白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿...白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿瘤、消化道肿瘤、乳腺癌、宫颈癌等。本综述旨在阐明IL1RAP介导的信号通路的生物学效应,以及IL1RAP在各类恶性肿瘤中作用机制的研究进展。Interleukin 1 receptor accessory protein (IL1RAP) is a co-receptor of the interleukin 1 (IL-1) family, which exerts biological effects by binding to the interleukin 1 receptor (IL-1R) to form a multimeric complex and activating the downstream signaling pathway. The signaling pathway mediated by IL1RAP shows pro-proliferative, pro-invasive, and migratory properties in various types of malignant tumors, including hematological tumors, gastrointestinal tract tumors, breast cancers, cervical cancer, etc. The aim of this review is to elucidate the biological effects of IL1RAP-mediated signaling pathway and the progress of the research on the mechanism of IL1RAP in various malignant tumors.展开更多
Objective:The objective of this study was to determine the level of methotrexate(MTX)toxicity in the intestines of mice and to evaluate the protective effect of probiotics composed of Streptococcus,Bifidobacterium,and...Objective:The objective of this study was to determine the level of methotrexate(MTX)toxicity in the intestines of mice and to evaluate the protective effect of probiotics composed of Streptococcus,Bifidobacterium,and Lactobacillus species on intestinal cells during MTX treatment.Methods:Mice were divided into three groups:control,MTX group(received MTX injections),and MTX+probiotics group(received MTX injections along with a diet containing probiotics).Morphological and histological changes,the level of mitochondrial DNA(mtDNA)damage,the level of lipid peroxidation products,and gene expression in the mice’s small intestine were assessed.Results:We demonstrated that intraperitoneal MTX injections significantly increased mtDNA damage in the liver(p<0.001),small intestine(p<0.001),and blood of mice(p<0.01).MTX elevated the quantity of lipid peroxidation products in the liver and small intestine,indicating its strong prooxidative properties.MTX induced structural changes in the mice’s intestines,characterized by leukocytic infiltration of tissues.Probiotic therapy in mice partially mitigated the morphological and histological changes in the small intestine induced by MTX,reduced oxidative stress,and promoted increased expression of quinone oxidoreductase 1(Nqo1),which participates in both cell protection against oxidative stress and drug/xenobiotic detoxification.Probiotics prevented the upregulation of the proinflammatory cytokine IL-1b in the small intestine and induced increased expression of genes associated with the Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)pathway,an important mechanism of cell protection.Conclusions:Probiotics can be considered an effective approach to reducing the toxicity of MTX during psoriasis or cancer treatment.展开更多
文摘白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿瘤、消化道肿瘤、乳腺癌、宫颈癌等。本综述旨在阐明IL1RAP介导的信号通路的生物学效应,以及IL1RAP在各类恶性肿瘤中作用机制的研究进展。Interleukin 1 receptor accessory protein (IL1RAP) is a co-receptor of the interleukin 1 (IL-1) family, which exerts biological effects by binding to the interleukin 1 receptor (IL-1R) to form a multimeric complex and activating the downstream signaling pathway. The signaling pathway mediated by IL1RAP shows pro-proliferative, pro-invasive, and migratory properties in various types of malignant tumors, including hematological tumors, gastrointestinal tract tumors, breast cancers, cervical cancer, etc. The aim of this review is to elucidate the biological effects of IL1RAP-mediated signaling pathway and the progress of the research on the mechanism of IL1RAP in various malignant tumors.
基金This research was carried out within the State Assignment of the Ministry of Science and Higher Education of the Russian Federation(project FZGW-2024-0003).
文摘Objective:The objective of this study was to determine the level of methotrexate(MTX)toxicity in the intestines of mice and to evaluate the protective effect of probiotics composed of Streptococcus,Bifidobacterium,and Lactobacillus species on intestinal cells during MTX treatment.Methods:Mice were divided into three groups:control,MTX group(received MTX injections),and MTX+probiotics group(received MTX injections along with a diet containing probiotics).Morphological and histological changes,the level of mitochondrial DNA(mtDNA)damage,the level of lipid peroxidation products,and gene expression in the mice’s small intestine were assessed.Results:We demonstrated that intraperitoneal MTX injections significantly increased mtDNA damage in the liver(p<0.001),small intestine(p<0.001),and blood of mice(p<0.01).MTX elevated the quantity of lipid peroxidation products in the liver and small intestine,indicating its strong prooxidative properties.MTX induced structural changes in the mice’s intestines,characterized by leukocytic infiltration of tissues.Probiotic therapy in mice partially mitigated the morphological and histological changes in the small intestine induced by MTX,reduced oxidative stress,and promoted increased expression of quinone oxidoreductase 1(Nqo1),which participates in both cell protection against oxidative stress and drug/xenobiotic detoxification.Probiotics prevented the upregulation of the proinflammatory cytokine IL-1b in the small intestine and induced increased expression of genes associated with the Nuclear factor erythroid 2-related factor 2/Antioxidant response element(Nrf2/ARE)pathway,an important mechanism of cell protection.Conclusions:Probiotics can be considered an effective approach to reducing the toxicity of MTX during psoriasis or cancer treatment.
