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关键词： CAR-T   STEAP1   CD8+T cells   IFN-gamma   Cancer immunotherapy   Hyperthermia   Febrile temperature   Thermal medicine  

摘要： ObjectiveBody temperature plays an important role in cancer, with febrile temperature generally associated with improved cancer resistance. In murine models, this resistance has been linked to the cytotoxic T cells, whose differentiation into cancer-killing effector cells is poor at lower but robust at elevated temperatures. If conserved, temperature-mediated potentiation of patient-derived T cells could be implemented to improve the existing cancer treatments, including the chimeric antigen receptor T-cell therapy (CAR T-cell therapy). Here, we tested this possibility using human STEAP1 CAR-T cells developed to target prostate *** mice, transient exposure to febrile temperature (39-40 degrees C) increases the production of IFN-gamma and the cancer-killing ability of CD8 + T cells. Using a similar temperature treatment, we observed elevated levels of IFN-gamma also in the human CAR-T cells. However, these cells displayed no improvement in their ability to kill cancer cells. Although we cannot discount the possibility that alternative protocols might lead to other outcomes, our findings suggest that incorporating thermal potentiation into existing protocols of CAR-T cell therapy may be more complicated than anticipated.

关键词： Immunosuppression   Colorectal Cancer   Immune modulatory   Macrophage  

摘要： Background Gut microbiota can significantly alter the risk or progression of cancer by maintaining gut immune system homeostasis. However, the exact mechanism by which the gut microbiota and its metabolites influence colorectal tumorigenesis is *** The roles of tryptophan metabolite indole-3-acetic acid (IAA) in inflammation and tumor development were investigated in dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS mouse models with or without IAA supplementation and with or without Lactobacillus reuteri-produced IAA. Pregnane X receptor (PXR) knockout (KO) mice and aryl hydrocarbon receptor KO mice were used to explore the mechanism by which IAA regulates interleukin (IL)-35 expression. IL-35+ immune cells were stimulated in vitro and analyzed by flow cytometry. Additionally, metabolites were analyzed by liquid chromatography-mass *** We found that IAA, a metabolite of tryptophan produced in the gut by L. reuteri, can inhibit the development of colitis by inducing IL-35 expression in immunosuppressant cells. HuREG3 alpha IECtg mice had high levels of intestinal microbiota-derived IAA, and these mice were resistant to AOM-DSS-induced cancer. Patients with colorectal cancer also had low peripheral blood levels of IAA. Further studies revealed that IAA-producing L. reuteri alleviated colitis symptoms and inhibited colon tumors by inducing macrophages, T cells, and B cells to produce IL-35. Finally, PXR KO completely abolished the effects of IAA on immune *** We demonstrate that gut microbiota-derived IAA can improve the precancerous colon inflammatory environment through IL-35, thereby inhibiting tumorigenesis, suggesting that IAA may be a preventive factor for colitis-related cancers.

摘要： This study assessed 552 allogeneic hematopoietic cell transplantation (HCT) recipients with posttransplant cyclophosphamide (PTCy) to evaluate the incidence, characteristics, risk factors, and impact of early posttransplant cytokine release syndrome (CRS) on outcomes. The cohort included 36% matched sibling donors (MSD), 34% matched unrelated donors (MUD), 27% haploidentical donors, and 4% mismatched unrelated donors (MMUD). CRS was observed in 182 patients, with the highest incidence in haploidentical transplants (80%) compared to MMUD (32%), MUD (23%), and MSD (8%). Most CRS cases were mild, with 93% classified as grade 1 and 6% as grade 2, with only one severe case of grade 3. In haploidentical transplants, CRS was linked to a lower risk of severe chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM), leading to improved overall survival. In contrast, among HLA-matched recipients (MSD and MUD), there were no significant differences in outcomes between those with or without CRS. However, subgroup analysis revealed that CRS in patients with myeloid malignancies, including acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms, was associated with a reduced relapse rate, improving survival outcomes. In conclusion, while CRS is typically mild and short-lived, it significantly impacts survival, particularly in haploidentical transplants and HLA-matched patients with myeloid malignancies.

关键词： 噬菌体展示文库   靶向锚定蛋白   人白细胞抗原-G  

摘要： 目的：基于噬菌体展示靶向锚定蛋白文库，以HLA-G为靶点筛选肿瘤靶向锚定蛋白，并鉴定评价其功能。方法：利用TCGA、GTEx等数据库，进行生物信息分析肿瘤HLA-G表达与临床预后、免疫浸润相关性。利用噬菌体展示靶向锚定蛋白文库对HLA-G胞外片段进行生物淘选并挑取随机单克隆测序。通过ELISA、免疫荧光染色，鉴定优势噬菌体克隆功能。利用原核体系生产纯化Anti-HLA-G靶向锚定蛋白，通过ELISA、SPR、免疫荧光染色评价其亲和力及肿瘤特异性结合能力。结果：生信分析发现HLA-G在肿瘤组织普遍高表达，与临床OS、免疫细胞浸润水平具有相关性。对HLA-G进行5轮噬菌体文库筛选后获得优势克隆，ELISA及免疫荧光染色均显示其对HLA-G阳性细胞结合显著强于阴性细胞。经纯化生产的Anti-HLA-G靶向锚定蛋白，亲和力可达1.7×10-8mol/L，并经ELISA、免疫荧光染色评价，该锚定蛋白对HLA-G阳性细胞结合显著强于阴性细胞。结论：经噬菌体展示文库筛选出的靶向锚定蛋白对HLA-G具有高亲和力，并可特异性结合肿瘤细胞表达的HLA-G。

关键词： Tollip   IL13 or IL-13   TNF-alpha signaling   Inflammatory response   Epithelial-mesenchymal transition   Basal cells   scRNA-seq  

摘要： ObjectiveToll-interacting protein (Tollip) suppresses excessive pro-inflammatory signaling, but its function in airway epithelial responses to IL-13, a key mediator in allergic diseases, remains unclear. This study investigates Tollip knockdown (TKD) effects in primary human airway epithelial cells using single-cell RNA sequencing, providing the first single-cell analysis of TKD and the first exploring its interaction with ***-13 treatment upregulated key genes, including SPDEF, MUC5AC, POSTN, ALOX15, and CCL26, confirming IL-13's effects and validating our methods. IL-13 reduced TNF-alpha signaling and epithelial-mesenchymal transition in certain cell types, suggesting a dual role in promoting type 2 inflammation while suppressing Th1-driven inflammation. Tollip deficiency alone significantly amplified TNF-alpha signaling and inflammatory pathways in goblet, club, and suprabasal cells. Comparisons between TKDIL13 vs IL13 and TKD vs CTR revealed that IL-13 does not substantially alter Tollip deficiency response in most cell types, reinforcing findings in TKD vs CTR. Tollip deficiency alters the response to IL-13 in a cell-type-specific manner, strongly downregulating TNF-alpha signaling in goblet cells but only weakly in basal and club cells. Tollip deficiency enhances IL-13's suppression of Th1 inflammatory responses in goblet cells. These novel insights in Tollip-IL-13 interactions offer potential therapeutic targets for asthma and related diseases.

关键词： IL-37   inflammation   oxidative stress   sepsis-induced lung injury   TGF-beta/Smad3  

摘要： Introduction: Sepsis is caused by an uncontrolled inflammatory response and immune dysfunction, with lung injury being the most common complication and one of the leading causes of death in clinically ill patients. Interleukin 37 (IL-37) is a multifunctional cytokine that plays a vital role in various pathophysiological processes, including inflammation, infection, and ***: The study involved both clinical and animal experiments (establishing an animal model of sepsis-induced lung injury). Firstly, 50 patients with sepsis-induced lung injury and 50 healthy controls were included. In addition, a more in-depth study was conducted using animal ***: IL-37, IL-6, PCT, and CRP levels were significantly higher in the sepsis-induced lung injury group. Correlation analysis revealed that IL-37 significantly correlated with IL-6, PCT, and CRP levels. In animal experiments, IL-37 significantly attenuated CLP-induced pulmonary edema and cellular injury while reducing the levels of inflammatory factors IL-6 and TNF-alpha, as well as sepsis-related inflammatory markers PCT and CRP. Moreover, IL-37 significantly downregulated the expression levels of genes and proteins of apoptosis-related molecules Caspase-3 and Bax and pathway molecules TGF-beta and Smad3. Discussion: The TGF-beta/Smad3 pathway is involved in the process of IL-37 inhibiting inflammatory response and ameliorating sepsis-induced lung injury.

关键词： modified Kugel repair   inguinal hernia   IL-6   CRP   MMP-9  

摘要： Objective To evaluate the effect of serum IL-6, C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal *** Clinical records of 42 patients with inguinal hernias who underwent modified preperitoneal Kugel repair were retrospectively analyzed. Serum IL-6, CRP, and MMP-9 were detected before surgery and after surgery. The patients were divided into the corresponding high-expression group and low-expression group. The basic data and clinical characteristics of patients were analyzed and compared, as well as postoperative *** In patients with inguinal hernia, serum IL-6, CRP, and MMP-9 increase first and then decrease after surgery, reaching the peak value around 24 or 48 h after surgery. Patients with high-expression of IL-6, CRP, and MMP-9 had longer hospital stays and time to return to normal activities, and were more likely to have chronic abdominal pain. In addition, high-expression of IL-6 and CRP had a higher probability of postoperative VAS values and wound infection, and high-expression of IL-6 and MMP-9 were also more likely to have wound healing *** Serum IL-6, CRP, and MMP-9 levels in patients with inguinal hernia can affect the efficacy of modified preperitoneal Kugel repair and the prognosis of patients.