Pub Date : 2024-08-01DOI: 10.1615/critrevimmunol.2024054889
Milan Medd
Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell-surface receptor belonging to the TREM family that is predominantly expressed on myeloid cells such as granulocytes, monocytes, osteocytes, macrophages, and microglia. While much of the functionality of TREM2 is not well understood at the molecular level, it is well-established that TREM2 plays a significant role in the regulation of a broad definition of macrophage inflammatory responses. Dysregulation of TREM2 has been implicated in a large number of diseases including Alzheimer’s disease, Nasu-Hakola disease, bone-related diseases, and atherosclerosis. The TREM2 gene is highly conserved evolutionarily and at the level of controlling its expression. The function of TREM2 is highly conserved across the broad definition of macrophages, including microglia, osteoclasts, and vascular macrophages. This genetic and physiological “niche conservatism” strongly suggests its pivotal role in regulating inflammatory responses. This mini-review summarizes our current understanding of the structure, expression, and function of TREM2 in the pathogenesis of macrophage-mediated diseases.
{"title":"TREM2 in Regulating Macrophage Inflammatory Responses and Disease Pathogenesis","authors":"Milan Medd","doi":"10.1615/critrevimmunol.2024054889","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024054889","url":null,"abstract":"Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell-surface receptor belonging to the TREM family that is predominantly expressed on myeloid cells such as granulocytes, monocytes, osteocytes, macrophages, and microglia. While much of the functionality of TREM2 is not well understood at the molecular level, it is well-established that TREM2 plays a significant role in the regulation of a broad definition of macrophage inflammatory responses. Dysregulation of TREM2 has been implicated in a large number of diseases including Alzheimer’s disease, Nasu-Hakola disease, bone-related diseases, and atherosclerosis. The TREM2 gene is highly conserved evolutionarily and at the level of controlling its expression. The function of TREM2 is highly conserved across the broad definition of macrophages, including microglia, osteoclasts, and vascular macrophages. This genetic and physiological “niche conservatism” strongly suggests its pivotal role in regulating inflammatory responses. This mini-review summarizes our current understanding of the structure, expression, and function of TREM2 in the pathogenesis of macrophage-mediated diseases.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"38 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1615/critrevimmunol.2024053766
Anahid Jewett, Sanaz Memarzadeh, Kawaljit Kaur
Despite advancements in cancer therapeutics such as checkpoint inhibitors and some targeted therapies, we have not achieved success in effectively treating ovarian cancer, since these therapeutics only benefit a subset of patients, and also provide short-term protection or cure. The use of chemotherapy and radiation therapy can cause depletion and/or lack of immune cells’ function. CAR-T therapy is found effective against several blood-based cancers, but limited success was seen against solid tumors. Targeting fewer antigens and significant side effects of therapy decreases the efficacy of CAR-T cells as immunotherapeutic in solid tumors, even though there is a great drive and significant effort to establish these therapies around the world. Bispecific and tri-specific antibodies have recently been advocated as effective cancer therapeutics. However, these also suffer the fate of CAR-Ts since the loss of antigen on tumor cells will render these therapeutics ineffective. At the moment we should design therapeutics that may have synergistic effects on killing/treating tumors. The only way we can establish that will be by learning the mechanisms of actions of immune therapeutics. Thus, advancement in the knowledge and effective strategies are required to develop cancer immuno-therapeutics
{"title":"Commentary: Ovarian cancer; path to effective treatments","authors":"Anahid Jewett, Sanaz Memarzadeh, Kawaljit Kaur","doi":"10.1615/critrevimmunol.2024053766","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024053766","url":null,"abstract":"Despite advancements in cancer therapeutics such as checkpoint inhibitors and some targeted therapies, we have not achieved success in effectively treating ovarian cancer, since these therapeutics only benefit a subset of patients, and also provide short-term protection or cure. The use of chemotherapy and radiation therapy can cause depletion and/or lack of immune cells’ function. CAR-T therapy is found effective against several blood-based cancers, but limited success was seen against solid tumors. Targeting fewer antigens and significant side effects of therapy decreases the efficacy of CAR-T cells as immunotherapeutic in solid tumors, even though there is a great drive and significant effort to establish these therapies around the world. Bispecific and tri-specific antibodies have recently been advocated as effective cancer therapeutics. However, these also suffer the fate of CAR-Ts since the loss of antigen on tumor cells will render these therapeutics ineffective. At the moment we should design therapeutics that may have synergistic effects on killing/treating tumors. The only way we can establish that will be by learning the mechanisms of actions of immune therapeutics. Thus, advancement in the knowledge and effective strategies are required to develop cancer immuno-therapeutics","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"100 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141253595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1615/critrevimmunol.2024053166
Qing Li, Changchun Zhang, Li Li
Background: Breast cancer (BC) is among the most prevalent malignant cancers in women. This paper proposed to investigate the function as well as the regulatory mechanism of N6-methyladenosine (m6A) reader leucine rich pentatricopeptide repeat containing (LRPPRC) in BC inflammation and progression. Methods: The levels of LRPPRC and C-X-C motif chemokine ligand 11 (CXCL11) were detected via qRT-PCR. The regulatory mechanisms between LRPPRC and CXCL11 were investigated by RIP, MeRIP, and mRNA stability experiments. Moreover, the bio-functions of LRPPRC and CXCL11 in BC cells were explored through the CCK8, wound healing, Transwell assays. ELISA was utilized to evaluate pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) levels. Results: LRPPRC had a considerably higher level in BC samples than in healthy samples, and LRPPRC overexpression predicted poor prognosis. LRPPRC lowexpression diminished BC cell viability, migration, and invasion, whereas overexpression facilitated malignancy. LRPPRC exerted its stimulative effect through CXCL11 m6A modification. CXCL11 upregulating suppressed the LRPPRC silencing’s antitumor effect on BC cells malignancy. CXCL11 upregulation enhances inflammatory factors secretion by BC cells. Conclusion: This study demonstrated that LRPPRC aggravated BC inflammation and malignancy by upregulating m6A modification of CXCL11. These findings offered a potential to be a target for BC patients’ therapy.
背景：乳腺癌（BC）是女性发病率最高的恶性肿瘤之一。本文拟研究含 N6-甲基腺苷（m6A）的富含亮氨酸五肽重复序列（LRPPRC）在 BC 炎症和进展中的功能及调控机制：方法：通过 qRT-PCR 检测 LRPPRC 和 C-X-C motif 趋化因子配体 11（CXCL11）的水平。方法：通过 qRT-PCR 检测 LRPPRC 和 C-X-C motif 趋化因子配体 11（CXCL11）的水平，通过 RIP、MeRIP 和 mRNA 稳定性实验研究 LRPPRC 和 CXCL11 之间的调控机制。此外，还通过 CCK8、伤口愈合和 Transwell 试验探讨了 LRPPRC 和 CXCL11 在 BC 细胞中的生物功能。利用酶联免疫吸附法评估了促炎细胞因子（TNF-α、IL-6、IL-1β）的水平：结果：LRPPRC在BC样本中的水平远高于健康样本，LRPPRC过表达预示着预后不良。LRPPRC 低表达会降低 BC 细胞的活力、迁移和侵袭，而过表达则会促进恶性肿瘤的发生。LRPPRC通过CXCL11 m6A修饰发挥刺激作用。CXCL11 上调抑制了 LRPPRC 沉默对 BC 细胞恶性肿瘤的抗肿瘤作用。CXCL11上调可促进BC细胞分泌炎症因子：本研究表明，LRPPRC通过上调CXCL11的m6A修饰，加重了BC细胞的炎症和恶性程度。这些发现有望成为治疗 BC 患者的靶点。
{"title":"N6-methyladenosine (m6A) reader LRPPRC-mediated CXCL11 induces cell inflammation to drive breast cancer cell malignancy","authors":"Qing Li, Changchun Zhang, Li Li","doi":"10.1615/critrevimmunol.2024053166","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024053166","url":null,"abstract":"Background: Breast cancer (BC) is among the most prevalent malignant cancers in women. This paper proposed to investigate the function as well as the regulatory mechanism of N6-methyladenosine (m6A) reader leucine rich pentatricopeptide repeat containing (LRPPRC) in BC inflammation and progression.\u0000Methods: The levels of LRPPRC and C-X-C motif chemokine ligand 11 (CXCL11) were detected via qRT-PCR. The regulatory mechanisms between LRPPRC and CXCL11 were investigated by RIP, MeRIP, and mRNA stability experiments. Moreover, the bio-functions of LRPPRC and CXCL11 in BC cells were explored through the CCK8, wound healing, Transwell assays. ELISA was utilized to evaluate pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) levels.\u0000Results: LRPPRC had a considerably higher level in BC samples than in healthy samples, and LRPPRC overexpression predicted poor prognosis. LRPPRC lowexpression diminished BC cell viability, migration, and invasion, whereas overexpression facilitated malignancy. LRPPRC exerted its stimulative effect through CXCL11 m6A modification. CXCL11 upregulating suppressed the LRPPRC silencing’s antitumor effect on BC cells malignancy. CXCL11 upregulation enhances inflammatory factors secretion by BC cells.\u0000Conclusion: This study demonstrated that LRPPRC aggravated BC inflammation and malignancy by upregulating m6A modification of CXCL11. These findings offered a potential to be a target for BC patients’ therapy.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"153 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141505469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1615/critrevimmunol.2024053504
Uddeshya Sharma
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder with multifactorial interactions among various susceptibility factors. Significant strides have been made in under-standing the pathogenesis of SLE, leading to the development of targeted therapies and the exploration of alternative treatments. The approval of new therapies has expanded patient treatment options, and ongoing clinical trials promise to enhance the treatment landscape fur-ther. The future of SLE treatment lies in personalized, targeted therapies that minimize side effects and improve patient outcomes. This review comprehensively analyzes SLE’s current and prospects based on recent studies, patents, clinical trials, and formulations. Continued research and clinical trials are crucial to uncovering new therapeutic options and ultimately transforming the treatment landscape for SLE. With sustained efforts and advancements in medical science, we can offer a better quality of life and improved survival rates for SLE pa-tients.
{"title":"The SLE Conundrum: A Comprehensive Analysis of Pathogenesis, Re-cent Developments, and the Future of Therapeutic Interventions","authors":"Uddeshya Sharma","doi":"10.1615/critrevimmunol.2024053504","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024053504","url":null,"abstract":"Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder with multifactorial interactions among various susceptibility factors. Significant strides have been made in under-standing the pathogenesis of SLE, leading to the development of targeted therapies and the exploration of alternative treatments. The approval of new therapies has expanded patient treatment options, and ongoing clinical trials promise to enhance the treatment landscape fur-ther. The future of SLE treatment lies in personalized, targeted therapies that minimize side effects and improve patient outcomes. This review comprehensively analyzes SLE’s current and prospects based on recent studies, patents, clinical trials, and formulations. Continued research and clinical trials are crucial to uncovering new therapeutic options and ultimately transforming the treatment landscape for SLE. With sustained efforts and advancements in medical science, we can offer a better quality of life and improved survival rates for SLE pa-tients.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"2016 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1615/critrevimmunol.2024052129
Feifan Wang, Lingshan Bei, Xiaoyan Zhang, Yangxi Fu
Objective Vitamin D deficiency is known to be a significant factor in metabolic diseases such as obesity and diabetes. However, there is currently a lack of evidence regarding the effects of vitamin D on hyperlipidemia, glucose metabolism, and bone mass in pediatric patients with obesity. Methods Our study aimed to determine the relationship between Serum 25(OH)D and metabolic syndrome, as well as investigate the effect of Vitamin D3 supplementation on hyperlipidemia, glucose metabolism, and bone mass in pediatric patients with obesity. We conducted a cross-sectional study between January 2018 and January 2020, with a total of 723 children invited to participate. Of these, 283 were in the supplemented group (SG) and 440 were in the placebo group (PG). We evaluated blood pressure, fasting glucose, high-density lipoprotein, total cholesterol, low-density lipoprotein, and bone mineral density (BMD) among all subjects. Results We found that cholesterol, triglyceride, and glucose levels were strongly associated with 25(OH)D3 levels at baseline. After vitamin D3 supplementation, we observed a significant increase in body mass index (BMI) (P=0.02) and serum 25(OH)D3(P<0.01) levels in the vitamin D3 group compared to the placebo group. Additionally, serum lipids such as total cholesterol(P<0.01), HDL-c(P<0.01), Total cholesterol/HDL-c (P<0.01), LDL-c/HDL-c (P<0.01), Triglycerides/HDL-c(P<0.01) were significantly decreased in the Vit D group compared to the placebo group. Serum 25(OH)D was inversely associated with cholesterol, triglycerides, and fasting glucose. Conclusion Our results suggest that vitamin D3 supplementation can enhance the beneficial effect of hyperlipi
{"title":"The effect of supplementation of vitamin D on hyperlipidemia and bone mass in the pediatric with obesity","authors":"Feifan Wang, Lingshan Bei, Xiaoyan Zhang, Yangxi Fu","doi":"10.1615/critrevimmunol.2024052129","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052129","url":null,"abstract":"Objective\u0000Vitamin D deficiency is known to be a significant factor in metabolic diseases such as obesity and diabetes. However, there is currently a lack of evidence regarding the effects of vitamin D on hyperlipidemia, glucose metabolism, and bone mass in pediatric patients with obesity.\u0000Methods\u0000Our study aimed to determine the relationship between Serum 25(OH)D and metabolic syndrome, as well as investigate the effect of Vitamin D3 supplementation on hyperlipidemia, glucose metabolism, and bone mass in pediatric patients with obesity. We conducted a cross-sectional study between January 2018 and January 2020, with a total of 723 children invited to participate. Of these, 283 were in the supplemented group (SG) and 440 were in the placebo group (PG). We evaluated blood pressure, fasting glucose, high-density lipoprotein, total cholesterol, low-density lipoprotein, and bone mineral density (BMD) among all subjects.\u0000Results\u0000We found that cholesterol, triglyceride, and glucose levels were strongly associated with 25(OH)D3 levels at baseline. After vitamin D3 supplementation, we observed a significant increase in body mass index (BMI) (P=0.02) and serum 25(OH)D3(P<0.01) levels in the vitamin D3 group compared to the placebo group. Additionally, serum lipids such as total cholesterol(P<0.01), HDL-c(P<0.01), Total cholesterol/HDL-c (P<0.01), LDL-c/HDL-c (P<0.01), Triglycerides/HDL-c(P<0.01) were significantly decreased in the Vit D group compared to the placebo group. Serum 25(OH)D was inversely associated with cholesterol, triglycerides, and fasting glucose.\u0000Conclusion\u0000Our results suggest that vitamin D3 supplementation can enhance the beneficial effect of hyperlipi","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1615/critrevimmunol.2024050244
Yan Fang, Shibo Sun, Chuang Xiao, Min Li, Yuanyuan Zheng, Anju Zu, Zhuang Luo
Objective: In this study, network pharmacology combined with biological experimental verification was utilized to screen the targets of Isoforskolin (ISOF) and investigate the potential underlying mechanism of ISOF acting on asthma. Methods: Asthma-related targets were screened from the Genecards and DisGeNET databases. SEA and Super-PRED databases were used to obtain the targets of ISOF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to identify key targets and enriched regulatory pathways of ISOF acting on asthma. Then, a protein-protein interaction (PPI) network was constructed via STRING database and hub genes of ISOF against asthma were further screened using molecular docking. Finally, CCK-8, qPCR, and western blotting were performed to assess the targets of ISOF in treating asthma. Results: A total of 96 drug-related-disease targets from the relevant databases were screened out. KEGG pathway enrichment analysis predicted that the target genes might be involved in the PI3K-Akt pathway. The core targets of ISOF in treating asthma were identified by the PPI network and molecular docking, including MAPK1, mTOR, and NFKB1. Consistently, in vitro experiments showed that ISOF acting on asthma was involved in inflammatory response by reducing the expression of MAPK1, mTOR, and NFKB1. Conclusions: The present study reveals that MAPK1, mTOR, and NFKB1 might be key targets of Isoforskolin in asthma treatment and the anti-asthma effect might be related to the PI3K-AKT signaling pathway.
{"title":"Exploring the mechanism of Isoforskolin against asthma based on network pharmacology and experimental verification","authors":"Yan Fang, Shibo Sun, Chuang Xiao, Min Li, Yuanyuan Zheng, Anju Zu, Zhuang Luo","doi":"10.1615/critrevimmunol.2024050244","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024050244","url":null,"abstract":"Objective: In this study, network pharmacology combined with biological experimental verification was utilized to screen the targets of Isoforskolin (ISOF) and investigate the potential underlying mechanism of ISOF acting on asthma.\u0000Methods: Asthma-related targets were screened from the Genecards and DisGeNET databases. SEA and Super-PRED databases were used to obtain the targets of ISOF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to identify key targets and enriched regulatory pathways of ISOF acting on asthma. Then, a protein-protein interaction (PPI) network was constructed via STRING database and hub genes of ISOF against asthma were further screened using molecular docking. Finally, CCK-8, qPCR, and western blotting were performed to assess the targets of ISOF in treating asthma.\u0000Results: A total of 96 drug-related-disease targets from the relevant databases were screened out. KEGG pathway enrichment analysis predicted that the target genes might be involved in the PI3K-Akt pathway. The core targets of ISOF in treating asthma were identified by the PPI network and molecular docking, including MAPK1, mTOR, and NFKB1. Consistently, in vitro experiments showed that ISOF acting on asthma was involved in inflammatory response by reducing the expression of MAPK1, mTOR, and NFKB1.\u0000Conclusions: The present study reveals that MAPK1, mTOR, and NFKB1 might be key targets of Isoforskolin in asthma treatment and the anti-asthma effect might be related to the PI3K-AKT signaling pathway.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"38 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1615/critrevimmunol.2024053203
Jian Shen, Minzhe Li
Background: Anoikis is a specialized form of programmed cell death and is also related mitophagy process. Objective:We aimed to identify an anoikis and mitophagy-related genes (AMRGs) prognostic model and explore the role of SPHK1 in colon cancer (CC). Methods: Bioinformatic methods were used to screen the AMRGs. Based on these genes, all the samples were divided into different subtypes. Furthermore, LASSO was conducted to optimized the AMRGs. Based on the optimal genes, a prognostic risk score model was established and evaluated. Finally, the effects of downregulated SPHK1 on the CC cell proliferation, migration, invasion, and anoikis were investigated. Results: Based on the AMRGs, all the CC samples were divided into subtype 1 and subtype 2. An AMRGs signature containing three key genes (SPHK1, CDC25C, and VPS37A) that exhibiting predicting ability in CC survival is confirmed. Subtype2 and low-risk groups exhibited better survival and higher immune cell infiltration. Moreover, down-regulated SPHK1 is related to lower cell proliferation, migration, and invasion ability, as well as higher anoikis in CC cell line (P < 0.01). Conclusion: The AMRGs risk score model exhibits promising predicting ability on patients with CC. SPHK1 might inhibit CC cell growth, migration, and invasion through stimulating anoikis.
背景：目的：我们的目的是确定一个与有丝分裂相关基因（AMRGs）的预后模型，并探索SPHK1在结肠癌（CC）中的作用：方法：采用生物信息学方法筛选AMRGs。方法：采用生物信息学方法筛选 AMRGs，并根据这些基因将所有样本分为不同的亚型。此外，还通过 LASSO 对 AMRGs 进行了优化。在优化基因的基础上，建立并评估了预后风险评分模型。最后，研究了下调的 SPHK1 对 CC 细胞增殖、迁移、侵袭和厌氧的影响：结果：根据 AMRGs，所有 CC 样本被分为亚型 1 和亚型 2。包含三个关键基因（SPHK1、CDC25C和VPS37A）的AMRGs特征被证实具有预测CC存活率的能力。亚型2和低风险组的生存率更高，免疫细胞浸润也更高。此外，SPHK1的下调与CC细胞系的细胞增殖、迁移和侵袭能力降低以及瘤变增加有关（P < 0.01）：AMRGs风险评分模型对CC患者具有良好的预测能力。结论：AMRGs风险评分模型对CC患者有很好的预测能力，SPHK1可能会通过刺激嗜酸性细胞抑制CC细胞的生长、迁移和侵袭。
{"title":"Anoikis and Mitophagy-Related Gene Signature for Predicting the Survival and Tumor Cell Progression in Colon Cancer","authors":"Jian Shen, Minzhe Li","doi":"10.1615/critrevimmunol.2024053203","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024053203","url":null,"abstract":"Background: Anoikis is a specialized form of programmed cell death and is also related mitophagy process.\u0000Objective:We aimed to identify an anoikis and mitophagy-related genes (AMRGs) prognostic model and explore the role of SPHK1 in colon cancer (CC).\u0000Methods: Bioinformatic methods were used to screen the AMRGs. Based on these genes, all the samples were divided into different subtypes. Furthermore, LASSO was conducted to optimized the AMRGs. Based on the optimal genes, a prognostic risk score model was established and evaluated. Finally, the effects of downregulated SPHK1 on the CC cell proliferation, migration, invasion, and anoikis were investigated.\u0000Results: Based on the AMRGs, all the CC samples were divided into subtype 1 and subtype 2. An AMRGs signature containing three key genes (SPHK1, CDC25C, and VPS37A) that exhibiting predicting ability in CC survival is confirmed. Subtype2 and low-risk groups exhibited better survival and higher immune cell infiltration. Moreover, down-regulated SPHK1 is related to lower cell proliferation, migration, and invasion ability, as well as higher anoikis in CC cell line (P < 0.01).\u0000Conclusion: The AMRGs risk score model exhibits promising predicting ability on patients with CC. SPHK1 might inhibit CC cell growth, migration, and invasion through stimulating anoikis.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"10 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Osteoarthritis (OA) is the primary cause of disability worldwide. Chondrocyte apoptosis has important implications for OA onset and progression. This work was designed to explore the mechanisms of chondrocyte apoptosis in OA and identify key chondrocyte apoptosis-related genes (CARGs). Methods: GSE32317 and GSE55235 datasets were acquired from the Gene Expression Omnibus (GEO) database. OA-associated module genes were determined via weighted gene co-expression network analysis (WGCNA) in GSE32317. CARGs were acquired from public databases. ClusterProfiler was employed for GO and KEGG analyses. Protein-protein interaction (PPI) network establishment was realized via STRING database and Cytoscape, and the hub genes were screened by MCC, MNC, and DMNC algorithms of cytoHubba. The diagnostic values of the hub CARGs in OA in GSE55235 was verified via receiver operating characteristic (ROC) curve analysis. C28/I2 cells were stimulated with IL-1β to establish the in vitro OA model. Results: WGCNA identified 9,141 OA-related genes and 248 CARGs, resulting in 75 CARGs in OA. GO and KEGG analyses demonstrated that the 75 CARGs were primarily enriched in response to lipopolysaccharide, transcription regulator complex, DNA-binding transcription factor binding, along with NF-kappa B and TNF signaling pathways. NFKB1 and ICAM1 were identified as the hub CARGs in OA through the three algorithms, which showed favorable prognostic values for OA. Notably, both bioinformatics analysis and in vitro assays revealed upregulated NFKB1 and ICAM1 expression in OA. Conclusions: NFKB1 and ICAM1 were the hub CARGs in OA, which might serve as the diagnostic signatures and therapeutic
目的：骨关节炎（OA）是导致全球残疾的主要原因。软骨细胞凋亡对 OA 的发生和发展具有重要影响。本研究旨在探索 OA 中软骨细胞凋亡的机制，并鉴定关键的软骨细胞凋亡相关基因（CARGs）：GSE32317和GSE55235数据集来自基因表达总库（GEO）数据库。通过加权基因共表达网络分析（WGCNA）确定 GSE32317 中与 OA 相关的模块基因。CARGs来自公共数据库。ClusterProfiler 用于 GO 和 KEGG 分析。通过 STRING 数据库和 Cytoscape 建立了蛋白质-蛋白质相互作用（PPI）网络，并利用 cytoHubba 的 MCC、MNC 和 DMNC 算法筛选了中心基因。通过接收者操作特征曲线（ROC）分析验证了GSE55235中的中枢CARGs在OA中的诊断价值。用 IL-1β 刺激 C28/I2 细胞，建立体外 OA 模型：WGCNA鉴定了9141个OA相关基因和248个CARGs，其中75个CARGs与OA有关。GO和KEGG分析表明，这75个CARGs主要富集在对脂多糖、转录调节因子复合体、DNA结合转录因子结合以及NF-kappa B和TNF信号通路的反应中。通过这三种算法，NFKB1 和 ICAM1 被确定为 OA 中的枢纽 CARGs，这两种 CARGs 对 OA 有良好的预后价值。值得注意的是，生物信息学分析和体外实验均显示，NFKB1和ICAM1在OA中表达上调：结论：NFKB1和ICAM1是OA的枢纽CARG，可作为诊断特征和治疗手段。
{"title":"Identification of key chondrocyte apoptosis-related genes in osteoarthritis based on weighted gene co-expression network analysis and experimental verification","authors":"Wei Wang, Junyi Hong, Tianyi Cao, Fusheng Ye, Junwei Gao, Shumei Qin","doi":"10.1615/critrevimmunol.2024051935","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051935","url":null,"abstract":"Objective: Osteoarthritis (OA) is the primary cause of disability worldwide. Chondrocyte apoptosis has important implications for OA onset and progression. This work was designed to explore the mechanisms of chondrocyte apoptosis in OA and identify key chondrocyte apoptosis-related genes (CARGs).\u0000Methods: GSE32317 and GSE55235 datasets were acquired from the Gene Expression Omnibus (GEO) database. OA-associated module genes were determined via weighted gene co-expression network analysis (WGCNA) in GSE32317. CARGs were acquired from public databases. ClusterProfiler was employed for GO and KEGG analyses. Protein-protein interaction (PPI) network establishment was realized via STRING database and Cytoscape, and the hub genes were screened by MCC, MNC, and DMNC algorithms of cytoHubba. The diagnostic values of the hub CARGs in OA in GSE55235 was verified via receiver operating characteristic (ROC) curve analysis. C28/I2 cells were stimulated with IL-1β to establish the in vitro OA model.\u0000Results: WGCNA identified 9,141 OA-related genes and 248 CARGs, resulting in 75 CARGs in OA. GO and KEGG analyses demonstrated that the 75 CARGs were primarily enriched in response to lipopolysaccharide, transcription regulator complex, DNA-binding transcription factor binding, along with NF-kappa B and TNF signaling pathways. NFKB1 and ICAM1 were identified as the hub CARGs in OA through the three algorithms, which showed favorable prognostic values for OA. Notably, both bioinformatics analysis and in vitro assays revealed upregulated NFKB1 and ICAM1 expression in OA.\u0000Conclusions: NFKB1 and ICAM1 were the hub CARGs in OA, which might serve as the diagnostic signatures and therapeutic","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"28 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Increase in cancer cases -numerically and etiologically encouraged research aiming development of novel treatment strategies, amongst which few are even implemented but with varying degrees of success along with specific limitations. For example, conventional treatment strategies viz. chemotherapy and radiotherapy have limited potential owing to their nonspecific cytotoxic nature thereby shifting focus towards immunotherapy. Recently, target specific immunotherapeutic regimens have been evaluated for their efficacy including 1) vaccines harnessing tumor specific/associated antigens, 2) checkpoint blockade therapy using monoclonal antibodies against PD1, CTLA-4 and others, 3) adoptive cell transfer approaches viz. CAR-cell-based therapies. Here we review recent advancements on these target specific translational immunotherapeutic strategies against cancer/s and concerned limitations.
癌症病例在数量上和病因上的增加鼓励了以开发新型治疗策略为目标的研究。例如，传统的治疗策略，即化疗和放疗，由于具有非特异性细胞毒性，其潜力有限，因此研究重点转向了免疫疗法。最近，人们对靶点特异性免疫治疗方案的疗效进行了评估，这些方案包括：1）利用肿瘤特异性/相关抗原的疫苗；2）使用针对 PD1、CTLA-4 等单克隆抗体的检查点阻断疗法；3）采用细胞转移方法，即基于 CAR 细胞的疗法。在此，我们将回顾这些针对癌症的特异性靶点转化免疫治疗策略的最新进展及相关局限性。
{"title":"Advances in Vaccines, Checkpoint Blockade and Chimeric Antigen Receptor based Cancer Immunotherapeutics","authors":"Disha Agarwal, Gaurav Sharma, Alka Khadwal, Devinder Toor, Pankaj Malhotra","doi":"10.1615/critrevimmunol.2024053025","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024053025","url":null,"abstract":"Increase in cancer cases -numerically and etiologically encouraged research aiming development of novel treatment strategies, amongst which few are even implemented but with varying degrees of success along with specific limitations. For example, conventional treatment strategies viz. chemotherapy and radiotherapy have limited potential owing to their nonspecific cytotoxic nature thereby shifting focus towards immunotherapy. Recently, target specific immunotherapeutic regimens have been evaluated for their efficacy including 1) vaccines harnessing tumor specific/associated antigens, 2) checkpoint blockade therapy using monoclonal antibodies against PD1, CTLA-4 and others, 3) adoptive cell transfer approaches viz. CAR-cell-based therapies. Here we review recent advancements on these target specific translational immunotherapeutic strategies against cancer/s and concerned limitations.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"57 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140833301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1615/critrevimmunol.2024051934
Jiawang Lang, Jianchang Luo, Luodan Wang, Wenbin Xu, Jie Jia, Zhipeng Zhao, Boxu Lang
Objective: Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Electroacupuncture (EA) has been shown to exert a neuroprotective effect in IS. However, the specific anti-IS mechanisms of EA remain to be further elucidated. Thus, we aimed to investigate the anti-IS role of EA and its mechanism. Methods: By constructing a rat IS (middle cerebral artery occlusion, MCAO) model and performing EA treatment, the neurological deficit score, brain water content, and cerebral infarction were evaluated. ELISA was used to measure the levels of oxidative stress (OS)-related molecules (MDA, SOD, GSH, and CAT). Ferroptosis-related proteins (GPX4, SLC7A11, TfR1, L-ferritin, and hepcidin), neurological damage-related proteins (GFAP, Iba-1, and Nestin), α7nAChR, and mTOR pathway-related proteins (mTOR, p-mTOR, and SREBP1) in rat brain penumbra were assessed using western blotting. Results: Following EA treatment, the neurological deficit score, brain water content, cerebral infarction, and GFAP, Iba-1, and Nestin expression were reduced in the brain penumbra of MCAO rats. Additionally, EA treatment decreased MDA level and increased SOD, GSH, and CAT levels in the brain penumbra of MCAO rats. Moreover, MCAO rats showed elevated GPX4 and SLC7A11 expression and reduced TfR1, L-ferritin, and hepcidin in the brain penumbra following EA treatment. After EA treatment, α7nAChR, mTOR, p-mTOR, and SREBP1 expression were upregulated in the brain penumbra of MCAO rats. Conclusions: EA treatment inhibited OS and ferroptosis to exert a neuroprotective effect in IS, which might be realized via the activation of mTOR/SREBP1 signaling.
目的：缺血性中风（IS）是导致全球死亡和残疾的主要原因之一。电针（EA）对缺血性中风有神经保护作用。然而，电针抗缺血性中风的具体机制仍有待进一步阐明。因此，我们旨在研究 EA 的抗 IS 作用及其机制：方法：通过构建大鼠 IS（大脑中动脉闭塞，MCAO）模型并进行 EA 治疗，评估神经功能缺损评分、脑水含量和脑梗死情况。采用 ELISA 法测量氧化应激（OS）相关分子（MDA、SOD、GSH 和 CAT）的水平。用 Western 印迹法评估了大鼠大脑半影中的铁氧化相关蛋白（GPX4、SLC7A11、TfR1、L-铁蛋白和 hepcidin）、神经损伤相关蛋白（GFAP、Iba-1 和 Nestin）、α7nAChR 和 mTOR 通路相关蛋白（mTOR、p-mTOR 和 SREBP1）：结果：EA治疗后，MCAO大鼠脑半影的神经功能缺损评分、脑含水量、脑梗死程度以及GFAP、Iba-1和Nestin的表达均有所降低。此外，EA 还能降低 MCAO 大鼠脑半影区的 MDA 水平，提高 SOD、GSH 和 CAT 水平。此外，EA 治疗后，MCAO 大鼠脑半影中 GPX4 和 SLC7A11 表达升高，TfR1、L-铁蛋白和血钙素降低。EA治疗后，MCAO大鼠脑半影中的α7nAChR、mTOR、p-mTOR和SREBP1表达上调：结论：EA治疗可抑制OS和铁突变，从而对IS产生神经保护作用，这可能是通过激活mTOR/SREBP1信号传导实现的。
{"title":"Electroacupuncture Alleviates Ischemic Stroke by Activating the mTOR/SREBP1 Pathway","authors":"Jiawang Lang, Jianchang Luo, Luodan Wang, Wenbin Xu, Jie Jia, Zhipeng Zhao, Boxu Lang","doi":"10.1615/critrevimmunol.2024051934","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051934","url":null,"abstract":"Objective: Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. Electroacupuncture (EA) has been shown to exert a neuroprotective effect in IS. However, the specific anti-IS mechanisms of EA remain to be further elucidated. Thus, we aimed to investigate the anti-IS role of EA and its mechanism.\u0000Methods: By constructing a rat IS (middle cerebral artery occlusion, MCAO) model and performing EA treatment, the neurological deficit score, brain water content, and cerebral infarction were evaluated. ELISA was used to measure the levels of oxidative stress (OS)-related molecules (MDA, SOD, GSH, and CAT). Ferroptosis-related proteins (GPX4, SLC7A11, TfR1, L-ferritin, and hepcidin), neurological damage-related proteins (GFAP, Iba-1, and Nestin), α7nAChR, and mTOR pathway-related proteins (mTOR, p-mTOR, and SREBP1) in rat brain penumbra were assessed using western blotting.\u0000Results: Following EA treatment, the neurological deficit score, brain water content, cerebral infarction, and GFAP, Iba-1, and Nestin expression were reduced in the brain penumbra of MCAO rats. Additionally, EA treatment decreased MDA level and increased SOD, GSH, and CAT levels in the brain penumbra of MCAO rats. Moreover, MCAO rats showed elevated GPX4 and SLC7A11 expression and reduced TfR1, L-ferritin, and hepcidin in the brain penumbra following EA treatment. After EA treatment, α7nAChR, mTOR, p-mTOR, and SREBP1 expression were upregulated in the brain penumbra of MCAO rats.\u0000Conclusions: EA treatment inhibited OS and ferroptosis to exert a neuroprotective effect in IS, which might be realized via the activation of mTOR/SREBP1 signaling.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"32 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140035956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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