Infection virus including HBV and HCV has been well recognized as a major cause inducing hepatocellular carcinoma (HCC). However, molecular investigations into the HTLV-1 (Human T-lymphotropic virus type-1) and HCC have been rare. In this study, we integrated several public datasets of HCC patients and filtered seven genes including CDC20 as the HTLV-1 infection-related genes which were differentially expressed in HCC. CDC20 was chosen for further investigation based on its promising prognostic power. The expression profiles, prognostic assessment, association with clinicopathologic characteristics, prediction of correlated signal pathways, and the immune-modulating function of CDC20 were assessed. We found that CDC20 expression was significantly increased in hepatocellular carcinoma tissues and cell lines, and was correlated with histologic grade, pathologic stage, tumor status, and patient age. CDC20 exhibited prognostic value on overall survival and disease specific survival and was an independent prognostic factor. It was primarily involved in several signal pathways, especially the omega-hydroxylase P450 and epoxygenase P450 signal pathways. Moreover, CDC20 expression showed significant positive associations with the levels of several immune cells such as T helper 2 cells and follicular helper T cells, immunostimulators including TNFRSF18 and MICB, immunoinhibitors including KDR and PDCD1LG2, chemokines including XCL1 and CCL26, and chemokine receptors including CCR10 and CXCR3. This study for the first time delineated the correlation of CDC20 with HTLV-1 infection-associated HCC. The disorder of expression and function of CDC20 makes it a probable biomarker for better etiological classification, prognostic prediction, and precision medicine.
{"title":"The bioinformatics and experimental analysis of the novel roles of virus infection-associated gene CDC20 for prognosis and immune infiltration in hepatocellular carcinoma","authors":"Juanni Li, Xiaofang Zhang, Lei Yao, K. Hu","doi":"10.18632/aging.204093","DOIUrl":"https://doi.org/10.18632/aging.204093","url":null,"abstract":"Infection virus including HBV and HCV has been well recognized as a major cause inducing hepatocellular carcinoma (HCC). However, molecular investigations into the HTLV-1 (Human T-lymphotropic virus type-1) and HCC have been rare. In this study, we integrated several public datasets of HCC patients and filtered seven genes including CDC20 as the HTLV-1 infection-related genes which were differentially expressed in HCC. CDC20 was chosen for further investigation based on its promising prognostic power. The expression profiles, prognostic assessment, association with clinicopathologic characteristics, prediction of correlated signal pathways, and the immune-modulating function of CDC20 were assessed. We found that CDC20 expression was significantly increased in hepatocellular carcinoma tissues and cell lines, and was correlated with histologic grade, pathologic stage, tumor status, and patient age. CDC20 exhibited prognostic value on overall survival and disease specific survival and was an independent prognostic factor. It was primarily involved in several signal pathways, especially the omega-hydroxylase P450 and epoxygenase P450 signal pathways. Moreover, CDC20 expression showed significant positive associations with the levels of several immune cells such as T helper 2 cells and follicular helper T cells, immunostimulators including TNFRSF18 and MICB, immunoinhibitors including KDR and PDCD1LG2, chemokines including XCL1 and CCL26, and chemokine receptors including CCR10 and CXCR3. This study for the first time delineated the correlation of CDC20 with HTLV-1 infection-associated HCC. The disorder of expression and function of CDC20 makes it a probable biomarker for better etiological classification, prognostic prediction, and precision medicine.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"27 1","pages":"4513 - 4529"},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78829026","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}
accelerates aging [1]. This effect is expected to become increasingly problematic because currently, in the United States, more than half of those infected with HIV are over 50 years old and thus are subjected to the combined effects of HIV and aging [1]. Antiretroviral therapy (ART) for HIV greatly suppresses viral loads and reduces HIV-related morbidity and mortality, enabling people living with HIV (PLWH) to have a much better quality-of-life and survive into old age. However, ART does not prevent neurological disturbances from developing in PLWH including disruptions in mood and cognitive ability and the development of intractable pain states. These comorbidities reduce quality-of-life and catalyze problematic behaviors including substance use disorders that worsen HIVand age-related outcomes. These sequelae occur in part because ART does not stop HIV reservoirs from synthesizing and releasing toxic proteins such as the transactivator of transcription (Tat) protein, appreciable levels of which are present in the central nervous system during ART (e.g., [2]). In particular, Tat is neurotoxic and it induces neuroinflammation, oxidative stress, and mitochondrial dysfunction (see [3]), effects that also are associated with aging [1].
{"title":"HIV-Tat protein-accelerated aging","authors":"M. Kaufman, Alaa N. Qrareya, J. Paris","doi":"10.18632/aging.204105","DOIUrl":"https://doi.org/10.18632/aging.204105","url":null,"abstract":"accelerates aging [1]. This effect is expected to become increasingly problematic because currently, in the United States, more than half of those infected with HIV are over 50 years old and thus are subjected to the combined effects of HIV and aging [1]. Antiretroviral therapy (ART) for HIV greatly suppresses viral loads and reduces HIV-related morbidity and mortality, enabling people living with HIV (PLWH) to have a much better quality-of-life and survive into old age. However, ART does not prevent neurological disturbances from developing in PLWH including disruptions in mood and cognitive ability and the development of intractable pain states. These comorbidities reduce quality-of-life and catalyze problematic behaviors including substance use disorders that worsen HIVand age-related outcomes. These sequelae occur in part because ART does not stop HIV reservoirs from synthesizing and releasing toxic proteins such as the transactivator of transcription (Tat) protein, appreciable levels of which are present in the central nervous system during ART (e.g., [2]). In particular, Tat is neurotoxic and it induces neuroinflammation, oxidative stress, and mitochondrial dysfunction (see [3]), effects that also are associated with aging [1].","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"37 1","pages":"4618 - 4619"},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80610856","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}
Objective: To determine survival rates and the underlying mechanism of genes in the TRIM family in Kidney Clear Cell Carcinoma (KIRC). Methods: Transcriptional and survival data of TRIM genes in KIRC patients were retrieved from the UCSC Xena, and GEPIA databases. The function of TRIM genes in KIRC was investigated, focusing on potential ubiquitination, miRNAs regulation, and enrichment analysis. Next, TRIM gene survival values were determined, followed by the development of a survival-related signature. Results: Only TRIM26 was down expressed in the carcinoma tissue and had a survival value in KIRC relative to control tissues, which was supplied by vitro experiment. The patients with lower expression of TRIM26 would have the chance to live a shorter time. SNRPB, which also plays a role in ubiquitination, directly interacted with TRIM26. Moreover, two miRNAs (hsa-let-7i-5p, and hsa-miR-1228-5p) that regulated levels of TRIM26 expression were also identified. Next, we constructed a signature (TRIM4/7/27/58/65/72) and found that high-risk scores of the signature were associated with poor survival rates in KIRC patients. while its resultant risk scores were correlated with immune cell components and markers. Conclusions: TRIM26 was differentially expressed between KIRC and normal tissues and had a survival value in the KIRC. hsa-let-7i-5p/hsa-miR-1228-5p-TRIM26-SNRPB was a potential mechanism axis that may play a role on the KIRC cells. A survival signature (TRIM4/7/27/58/65/72) was successfully established to predict the survival of KIRC patients.
{"title":"Comprehensive analysis of expression profiles and prognosis of TRIM genes in human kidney clear cell carcinoma","authors":"Junwen Shen, Rong-jiang Wang, Yu Chen, Zhihai Fang, Jian-er Tang, Jianxiang Yao, Jian-guo Gao, Wenxia Zhou, Xiongnong Chen","doi":"10.18632/aging.204102","DOIUrl":"https://doi.org/10.18632/aging.204102","url":null,"abstract":"Objective: To determine survival rates and the underlying mechanism of genes in the TRIM family in Kidney Clear Cell Carcinoma (KIRC). Methods: Transcriptional and survival data of TRIM genes in KIRC patients were retrieved from the UCSC Xena, and GEPIA databases. The function of TRIM genes in KIRC was investigated, focusing on potential ubiquitination, miRNAs regulation, and enrichment analysis. Next, TRIM gene survival values were determined, followed by the development of a survival-related signature. Results: Only TRIM26 was down expressed in the carcinoma tissue and had a survival value in KIRC relative to control tissues, which was supplied by vitro experiment. The patients with lower expression of TRIM26 would have the chance to live a shorter time. SNRPB, which also plays a role in ubiquitination, directly interacted with TRIM26. Moreover, two miRNAs (hsa-let-7i-5p, and hsa-miR-1228-5p) that regulated levels of TRIM26 expression were also identified. Next, we constructed a signature (TRIM4/7/27/58/65/72) and found that high-risk scores of the signature were associated with poor survival rates in KIRC patients. while its resultant risk scores were correlated with immune cell components and markers. Conclusions: TRIM26 was differentially expressed between KIRC and normal tissues and had a survival value in the KIRC. hsa-let-7i-5p/hsa-miR-1228-5p-TRIM26-SNRPB was a potential mechanism axis that may play a role on the KIRC cells. A survival signature (TRIM4/7/27/58/65/72) was successfully established to predict the survival of KIRC patients.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"22 1","pages":"4606 - 4617"},"PeriodicalIF":0.0,"publicationDate":"2022-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82281324","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}
Hsueh-Ju Lu, C. Chuang, Mu-Kuan Chen, Chun-Wen Su, Wei‐En Yang, Chia-Ming Yeh, K. Lai, Chih-Hsin Tang, Chiao-Wen Lin, Shun-Fa Yang
The gene encoding aldehyde dehydrogenase 7 family member A1 (ALDH7A1) has been associated with the development and prognosis in multiple cancers; however, the role of ALDH7A1 polymorphisms in oral cancer remains unknown. For this purpose, the influences of ALDH7A1 rs13182402 and rs12659017 on oral cancer development and prognosis were analyzed. Our resulted showed that ALDH7A1 rs13182402 genotype had less pathologic nodal metastasis among betel quid chewer. ALDH7A1 rs13182402 also corresponded to higher expressions in upper aerodigestive mucosa, whole blood, the musculoskeletal system and oral cancer tissues than did the ALDH7A1 wild type. Furthermore, ALDH7A1 overexpression in oral cancer cells increased in vitro migration, whereas its silencing reduced cell migration. Conversely, ALDH7A1 expression in tumor tissues and in patients with advanced disease was lower than that in normal tissues and in patients with early-stage disease. When the patients were classified into ALDH7A1-high and -low-expression groups, the high-ALDH7A1 group had superior outcomes in progression-free survival than the low-ALDH7A1 group (5-year survival of 58.7% vs. 48.0%, P = 0.048) did. In conclusion, patients with high ALDH7A1 expression might, however, have more favorable prognoses than those with low ALDH7A1 expression have.
编码醛脱氢酶7家族成员A1 (ALDH7A1)的基因与多种癌症的发展和预后相关;然而，ALDH7A1多态性在口腔癌中的作用尚不清楚。为此，我们分析ALDH7A1 rs13182402和rs12659017对口腔癌发展及预后的影响。结果表明，ALDH7A1 rs13182402基因型在槟榔咀嚼者中有较少的病理性淋巴结转移。ALDH7A1 rs13182402在上气消化粘膜、全血、肌肉骨骼系统和口腔癌组织中的表达也高于ALDH7A1野生型。此外，ALDH7A1在口腔癌细胞中的过表达增加了体外迁移，而其沉默则减少了细胞迁移。相反，ALDH7A1在肿瘤组织和晚期疾病患者中的表达低于正常组织和早期疾病患者。将患者分为aldh7a1高表达组和aldh7a1低表达组，高表达组在无进展生存方面优于低表达组(5年生存率58.7% vs 48.0%， P = 0.048)。总之，ALDH7A1高表达的患者可能比ALDH7A1低表达的患者有更好的预后。
{"title":"The impact of ALDH7A1 variants in oral cancer development and prognosis","authors":"Hsueh-Ju Lu, C. Chuang, Mu-Kuan Chen, Chun-Wen Su, Wei‐En Yang, Chia-Ming Yeh, K. Lai, Chih-Hsin Tang, Chiao-Wen Lin, Shun-Fa Yang","doi":"10.18632/aging.204099","DOIUrl":"https://doi.org/10.18632/aging.204099","url":null,"abstract":"The gene encoding aldehyde dehydrogenase 7 family member A1 (ALDH7A1) has been associated with the development and prognosis in multiple cancers; however, the role of ALDH7A1 polymorphisms in oral cancer remains unknown. For this purpose, the influences of ALDH7A1 rs13182402 and rs12659017 on oral cancer development and prognosis were analyzed. Our resulted showed that ALDH7A1 rs13182402 genotype had less pathologic nodal metastasis among betel quid chewer. ALDH7A1 rs13182402 also corresponded to higher expressions in upper aerodigestive mucosa, whole blood, the musculoskeletal system and oral cancer tissues than did the ALDH7A1 wild type. Furthermore, ALDH7A1 overexpression in oral cancer cells increased in vitro migration, whereas its silencing reduced cell migration. Conversely, ALDH7A1 expression in tumor tissues and in patients with advanced disease was lower than that in normal tissues and in patients with early-stage disease. When the patients were classified into ALDH7A1-high and -low-expression groups, the high-ALDH7A1 group had superior outcomes in progression-free survival than the low-ALDH7A1 group (5-year survival of 58.7% vs. 48.0%, P = 0.048) did. In conclusion, patients with high ALDH7A1 expression might, however, have more favorable prognoses than those with low ALDH7A1 expression have.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"5 1","pages":"4556 - 4571"},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83154294","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}
Background: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. Objective: To explore IDD pathogenesis at the cellular and gene levels and investigate lactotransferrin (LTF) expression in IDD patients and its possible mechanism. Methods: We downloaded the IDD data set from the Gene Expression Omnibus (GEO) database, screened the differentially expressed genes (DEGs) and hub genes and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to construct a protein–protein interaction (PPI) network. Subsequently, we verified LTF's regulatory mechanism through cell experiments. IL-1β was used to intervene in nucleus pulposus cells (NPCs) to construct the IDD cell model, and LTF and Fas expression was detected by qRT–PCR. LTF inhibitor, Fas inhibitor, LTF mimic, and Fas mimic were used to intervene in each group. Western blotting was used to detect Fas, Caspase-3, Bax, and Bcl-2 expression. Results: A total of 131 DEGs and 10 hub genes were screened. LTF mRNA in the IDD model was significantly higher than that in the control group, while Fas' mRNA was significantly lower. When LTF was upregulated or downregulated in NPCs, apoptosis marker expression showed the opposite trend. The rescue test showed that LTF and Fas' overexpression greatly enhanced NPC apoptosis. Conclusion: LTF promotes IDD progression by regulating Fas in NPCs, and it may be an effective gene therapy target.
背景:近年来，椎间盘退变(IDD)随年龄增长而增加。临床上仍然缺乏有效的治疗方法，无法从病因层面改善缺乏症的状况。目的:探讨IDD在细胞和基因水平上的发病机制，探讨乳转铁蛋白(LTF)在IDD患者中的表达及其可能的机制。方法:从Gene Expression Omnibus (GEO)数据库下载IDD数据集，筛选差异表达基因(DEGs)和枢纽基因(hub)，并进行京都基因与基因组百科全书(KEGG)分析，构建蛋白-蛋白相互作用(PPI)网络。随后，我们通过细胞实验验证了LTF的调控机制。采用IL-1β干预髓核细胞(NPCs)构建IDD细胞模型，采用qRT-PCR检测LTF和Fas的表达。各组分别采用LTF抑制剂、Fas抑制剂、LTF模拟物和Fas模拟物进行干预。Western blotting检测Fas、Caspase-3、Bax、Bcl-2的表达。结果:共筛选到131个deg基因和10个hub基因。IDD模型的LTF mRNA显著高于对照组，Fas mRNA显著低于对照组。当LTF在NPCs中上调或下调时，凋亡标志物的表达呈现相反的趋势。挽救实验显示，LTF和Fas过表达显著促进鼻咽癌细胞凋亡。结论:LTF通过调节NPCs的Fas来促进IDD的进展，可能是一个有效的基因治疗靶点。
{"title":"Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis","authors":"Xiao-Bo Zhang, Si-Qi Xu, Yi-Geng Hui, Hai-Yu Zhou, Yi-cun Hu, Rui-hao Zhang, Xi-dan Gao, Chang-Ming Zheng","doi":"10.18632/aging.204100","DOIUrl":"https://doi.org/10.18632/aging.204100","url":null,"abstract":"Background: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. Objective: To explore IDD pathogenesis at the cellular and gene levels and investigate lactotransferrin (LTF) expression in IDD patients and its possible mechanism. Methods: We downloaded the IDD data set from the Gene Expression Omnibus (GEO) database, screened the differentially expressed genes (DEGs) and hub genes and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to construct a protein–protein interaction (PPI) network. Subsequently, we verified LTF's regulatory mechanism through cell experiments. IL-1β was used to intervene in nucleus pulposus cells (NPCs) to construct the IDD cell model, and LTF and Fas expression was detected by qRT–PCR. LTF inhibitor, Fas inhibitor, LTF mimic, and Fas mimic were used to intervene in each group. Western blotting was used to detect Fas, Caspase-3, Bax, and Bcl-2 expression. Results: A total of 131 DEGs and 10 hub genes were screened. LTF mRNA in the IDD model was significantly higher than that in the control group, while Fas' mRNA was significantly lower. When LTF was upregulated or downregulated in NPCs, apoptosis marker expression showed the opposite trend. The rescue test showed that LTF and Fas' overexpression greatly enhanced NPC apoptosis. Conclusion: LTF promotes IDD progression by regulating Fas in NPCs, and it may be an effective gene therapy target.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"14 1","pages":"4572 - 4585"},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87522600","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}
Si Chen, Haolong Li, H. Zhan, Xiaoli Zeng, Hui Yuan, Yongzhe Li
Objective: Polymyositis (PM) and dermatomyositis (DM) are heterogeneous disorders. However, the etiology of PM/DM development has not been thoroughly clarified. Methods: Gene expression data of PM/DM were obtained from Gene Expression Omnibus. We used robust rank aggregation (RRA) to identify differentially expressed genes (DEGs). Gene Ontology functional enrichment and pathway analyses were used to investigate potential functions of the DEGs. Weighted gene co-expression network analysis (WGCNA) was used to establish a gene co-expression network. CIBERSORT was utilized to analyze the pattern of immune cell infiltration in PM/DM. Protein–protein interaction (PPI) network, Venn, and association analyses between core genes and muscle injury were performed to identify hub genes. Receiver operating characteristic analyses were executed to investigate the value of hub genes in the diagnosis of PM/DM, and the results were verified using the microarray dataset GSE48280. Results: Five datasets were included. The RRA integrated analysis identified 82 significant DEGs. Functional enrichment analysis revealed that immune function and the interferon signaling pathway were enriched in PM/DM. WGCNA outcomes identified MEblue and MEturquoise as key target modules in PM/DM. Immune cell infiltration analysis revealed greater macrophage infiltration and lower regulatory T-cell infiltration in PM/DM patients than in healthy controls. PPI network, Venn, and association analyses of muscle injury identified five putative hub genes: TRIM22, IFI6, IFITM1, IFI35, and IRF9. Conclusions: Our bioinformatics analysis identified new genetic biomarkers of the pathogenesis of PM/DM. We demonstrated that immune cell infiltration plays a pivotal part in the occurrence of PM/DM.
{"title":"Identification of hub biomarkers and immune cell infiltration in polymyositis and dermatomyositis","authors":"Si Chen, Haolong Li, H. Zhan, Xiaoli Zeng, Hui Yuan, Yongzhe Li","doi":"10.18632/aging.204098","DOIUrl":"https://doi.org/10.18632/aging.204098","url":null,"abstract":"Objective: Polymyositis (PM) and dermatomyositis (DM) are heterogeneous disorders. However, the etiology of PM/DM development has not been thoroughly clarified. Methods: Gene expression data of PM/DM were obtained from Gene Expression Omnibus. We used robust rank aggregation (RRA) to identify differentially expressed genes (DEGs). Gene Ontology functional enrichment and pathway analyses were used to investigate potential functions of the DEGs. Weighted gene co-expression network analysis (WGCNA) was used to establish a gene co-expression network. CIBERSORT was utilized to analyze the pattern of immune cell infiltration in PM/DM. Protein–protein interaction (PPI) network, Venn, and association analyses between core genes and muscle injury were performed to identify hub genes. Receiver operating characteristic analyses were executed to investigate the value of hub genes in the diagnosis of PM/DM, and the results were verified using the microarray dataset GSE48280. Results: Five datasets were included. The RRA integrated analysis identified 82 significant DEGs. Functional enrichment analysis revealed that immune function and the interferon signaling pathway were enriched in PM/DM. WGCNA outcomes identified MEblue and MEturquoise as key target modules in PM/DM. Immune cell infiltration analysis revealed greater macrophage infiltration and lower regulatory T-cell infiltration in PM/DM patients than in healthy controls. PPI network, Venn, and association analyses of muscle injury identified five putative hub genes: TRIM22, IFI6, IFITM1, IFI35, and IRF9. Conclusions: Our bioinformatics analysis identified new genetic biomarkers of the pathogenesis of PM/DM. We demonstrated that immune cell infiltration plays a pivotal part in the occurrence of PM/DM.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"6 1","pages":"4530 - 4555"},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90292201","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}
Shan Zhong, Li Yang, Naijia Liu, Guangkeng Zhou, Zhangli Hu, Chengshui Chen, Yun Wang
Chronic obstructive pulmonary disease (COPD) is a serious chronic respiratory disorder. One of the major risk factors for COPD progression is aging. Therefore, we investigated aging-related genes in COPD using bioinformatic analyses. Firstly, the Aging Atlas database containing 500 aging-related genes and the Gene Expression Omnibus database (GSE38974) were utilized to screen candidates. A total of 24 candidate genes were identified related to both COPD and aging. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we found that this list of 24 genes was enriched in genes associated with cytokine activity, cell apoptosis, NF-κB and IL-17 signaling. Four of these genes (CDKN1A, HIF1A, MXD1 and SOD2) were determined to be significantly upregulated in clinical COPD samples and in cigarette smoke extract-exposed Beas-2B cells in vitro, and their expression was negatively correlated with predicted forced expiratory volume and forced vital capacity. In addition, the combination of expression levels of these four genes had a good discriminative ability for COPD patients (AUC = 0.794, 95% CI 0.743–0.845). All four were identified as target genes of hsa-miR-519d-3p, which was significantly down-regulated in COPD patients. The results from this study proposed that regulatory network of hsa-miR-519d-3p/CDKN1A, HIF1A, MXD1, and SOD2 closely associated with the progression of COPD, which provides a theoretical basis to link aging effectors with COPD progression, and may suggest new diagnostic and therapeutic targets of this disease.
慢性阻塞性肺病(COPD)是一种严重的慢性呼吸系统疾病。慢性阻塞性肺病进展的主要危险因素之一是衰老。因此，我们使用生物信息学分析来研究COPD的衰老相关基因。首先，利用包含500个衰老相关基因的Aging Atlas数据库和Gene Expression Omnibus数据库(GSE38974)筛选候选基因。共有24个候选基因被确定与COPD和衰老相关。利用基因本体和《京都基因与基因组百科全书》的富集分析，我们发现这24个基因中富集了与细胞因子活性、细胞凋亡、NF-κB和IL-17信号通路相关的基因。其中4个基因(CDKN1A、HIF1A、MXD1和SOD2)在临床COPD样本和暴露于香烟烟雾提取物的Beas-2B细胞中显著上调，其表达与预测的用力呼气量和用力肺活量呈负相关。此外，这四个基因的联合表达水平对COPD患者具有较好的鉴别能力(AUC = 0.794, 95% CI 0.743-0.845)。这四种基因均为hsa-miR-519d-3p的靶基因，在COPD患者中显著下调。本研究结果提示hsa-miR-519d-3p/CDKN1A、HIF1A、MXD1、SOD2调控网络与COPD的进展密切相关，为衰老效应物与COPD进展的关联提供了理论依据，并可能提示该病新的诊断和治疗靶点。
{"title":"Identification and validation of aging-related genes in COPD based on bioinformatics analysis","authors":"Shan Zhong, Li Yang, Naijia Liu, Guangkeng Zhou, Zhangli Hu, Chengshui Chen, Yun Wang","doi":"10.18632/aging.204064","DOIUrl":"https://doi.org/10.18632/aging.204064","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a serious chronic respiratory disorder. One of the major risk factors for COPD progression is aging. Therefore, we investigated aging-related genes in COPD using bioinformatic analyses. Firstly, the Aging Atlas database containing 500 aging-related genes and the Gene Expression Omnibus database (GSE38974) were utilized to screen candidates. A total of 24 candidate genes were identified related to both COPD and aging. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we found that this list of 24 genes was enriched in genes associated with cytokine activity, cell apoptosis, NF-κB and IL-17 signaling. Four of these genes (CDKN1A, HIF1A, MXD1 and SOD2) were determined to be significantly upregulated in clinical COPD samples and in cigarette smoke extract-exposed Beas-2B cells in vitro, and their expression was negatively correlated with predicted forced expiratory volume and forced vital capacity. In addition, the combination of expression levels of these four genes had a good discriminative ability for COPD patients (AUC = 0.794, 95% CI 0.743–0.845). All four were identified as target genes of hsa-miR-519d-3p, which was significantly down-regulated in COPD patients. The results from this study proposed that regulatory network of hsa-miR-519d-3p/CDKN1A, HIF1A, MXD1, and SOD2 closely associated with the progression of COPD, which provides a theoretical basis to link aging effectors with COPD progression, and may suggest new diagnostic and therapeutic targets of this disease.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"3 1","pages":"4336 - 4356"},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88200242","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}
Yi Hong, A. Yang, James K. S. Wong, Kunanya Masodsai, Shin-Da Lee, Yi-Yuan Lin
Background: An inappropriate accumulation of fibrillar collagen is a common pathologic feature of early aged hypertensive heart disease, but little information regarding the effects of exercise training on cardiac fibrosis in hypertension is available. The purpose of this study was to evaluate the effects of exercise training on cardiac fibrotic pathways in early aged hypertensive rats. Methods: Masson’s trichrome staining and Western blotting were performed on the excised left ventricle from twenty male spontaneously hypertensive rats at age of 48 weeks, which were randomly divided into either a sedentary hypertensive group (SHR) or exercise hypertensive group (SHR-EX, running on a treadmill running occurred 5 days/week for 60 min/day, for 12 weeks), and from age-matched male Wistar–Kyoto normotensive controls (WKY). Results: Interstitial fibrosis was reduced in the SHR-Ex group when compared with the SHR group. The fibrotic-related protein levels of AT1R, FGF23, LOX-2, TGF-β, CTGF, p-Smad 2/3, MMP-2/TIMP-2, MMP-9/TIMP-1, uPA and collagen I were decreased in the SHR-EX group, when compared with the SHR group. Conclusions: Exercise training suppresses early aged hypertensive heart-induced LOX-2/TGF-β-mediated fibrotic pathways associated with decreasing AT1R and FGF23, which might provide a new therapeutic effect for exercise training to prevent adverse cardiac fibrosis and myocardial abnormalities in early aged hypertension.
{"title":"Exercise intervention prevents early aged hypertension-caused cardiac dysfunction through inhibition of cardiac fibrosis","authors":"Yi Hong, A. Yang, James K. S. Wong, Kunanya Masodsai, Shin-Da Lee, Yi-Yuan Lin","doi":"10.18632/aging.204077","DOIUrl":"https://doi.org/10.18632/aging.204077","url":null,"abstract":"Background: An inappropriate accumulation of fibrillar collagen is a common pathologic feature of early aged hypertensive heart disease, but little information regarding the effects of exercise training on cardiac fibrosis in hypertension is available. The purpose of this study was to evaluate the effects of exercise training on cardiac fibrotic pathways in early aged hypertensive rats. Methods: Masson’s trichrome staining and Western blotting were performed on the excised left ventricle from twenty male spontaneously hypertensive rats at age of 48 weeks, which were randomly divided into either a sedentary hypertensive group (SHR) or exercise hypertensive group (SHR-EX, running on a treadmill running occurred 5 days/week for 60 min/day, for 12 weeks), and from age-matched male Wistar–Kyoto normotensive controls (WKY). Results: Interstitial fibrosis was reduced in the SHR-Ex group when compared with the SHR group. The fibrotic-related protein levels of AT1R, FGF23, LOX-2, TGF-β, CTGF, p-Smad 2/3, MMP-2/TIMP-2, MMP-9/TIMP-1, uPA and collagen I were decreased in the SHR-EX group, when compared with the SHR group. Conclusions: Exercise training suppresses early aged hypertensive heart-induced LOX-2/TGF-β-mediated fibrotic pathways associated with decreasing AT1R and FGF23, which might provide a new therapeutic effect for exercise training to prevent adverse cardiac fibrosis and myocardial abnormalities in early aged hypertension.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"14 1","pages":"4390 - 4401"},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73281801","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}
T. Doeppner, C. Coman, Daiana Burdusel, D. Ancuta, U. Brockmeier, D. Pirici, Y. Kuang, D. Hermann, A. Popa-Wagner
Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given in the drinking water on the lifespan and organ pathology of male middle-aged NMRI mice. We report that, surprisingly, daily treatment with chloroquine extended the median life span by 11.4% and the maximum life span of the middle-aged male NMRI mice by 11.8%. Subsequent experiments show that the chloroquine-induced lifespan elevation is associated with dose-dependent increase in LC3B-II, a marker of autophagosomes, in the liver and heart that was confirmed by transmission electron microscopy. Quite intriguingly, chloroquine treatment was also associated with a decrease in glycogenolysis in the liver suggesting a compensatory mechanism to provide energy to the cell. Accumulation of autophagosomes was paralleled by an inhibition of proteasome-dependent proteolysis in the liver and the heart as well as with decreased serum levels of insulin growth factor binding protein-3 (IGFBP3), a protein associated with longevity. We propose that inhibition of proteasome activity in conjunction with an increased number of autophagosomes and decreased levels of IGFBP3 might play a central role in lifespan extension by chloroquine in male NMRI mice.
{"title":"Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism","authors":"T. Doeppner, C. Coman, Daiana Burdusel, D. Ancuta, U. Brockmeier, D. Pirici, Y. Kuang, D. Hermann, A. Popa-Wagner","doi":"10.18632/aging.204069","DOIUrl":"https://doi.org/10.18632/aging.204069","url":null,"abstract":"Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given in the drinking water on the lifespan and organ pathology of male middle-aged NMRI mice. We report that, surprisingly, daily treatment with chloroquine extended the median life span by 11.4% and the maximum life span of the middle-aged male NMRI mice by 11.8%. Subsequent experiments show that the chloroquine-induced lifespan elevation is associated with dose-dependent increase in LC3B-II, a marker of autophagosomes, in the liver and heart that was confirmed by transmission electron microscopy. Quite intriguingly, chloroquine treatment was also associated with a decrease in glycogenolysis in the liver suggesting a compensatory mechanism to provide energy to the cell. Accumulation of autophagosomes was paralleled by an inhibition of proteasome-dependent proteolysis in the liver and the heart as well as with decreased serum levels of insulin growth factor binding protein-3 (IGFBP3), a protein associated with longevity. We propose that inhibition of proteasome activity in conjunction with an increased number of autophagosomes and decreased levels of IGFBP3 might play a central role in lifespan extension by chloroquine in male NMRI mice.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"5 1","pages":"4195 - 4210"},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90178294","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}
Wu Xiong, Cong Li, G. Kong, B. Wan, Siming Wang, Jin Fan
Glioblastoma is classified as an immunocompromised tumor. The immune pattern beneath the cold tumor surface, however, has yet to be confirmed. Understanding the immune pattern of glioblastoma will aid in the development of effective treatment strategies. We performed weighted gene co-expression network analysis on all immune-related genes in TCGA-GBM transcriptional data and screened 35 prognosis-related immune genes. Unsupervised consistent clustering of these genes was used to analyze the immunological pattern of GBM. A glioblastoma immune prognostic score was developed by using 13 genes discovered by cox regression methods and verified with the GEO dataset to assess the immune profile, prognosis, and immunotherapy effects in individual patients. Glioblastoma has two immune modalities, immune tolerance and immunodeficiency, with distinct immune microenvironments, tumor-associated macrophages being one of the most promising new therapeutic targets. GIPS is a promising biomarker for assessing immune evasion mechanisms, immunotherapy responses, and prognosis in patients.
{"title":"Glioblastoma: two immune subtypes under the surface of the cold tumor","authors":"Wu Xiong, Cong Li, G. Kong, B. Wan, Siming Wang, Jin Fan","doi":"10.18632/aging.204067","DOIUrl":"https://doi.org/10.18632/aging.204067","url":null,"abstract":"Glioblastoma is classified as an immunocompromised tumor. The immune pattern beneath the cold tumor surface, however, has yet to be confirmed. Understanding the immune pattern of glioblastoma will aid in the development of effective treatment strategies. We performed weighted gene co-expression network analysis on all immune-related genes in TCGA-GBM transcriptional data and screened 35 prognosis-related immune genes. Unsupervised consistent clustering of these genes was used to analyze the immunological pattern of GBM. A glioblastoma immune prognostic score was developed by using 13 genes discovered by cox regression methods and verified with the GEO dataset to assess the immune profile, prognosis, and immunotherapy effects in individual patients. Glioblastoma has two immune modalities, immune tolerance and immunodeficiency, with distinct immune microenvironments, tumor-associated macrophages being one of the most promising new therapeutic targets. GIPS is a promising biomarker for assessing immune evasion mechanisms, immunotherapy responses, and prognosis in patients.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"39 1","pages":"4357 - 4375"},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89404736","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：