Pub Date : 2024-02-01DOI: 10.1615/critrevimmunol.2024051467
Jianghui Wang, Shufang Ni, Kai Zheng, Yan Zhao, peihong zhang, Hong Chang
Background: We investigated the potential arthritis-inducing effects of Phillygenin and its underlying mechanisms.Methods: RAW264.7 cells were stimulated with lipopolysaccharide to induce inflammation.Results: Phillygenin was found to reduce arthritis score, histopathological changes, paw edema, spleen index, and ALP levels in a dose-dependent manner in a model of arthritis. Additionally, Phillygenin was able to decrease levels of inflammation markers in serum samples of mice with arthritis and also inhibited inflammation markers in the cell supernatant of an in vitro model of arthritis. Phillygenin increased cell viability and JC-1 disaggregation, enhanced calcien-AM/CoCl2, reduced LDH activity levels and IL-1α levels, and inhibited Calcein/PI levels and iron concentration in an in vitro model. Phillygenin was also found to reduce ROS-induced oxidative stress and Ferroptosis, and suppress the NLRP3 inflammasome in both in vivo and in vitro models through AMPK. In the in vivo model, Phillygenin was observed to interact with AMPK protein.Conclusions: These findings suggest that Phillygenin may be a potential therapeutic target for preventing arthritis by inhibiting NLRP3 inflammasome and Ferroptosis through AMPK. This indicates that Phillygenin could have disease-modifying effects on arthritis.
{"title":"Phillygenin alleviated arthritis through the inhibition of NLRP3 inflammasome and Ferroptosis by AMPK","authors":"Jianghui Wang, Shufang Ni, Kai Zheng, Yan Zhao, peihong zhang, Hong Chang","doi":"10.1615/critrevimmunol.2024051467","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051467","url":null,"abstract":"Background: We investigated the potential arthritis-inducing effects of Phillygenin and its underlying mechanisms.\u0000Methods: RAW264.7 cells were stimulated with lipopolysaccharide to induce inflammation.\u0000Results: Phillygenin was found to reduce arthritis score, histopathological changes, paw edema, spleen index, and ALP levels in a dose-dependent manner in a model of arthritis. Additionally, Phillygenin was able to decrease levels of inflammation markers in serum samples of mice with arthritis and also inhibited inflammation markers in the cell supernatant of an in vitro model of arthritis. Phillygenin increased cell viability and JC-1 disaggregation, enhanced calcien-AM/CoCl2, reduced LDH activity levels and IL-1α levels, and inhibited Calcein/PI levels and iron concentration in an in vitro model. Phillygenin was also found to reduce ROS-induced oxidative stress and Ferroptosis, and suppress the NLRP3 inflammasome in both in vivo and in vitro models through AMPK. In the in vivo model, Phillygenin was observed to interact with AMPK protein.Conclusions: These findings suggest that Phillygenin may be a potential therapeutic target for preventing arthritis by inhibiting NLRP3 inflammasome and Ferroptosis through AMPK. This indicates that Phillygenin could have disease-modifying effects on arthritis.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"16 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754833","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.2024052486
Tu Nguyen, Po-Chun Chen, Janet Pham, Kawaljit Kaur, Steven Raman, Anahid Jewett, Jason Chiang
Natural killer (NK) cells are innate lymphoid cells that exhibit high levels of cytotoxicity against NK-specific targets, produce various cytokines, and interact with T cells, B cells, and dendritic cells to effectively serve as frontliners of the innate immune system. Moreover, NK cells constitue the second most frequent immune cell in the liver. These properties have drawn significant attention towards leveraging NK cells in treating liver cancer, especially hepatocellular carcinoma (HCC), which accounts for 75% of all liver cancer and is the fourth leading cause of cancer-related death worldwide. Notable anti-cancer functions of NK cells against HCC include activating antibody-dependent cell cytotoxicity (ADCC), facilitating Gasdermin E-mediated pyroptosis of HCC cells, and initiating an antitumor response via the cGAS-STING signaling pathway. In this review, we describe how these mechanisms work in the context of HCC. We will then discuss the existing preclinical and clinical studies that leverage NK cell activity to create single and combined immunotherapies.
自然杀伤（NK）细胞是一种先天性淋巴细胞，对 NK 特异性靶点具有高水平的细胞毒性，能产生各种细胞因子，并能与 T 细胞、B 细胞和树突状细胞相互作用，有效地充当先天性免疫系统的前线。此外，NK 细胞是肝脏中第二常见的免疫细胞。肝癌占所有肝癌的 75%，是全球癌症相关死亡的第四大原因。NK 细胞对 HCC 的显著抗癌功能包括激活抗体依赖性细胞毒性（ADCC）、促进 Gasdermin E 介导的 HCC 细胞热解，以及通过 cGAS-STING 信号通路启动抗肿瘤反应。在本综述中，我们将介绍这些机制如何在 HCC 中发挥作用。然后，我们将讨论现有的临床前和临床研究，这些研究利用 NK 细胞的活性创造了单一和联合免疫疗法。
{"title":"The Current and Future States of Natural Killer Cell-Based Immunotherapy in Hepatocellular Carcinoma","authors":"Tu Nguyen, Po-Chun Chen, Janet Pham, Kawaljit Kaur, Steven Raman, Anahid Jewett, Jason Chiang","doi":"10.1615/critrevimmunol.2024052486","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052486","url":null,"abstract":"Natural killer (NK) cells are innate lymphoid cells that exhibit high levels of cytotoxicity against NK-specific targets, produce various cytokines, and interact with T cells, B cells, and dendritic cells to effectively serve as frontliners of the innate immune system. Moreover, NK cells constitue the second most frequent immune cell in the liver. These properties have drawn significant attention towards leveraging NK cells in treating liver cancer, especially hepatocellular carcinoma (HCC), which accounts for 75% of all liver cancer and is the fourth leading cause of cancer-related death worldwide. Notable anti-cancer functions of NK cells against HCC include activating antibody-dependent cell cytotoxicity (ADCC), facilitating Gasdermin E-mediated pyroptosis of HCC cells, and initiating an antitumor response via the cGAS-STING signaling pathway. In this review, we describe how these mechanisms work in the context of HCC. We will then discuss the existing preclinical and clinical studies that leverage NK cell activity to create single and combined immunotherapies.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"25 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754891","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.2024052378
Muhammad Imran Qadir, Bilal Ahmed, Nadir Hussain
Gene therapy is a particularly useful treatment for nervous system genetic illnesses, including those induced especially by infectious organisms and antigens, and is being utilized to treat Hodgkin's disease. Due to the possible clonal relationship between both disorders, immunotherapy directed against CD20 positive cells may be a more effective treatment in patients with persistent HD and NHL.HL growth can be inhibited both in vitro and in vivo by AdsIL-13Ralpha2. High-dose treatment combined with stem cell transplantation has been effective in treating HIV-negative lymphoma that has progressed to high-risk or relapsed illness. For therapy, LMP2-specific CTL will be used. Furthermore, it is possible to view the cytotoxicity of genetically modified adenoviruses that express proteins such as p27Kip1, p21Waf1, and p16INK4A as a foundational element for (2;5)-derived ALCL genetic treatment for Hodgkin's disease
基因疗法是治疗神经系统遗传疾病（包括由传染性生物体和抗原诱发的疾病）的一种特别有效的方法，目前正被用于治疗霍奇金病。由于这两种疾病之间可能存在克隆关系，针对 CD20 阳性细胞的免疫疗法可能是治疗顽固性 HD 和 NHL 患者的更有效方法。AdsIL-13Ralpha2 可在体外和体内抑制 HL 的生长。大剂量治疗结合干细胞移植对治疗进展为高危或复发的HIV阴性淋巴瘤很有效。在治疗中，将使用 LMP2 特异性 CTL。此外，还可以将表达p27Kip1、p21Waf1和p16INK4A等蛋白的转基因腺病毒的细胞毒性视为（2;5）衍生ALCL基因治疗霍奇金病的基础要素
{"title":"Efficacy and Nuances of Precision Molecular Engineering for Hodgkin's Disease to a Gene Therapeutic Approach","authors":"Muhammad Imran Qadir, Bilal Ahmed, Nadir Hussain","doi":"10.1615/critrevimmunol.2024052378","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052378","url":null,"abstract":"Gene therapy is a particularly useful treatment for nervous system genetic illnesses, including those induced especially by infectious organisms and antigens, and is being utilized to treat Hodgkin's disease. Due to the possible clonal relationship between both disorders, immunotherapy directed against CD20 positive cells may be a more effective treatment in patients with persistent HD and NHL.HL growth can be inhibited both in vitro and in vivo by AdsIL-13Ralpha2. High-dose treatment combined with stem cell transplantation has been effective in treating HIV-negative lymphoma that has progressed to high-risk or relapsed illness. For therapy, LMP2-specific CTL will be used. Furthermore, it is possible to view the cytotoxicity of genetically modified adenoviruses that express proteins such as p27Kip1, p21Waf1, and p16INK4A as a foundational element for (2;5)-derived ALCL genetic treatment for Hodgkin's disease","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139656290","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 : 2024-01-01DOI: 10.1615/critrevimmunol.2024051787
Dong Song, Lun Dong, Mei Wang, Xiaoping Gao
Laryngeal cancer (LC) is a prevailing tumor with a high mortality rate. The pivotal role of mitophagy in LC is acknowledged; however, a comprehensive analysis of the corresponding genes has not been conducted. In the present study, we proposed a prognostic model consisting of mitophagy-related genes in LC. Clinical information and transcriptome profiling of patients with LC and mitophagy-related genes were retrieved from open-source databases. Gene set variation analysis (GSVA) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to identify core mitophagy-related genes and construct gene co-expression networks. Functional enrichment analysis was employed to analyze the enriched regulatory pathways of the mitophagy-related genes. Kaplan-Meier curves (KM), Cox, and LASSO regression were applied to explore their prognostic effects. Finally, quantitative real-time PCR (RT-qPCR) further verified the bioinformatics prediction. A total of 45 genes related to mitochondrial pathways was collected. GSVA analysis demonstrated that these genes in tumor samples mainly referred to the mitochondrial pathway. Among these genes, five mitophagy-related-gene signatures (CERCAM, CHPF, EPHX3, EXT2, and MED15) were further identified to construct the prognostic model. KM and Cox regression analyses indicated that this model had an accurate prognostic prediction for LC. RT-qPCR showed that CERCAM, CHPF, EXT2, and MED15 expression were upregulated, and EPHX3 level was decreased in LC cells. The present study established a five-mitophagy-related-gene model that can predict the prognosis of LC patients, thus laying the foundation for a better understanding and potential advancements in clinical treatments for LC.
{"title":"Identification of a Novel Five-Gene Prognostic Model for Laryngeal Cancer Associated with Mitophagy Using Integrated Bioinformatics Analysis and Experimental Verification","authors":"Dong Song, Lun Dong, Mei Wang, Xiaoping Gao","doi":"10.1615/critrevimmunol.2024051787","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051787","url":null,"abstract":"Laryngeal cancer (LC) is a prevailing tumor with a high mortality rate. The pivotal role of mitophagy in LC is acknowledged; however, a comprehensive analysis of the corresponding genes has not been conducted. In the present study, we proposed a prognostic model consisting of mitophagy-related genes in LC. Clinical information and transcriptome profiling of patients with LC and mitophagy-related genes were retrieved from open-source databases. Gene set variation analysis (GSVA) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to identify core mitophagy-related genes and construct gene co-expression networks. Functional enrichment analysis was employed to analyze the enriched regulatory pathways of the mitophagy-related genes. Kaplan-Meier curves (KM), Cox, and LASSO regression were applied to explore their prognostic effects. Finally, quantitative real-time PCR (RT-qPCR) further verified the bioinformatics prediction. A total of 45 genes related to mitochondrial pathways was collected. GSVA analysis demonstrated that these genes in tumor samples mainly referred to the mitochondrial pathway. Among these genes, five mitophagy-related-gene signatures (<i>CERCAM, CHPF, EPHX3, EXT2</i>, and <i>MED15</i>) were further identified to construct the prognostic model. KM and Cox regression analyses indicated that this model had an accurate prognostic prediction for LC. RT-qPCR showed that <i>CERCAM, CHPF, EXT2</i>, and <i>MED15</i> expression were upregulated, and <i>EPHX3</i> level was decreased in LC cells. The present study established a five-mitophagy-related-gene model that can predict the prognosis of LC patients, thus laying the foundation for a better understanding and potential advancements in clinical treatments for LC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"296 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805096","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 : 2024-01-01DOI: 10.1615/critrevimmunol.2023051509
Juan Du
Bupi Yichang formula (BPYCF) has shown the anti-cancer potential; however, its effects on colon cancer and the mechanisms remain unknown. This study intended to explore the effects of BPYC on colon cancer and its underlying mechanisms. BPYCF-related and colon cancer-related targets were acquired from public databases, followed by differentially expressed genes (DEG) identification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using clusterProfiler. A protein-protein interaction (PPI) network was constructed using STRING database. CytoHubba and MCODE to screen the hub targets. A diagnostic model was built using random forest algorithm. Molecular docking was conducted using PyMOL and AutoDock. High-performance liquid chromatograph-mass spectrometry (HPLC-MS) analysis and in vitro validation were performed. Forty-six overlapping targets of BPYCF-related, colon cancer-related targets, and DEGs were obtained. GO and KEGG analyses showed that the targets were mainly enriched in response to lipopolysaccharide, neuronal cell body, protein serine/threonine/tyrosine, as well as C-type lectin receptor, NOD-like receptor, and TNF signaling pathways. Five targets were identified as the pivotal targets, among which, NOS3, CASP8, RIPK3, and TNFRSF10B were stably docked with the core active component, naringenin. Naringenin was also identified from the BPYCF sample through HPLC-MS analysis. In vitro experiments showed that BPYCF inhibited cell viability, reduced NOS3 expression, and elevated CASP8, RIPK3, and TNFRSF10B expression in colon cancer cells. BPYCF might treat colon cancer mainly by regulating NOS3, CASP8, RIPK3, and TN-FRSF10B. This study first revealed the therapeutic effects and mechanisms of BPYCF against colon cancer, paving the path for the development of targeted therapeutic strategies for this cancer in the clinic.
{"title":"Study of Therapeutic Mechanisms of Bupi Yichang Formula against Colon Cancer Based on Network Pharmacology, Machine Learning, and Experimental Verification","authors":"Juan Du","doi":"10.1615/critrevimmunol.2023051509","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023051509","url":null,"abstract":"Bupi Yichang formula (BPYCF) has shown the anti-cancer potential; however, its effects on colon cancer and the mechanisms remain unknown. This study intended to explore the effects of BPYC on colon cancer and its underlying mechanisms. BPYCF-related and colon cancer-related targets were acquired from public databases, followed by differentially expressed genes (DEG) identification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using clusterProfiler. A protein-protein interaction (PPI) network was constructed using STRING database. CytoHubba and MCODE to screen the hub targets. A diagnostic model was built using random forest algorithm. Molecular docking was conducted using PyMOL and AutoDock. High-performance liquid chromatograph-mass spectrometry (HPLC-MS) analysis and <i>in vitro</i> validation were performed. Forty-six overlapping targets of BPYCF-related, colon cancer-related targets, and DEGs were obtained. GO and KEGG analyses showed that the targets were mainly enriched in response to lipopolysaccharide, neuronal cell body, protein serine/threonine/tyrosine, as well as C-type lectin receptor, NOD-like receptor, and TNF signaling pathways. Five targets were identified as the pivotal targets, among which, NOS3, CASP8, RIPK3, and TNFRSF10B were stably docked with the core active component, naringenin. Naringenin was also identified from the BPYCF sample through HPLC-MS analysis. <i>In vitro</i> experiments showed that BPYCF inhibited cell viability, reduced NOS3 expression, and elevated CASP8, RIPK3, and TNFRSF10B expression in colon cancer cells. BPYCF might treat colon cancer mainly by regulating NOS3, CASP8, RIPK3, and TN-FRSF10B. This study first revealed the therapeutic effects and mechanisms of BPYCF against colon cancer, paving the path for the development of targeted therapeutic strategies for this cancer in the clinic.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139421559","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 : 2024-01-01DOI: 10.1615/critrevimmunol.2024051776
Fan Fang, Cheng Chen
Alzheimer's disease (AD) is the most common form of dementia. Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of AD. In a large case-control study recruiting 208 patients with AD and 205 elderly control subjects, miRNA-let-7d-5p attracted our attention for its downregulated level in patients with AD. However, the biological functions of let-7d-5p in AD pathogenesis have not been investigated. This study emphasized the functions and mechanisms of let-7d-5p in the pathogenesis of AD. Mouse microglial BV2 cells treated with amyloid-β (Aβ)1-42 were used as in vitro AD inflammation models. We reported that let-7d-5p was downregulated in Aβ 1-42-stimulated BV2 cells, and upregulation of let-7d-5p promoted the transversion of microglial cells from Ml phenotype to M2 phenotype. Then, the binding relationship between let-7d-5p and Map3k1 was verified by luciferase reporter assays. Mechanistically, let-7d-5p could target Map3k1 3'UTR to inactivate ERK/p38 MAPK signaling. Therefore, it was suggested that let-7d-5p might be a novel modulator of microglial neuroinflammation and serve as a novel target for diagnosis and treatment of AD.
阿尔茨海默病（AD）是最常见的痴呆症。微RNA（miRNA）的异常调控与阿尔茨海默病的发病机制有关。在一项招募了208名AD患者和205名老年对照受试者的大型病例对照研究中，miRNA-let-7d-5p因其在AD患者中的下调水平而引起了我们的注意。然而，let-7d-5p 在 AD 发病机制中的生物学功能尚未得到研究。本研究强调了let-7d-5p在AD发病机制中的功能和机制。我们用淀粉样蛋白-β（Aβ）1-42处理的小鼠小胶质细胞BV2作为体外AD炎症模型。我们发现，let-7d-5p在Aβ 1-42刺激的BV2细胞中被下调，而let-7d-5p的上调促进了小胶质细胞从Ml表型向M2表型的转化。然后，通过荧光素酶报告实验验证了let-7d-5p与Map3k1的结合关系。从机理上讲，let-7d-5p可以靶向Map3k1的3'UTR，使ERK/p38 MAPK信号失活。因此，let-7d-5p可能是一种新型的小胶质细胞神经炎症调节剂，并可作为诊断和治疗AD的新靶点。
{"title":"MiRNA let-7d-5p Alleviates Inflammatory Responses by Targeting Map3k1 and Inactivating ERK/p38 MAPK Signaling in Microglia","authors":"Fan Fang, Cheng Chen","doi":"10.1615/critrevimmunol.2024051776","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051776","url":null,"abstract":"Alzheimer's disease (AD) is the most common form of dementia. Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of AD. In a large case-control study recruiting 208 patients with AD and 205 elderly control subjects, miRNA-let-7d-5p attracted our attention for its downregulated level in patients with AD. However, the biological functions of let-7d-5p in AD pathogenesis have not been investigated. This study emphasized the functions and mechanisms of let-7d-5p in the pathogenesis of AD. Mouse microglial BV2 cells treated with amyloid-β (Aβ)<sub>1-42</sub> were used as <i>in vitro</i> AD inflammation models. We reported that let-7d-5p was downregulated in Aβ <sub>1-42</sub>-stimulated BV2 cells, and upregulation of let-7d-5p promoted the transversion of microglial cells from Ml phenotype to M2 phenotype. Then, the binding relationship between let-7d-5p and Map3k1 was verified by luciferase reporter assays. Mechanistically, let-7d-5p could target Map3k1 3'UTR to inactivate ERK/p38 MAPK signaling. Therefore, it was suggested that let-7d-5p might be a novel modulator of microglial neuroinflammation and serve as a novel target for diagnosis and treatment of AD.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"29 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140313099","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 : 2024-01-01DOI: 10.1615/critrevimmunol.2023051066
Baoshan Ning, Yine Mei
Laminin subunit alpha 3 (LAMA3) is a cancer regulator. However, its effects and regulatory pathways in oral squamous cell carcinoma (OSCC) progression remain unknown. This research aimed to determine the influence of LAMA3 regulation via methyltransferase-like 3 (METTL3) on OSCC progression. Using quantitative real-time polymerase chain reaction and bioinformatics analysis, the expression levels of LAMA3 and METTL3 in OSCC tissues were examined. The functional roles of LAMA3 and METTL3 were analyzed using cell functional experiments. Using methylated RNA immunoprecipitation and mRNA stability assays, LAMA3 and METTL3 regulation was investigated. In OSCC tissues, LAMA3 was upregulated. LAMA3 inhibition hampered OSCC cell proliferation, invasion, and migration while its overexpression facilitated OSCC cell progression. METTL3 serves as a crucial upstream regulator of LAMA3 in OSCC and upregulates LAMA3 expression via an m6A-dependent mechanism. The low METTL3 expression partially restored the enhanced malignant phenotype induced by LAMA3 overexpression. Our findings indicate that METTL3 and LAMA3 act as pro-oncogenic factors in OSCC, with METTL3 promoting OSCC malignancy via m6A modification-dependent stabilization of LAMA3 transcripts, representing a novel regulatory mechanism in OSCC.
{"title":"LAMA3 Promotes Tumorigenesis of Oral Squamous Cell Carcinoma by METTL3-Mediated N6-Methyladenosine Modification","authors":"Baoshan Ning, Yine Mei","doi":"10.1615/critrevimmunol.2023051066","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023051066","url":null,"abstract":"Laminin subunit alpha 3 (LAMA3) is a cancer regulator. However, its effects and regulatory pathways in oral squamous cell carcinoma (OSCC) progression remain unknown. This research aimed to determine the influence of LAMA3 regulation via methyltransferase-like 3 (METTL3) on OSCC progression. Using quantitative real-time polymerase chain reaction and bioinformatics analysis, the expression levels of LAMA3 and METTL3 in OSCC tissues were examined. The functional roles of LAMA3 and METTL3 were analyzed using cell functional experiments. Using methylated RNA immunoprecipitation and mRNA stability assays, LAMA3 and METTL3 regulation was investigated. In OSCC tissues, LAMA3 was upregulated. LAMA3 inhibition hampered OSCC cell proliferation, invasion, and migration while its overexpression facilitated OSCC cell progression. METTL3 serves as a crucial upstream regulator of LAMA3 in OSCC and upregulates LAMA3 expression via an m6A-dependent mechanism. The low METTL3 expression partially restored the enhanced malignant phenotype induced by LAMA3 overexpression. Our findings indicate that METTL3 and LAMA3 act as pro-oncogenic factors in OSCC, with METTL3 promoting OSCC malignancy via m6A modification-dependent stabilization of LAMA3 transcripts, representing a novel regulatory mechanism in OSCC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"19 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138537043","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}
Non-tuberculous mycobacteria (NTM) infection is common in bronchiectasis, with rising incidence globally. However, investigation into NTM in bronchiectasis patients in China remains relatively limited. This work aimed to identify and understand the features of NTM in bronchiectasis patient in Fuzhou district of China. The pulmonary samples were collected from 281 bronchiectasis patients with suspected NTM infection in Fuzhou, 2018-2022. MPB64 antigen detection was employed for the preliminary evaluation of NTM. Further NTM identification was realized using gene chip and gene sequencing. Among 281 patients, 172 (61.21%) patients were NTM-positive (58.72%) according to MPB64 antigen detection, with females (58.72%) outnumbering males (41.28%) and the highest prevalence in the age group of 46-65 years. In total, 47 NTM single infections and 3 mixed infections (1 Mycobacterium tuberculosis complex-M. intracellulare, 1 M. avium-M. intracellulare, and 1 M. abscessus-M. intracellulare) were identified through multicolor melting curve analysis (MMCA), which was compared with gene sequencing results. Both methods suggested Mycobacterium (M.) intracellulare, M. abscessus, and M. avium as the primary NTM species affecting bronchiectasis patients. M. intracellulare and M. abscessus were more frequent in females than males with the highest prevalence in the age group of 46-65 years according to MMCA. This research provides novel insights into the epidemiological and clinical features of NTM in bronchiectasis patients in Southeastern China. Significantly, M. intracellulare, M. abscessus, and M. avium were identified as the major NTM species, contributing to a better understanding and management of bronchiectasis accompanied by NTM infection.
{"title":"Employing Multicolor Melting Curve Analysis to Rapidly Identify Non-Tuberculous Mycobacteria in Patients with Bronchiectasis: A Study from a Pulmonary Hospital in the Fuzhou District of China, 2018−2022","authors":"Mintao Zheng, Xinchao Chen, Qiaoqian Chen, Xiaohong Chen, Mingxiang Huang","doi":"10.1615/critrevimmunol.2024052213","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052213","url":null,"abstract":"Non-tuberculous mycobacteria (NTM) infection is common in bronchiectasis, with rising incidence globally. However, investigation into NTM in bronchiectasis patients in China remains relatively limited. This work aimed to identify and understand the features of NTM in bronchiectasis patient in Fuzhou district of China. The pulmonary samples were collected from 281 bronchiectasis patients with suspected NTM infection in Fuzhou, 2018-2022. MPB64 antigen detection was employed for the preliminary evaluation of NTM. Further NTM identification was realized using gene chip and gene sequencing. Among 281 patients, 172 (61.21%) patients were NTM-positive (58.72%) according to MPB64 antigen detection, with females (58.72%) outnumbering males (41.28%) and the highest prevalence in the age group of 46-65 years. In total, 47 NTM single infections and 3 mixed infections (1 <i>Mycobacterium tuberculosis complex-M. intracellulare</i>, 1 <i>M. avium-M. intracellulare</i>, and 1 <i>M. abscessus-M. intracellulare</i>) were identified through multicolor melting curve analysis (MMCA), which was compared with gene sequencing results. Both methods suggested <i>Mycobacterium (M.) intracellulare, M. abscessus</i>, and <i>M. avium</i> as the primary NTM species affecting bronchiectasis patients. <i>M. intracellulare</i> and <i>M. abscessus </i>were more frequent in females than males with the highest prevalence in the age group of 46-65 years according to MMCA. This research provides novel insights into the epidemiological and clinical features of NTM in bronchiectasis patients in Southeastern China. Significantly, <i>M. intracellulare, M. abscessus,</i> and <i>M. avium</i> were identified as the major NTM species, contributing to a better understanding and management of bronchiectasis accompanied by NTM infection.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"52 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663583","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 : 2024-01-01DOI: 10.1615/critrevimmunol.2023051250
Bin Huang, Chang Xin, Huanjun Yan, Zhewei Yu
This study aimed to construct a blood diagnostic model for pancreatic cancer (PC) using miRNA signatures by a combination of machine learning and biological experimental verification. Gene expression profiles of patients with PC and transcriptome normalization data were obtained from the Gene Expression Omnibus (GEO) database. Using random forest algorithm, lasso regression algorithm, and multivariate cox regression analyses, the classifier of differentially expressed miRNAs was identified based on algorithms and functional properties. Next, the ROC curve analysis was used to evaluate the predictive performance of the diagnostic model. Finally, we analyzed the expression of two specific miRNAs in Capan-1, PANC-1, and MIA PaCa-2 pancreatic cells using qRT-PCR. Integrated microarray analysis revealed that 33 common miRNAs exhibited significant differences in expression profiles between tumor and normal groups (P value < 0.05 and |logFC| > 0.3). Pathway analysis showed that differentially expressed miRNAs were related to P00059 p53 pathway, hsa04062 chemokine signaling pathway, and cancer-related pathways including PC. In ENCORI database, the hsa-miR-4486 and hsa-miR-6075 were identified by random forest algorithm and lasso regression algorithm and introduced as major miRNA markers in PC diagnosis. Further, the receiver operating characteristic curve analysis achieved the area under curve score > 80%, showing good sensitivity and specificity of the two-miRNA signature model in PC diagnosis. Additionally, hsa-miR-4486 and hsa-miR-6075 genes expressions in three pancreatic cells were all up-regulated by qRT-PCR. In summary, these findings suggest that the two miRNAs, hsa-miR-4486 and hsa-miR-6075, could serve as valuable prognostic markers for PC.
{"title":"A Machine Learning Method for a Blood Diagnostic Model of Pancreatic Cancer Based on microRNA Signatures","authors":"Bin Huang, Chang Xin, Huanjun Yan, Zhewei Yu","doi":"10.1615/critrevimmunol.2023051250","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023051250","url":null,"abstract":"This study aimed to construct a blood diagnostic model for pancreatic cancer (PC) using miRNA signatures by a combination of machine learning and biological experimental verification. Gene expression profiles of patients with PC and transcriptome normalization data were obtained from the Gene Expression Omnibus (GEO) database. Using random forest algorithm, lasso regression algorithm, and multivariate cox regression analyses, the classifier of differentially expressed miRNAs was identified based on algorithms and functional properties. Next, the ROC curve analysis was used to evaluate the predictive performance of the diagnostic model. Finally, we analyzed the expression of two specific miRNAs in Capan-1, PANC-1, and MIA PaCa-2 pancreatic cells using qRT-PCR. Integrated microarray analysis revealed that 33 common miRNAs exhibited significant differences in expression profiles between tumor and normal groups (<i>P</i> value < 0.05 and |logFC| > 0.3). Pathway analysis showed that differentially expressed miRNAs were related to P00059 p53 pathway, hsa04062 chemokine signaling pathway, and cancer-related pathways including PC. In ENCORI database, the hsa-miR-4486 and hsa-miR-6075 were identified by random forest algorithm and lasso regression algorithm and introduced as major miRNA markers in PC diagnosis. Further, the receiver operating characteristic curve analysis achieved the area under curve score > 80%, showing good sensitivity and specificity of the two-miRNA signature model in PC diagnosis. Additionally, hsa-miR-4486 and hsa-miR-6075 genes expressions in three pancreatic cells were all up-regulated by qRT-PCR. In summary, these findings suggest that the two miRNAs, hsa-miR-4486 and hsa-miR-6075, could serve as valuable prognostic markers for PC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"35 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139376316","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 : 2024-01-01DOI: 10.1615/critrevimmunol.2024051136
Fei Li, Ying-pei Ling, Pan Wang, Shi-cheng Gu, Hao Jiang, Jie Zhu
Objective: This study aimed to elucidate the role of microRNA-503 (miR-503) in pancreatic cancer (PC) progression and the underlying regulatory mechanisms.Methods: We acquired miR-503-3p and miR-503-5p expression data along with survival times of PC and normal samples from the UCSC Xena database. Using the t-test, we compared the expression of miR-503-3p and miR-503-5p between PC and normal samples, and evaluated their prognostic significance via Kaplan-Meier survival analysis. The expression of miR-503-5p in PC cells was detected by quantitative PCR. We subsequently overexpressed miR-503-5p in PC cells and examined cell viability, apoptosis, and migration through CCK8 assay, flow cytometry, and Transwell assay, respectively. Potential functional targets were identified using miRTarBase and validated by dual-luciferase reporter assay.Results: Both miR-503-3p and miR-503-5p expression were found to be downregulated in PC; however, only miR-503-5p was linked to cancer prognosis based on public data. In vitro experiments demonstrated that overexpression of miR-503-5p substantially decreased cell viability, induced apoptosis, caused G0/G1 arrest, and inhibited cell migration. miR-503-5p was found to target cyclin E2 (CCNE2), and overexpression of CCNE2 could counteract the effects of miR-503-5p on PC cells.Conclusion: The downregulation of miR-503-5p enhances the progression of PC by targeting CCNE2. The detection of miR-503-5p expression may provide valuable insights for the prevention and prognostic evaluation of PC.
研究目的本研究旨在阐明microRNA-503（miR-503）在胰腺癌（PC）进展中的作用及其潜在调控机制：方法：我们从 UCSC Xena 数据库中获取了 miR-503-3p 和 miR-503-5p 的表达数据以及 PC 和正常样本的生存时间。我们用t检验比较了PC样本和正常样本中miR-503-3p和miR-503-5p的表达，并通过Kaplan-Meier生存分析评估了它们的预后意义。我们通过定量 PCR 检测了 miR-503-5p 在 PC 细胞中的表达。随后，我们在 PC 细胞中过表达了 miR-503-5p，并通过 CCK8 检测法、流式细胞术和 Transwell 检测法分别检测了细胞活力、凋亡和迁移。利用 miRTarBase 鉴定了潜在的功能靶点，并通过双荧光素酶报告实验进行了验证：结果：研究发现，miR-503-3p和miR-503-5p在PC中的表达均出现下调；然而，根据公开数据，只有miR-503-5p与癌症预后有关。体外实验表明，miR-503-5p的过表达会大幅降低细胞活力、诱导细胞凋亡、导致G0/G1停滞和抑制细胞迁移。研究发现，miR-503-5p以细胞周期蛋白E2（CCNE2）为靶标，而CCNE2的过表达可抵消miR-503-5p对PC细胞的影响：结论：miR-503-5p的下调通过靶向CCNE2促进PC的进展。结论：miR-503-5p的下调通过靶向CCNE2而促进PC的进展，检测miR-503-5p的表达可为PC的预防和预后评估提供有价值的见解。
{"title":"Downregulation of miR-503-5p promotes the development of pancreatic cancer via targeting cyclin E2","authors":"Fei Li, Ying-pei Ling, Pan Wang, Shi-cheng Gu, Hao Jiang, Jie Zhu","doi":"10.1615/critrevimmunol.2024051136","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051136","url":null,"abstract":"Objective: This study aimed to elucidate the role of microRNA-503 (miR-503) in pancreatic cancer (PC) progression and the underlying regulatory mechanisms.\u0000Methods: We acquired miR-503-3p and miR-503-5p expression data along with survival times of PC and normal samples from the UCSC Xena database. Using the t-test, we compared the expression of miR-503-3p and miR-503-5p between PC and normal samples, and evaluated their prognostic significance via Kaplan-Meier survival analysis. The expression of miR-503-5p in PC cells was detected by quantitative PCR. We subsequently overexpressed miR-503-5p in PC cells and examined cell viability, apoptosis, and migration through CCK8 assay, flow cytometry, and Transwell assay, respectively. Potential functional targets were identified using miRTarBase and validated by dual-luciferase reporter assay.\u0000Results: Both miR-503-3p and miR-503-5p expression were found to be downregulated in PC; however, only miR-503-5p was linked to cancer prognosis based on public data. In vitro experiments demonstrated that overexpression of miR-503-5p substantially decreased cell viability, induced apoptosis, caused G0/G1 arrest, and inhibited cell migration. miR-503-5p was found to target cyclin E2 (CCNE2), and overexpression of CCNE2 could counteract the effects of miR-503-5p on PC cells.\u0000Conclusion: The downregulation of miR-503-5p enhances the progression of PC by targeting CCNE2. The detection of miR-503-5p expression may provide valuable insights for the prevention and prognostic evaluation of PC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139461577","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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