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}
Steroid receptor coactivator (SRC) family members (SRC1, SRC2 and SRC3) are transcriptional co-regulators. SRCs orchestrate gene transcription by inducing transactivation of nuclear receptors and other transcription factors. Overexpression of SRCs is widely implicated in a range of cancers, especially hormone-related cancers. As coactivators, SRCs regulate multiple metabolic pathways involved in tumor growth, invasion, metastasis, and chemo-resistance. Emerging evidence in recent years suggest that SRCs also regulate maturation, differentiation, and cytotoxicity of T cells by controlling metabolic activities. In this review, we summarize the current understanding of the function of SRCs in T cells as well as cancer cells. Importantly, the controversies of targeting SRCs for cancer immunotherapy as well as possible reconciliation strategies are also discussed.
类固醇受体辅激活因子（SRC）家族成员（SRC1、SRC2 和 SRC3）是转录协同调控因子。SRC 通过诱导核受体和其他转录因子的转录激活来协调基因转录。SRCs的过度表达与一系列癌症，尤其是与激素相关的癌症有广泛联系。作为辅助激活因子，SRCs 可调节涉及肿瘤生长、侵袭、转移和化疗抗性的多种代谢途径。近年来新出现的证据表明，SRCs 还能通过控制代谢活动来调节 T 细胞的成熟、分化和细胞毒性。在这篇综述中，我们总结了目前对 SRCs 在 T 细胞和癌细胞中功能的理解。重要的是，我们还讨论了针对 SRCs 进行癌症免疫疗法的争议以及可能的调和策略。
{"title":"Function of steroid receptor coactivators (SRCs) in T cells and cancers: Implications for cancer immunotherapy","authors":"Wencan Zhang, Xu Cao, Hongmin Wu, Xiancai Zhong, Yun Shi, Zuoming Sun","doi":"10.1615/critrevimmunol.2024051613","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051613","url":null,"abstract":"Steroid receptor coactivator (SRC) family members (SRC1, SRC2 and SRC3) are transcriptional co-regulators. SRCs orchestrate gene transcription by inducing transactivation of nuclear receptors and other transcription factors. Overexpression of SRCs is widely implicated in a range of cancers, especially hormone-related cancers. As coactivators, SRCs regulate multiple metabolic pathways involved in tumor growth, invasion, metastasis, and chemo-resistance. Emerging evidence in recent years suggest that SRCs also regulate maturation, differentiation, and cytotoxicity of T cells by controlling metabolic activities. In this review, we summarize the current understanding of the function of SRCs in T cells as well as cancer cells. Importantly, the controversies of targeting SRCs for cancer immunotherapy as well as possible reconciliation strategies are also discussed.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"12 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140069872","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 : 2024-02-01DOI: 10.1615/critrevimmunol.2024052728
Di Xu, Ziming Wang, Fajiu Li
Background: Sustained expression of LINC01106 in tumors is crucial for malignant phenotype of tumor cells; Nevertheless, LINC01106’s mechanisms and clinical effects in lung adenocarcinoma (LUAD) is confined. This report focus on reveal the effect of vir-like m6A methyltransferase associated (KIAA1429)-mediated N6-methyladenosine (m6A) modification to steady LINC01106 expression on LUAD progression.Methods: qRT-PCR was conducted to clarify the LINC01106 and KIAA1429 levels in LUAD tissues. LINC01106’s and KIAA1429’s functional roles were analyzed utilizing Transwell, EdU as well as CCK-8 assays. Xenograft was cconducted to verify the function of silencing LINC01106 in tumor growth. The regulatory role between LINC01106 was investigated using MeRIP, qRT-PCR as well as Actinomycin D assay. Key proteins of JAK/STAT3 (JAK2, STAT3) pathway were revealed via western blotting.Results: LINC01106 and KIAA1429 were high-expressed in LUAD, and LINC01106 were interconnected with high tumor grade, stage, and poor prognosis. Data revealed LINC01106 inhibition reduced LUAD cell proliferation, invasion as well as migration, and restrained LUAD cell tumorigenicity. Additionally, phosphorylated JAK2, STAT3 levels were reduced by LINC01106 silencing. LINC01106 was mediated by KIAA1429 to enhance its m6A modification and expression in LUAD cells. Moreover, KIAA1429 promotion abolished the malignant phenotypic suppression induced by LINC01106 lowexpression in LUAD cells.Conclusion: This research revealed LINC01106 m6A modification was enhanced by KIAA1429 to play the promotive role in LUAD development. The results may conduce to the comprehending of the act of KIAA1429-m6A-LINC0110
{"title":"KIAA1429 induces the m6A modification of LINC01106 to enhance the malignancy of lung adenocarcinoma cell via JAK/STAT3 pathway","authors":"Di Xu, Ziming Wang, Fajiu Li","doi":"10.1615/critrevimmunol.2024052728","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052728","url":null,"abstract":"Background: Sustained expression of LINC01106 in tumors is crucial for malignant phenotype of tumor cells; Nevertheless, LINC01106’s mechanisms and clinical effects in lung adenocarcinoma (LUAD) is confined. This report focus on reveal the effect of vir-like m6A methyltransferase associated (KIAA1429)-mediated N6-methyladenosine (m6A) modification to steady LINC01106 expression on LUAD progression.\u0000Methods: qRT-PCR was conducted to clarify the LINC01106 and KIAA1429 levels in LUAD tissues. LINC01106’s and KIAA1429’s functional roles were analyzed utilizing Transwell, EdU as well as CCK-8 assays. Xenograft was cconducted to verify the function of silencing LINC01106 in tumor growth. The regulatory role between LINC01106 was investigated using MeRIP, qRT-PCR as well as Actinomycin D assay. Key proteins of JAK/STAT3 (JAK2, STAT3) pathway were revealed via western blotting.\u0000Results: LINC01106 and KIAA1429 were high-expressed in LUAD, and LINC01106 were interconnected with high tumor grade, stage, and poor prognosis. Data revealed LINC01106 inhibition reduced LUAD cell proliferation, invasion as well as migration, and restrained LUAD cell tumorigenicity. Additionally, phosphorylated JAK2, STAT3 levels were reduced by LINC01106 silencing. LINC01106 was mediated by KIAA1429 to enhance its m6A modification and expression in LUAD cells. Moreover, KIAA1429 promotion abolished the malignant phenotypic suppression induced by LINC01106 lowexpression in LUAD cells.\u0000Conclusion: This research revealed LINC01106 m6A modification was enhanced by KIAA1429 to play the promotive role in LUAD development. The results may conduce to the comprehending of the act of KIAA1429-m6A-LINC0110","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"18 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977763","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 : 2024-02-01DOI: 10.1615/critrevimmunol.2024052389
Kawaljit Kaur, Anahid Jewett
Despite advancements in the field of cancer therapeutics the five-year survival rate remains low in oral cancer patients. There, the effective therapeutics are needed to control the disease. Also, several studies including ours have shown severely suppressed function and number of NK cells in oral cancer patients. In this review, we discuss the approach to inhibit the tumor growth and metastasis by direct killing or NK cell-mediated tumor differentiation. This review also provides the overview on supercharging NK cells using osteoclasts and probiotic bacteria, and their efficacy as cancer immunotherapeutic in humanized-BLT mice.
尽管癌症治疗领域取得了进步，但口腔癌患者的五年生存率仍然很低。因此，需要有效的治疗方法来控制病情。此外，包括我们在内的多项研究表明，口腔癌患者的 NK 细胞功能和数量受到严重抑制。在这篇综述中，我们讨论了通过直接杀伤或 NK 细胞介导的肿瘤分化来抑制肿瘤生长和转移的方法。本综述还概述了利用破骨细胞和益生菌增殖 NK 细胞的方法，以及它们在人源化 BLT 小鼠中作为癌症免疫疗法的疗效。
{"title":"Oral Cancer: Past, present and future of NK cell-based cancer immunotherapy","authors":"Kawaljit Kaur, Anahid Jewett","doi":"10.1615/critrevimmunol.2024052389","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052389","url":null,"abstract":"Despite advancements in the field of cancer therapeutics the five-year survival rate remains low in oral cancer patients. There, the effective therapeutics are needed to control the disease. Also, several studies including ours have shown severely suppressed function and number of NK cells in oral cancer patients. In this review, we discuss the approach to inhibit the tumor growth and metastasis by direct killing or NK cell-mediated tumor differentiation. This review also provides the overview on supercharging NK cells using osteoclasts and probiotic bacteria, and their efficacy as cancer immunotherapeutic in humanized-BLT mice.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"12 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754824","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}
Background: Estrogen receptor (ER) signaling plays an important role in the development and functional differentiation of breast and participates in the process of breast cancer. Activated ER can affect various aspects of the cell’s behavior, including proliferation， via modulating the expression of many downstream target genes. Phosphorylation is one of the activation pathways of ER. However, the relationship between estrogen receptor phosphorylation sites and breast development and carcinogenesis is not clear.Methods: Using Crisper-Cas9 gene editing technology, we constructed ER S309A mutant mice. Using carmine staining of mammary gland of mice at different developmental stages, we examined breast development of ER S309Amice. Using HE staining of vaginal smears of mice at the same time for 5 consecutive days, we measured the vaginal epithelial keratinocytes.Results: We established ER S309A mutant mice and observed breast defects in ER S309A mice. In addition, we observed decreased reproductive ability, estrous cycle disorder in ER S309A mice. And number of vaginal epithelial keratinocytes in the estrous cycle of ER S309A mice was decreased.Conclusion: These results suggest that phosphorylation site of ER at serine 309 is important for ER function and breast development.
{"title":"Effect of p-estrogen receptor at serine on its function and breast growth","authors":"Yuan Liang, Junhui Qin, Tiancheng Ma, Tong Yang, Zhenyu Ke, Ruian Wang","doi":"10.1615/critrevimmunol.2024052499","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052499","url":null,"abstract":"Background: Estrogen receptor (ER) signaling plays an important role in the development and functional differentiation of breast and participates in the process of breast cancer. Activated ER can affect various aspects of the cell’s behavior, including proliferation， via modulating the expression of many downstream target genes. Phosphorylation is one of the activation pathways of ER. However, the relationship between estrogen receptor phosphorylation sites and breast development and carcinogenesis is not clear.\u0000Methods: Using Crisper-Cas9 gene editing technology, we constructed ER S309A mutant mice. Using carmine staining of mammary gland of mice at different developmental stages, we examined breast development of ER S309Amice. Using HE staining of vaginal smears of mice at the same time for 5 consecutive days, we measured the vaginal epithelial keratinocytes.\u0000Results: We established ER S309A mutant mice and observed breast defects in ER S309A mice. In addition, we observed decreased reproductive ability, estrous cycle disorder in ER S309A mice. And number of vaginal epithelial keratinocytes in the estrous cycle of ER S309A mice was decreased.\u0000Conclusion: These results suggest that phosphorylation site of ER at serine 309 is important for ER function and breast development.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"6 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139918547","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 : 2024-02-01DOI: 10.1615/critrevimmunol.2024051413
Hao Zhou
Systemic immune-inflammation index (SII) and T cell subsets show involvement in mortality risk in septic patients, and we explored their predictive value in sepsis. Subjects were categorized into the Sepsis (SP)/Septic Shock (SSP)/Septic Shock (SPS) groups. T cell subsets [T-helper (Th)1, Th2, regulatory T cells (Treg), Th17]/platelets (PLT)/neutrophils (NEU)/lymphocytes (LYM)/C-reactive protein (CRP)/procalcitonin (PCT)/interleukin (IL)-4/IL-10/fibrinogen (FIB) were measured by an automatic blood biochemical analyzer/flow cytometry/Countess II FL automatic blood cell analyzer, with SII calculated. The correlations between SII/T cell subsets with Acute Physiology and Chronic Health Evaluation (APACH) II/Sequential Organ Failure Assessment (SOFA) scores and the predictive value of SII/Th1/Th2 for septic diagnosis/prognosis were analyzed using Spearman/ROC curve/Kaplan-Meier. The three groups varied in PLT/NEU/LYM/CRP/PCT/IL-4/IL-10/FIB levels and APACH II/SOFA scores. Compared with the SP group, the other two groups showed elevated APACH II/SOFA scores and SII/Th1/Th2/Th17/Treg levels. SII/Th1/Th2 levels significantly positively correlated with APACH II/SOFA scores. SII/Th1/Th2 levels had high predictive value for septic diagnosis/prognosis, with their combination exhibiting higher predictive value. Septic patients with high SII/Th1/Th2 levels exhibited lower survival rates. Altogether, SII, Th1, and Th2 had good predictive value for the diagnosis and prognosis of patients with varying severity of sepsis, with their high levels increasing mortality in septic patients.
{"title":"The value of systemic immune-inflammation index and T cell subsets in the severity and prognosis of sepsis","authors":"Hao Zhou","doi":"10.1615/critrevimmunol.2024051413","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051413","url":null,"abstract":"Systemic immune-inflammation index (SII) and T cell subsets show involvement in mortality risk in septic patients, and we explored their predictive value in sepsis. Subjects were categorized into the Sepsis (SP)/Septic Shock (SSP)/Septic Shock (SPS) groups. T cell subsets [T-helper (Th)1, Th2, regulatory T cells (Treg), Th17]/platelets (PLT)/neutrophils (NEU)/lymphocytes (LYM)/C-reactive protein (CRP)/procalcitonin (PCT)/interleukin (IL)-4/IL-10/fibrinogen (FIB) were measured by an automatic blood biochemical analyzer/flow cytometry/Countess II FL automatic blood cell analyzer, with SII calculated. The correlations between SII/T cell subsets with Acute Physiology and Chronic Health Evaluation (APACH) II/Sequential Organ Failure Assessment (SOFA) scores and the predictive value of SII/Th1/Th2 for septic diagnosis/prognosis were analyzed using Spearman/ROC curve/Kaplan-Meier. The three groups varied in PLT/NEU/LYM/CRP/PCT/IL-4/IL-10/FIB levels and APACH II/SOFA scores. Compared with the SP group, the other two groups showed elevated APACH II/SOFA scores and SII/Th1/Th2/Th17/Treg levels. SII/Th1/Th2 levels significantly positively correlated with APACH II/SOFA scores. SII/Th1/Th2 levels had high predictive value for septic diagnosis/prognosis, with their combination exhibiting higher predictive value. Septic patients with high SII/Th1/Th2 levels exhibited lower survival rates. Altogether, SII, Th1, and Th2 had good predictive value for the diagnosis and prognosis of patients with varying severity of sepsis, with their high levels increasing mortality in septic patients.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"2 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663580","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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