-1) directly targets and destroys tumor cells while selectively infecting surrounding tumor tissue and releasing progeny viruses to continue the attack. We engineered the replicative HSV-1 vector, including the oncolytic HSV-1 (oHSV) with deleted inverted repeat and alpha 47 gene, and then the oHSV expressing interleukin-15 (IL-15) gene and the oHSV expressing IL-15 and interleukin-12 (IL-12) gene. We evaluated the titer and growth characteristics of the oHSV-1 in Vero and cancer cell lines. Furthermore, we rigorously assessed the antitumor efficacy of HSV-1 in CT26 and B16-F10 cells, along with murine tumor models. The engineered oHSV-1 demonstrated growth patterns comparable to wild-type HSV-1. The viral titers exhibited consistency within the same tumor cells. Treatment with RG2006 significantly reduced tumor growth and extended survival rates compared to other forms of oHSV-1. Analyses indicated a marked elevation in T cell and NK cell activation in mice receiving RG2006. Our findings unequivocally demonstrate that including IL-15 and IL-12 can significantly enhance antitumor immunity when deploying oncolytic herpes simplex virus. This has substantial practical implications, suggesting that integrating multiple therapeutic genes alongside oncolytic viral therapy and immunotherapy could pave the way for more effective clinical strategies in cancer treatment.

关键词： aquaculture genetics   Clarias catfish   genetic diversity   MHC class I   positive selection  

摘要： Background/Objectives: Understanding variabilities in the Major Histocompatibility Complex class I (MHC I) gene is essential for evaluating immunogenetic diversity in clariid catfish. MHC I plays a critical role in immune defense by presenting endogenous antigens to cytotoxic T cells. Therefore, we aimed to investigate the genetic diversity, selection patterns, and phylogenetic relationships of MHC I alleles in three important clariid catfish species (Clarias gariepinus, Clarias macrocephalus, and Clarias batrachus) across wild and hatchery populations in Thailand. Methods: Targeted next-generation sequencing of a 174 bp fragment partial exon 6 of MHC I-UAA gene was performed, along with phylogenetic analyses, neutrality tests and dN/dS analyses. Results: Overall, 91 novel alleles were identified in 674 individuals, all of which were novel (100% novelty), with none matching existing reference sequences, thereby revealing extensive variation in population-specific variants. Phylogenetic analyses revealed allele sharing among species, which was consistent with balanced selection. Neutrality tests and dN/dS analyses provided evidence of both purifying and diversifying selection, with episodic positive selection detected at multiple codon sites associated with the antigen-binding alpha 1 domain. Distinct selection patterns among populations, influenced by local environmental conditions and human pressures, along with high allele richness, are reflected in the diversity of immunogenetic variations. Conclusions: These findings provide critical insights into immune adaptation and highlight the potential of MHC I as a functional marker for genetic monitoring. Although a causal relationship between MHC I polymorphism and disease resistance is debated, studies suggest associations with pathogen survival, indicating future implications for aquaculture breeding and conservation, particularly in marker-assisted selection for broodstock management in Thailand.

关键词： HLA-A   Japanese population   next-generation sequencing   NGS   novel allele  

摘要： HLA-A*24:02:187 differs from HLA-A*24:02:01:01 by a single nucleotide substitution at position 222G>T.

关键词： interferon   innate   dendritic   toll-like receptor - TLR   pathogen-associated molecular pattern - PAMP  

摘要： The role of type I interferon (IFN) in mediating tumor immunosurveillance, in situ vaccination, and response to other cancer immunotherapies is well established. The biologic and species-specific differences between type I IFN family members have not been sufficiently addressed. Recombinant IFN-alpha 2 has been approved for the treatment of chronic viral infections (hepatitis B virus, hepatitis C virus) and some forms of cancer. IFN-beta was approved to treat patients with multiple sclerosis but failed in the treatment of chronic viral infections or cancer. These distinct therapeutic applications most likely reflect distinct biologic roles of the individual IFNs that unfortunately remain poorly understood. IFN-beta can be secreted by essentially all nucleated cells activated through most pattern recognition receptors (PRR). By contrast, IFN-alpha is predominantly secreted by the P1 subset of plasmacytoid dendritic cells (pDCs), which mediate viral defense and successful cancer immunotherapy following their activation by toll-like receptor (TLR)7 or TLR9 agonists. The biologic effects of TLR7 and TLR9 agonists depend critically on their structure and their ability to be processed by endosomal nucleases into fragments capable of binding two distinct agonist binding sites. The clinical activity of TLR7 and TLR9 agonists in cancer immunotherapy is associated with their induction of IFN-alpha secretion and P1 pDC differentiation. CD8+ T cells likely evolved for the primary purpose of killing viral/retroviral-infected cells. Immune cells detect viral/retroviral infected cells using TLR7 and TLR8 to distinguish viral GU-nucleotide-rich RNA from self-RNA modified with pseudouridine, and TLR9 to distinguish viral unmethylated CpG DNA from self-DNA modified with 5-methylcytosine. Recent studies have defined antagonist pockets in TLR7, TLR8 and TLR9 that bind degradation products of endogenous modified RNA and DNA to inhibit responses to host nucleic acids. These findings poin

关键词： asthma   interstitial lung disease pulmonary fibroblasts   TNFSF14 and LIGHT  

摘要： Fibroblasts are structural cells primarily involved in tissue remodeling, but recent single-cell RNA sequencing (RNA-seq) transcriptomic data have highlighted their potential to display molecules linked to inflammation. The factors that drive such inflammatory transcriptional signatures found in patients are not clear. LIGHT (TNFSF14) is a cytokine that we previously suggested may be central to lung diseases exhibiting fibrosis and inflammation, including asthma and interstitial lung disease. With bulk RNA-seq, we then investigated the transcriptional activity of LIGHT in human pulmonary fibroblasts compared with interleukin (IL)-13 and IL-17, two other cytokines linked to lung disease. While all 3 cytokines individually induced unique and overlapping gene transcripts, when fibroblasts were stimulated with LIGHT and IL-13 they upregulated more inflammatory transcripts including CCL2, CCL26, CXCL2, CXCL3, CXCL5, CXCL6, IL32, CSF2, VCAM1, ICAM1, IL18R1, IL1RL1, TNFRSF12A, TNFRSF4, TNFRSF8, ITGA2, ITGA4, and ITGAV, and when stimulated with LIGHT and IL-17, inflammatory transcripts included CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, IL32, IL33, CSF2, TSLP, IL1A, IL6, IL18, VCAM1, ICAM1, IL18R1, IL1RL1, TNFSF4, TNFRSF4, TNFRSF8, ITGA2, ITGA4, and ITGAV. Furthermore, multiple cell cycle-related transcripts were induced with these combinations. Providing potential disease significance, portions of the fibroblast transcriptional signatures induced in vitro were found to be present in subsets of fibroblasts defined by single-cell RNA-seq isolated from patients with interstitial lung disease. This study therefore highlights the synergistic activities of LIGHT with other classical cytokines to regulate transcription in pulmonary fibroblasts and infers the involvement of LIGHT in shaping fibroblast phenotypes observed in chronic lung disease. © The Author(s) 2025. Published by Oxford University Press on behalf of The American Association of Immunologists.

关键词： Green catalyst   green solvent   sustainable catalyst   sustainable solvent   green method   sustainable method   imidazoles  

摘要： In the current scenario, the use of nature-friendly methods in organic synthesis is regarded as invaluable and irreplaceable. Significant progress has been made in developing more sustainable and eco-friendly approaches for various organic syntheses and transformations. Within the scope of green synthesis, ILs have attracted a lot of interest since their special features fit for sustainable chemistry. Organic synthesis has increasingly utilized ILs as green catalysts and solvents for the development of countless heterocycles. Among these, imidazole is recognized as a highly valuable and preferred heterocyclic motif. It presents interesting chances for finding ideal structures in the synthesis of synthetic compounds with possible therapeutic uses and other major prospects. A diverse array of ILs has been successfully exploited toward the development of imidazoles. Therefore, this review article offers a thorough review of current studies on the function of ecologically safe ILs in producing a wide range of valuable imidazoles.

关键词： Cancer treatment   Cancers and neoplasms   Malignant tumors   Mouse models   Breast cancer   Gene expression   Oncogenic signaling   STAT signaling  

摘要： Effective therapies for retroperitoneal (RP) dedifferentiated liposarcoma (DDLPS) remain unavailable. Loco-regional recurrence occurs in >80% of cases;5-year disease-specific survival is only 20%. DDLPS is especially prevalent in the retroperitoneum and abdomen;evaluation of the DDLPS microenvironment in these high-fat compartments appears pertinent. Adipose is a main supplier of interleukin-6 (IL6);excessive activation of IL6 signal transducer glycoprotein 130 (GP130) underlies the development of some diseases. The role of GP130 pathway activation remains unstudied in DDLPS, so we examined the role of microenvironment fat cell activation of the IL6/GP130 signaling cascade in DDLPS. All DDLPS tumors and cell lines studied expressed elevated levels of the GP130-encoding gene IL6ST and GP130 protein compared to normal tissue and cell line controls. IL6 increased DDLPS cell growth and migration, possibly through increased signal transducer and activator of transcription 1 (STAT1) and 3 (STAT3) activation, and upregulated mouse double minute 2 (MDM2). GP130 loss conveyed opposite effects;pharmacological blockade of GP130 by SC144 produced the MDM2 splice variant MDM2-ALT1, known to inhibit full length MDM2 (MDM2-FL). Although genomic MDM2 amplification is pathognomonic for DDLPS, mechanisms driving MDM2 expression, regulation, and function beyond the MDM2:p53 negative feedback loop are poorly understood. Our findings suggest a novel preadipocyte DDLPS-promoting role due to IL6 release, via upregulation of DDLPS MDM2 expression. Pharmacological GP130 blockade reduced the IL6-induced increase in DDLPS MDM2 mRNA and protein levels, possibly through enhanced expression of MDM2-ALT1, a possibly targetable pathway with potential as future DDLPS patient therapy.

关键词： alternatively activated macrophage   dendritic epidermal T cell   intraepithelial lymphocyte   M2 macrophage   wound repair  

摘要： Murine epidermal gamma delta T cells, known as dendritic epidermal T cells (DETCs), play critical roles in cutaneous wound healing by secreting chemokines, cytokines and growth factors. Although DETCs predominantly produce IL-13 early after activation, the specific role of DETC-derived IL-13 in wound repair remains unknown. Here, we show that periwound DETCs are the primary source of IL-13 at early wound sites (4 h after full-thickness skin wounding). The delayed wound closure in DETC-deficient Tcrd -/- mice was restored by the local application of IL-13 immediately after wounding. Previous studies have demonstrated that macrophages infiltrating the wound granulation tissue undergo a phenotypic shift from iNOS-positive, proinflammatory type to arginase-1-positive, anti-inflammatory type during the late inflammatory phase (3-5 days post injury). At 24 h post wounding, however, most macrophages infiltrating the periwound hypodermis expressed arginase-1. In Tcrd -/- mice, both the number of macrophages in the periwound hypodermis and their arginase-1 expression were significantly reduced. Local IL-13 administration restored arginase-1 expression in the hypodermal macrophages without altering their overall number in Tcrd -/- mice. These results indicate that IL-13 rapidly produced by DETCs upon skin injury plays a critical role in wound healing by inducing arginase-1-positive macrophages in the periwound hypodermis during the early inflammatory phase.

关键词： WJ-MSC   CB-MSC   PBMC   HLA-G  

摘要： Objectives: A special group of stem cells with multipotent and immunomodulatory properties are mesenchymal stem cells (MSCs). Many modulatory factors are thought to mediate immunomodulatory properties of MSCs. One of these modulatory factors is thought to be HLA-G, one of human leukocyte antigens (HLA). This study aimed to compare HLA-G levels in both stimulated and unstimulated of peripheral blood mononuclear cell (PBMC) cultures with "cord blood-MSC" (CB-MSC) and "Wharton's jelly-MSC" (WJ-MSC) at different rates and different incubation periods. Methods: WJ-MSCs were obtained by explant method, and CB-MSCs using Ficoll-paque. They were characterized by flow cytometry. MSCs and PBMCs were directly co-cultured for 24 and 72 h at 1:5 and 1:10, respectively. After incubations, the media were collected and HLA-G levels were measured by ELISA. Results: In the unstimulated group, the highest HLA-G level was found in the PBMC:WJ-MSC-72-1:5 group, while the lowest HLA-G level was found in the PBMC:CB-MSC-72-1:5. When 24-1:5 and 72-1:5 groups were examined, the HLA-G level decreased significantly in CB-MSC groups compared to WJ-MSC, while it increased significantly in the 24-1:10 and 72-1:10 groups (p<0.05). In stimulated groups, the highest HLA-G level was observed in the PBMC:CB-MSC-24-1:5. Conclusions: Our study aimed to evaluate the immunomodulatory effect of MSCs via HLA-G molecule. HLA-G levels changed with different incubation times of two different MSC sources. In this study, we suggest that MSCs as a cell therapy, in particular for immune system-related disease, may be a preliminary in vitro approach to evaluate the immunomodulatory effect via HLA-G.