Seleno-chitooligosaccharide-induced modulation of intestinal barrier function: Role of inflammatory cytokines, tight junction proteins, and gut microbiota in miceHe, Jin, Chen
et alJ Appl Biomed (2025) 23 (1), 45-55
Abstract: This study aimed to explore the function of Seleno-chitooligosaccharide (SOA) on the intestinal barrier through regulation of inflammatory cytokines, tight junction protein, and gut microbiota in mice. The results of ELISA assay demonstrated that SOA significantly increased the levels of IL-2, IL-10, and IFN-γ in serum and ileum. Meanwhile, SOA increased the levels of IL-4 in the ileum (p < 0.05). In addition, Diamine Oxidase (DAO) concentration was decreased in ileum by SOA treatments (p < 0.05). The administration of SOA significantly upregulated the expression of ZO-1 and Occludin in the ileum (p < 0.05). By 16S rDNA sequencing, reduced ratio of Bacillota/Bacteroidota was observed in SOA treated mice. Within the phylum of Bacteroidota, SOA increased the relative abundance of Deferribacterota, uncultured Bacteroidales bacterium, and Bacteroides. Within the phylum of Bacillota, increased relative abundance of Erysipelatoclostridium and Lachnoclostridium, and reduced relative abundance of Ruminococcaceae UCG-010 were observed with SOA supplement. In summary, SOA has the potential to modulate the function of intestinal barrier function and prevent intestinal diseases.
Anti-CD137 agonist antibody-independent and clinically feasible preparation of tumor-infiltrating lymphocytes from soft tissue sarcoma and osteosarcomaJin, Jia, Xia
et alFront Immunol (2025) 16, 1557006
Abstract: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist to expand nonselected TILs in 2-3 weeks, then rapidly expanded them over 2 weeks. Their phenotypes were characterized using flow cytometry. Their antitumor activity was validated in vitro using cytotoxic T lymphocyte assays measuring CD107a on the TILs and the viability of tumor cells and in vivo using an autologous patient-derived xenograft (PDX) tumor model.We successfully expanded TILs in > 90% of collected samples. TILs generated preferentially increased CD8+ T cells but suppressed CD4+ T cells. A small portion of TILs were resident memory T cells. The expanded TILs reduced autologous tumor cells by 37.5% within 24 hours. Infusion of TILs in mice bearing autologous PDX tumors strongly inhibited liposarcoma growth. FDA has approved use of this GMP-feasible protocol in our clinical trial (IND 30562).It is feasible to generate antitumor TILs using CD3/CD28 activator to replace the unavailable anti-CD137 agonist. Our study supports the further development of TIL-based therapy.Copyright © 2025 Jin, Jia, Xia, Gordon, Ludwig, Somaiah and Li.
Effects of lipopolysaccharide administration on thymus damage, antioxidant capacity and immune function in weaned pigletsBai, Jiang, Li
et alJ Vet Res (2025) 69 (1), 111-119
Abstract: Piglets are vulnerable to stress during weaning because of changes in the feeding environment, nutrients, and other growth-impacting conditions. In this study, stress injury was modelled by continuous intraperitoneal injection of lipopolysaccharide (LPS) and was used to investigate the dynamics of antioxidant indices and immunoinflammatory factors in the piglet thymus.Forty-eight weaned piglets were divided into an LPS group and a control group. One group was injected with LPS solution (100 μg/kg) and the other with sterile saline daily. The experiment ran over 13 days, and six piglets from each group were euthanised for necropsy on days 1, 5, 9 and 13. Thymic tissues were collected, and the antioxidant indices and mRNA expression levels of related genes were measured by enzyme activity assay and reverse-transcription quantitative PCR.In the LPS group, catalase activities were significantly increased on days 1 and 5, that of superoxide dismutase was significantly higher on day 9 and glutathione activity was elevated throughout. Messenger RNA (mRNA) expression of the toll-like receptor 4 (TLR4) pathway, interleukin (IL) 6, and IL-2 increased in the thymus on day 1. By day 5, the mRNA expression of the TLR pathway, the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, tumour necrosis factor α, IL-10, IL-6 and IL-2 were decreased. On day 13, the mRNA expression levels of the TLR4 and Keap1/Nrf2 pathways, TNF-α, IL-10 and IL-6 increased again.Continuous LPS induction led to high activation of the thymic immune system in piglets during the prophase. However, this activation was accompanied by atrophy and immunosuppression mid-experiment. Nevertheless, the immune function gradually recovered in the later stages.© 2025 Lingna Bai et al., published by Sciendo.
Markers of T Lymphocyte Activation in Children With Kawasaki Disease: An Experimental Study From North IndiaSharma, Vignesh, Mondal
et alInt J Rheum Dis (2025) 28 (4), e70191
Abstract: The exact pathogenesis of Kawasaki disease (KD) is unknown despite extensive research in the area. Several studies have also implicated CD8+ T lymphocytes in the pathogenesis of KD. However, studies on the activation status of T lymphocytes have shown conflicting results.In this prospective study, early (CD69) and late activation (HLA-DR) markers were assessed in T lymphocytes by flow cytometry. We assessed serum levels of soluble CD25 (sCD25) by enzyme-linked immunosorbent assay. We compared these activation markers between children with KD (n = 10), febrile controls (n = 9), and healthy controls (n = 10). Furthermore, we studied the HLA-DRA and HLA-DRB gene expression in subgroups of KD with or without coronary artery aneurysms (CAAs).A significantly higher percentage of CD69 in CD3+ and CD3 + CD4+ T lymphocytes was noted in KD and febrile controls compared with healthy controls. We found no significant increase in late activation marker HLA-DR in CD3, CD3 + CD4+, and CD3 + CD8+ lymphocytes between KD, febrile, and healthy controls. We observed higher levels of sCD25 in KD and febrile controls than in healthy controls. Longitudinal follow-up in KD showed a decreasing trend of CD69 expression in CD3 + CD8+ lymphocytes and sCD25 levels over time. HLA-DRA and HLABRB expression was comparable between children with CAAs and those without CAAs.Our study showed early but not late activation of T lymphocytes in children with KD. Markers of lymphocyte activation do fall with subsidence of systemic inflammation following intravenous immunoglobulin therapy in KD.© 2025 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
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