Yiyang Chen, Zeyu Li, Jianfeng Liang, Jiayu Liu, J. Hao, Q. Wan, Jiameng Liu, Chongdai Luo, Zhiyuan Lu
Introduction: CircRNAs are engaged in the tumorigenesis and progression of oral squamous cancer cells (OSCC). However, the function and underlying mechanism of circRNAs on tumor-associated immunity escape are largely unknown. Materials and methods: We analyzed the expression pattern of has_circ_0069313 in our in-house database and its correlation with OSCC prognosis. Immunohistochemistry was applied to detected PDL1 expression. RNA fluorescence in situ hybridization was applied to detect subcellular location of circRNA. A luciferase activity assay was used to detect the interaction of has_circ_0069313 and miR-325-3p and its downstream target, Foxp3. Exosomes were collected to detect the exosomal circRNAs and co-culture assays were performed to detect the function of exosomal circRNAs on Tregs. Results: has_circ_0069313 was upregulated in OSCC tissues and predicts poor prognosis. has_circ_0069313 promotes immunity escape through inhibiting miR-325-3p-induced Foxp3 degradation. has_circ_0069313 is an exosomal circRNA and the transfer of has_circ_0069313 to Treg cells promotes the Treg function through maintaining Foxp3 levels. Conclusion: Our results indicate that has_circ_0069313 induces OSCC immunity escape via the miR-325-3p-Foxp3 axis in both OSCC cells and Treg cells.
{"title":"CircRNA has_circ_0069313 induced OSCC immunity escape by miR-325-3p-Foxp3 axes in both OSCC cells and Treg cells","authors":"Yiyang Chen, Zeyu Li, Jianfeng Liang, Jiayu Liu, J. Hao, Q. Wan, Jiameng Liu, Chongdai Luo, Zhiyuan Lu","doi":"10.18632/aging.204068","DOIUrl":"https://doi.org/10.18632/aging.204068","url":null,"abstract":"Introduction: CircRNAs are engaged in the tumorigenesis and progression of oral squamous cancer cells (OSCC). However, the function and underlying mechanism of circRNAs on tumor-associated immunity escape are largely unknown. Materials and methods: We analyzed the expression pattern of has_circ_0069313 in our in-house database and its correlation with OSCC prognosis. Immunohistochemistry was applied to detected PDL1 expression. RNA fluorescence in situ hybridization was applied to detect subcellular location of circRNA. A luciferase activity assay was used to detect the interaction of has_circ_0069313 and miR-325-3p and its downstream target, Foxp3. Exosomes were collected to detect the exosomal circRNAs and co-culture assays were performed to detect the function of exosomal circRNAs on Tregs. Results: has_circ_0069313 was upregulated in OSCC tissues and predicts poor prognosis. has_circ_0069313 promotes immunity escape through inhibiting miR-325-3p-induced Foxp3 degradation. has_circ_0069313 is an exosomal circRNA and the transfer of has_circ_0069313 to Treg cells promotes the Treg function through maintaining Foxp3 levels. Conclusion: Our results indicate that has_circ_0069313 induces OSCC immunity escape via the miR-325-3p-Foxp3 axis in both OSCC cells and Treg cells.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"1 1","pages":"4376 - 4389"},"PeriodicalIF":0.0,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76129954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
increases cardiovascular disease risk (e.g., hypertension). Engagement in sufficient moderate-tovigorous physical activity to maintain a high cardiorespiratory fitness (CRF) attenuates the negative cardiovascular impact of aging. The vasoconstrictor arm of the sympathetic nervous system is critical for effective short-term arterial blood pressure regulation. Sympathetic neural activity directed towards skeletal muscle resistance vessels (muscle sympathetic nerve activity; MSNA) causes peripheral vasoconstriction, which is exaggerated in older adults [1]. Signal averaging techniques have been developed [2], and refined [3], to quantify the communication between MSNA and the corresponding pressor or local vascular responses (i.e., sympathetic transduction). The assessment of sympathetic transduction may help uncover the divergent cardiovascular implications of inactive (lower CRF) versus active (higher CRF) aging.
{"title":"Aging, cardiorespiratory fitness and sympathetic transduction","authors":"M. O'Brien, S. Mekary, D. Kimmerly","doi":"10.18632/aging.204091","DOIUrl":"https://doi.org/10.18632/aging.204091","url":null,"abstract":"increases cardiovascular disease risk (e.g., hypertension). Engagement in sufficient moderate-tovigorous physical activity to maintain a high cardiorespiratory fitness (CRF) attenuates the negative cardiovascular impact of aging. The vasoconstrictor arm of the sympathetic nervous system is critical for effective short-term arterial blood pressure regulation. Sympathetic neural activity directed towards skeletal muscle resistance vessels (muscle sympathetic nerve activity; MSNA) causes peripheral vasoconstriction, which is exaggerated in older adults [1]. Signal averaging techniques have been developed [2], and refined [3], to quantify the communication between MSNA and the corresponding pressor or local vascular responses (i.e., sympathetic transduction). The assessment of sympathetic transduction may help uncover the divergent cardiovascular implications of inactive (lower CRF) versus active (higher CRF) aging.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"42 1","pages":"4189 - 4190"},"PeriodicalIF":0.0,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86587428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inflammation plays a crucial role in the etiology and pathogenesis of AMD (Age-related Macular Degeneration). Humanin G (HNG) is a Mitochondrial Derived Peptide (MDP) that is cytoprotective in AMD and can protect against mitochondrial and cellular stress induced by damaged AMD mitochondria. The goal of this study was to test our hypothesis that inflammation-associated marker protein levels are increased in AMD and treatment with HNG leads to reduction in their protein levels. Humanin protein levels were measured in the plasma of AMD patients and normal subjects using ELISA assay. Humanin G was added to AMD and normal (control) cybrids which had identical nuclei from mitochondria-deficient ARPE-19 cells but differed in mitochondrial DNA (mtDNA) content derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal cybrids, and the Luminex XMAP multiplex assay was used to measure the levels of inflammatory proteins. AMD plasma showed reduced Humanin protein levels, but higher protein levels of inflammation markers compared to control plasma samples. In AMD RPE cybrid cells, Humanin G reduced the CD62E/ E-Selectin, CD62P/ P-Selectin, ICAM-1, TNF-α, MIP-1α, IFN–γ, IL-1β, IL-13, and IL-17A protein levels, thereby suggesting that Humanin G may rescue from mtDNA-mediated inflammation in AMD cybrids. In conclusion, we present novel findings that: A) show reduced Humanin protein levels in AMD plasma vs. normal plasma; B) suggest the role of inflammatory markers in AMD pathogenesis, and C) highlight the positive effects of Humanin G in reducing inflammation in AMD.
炎症在AMD(年龄相关性黄斑变性)的病因和发病机制中起着至关重要的作用。Humanin G (HNG)是一种线粒体衍生肽(MDP)，在AMD中具有细胞保护作用，可以防止AMD线粒体损伤引起的线粒体和细胞应激。本研究的目的是验证我们的假设，即炎症相关标志物蛋白水平在AMD中升高，而用HNG治疗会导致其蛋白水平降低。采用ELISA法测定AMD患者和正常人血浆中的人蛋白水平。将Humanin G添加到AMD和正常(对照)杂交体中，这些杂交体具有相同的细胞核，来自线粒体缺陷的ARPE-19细胞，但线粒体DNA (mtDNA)含量不同，来自临床特征的AMD患者和正常(对照)受试者。从未处理和ng处理的AMD和正常细胞系中提取细胞裂解液，并使用Luminex XMAP多重检测法测量炎症蛋白水平。与对照血浆样品相比，AMD血浆显示人蛋白水平降低，但炎症标志物的蛋白质水平较高。在AMD RPE杂交细胞中，Humanin G可降低CD62E/ e -选择素、CD62P/ p -选择素、ICAM-1、TNF-α、MIP-1α、IFN -γ、IL-1β、IL-13和IL-17A蛋白水平，提示Humanin G可缓解mtdna介导的AMD杂交细胞炎症。总之，我们提出了新的发现:A)与正常血浆相比，AMD血浆中Humanin蛋白水平降低;B)提示炎症标志物在AMD发病机制中的作用，C)强调Humanin G在减轻AMD炎症中的积极作用。
{"title":"Effect of Humanin G (HNG) on inflammation in age-related macular degeneration (AMD)","authors":"Sonali Nashine, Pinchas Cohen, J. Wan, C. Kenney","doi":"10.18632/aging.204074","DOIUrl":"https://doi.org/10.18632/aging.204074","url":null,"abstract":"Inflammation plays a crucial role in the etiology and pathogenesis of AMD (Age-related Macular Degeneration). Humanin G (HNG) is a Mitochondrial Derived Peptide (MDP) that is cytoprotective in AMD and can protect against mitochondrial and cellular stress induced by damaged AMD mitochondria. The goal of this study was to test our hypothesis that inflammation-associated marker protein levels are increased in AMD and treatment with HNG leads to reduction in their protein levels. Humanin protein levels were measured in the plasma of AMD patients and normal subjects using ELISA assay. Humanin G was added to AMD and normal (control) cybrids which had identical nuclei from mitochondria-deficient ARPE-19 cells but differed in mitochondrial DNA (mtDNA) content derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal cybrids, and the Luminex XMAP multiplex assay was used to measure the levels of inflammatory proteins. AMD plasma showed reduced Humanin protein levels, but higher protein levels of inflammation markers compared to control plasma samples. In AMD RPE cybrid cells, Humanin G reduced the CD62E/ E-Selectin, CD62P/ P-Selectin, ICAM-1, TNF-α, MIP-1α, IFN–γ, IL-1β, IL-13, and IL-17A protein levels, thereby suggesting that Humanin G may rescue from mtDNA-mediated inflammation in AMD cybrids. In conclusion, we present novel findings that: A) show reduced Humanin protein levels in AMD plasma vs. normal plasma; B) suggest the role of inflammatory markers in AMD pathogenesis, and C) highlight the positive effects of Humanin G in reducing inflammation in AMD.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"42 1","pages":"4247 - 4269"},"PeriodicalIF":0.0,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87114328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To master the technology of reprogramming mouse somatic cells to induced pluripotent stem cells (iPSCs), which will lay a good foundation for setting up a technology platform on reprogramming human cancer cells into iPSCs. Mouse iPSCs (i.e., Oct4-GFP miPSCs) was successfully generated from mouse embryonic fibroblasts (MEFs) harboring Oct4-EGFP transgene by introducing four factors, Oct4, Sox2, c-Myc and Klf4, under mESC (Murine embryonic stem cells) culture conditions. Oct4-GFP miPSCs were similar to mESCs in morphology, proliferation, mESC-specific surface antigens and gene expression. Additionally, Oct4-GFP miPSCs could be cultured in suspension to form embryoid bodies (EBs) and differentiate into cell types of the three germ layers in vitro. Moreover, Oct4-GFP miPSCs could develop to teratoma and chimera in vivo. Unlike cell cycle distribution of MEFs, Oct4-GFP miPSCs are similar to mESCs in the cell cycle structure which consists of higher S phase and lower G1 phase. More importantly, our data demonstrated that MEFs harboring Oct4-EGFP transgene did not express GFP, until they were reprogrammed to the pluripotent stage (iPSCs), while the GFP expression was progressively lost when these pluripotent Oct4-GFP miPSCs exposed to EB-mediated differentiation conditions, suggesting the pluripotency of Oct4-GFP miPSCs can be real-time monitored over long periods of time via GFP assay. Altogether, our findings demonstrate that Oct4-GFP miPSC line is successfully established, which will lay a solid foundation for setting up a technology platform on reprogramming cancer cells into iPSCs. Furthermore, this pluripotency reporter system permits the long-term real-time monitoring of pluripotency changes in a live single-cell, and its progeny.
{"title":"A real-time pluripotency reporter for the long-term and real-time monitoring of pluripotency changes in induced pluripotent stem cells","authors":"Hong-fen Shen, Yonglong Li, Shijiang Huang, Jia-Wei Xia, Zhiguang Yao, Gaofang Xiao, Ying Zhou, Yingchun Li, Jun-Wen Shi, Xiao-Lin Lin, Wen-tao Zhao, Yan Sun, Yu-guang Tian, Jun-shuang Jia, Dong Xiao","doi":"10.18632/aging.204083","DOIUrl":"https://doi.org/10.18632/aging.204083","url":null,"abstract":"To master the technology of reprogramming mouse somatic cells to induced pluripotent stem cells (iPSCs), which will lay a good foundation for setting up a technology platform on reprogramming human cancer cells into iPSCs. Mouse iPSCs (i.e., Oct4-GFP miPSCs) was successfully generated from mouse embryonic fibroblasts (MEFs) harboring Oct4-EGFP transgene by introducing four factors, Oct4, Sox2, c-Myc and Klf4, under mESC (Murine embryonic stem cells) culture conditions. Oct4-GFP miPSCs were similar to mESCs in morphology, proliferation, mESC-specific surface antigens and gene expression. Additionally, Oct4-GFP miPSCs could be cultured in suspension to form embryoid bodies (EBs) and differentiate into cell types of the three germ layers in vitro. Moreover, Oct4-GFP miPSCs could develop to teratoma and chimera in vivo. Unlike cell cycle distribution of MEFs, Oct4-GFP miPSCs are similar to mESCs in the cell cycle structure which consists of higher S phase and lower G1 phase. More importantly, our data demonstrated that MEFs harboring Oct4-EGFP transgene did not express GFP, until they were reprogrammed to the pluripotent stage (iPSCs), while the GFP expression was progressively lost when these pluripotent Oct4-GFP miPSCs exposed to EB-mediated differentiation conditions, suggesting the pluripotency of Oct4-GFP miPSCs can be real-time monitored over long periods of time via GFP assay. Altogether, our findings demonstrate that Oct4-GFP miPSC line is successfully established, which will lay a solid foundation for setting up a technology platform on reprogramming cancer cells into iPSCs. Furthermore, this pluripotency reporter system permits the long-term real-time monitoring of pluripotency changes in a live single-cell, and its progeny.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"404 1","pages":"4445 - 4458"},"PeriodicalIF":0.0,"publicationDate":"2022-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85500029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Wei, X. Ying, Liang Chen, Qingmei Sun, Xiaohuan Lu, Yang Xia, R. Xu, Zhechen Zhu, Dong Zhang, Q. Tang, Li Li, Jiaheng Xie, Hongzhu Yu
Background: RecQ mediated genome instability 2 (RMI2) is an essential component of the BLM-TopoIIIa-RMI1-RMI2 (BTR) complex. However, the mysterious veil of the potential immunological relationship of RMI2 in tumorigenesis and development has not been revealed. Methods: We conducted the differential expression (DE) analysis of the RMI2 in pan-cancer using data onto Oncomine, TIMER, and GEPIA databases. Afterward, survival analysis and clinical-stage correlation analysis were performed via the TCGA database. Subsequently, we used R software to further explore the relationship between the expression level of RMI2 and tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), tumor immune-infiltrated cells (TILs), immune checkpoints (ICP), mismatch repairs (MMRs) -related genes, m6A-related genes, DNA methylation-related genes. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional networks were also performed for annotation via gene set enrichment analysis (GSEA). Results: The RMI2 expressed remarkably high in most cancer types compared to cancer adjacent normal tissues (P < 0.05). High expression of RMI2 was linked to unfavorable prognosis and advanced stage of disease, especially in LIHC and PAAD. RMI2 expression was related to TMB in 16 cancer types and MSI in 8 cancer types. Furthermore, it is significant positive correlations between RMI2 and stromal and immune cells, ICP-related genes, MMRs-related genes, m6A-related genes, and DNA methylation-related genes. Finally, GSEA analysis revealed that RMI2 was engaged in a variety of signaling pathways in pan-cancers. Conclusions: RMI2 may serve as a potential biological target and probably assume a crucial part in tumorigenesis and progression.
{"title":"RecQ mediated genome instability 2 (RMI2): a potential prognostic and immunological biomarker for pan-cancers","authors":"Wei Wei, X. Ying, Liang Chen, Qingmei Sun, Xiaohuan Lu, Yang Xia, R. Xu, Zhechen Zhu, Dong Zhang, Q. Tang, Li Li, Jiaheng Xie, Hongzhu Yu","doi":"10.18632/aging.204076","DOIUrl":"https://doi.org/10.18632/aging.204076","url":null,"abstract":"Background: RecQ mediated genome instability 2 (RMI2) is an essential component of the BLM-TopoIIIa-RMI1-RMI2 (BTR) complex. However, the mysterious veil of the potential immunological relationship of RMI2 in tumorigenesis and development has not been revealed. Methods: We conducted the differential expression (DE) analysis of the RMI2 in pan-cancer using data onto Oncomine, TIMER, and GEPIA databases. Afterward, survival analysis and clinical-stage correlation analysis were performed via the TCGA database. Subsequently, we used R software to further explore the relationship between the expression level of RMI2 and tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), tumor immune-infiltrated cells (TILs), immune checkpoints (ICP), mismatch repairs (MMRs) -related genes, m6A-related genes, DNA methylation-related genes. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional networks were also performed for annotation via gene set enrichment analysis (GSEA). Results: The RMI2 expressed remarkably high in most cancer types compared to cancer adjacent normal tissues (P < 0.05). High expression of RMI2 was linked to unfavorable prognosis and advanced stage of disease, especially in LIHC and PAAD. RMI2 expression was related to TMB in 16 cancer types and MSI in 8 cancer types. Furthermore, it is significant positive correlations between RMI2 and stromal and immune cells, ICP-related genes, MMRs-related genes, m6A-related genes, and DNA methylation-related genes. Finally, GSEA analysis revealed that RMI2 was engaged in a variety of signaling pathways in pan-cancers. Conclusions: RMI2 may serve as a potential biological target and probably assume a crucial part in tumorigenesis and progression.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"33 1","pages":"4107 - 4136"},"PeriodicalIF":0.0,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85029223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xin Yang, Minhui Mei, Jing-Hong Yang, Jinlu Guo, F. Du, Shi Liu
Background: Hepatocellular Carcinoma (HCC) is a highly heterogeneous malignant tumor, and its prognostic prediction is extremely challenging. Ferroptosis is a cell mechanism dependent on iron, which is very significant for HCC development. Long non-coding RNA (lncRNA) is also linked to HCC progression. This work aimed to establish a prognosis risk model for HCC and to discover a possible biomarker and therapeutic target. Methods: The Cancer Genome Atlas (TCGA) database was used to obtain RNA-seq transcriptome data and clinic information of HCC patients. Firstly, univariate Cox was utilized to identify 66 prognostic ferroptosis-related lncRNAs. Then, the identified lncRNAs were further included in the multivariate Cox analysis to construct the prognostic model. Eventually, we performed quantitative polymerase chain reaction (q-PCR) to validate the risk model. Results: We established a prognostic seventeen-ferroptosis-related lncRNA signature model. The signature could categorize patients into two risk subgroups, with the low-risk subgroup associated with a better prognosis. Additionally, the area under the curve (AUC) of the lncRNAs signature was 0.801, indicating their reliability in forecasting HCC prognosis. Risk score was an independent prognostic factor by regression analyses. Gene set enrichment analysis (GSEA) analyses demonstrated a remarkable enrichment of cancer-related and immune-related pathways in the high-risk group. Besides, the immune status was decreased in the high-risk group. Eventually, three prognostic lncRNAs were validated in human HCCLM3 cell lines. Conclusions: The risk model based on seventeen-ferroptosis-related lncRNA has significant prognostic value for HCC and may be therapeutic targets associated with ferroptosis in clinical ways.
{"title":"Ferroptosis-related long non-coding RNA signature predicts the prognosis of hepatocellular carcinoma","authors":"Xin Yang, Minhui Mei, Jing-Hong Yang, Jinlu Guo, F. Du, Shi Liu","doi":"10.18632/aging.204073","DOIUrl":"https://doi.org/10.18632/aging.204073","url":null,"abstract":"Background: Hepatocellular Carcinoma (HCC) is a highly heterogeneous malignant tumor, and its prognostic prediction is extremely challenging. Ferroptosis is a cell mechanism dependent on iron, which is very significant for HCC development. Long non-coding RNA (lncRNA) is also linked to HCC progression. This work aimed to establish a prognosis risk model for HCC and to discover a possible biomarker and therapeutic target. Methods: The Cancer Genome Atlas (TCGA) database was used to obtain RNA-seq transcriptome data and clinic information of HCC patients. Firstly, univariate Cox was utilized to identify 66 prognostic ferroptosis-related lncRNAs. Then, the identified lncRNAs were further included in the multivariate Cox analysis to construct the prognostic model. Eventually, we performed quantitative polymerase chain reaction (q-PCR) to validate the risk model. Results: We established a prognostic seventeen-ferroptosis-related lncRNA signature model. The signature could categorize patients into two risk subgroups, with the low-risk subgroup associated with a better prognosis. Additionally, the area under the curve (AUC) of the lncRNAs signature was 0.801, indicating their reliability in forecasting HCC prognosis. Risk score was an independent prognostic factor by regression analyses. Gene set enrichment analysis (GSEA) analyses demonstrated a remarkable enrichment of cancer-related and immune-related pathways in the high-risk group. Besides, the immune status was decreased in the high-risk group. Eventually, three prognostic lncRNAs were validated in human HCCLM3 cell lines. Conclusions: The risk model based on seventeen-ferroptosis-related lncRNA has significant prognostic value for HCC and may be therapeutic targets associated with ferroptosis in clinical ways.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"38 1","pages":"4069 - 4084"},"PeriodicalIF":0.0,"publicationDate":"2022-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76317042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Administration of non-thermal plasma therapy via the use of plasma-activated medium (PAM) might be a novel strategy for cancer treatment, as it induces apoptosis by increasing reactive oxygen species (ROS) levels. Peroxiredoxin V (PRDX5) scavenges ROS and reactive nitrogen species and is known to regulate several physiological and pathological reactions. However, its role in lung cancer cells exposed to PAM is unknown. Here, we investigated the effect of PRDX5 in PAM-treated A549 lung cancer cells and determined the mechanism underlying its cytotoxicity. Cell culture medium was treated with low temperature plasma at 16.4 kV for 0, 60, 120, or 180 s to develop PAM. PRDX5 was knocked down in A549 cells via transfection with short hairpin RNA targeting PRDX5. Colony formation and wound healing assays, flow cytometry, fluorescence microscopy, and western blotting were performed to detect the effect of PRDX5 knockdown on PAM-treated A549 cells. PAM showed higher cytotoxicity in lung cancer cells than in control cells, downregulated the mitogen-activated protein kinase signaling pathway, and induced apoptosis. PRDX5 knockdown significantly inhibited cell colony formation and migration, increased ROS accumulation, and reduced mitochondrial membrane potential in lung cancer cells. Hence, PRDX5 knockdown combined with PAM treatment represents an effective option for lung cancer treatment.
{"title":"Knockdown of Peroxiredoxin V increased the cytotoxicity of non-thermal plasma-treated culture medium to A549 cells","authors":"Hu-Nan Sun, Xiao-Yu Guo, Dan-Ping Xie, Xiao-Ming Wang, Chen-Xi Ren, Ying-Hao Han, Nan-Nan Yu, Yu-lan Huang, Taeho Kwon","doi":"10.18632/aging.204063","DOIUrl":"https://doi.org/10.18632/aging.204063","url":null,"abstract":"Administration of non-thermal plasma therapy via the use of plasma-activated medium (PAM) might be a novel strategy for cancer treatment, as it induces apoptosis by increasing reactive oxygen species (ROS) levels. Peroxiredoxin V (PRDX5) scavenges ROS and reactive nitrogen species and is known to regulate several physiological and pathological reactions. However, its role in lung cancer cells exposed to PAM is unknown. Here, we investigated the effect of PRDX5 in PAM-treated A549 lung cancer cells and determined the mechanism underlying its cytotoxicity. Cell culture medium was treated with low temperature plasma at 16.4 kV for 0, 60, 120, or 180 s to develop PAM. PRDX5 was knocked down in A549 cells via transfection with short hairpin RNA targeting PRDX5. Colony formation and wound healing assays, flow cytometry, fluorescence microscopy, and western blotting were performed to detect the effect of PRDX5 knockdown on PAM-treated A549 cells. PAM showed higher cytotoxicity in lung cancer cells than in control cells, downregulated the mitogen-activated protein kinase signaling pathway, and induced apoptosis. PRDX5 knockdown significantly inhibited cell colony formation and migration, increased ROS accumulation, and reduced mitochondrial membrane potential in lung cancer cells. Hence, PRDX5 knockdown combined with PAM treatment represents an effective option for lung cancer treatment.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"110 1","pages":"4000 - 4013"},"PeriodicalIF":0.0,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78531434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite the well-established role of long non-coding RNAs (lncRNAs) across various biological processes, their mechanisms in acute myocardial infarction (AMI) are not fully elucidated. The GSE34198 dataset from the Gene Expression Omnibus (GEO) database, which comprised 49 specimens from individuals with AMI and 47 specimens from controls, was extracted and analysed using the weighted gene co-expression network analysis (WGCNA) package. Twenty-seven key genes were identified through a combination of the degree and gene significance (GS) values, and the CDC42 (degree = 64), JAK2 (degree = 41), and CHUK (degree = 30) genes were identified as having the top three-degree values among the 27 genes. Potential interactions between lncRNA, miRNAs and mRNAs were predicted using the starBase V3.0 database, and a lncRNA-miRNA-mRNA triple network containing the lncRNA XIST, twenty-one miRNAs and three hub genes (CDC42, JAK2 and CHUK) was identified. RT–qPCR validation showed that the expression of the JAK2 and CDC42 genes and the lncRNA XIST was noticeably increased in samples from patients with AMI compared to normal samples. Pearson’s correlation analysis also proved that JAK2 and CDC42 expression levels correlated positively with lncRNA XIST expression levels. The area under ROC curve (AUC) of lncRNA XIST was 0.886, and the diagnostic efficacy of the lncRNA XIST was significantly better than that of JAK2 and CDC42. The results suggested that the lncRNA XIST appears to be a risk factor for AMI likely through its ability to regulate JAK2 and CDC42 gene expressions, and it is expected to be a novel and reliable biomarker for the diagnosis of AMI.
{"title":"A novel lncRNA-miRNA-mRNA triple network identifies lncRNA XIST as a biomarker for acute myocardial infarction","authors":"P. Zheng, Lu-Zhu Chen, Peng Liu, H. Pan","doi":"10.18632/aging.204075","DOIUrl":"https://doi.org/10.18632/aging.204075","url":null,"abstract":"Despite the well-established role of long non-coding RNAs (lncRNAs) across various biological processes, their mechanisms in acute myocardial infarction (AMI) are not fully elucidated. The GSE34198 dataset from the Gene Expression Omnibus (GEO) database, which comprised 49 specimens from individuals with AMI and 47 specimens from controls, was extracted and analysed using the weighted gene co-expression network analysis (WGCNA) package. Twenty-seven key genes were identified through a combination of the degree and gene significance (GS) values, and the CDC42 (degree = 64), JAK2 (degree = 41), and CHUK (degree = 30) genes were identified as having the top three-degree values among the 27 genes. Potential interactions between lncRNA, miRNAs and mRNAs were predicted using the starBase V3.0 database, and a lncRNA-miRNA-mRNA triple network containing the lncRNA XIST, twenty-one miRNAs and three hub genes (CDC42, JAK2 and CHUK) was identified. RT–qPCR validation showed that the expression of the JAK2 and CDC42 genes and the lncRNA XIST was noticeably increased in samples from patients with AMI compared to normal samples. Pearson’s correlation analysis also proved that JAK2 and CDC42 expression levels correlated positively with lncRNA XIST expression levels. The area under ROC curve (AUC) of lncRNA XIST was 0.886, and the diagnostic efficacy of the lncRNA XIST was significantly better than that of JAK2 and CDC42. The results suggested that the lncRNA XIST appears to be a risk factor for AMI likely through its ability to regulate JAK2 and CDC42 gene expressions, and it is expected to be a novel and reliable biomarker for the diagnosis of AMI.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"27 1","pages":"4085 - 4106"},"PeriodicalIF":0.0,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90169074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Yuan, Yang Zhang, Runzi Zheng, Hongjun Yuan, Ruoyu Zhou, Shuting Jia, Jing Liu
Si Jun Zi Tang (SJZT) is a classic Traditional Chinese Medicine (TCM) prescription used to treat aging-related diseases. However, the potential molecular mechanisms of the anti-aging effects of the bioactive compounds and their targets remain elusive. In this study, we combined network pharmacology and molecular docking with in vivo experiments to elucidate the anti-aging molecular mechanism of SJZT. A series of network pharmacology strategies were used to predict potential targets and therapeutic mechanisms of SJZT, including compound screening, pathway enrichment analysis and molecular docking studies. Based on the network pharmacology predictions and observation of outward signs of aging, the expression levels of selected genes and proteins and possible key targets were subsequently validated and analysed using qRT-PCR and immunoblotting. Using a data mining approach, 235 effective targets of SJZT and aging were obtained. AKT1, STAT3, JUN, MAPK3, TP53, MAPK1, TNF, RELA, MAPK14 and IL6 were identified as core genes in the Protein-Protein Interaction Networks (PPI) analysis. The results of the effective target Gene Ontology (Go) functional enrichment analysis suggested that SJZT may be involved aging and antiapoptotic biological processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the anti-aging mechanism of SJZT may be associated with the PI3K-AKT and P38 MAPK signalling pathways. Molecular docking analysis suggested that kaempferol and quercetin could fit in the binding pockets of the core targets. In addition, SJZT alleviated the aging symptoms of mice such as osteoporosis and hair loss. In conclusion, the anti-aging effect of SJZT was associated with the inhibition of the PI3K-AKT and P38 MAPK signalling pathways, and these findings were consistent with the network pharmacology prediction.
{"title":"Elucidating the anti-aging mechanism of Si Jun Zi Tang by integrating network pharmacology and experimental validation in vivo","authors":"Yang Yuan, Yang Zhang, Runzi Zheng, Hongjun Yuan, Ruoyu Zhou, Shuting Jia, Jing Liu","doi":"10.18632/aging.204055","DOIUrl":"https://doi.org/10.18632/aging.204055","url":null,"abstract":"Si Jun Zi Tang (SJZT) is a classic Traditional Chinese Medicine (TCM) prescription used to treat aging-related diseases. However, the potential molecular mechanisms of the anti-aging effects of the bioactive compounds and their targets remain elusive. In this study, we combined network pharmacology and molecular docking with in vivo experiments to elucidate the anti-aging molecular mechanism of SJZT. A series of network pharmacology strategies were used to predict potential targets and therapeutic mechanisms of SJZT, including compound screening, pathway enrichment analysis and molecular docking studies. Based on the network pharmacology predictions and observation of outward signs of aging, the expression levels of selected genes and proteins and possible key targets were subsequently validated and analysed using qRT-PCR and immunoblotting. Using a data mining approach, 235 effective targets of SJZT and aging were obtained. AKT1, STAT3, JUN, MAPK3, TP53, MAPK1, TNF, RELA, MAPK14 and IL6 were identified as core genes in the Protein-Protein Interaction Networks (PPI) analysis. The results of the effective target Gene Ontology (Go) functional enrichment analysis suggested that SJZT may be involved aging and antiapoptotic biological processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the anti-aging mechanism of SJZT may be associated with the PI3K-AKT and P38 MAPK signalling pathways. Molecular docking analysis suggested that kaempferol and quercetin could fit in the binding pockets of the core targets. In addition, SJZT alleviated the aging symptoms of mice such as osteoporosis and hair loss. In conclusion, the anti-aging effect of SJZT was associated with the inhibition of the PI3K-AKT and P38 MAPK signalling pathways, and these findings were consistent with the network pharmacology prediction.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"5 4 1","pages":"3941 - 3955"},"PeriodicalIF":0.0,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73178521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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