Pub Date : 2022-05-22DOI: 10.1101/2022.05.20.22275270
D. Michaud, M. Chung, N. Zhao, D. Koestler, Jiayun Lu, E. Platz, K. Kelsey
Background: Epigenetic age, a robust marker of biological aging, has been associated with obesity, low-grade inflammation and metabolic diseases. However, few studies have examined associations between different epigenetic age measures and risk of lung cancer, despite great interest in finding biomarkers to assist in risk stratification for lung cancer screening. Methods: A nested case-control study of lung cancer from the CLUE II cohort study was conducted using incidence density sampling with 1:1 matching of controls to lung cancer cases (n=208 matched pairs). Prediagnostic blood samples were collected in 1989 (CLUE II study baseline) and stored at -70 degrees Celsius. DNA was extracted from buffy coat and DNA methylation levels were measured using Illumina MethylationEPIC BeadChip Arrays. Three epigenetic age acceleration (i.e., biological age is greater than chronological age) measurements (Horvath, Hannum and PhenoAge) were examined in relation to lung cancer risk using conditional logistic regression. Results: We did not observe associations between the three epigenetic age acceleration measurements and risk of lung cancer overall; however, inverse associations for the two Hannum age acceleration measures (intrinsic and extrinsic) were observed in men and among younger participants, but not in women or older participants. We did not observe effect modification by time from blood draw to diagnosis. Conclusion: Findings from this study do not support a positive association between three different biological age acceleration measures and risk of lung cancer. Additional studies are needed to address whether epigenetic age is associated with lung cancer in never smokers.
{"title":"Epigenetic age and lung cancer risk in the CLUE II prospective cohort study","authors":"D. Michaud, M. Chung, N. Zhao, D. Koestler, Jiayun Lu, E. Platz, K. Kelsey","doi":"10.1101/2022.05.20.22275270","DOIUrl":"https://doi.org/10.1101/2022.05.20.22275270","url":null,"abstract":"Background: Epigenetic age, a robust marker of biological aging, has been associated with obesity, low-grade inflammation and metabolic diseases. However, few studies have examined associations between different epigenetic age measures and risk of lung cancer, despite great interest in finding biomarkers to assist in risk stratification for lung cancer screening. Methods: A nested case-control study of lung cancer from the CLUE II cohort study was conducted using incidence density sampling with 1:1 matching of controls to lung cancer cases (n=208 matched pairs). Prediagnostic blood samples were collected in 1989 (CLUE II study baseline) and stored at -70 degrees Celsius. DNA was extracted from buffy coat and DNA methylation levels were measured using Illumina MethylationEPIC BeadChip Arrays. Three epigenetic age acceleration (i.e., biological age is greater than chronological age) measurements (Horvath, Hannum and PhenoAge) were examined in relation to lung cancer risk using conditional logistic regression. Results: We did not observe associations between the three epigenetic age acceleration measurements and risk of lung cancer overall; however, inverse associations for the two Hannum age acceleration measures (intrinsic and extrinsic) were observed in men and among younger participants, but not in women or older participants. We did not observe effect modification by time from blood draw to diagnosis. Conclusion: Findings from this study do not support a positive association between three different biological age acceleration measures and risk of lung cancer. Additional studies are needed to address whether epigenetic age is associated with lung cancer in never smokers.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"6 1","pages":"617 - 629"},"PeriodicalIF":0.0,"publicationDate":"2022-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75326287","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}
Noncoding RNAs play an important role in regulating osteoclast differentiation. We investigated whether and how potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1), a long noncoding RNA, regulates osteoclast differentiation. We found that the expression of KCNQ1OT1 was downregulated in osteoporotic bone tissue. Then transfection of KCNQ1OT1 overexpression vectors or small interfering RNAs showed that the proliferation, migration, and osteoclast differentiation of RAW 264.7 cells were inhibited by KCNQ1OT1 upregulation, while they were promoted by KCNQ1OT1 knockdown. Interestingly, we found and confirmed that miR-128-3p was a target of KCNQ1OT1 using online databases, dual luciferase reporter assays and quantitative real-time polymerase chain reaction, and that it inhibited the expression of miR-128-3p. Moreover, we confirmed that miR-128-3p directly targeted nuclear factor of activated T cell 5 (NFAT5), a protein that combines with osteoprotegerin and thus regulates osteoclastogenesis with the presence of the receptor activator of nuclear factor κB ligand. Furthermore, we demonstrated that both the knockdown of KCNQ1OT1 and the overexpression of miR-128-3p attenuate the expression of NFAT5, while upregulating the osteoclastogenesis markers c-Fos, NFATc1, and Ctsk. The results from overexpression of KCNQ1OT1 and the inhibition of miR-128-3p were contrary to the above. Finally, we found that the inhibition of osteoclast differentiation by KCNQ1OT1 overexpression could be rescued using a miR-128-3p mimic, while the enhancement of migration and osteoclast differentiation by si-NFAT5 could be reversed with a miR-128-3p inhibitor. These results suggested that KCNQ1OT1 regulates the osteoclast differentiation via the miR-128-3p/NFAT5 axis.
{"title":"Long noncoding RNA KCNQ1OT1 inhibits osteoclast differentiation by regulating the miR-128-3p/NFAT5 axis","authors":"Hengshuo Zhang, Lu Chen, Ziyu Wang, Zhen Sun, Yu Shan, Qinghui Li, Linzeng Qi, Hongliang Wang, Yunzhen Chen","doi":"10.18632/aging.204088","DOIUrl":"https://doi.org/10.18632/aging.204088","url":null,"abstract":"Noncoding RNAs play an important role in regulating osteoclast differentiation. We investigated whether and how potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1), a long noncoding RNA, regulates osteoclast differentiation. We found that the expression of KCNQ1OT1 was downregulated in osteoporotic bone tissue. Then transfection of KCNQ1OT1 overexpression vectors or small interfering RNAs showed that the proliferation, migration, and osteoclast differentiation of RAW 264.7 cells were inhibited by KCNQ1OT1 upregulation, while they were promoted by KCNQ1OT1 knockdown. Interestingly, we found and confirmed that miR-128-3p was a target of KCNQ1OT1 using online databases, dual luciferase reporter assays and quantitative real-time polymerase chain reaction, and that it inhibited the expression of miR-128-3p. Moreover, we confirmed that miR-128-3p directly targeted nuclear factor of activated T cell 5 (NFAT5), a protein that combines with osteoprotegerin and thus regulates osteoclastogenesis with the presence of the receptor activator of nuclear factor κB ligand. Furthermore, we demonstrated that both the knockdown of KCNQ1OT1 and the overexpression of miR-128-3p attenuate the expression of NFAT5, while upregulating the osteoclastogenesis markers c-Fos, NFATc1, and Ctsk. The results from overexpression of KCNQ1OT1 and the inhibition of miR-128-3p were contrary to the above. Finally, we found that the inhibition of osteoclast differentiation by KCNQ1OT1 overexpression could be rescued using a miR-128-3p mimic, while the enhancement of migration and osteoclast differentiation by si-NFAT5 could be reversed with a miR-128-3p inhibitor. These results suggested that KCNQ1OT1 regulates the osteoclast differentiation via the miR-128-3p/NFAT5 axis.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"12 1","pages":"4486 - 4499"},"PeriodicalIF":0.0,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84848234","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 Ding, Yung‐Wei Lin, W. Chiu, Chiao-Wen Lin, Yi-Chieh Yang, L. Chang, Jungshan Chang, Shun-Fa Yang, M. Chien
Oral squamous cell carcinoma (OSCC) is the most frequently encountered type of oral cancer. Histamine receptor H1 (HRH1) was reported to play a crucial role in OSCC carcinogenesis, but impacts of genetic variants of HRH1 on OSCC remain unclear. Herein, we investigated the association between functional single-nucleotide polymorphisms (SNPs) of HRH1 and OSCC susceptibility or clinicopathologic variables by logistic regression models. HRH1 genotypes at four loci (rs346074, rs346076, rs901865, and rs2606731) were analyzed by a TaqMan allelic discrimination assay, and we found that patients harboring HRH1 rs901865 T and rs346074 T alleles had a significantly lower risk of developing larger tumor sizes (>T2) under a dominant model. Based on the environmental carcinogen exposure status, we observed that HRH1 rs901865 polymorphic variants were also associated with a lower risk of developing more-advanced clinical stages (III or IV) in patients with a betel-quid-chewing habit. Moreover, genotype screening of rs901865 and rs346074 in OSCC cell lines showed that cells respectively carrying the CT and TT genotypes expressed lower HRH1 levels compared to cells carrying the CC genotype of rs901865 and rs346074. Furthermore, analyses of TCGA and GEO databases revealed that HRH1 expression levels were upregulated in head and neck squamous cell carcinoma (HNSCC) and OSCC tissues compared to normal tissues and were correlated with larger tumor sizes and poorer prognoses. These results indicated the involvement of HRH1 SNPs rs901865 and rs346074 in OSCC development and support the interaction between HRH1 gene polymorphisms and an environmental carcinogen as a predisposing factor for OSCC progression.
口腔鳞状细胞癌(OSCC)是最常见的口腔癌。据报道，组胺受体H1 (HRH1)在OSCC的癌变中起着至关重要的作用，但HRH1基因变异对OSCC的影响尚不清楚。在此，我们通过逻辑回归模型研究了HRH1的功能单核苷酸多态性(snp)与OSCC易感性或临床病理变量之间的关系。采用TaqMan等位基因鉴别法分析了4个位点(rs346074、rs346076、rs901865和rs2606731)的HRH1基因型，发现在显性模型下，携带HRH1 rs901865 T和rs346074 T等位基因的患者发生较大肿瘤(>T2)的风险显著降低。基于环境致癌物暴露状态，我们观察到HRH1 rs901865多态性变异也与嚼槟榔习惯患者发展为更晚期临床阶段(III或IV)的风险较低相关。此外，在OSCC细胞系中对rs901865和rs346074进行基因型筛选发现，分别携带CT和TT基因型的细胞比携带rs901865和rs346074 CC基因型的细胞表达更低的HRH1水平。此外，TCGA和GEO数据库的分析显示，与正常组织相比，HRH1表达水平在头颈部鳞状细胞癌(HNSCC)和OSCC组织中上调，并且与较大的肿瘤大小和较差的预后相关。这些结果表明HRH1 snp rs901865和rs346074参与了OSCC的发展，并支持HRH1基因多态性与环境致癌物之间的相互作用是OSCC进展的易感因素。
{"title":"Combined impacts of histamine receptor H1 gene polymorphisms and an environmental carcinogen on the susceptibility to and progression of oral squamous cell carcinoma","authors":"Yi Ding, Yung‐Wei Lin, W. Chiu, Chiao-Wen Lin, Yi-Chieh Yang, L. Chang, Jungshan Chang, Shun-Fa Yang, M. Chien","doi":"10.18632/aging.204089","DOIUrl":"https://doi.org/10.18632/aging.204089","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is the most frequently encountered type of oral cancer. Histamine receptor H1 (HRH1) was reported to play a crucial role in OSCC carcinogenesis, but impacts of genetic variants of HRH1 on OSCC remain unclear. Herein, we investigated the association between functional single-nucleotide polymorphisms (SNPs) of HRH1 and OSCC susceptibility or clinicopathologic variables by logistic regression models. HRH1 genotypes at four loci (rs346074, rs346076, rs901865, and rs2606731) were analyzed by a TaqMan allelic discrimination assay, and we found that patients harboring HRH1 rs901865 T and rs346074 T alleles had a significantly lower risk of developing larger tumor sizes (>T2) under a dominant model. Based on the environmental carcinogen exposure status, we observed that HRH1 rs901865 polymorphic variants were also associated with a lower risk of developing more-advanced clinical stages (III or IV) in patients with a betel-quid-chewing habit. Moreover, genotype screening of rs901865 and rs346074 in OSCC cell lines showed that cells respectively carrying the CT and TT genotypes expressed lower HRH1 levels compared to cells carrying the CC genotype of rs901865 and rs346074. Furthermore, analyses of TCGA and GEO databases revealed that HRH1 expression levels were upregulated in head and neck squamous cell carcinoma (HNSCC) and OSCC tissues compared to normal tissues and were correlated with larger tumor sizes and poorer prognoses. These results indicated the involvement of HRH1 SNPs rs901865 and rs346074 in OSCC development and support the interaction between HRH1 gene polymorphisms and an environmental carcinogen as a predisposing factor for OSCC progression.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"24 1","pages":"4500 - 4512"},"PeriodicalIF":0.0,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78577426","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}
degenerative diseases. Therefore, unravelling the basic mechanisms of aging is essential to improve the quality of life of older people. Among others, mitochondrial dysfunction and genomic instability have been considered key hallmarks of aging, and these deficiencies seem to play important roles in age associated cognitive decline [1]. Mitochondrial bioenergetic deterioration together with reactive oxygen species (ROS) induced mitochondrial DNA damage have been shown to accumulate with aging [2]. DNA repair pathways, which are involved in maintaining genomic stability, also seem to change with aging. Most oxidative DNA lesions are repaired by the Base Excision Repair (BER) pathway, in which the major endonuclease at the limiting step is AP endonuclease 1 (APE1), which has also been linked to cognitive decline [3]. Mitochondrial function and DNA repair activity are affected by nicotinamide adenine dinucleotide (NAD) depletion, which is also observed with aging. NAD is an essential co-enzyme involved in mitochondrial health and functions as a cofactor for the DNA repair protein poly (ADP-ribose) polymerase 1 (PARP-1) [4]. Another factor that has been shown to decline with aging and be reduced in neurodegenerative diseases is brain derived neurotrophic factor (BDNF). Importantly, BDNF has been shown to enhance neuronal DNA repair by stimulating APE1 expression and activity [5].
{"title":"Molecular markers associated with cognitive impairment in centenarians","authors":"T. Stevnsner, Inés Sánchez-Román","doi":"10.18632/aging.204094","DOIUrl":"https://doi.org/10.18632/aging.204094","url":null,"abstract":"degenerative diseases. Therefore, unravelling the basic mechanisms of aging is essential to improve the quality of life of older people. Among others, mitochondrial dysfunction and genomic instability have been considered key hallmarks of aging, and these deficiencies seem to play important roles in age associated cognitive decline [1]. Mitochondrial bioenergetic deterioration together with reactive oxygen species (ROS) induced mitochondrial DNA damage have been shown to accumulate with aging [2]. DNA repair pathways, which are involved in maintaining genomic stability, also seem to change with aging. Most oxidative DNA lesions are repaired by the Base Excision Repair (BER) pathway, in which the major endonuclease at the limiting step is AP endonuclease 1 (APE1), which has also been linked to cognitive decline [3]. Mitochondrial function and DNA repair activity are affected by nicotinamide adenine dinucleotide (NAD) depletion, which is also observed with aging. NAD is an essential co-enzyme involved in mitochondrial health and functions as a cofactor for the DNA repair protein poly (ADP-ribose) polymerase 1 (PARP-1) [4]. Another factor that has been shown to decline with aging and be reduced in neurodegenerative diseases is brain derived neurotrophic factor (BDNF). Importantly, BDNF has been shown to enhance neuronal DNA repair by stimulating APE1 expression and activity [5].","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"7 1","pages":"4191 - 4192"},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82716550","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}
Yiyue Xu, B. Zou, B. Fan, Butuo Li, Jinming Yu, Linlin Wang, Jin Zhang
The development of novel treatments for breast invasive carcinoma (BC) has been stagnant. P2RX1, a member of the purinergic receptor family, has been found to have a prognostic impact in several tumors. Therefore, we analyzed the expression pattern of P2RX1 in pan-cancers including BC and its impact on survival and found that the expression level of P2RX1 was lower in BC compared with para-cancerous tissues, and higher P2RX1 expression indicated better prognoses. But real-time quantitative reverse transcription PCR (RT-qPCR) and Western blot detected that the P2RX1 expression in normal mammary epithelial cells was lower than that in tumor cells. Then we comprehensively analyzed the regulatory mechanism and protein-protein interaction network, and found that P2RX1 was significantly positively linked with immune cell infiltration and immune checkpoints.
{"title":"NcRNAs-mediated P2RX1 expression correlates with clinical outcomes and immune infiltration in patients with breast invasive carcinoma","authors":"Yiyue Xu, B. Zou, B. Fan, Butuo Li, Jinming Yu, Linlin Wang, Jin Zhang","doi":"10.18632/aging.204087","DOIUrl":"https://doi.org/10.18632/aging.204087","url":null,"abstract":"The development of novel treatments for breast invasive carcinoma (BC) has been stagnant. P2RX1, a member of the purinergic receptor family, has been found to have a prognostic impact in several tumors. Therefore, we analyzed the expression pattern of P2RX1 in pan-cancers including BC and its impact on survival and found that the expression level of P2RX1 was lower in BC compared with para-cancerous tissues, and higher P2RX1 expression indicated better prognoses. But real-time quantitative reverse transcription PCR (RT-qPCR) and Western blot detected that the P2RX1 expression in normal mammary epithelial cells was lower than that in tumor cells. Then we comprehensively analyzed the regulatory mechanism and protein-protein interaction network, and found that P2RX1 was significantly positively linked with immune cell infiltration and immune checkpoints.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"41 1","pages":"4471 - 4485"},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85460259","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}
Li Yang, Wen-ping Xiang, Jinfeng Zhang, Jiangxia Pang, Jingbo Wang, Baojun Wang
Background: Excessive sympathoexcitation could lead to stroke associated infection. Inhibiting sympathetic excitation may reduce the infection risk after stroke. Thus, the present study aimed to determine the protective effect of beta blockers on stroke associated infection through systematic review and meta-analysis. Methods: A systematic search of multiple databases were performed up to February 2022. The included studies required beta blockers therapy in stroke patients and assessed the incidence of stroke-associated infections. Outcomes of interest included infections, pneumonia, urinary tract infection and sepsis. Random-effects model was used for analysis. Heterogeneity was evaluated using I2 statistics and publication bias was evaluated by the funnel plot. Result: A total of 83 potentially relevant publications was identified in the initial search. Six studies met the inclusion criteria for meta-analysis. The risk of bias in the included articles satisfies the quality requirement of meta-analysis. No significant associations between beta blockers therapy and the prevention of stroke associated infection, stroke associated pneumonia and septicemia were found, However, subgroup analyses revealed an association between beta blockers treatment and the increased risk of post-stroke urinary tract infection or stroke associated pneumonia in some stroke patients (OR = 1.69 [1.33, 2.14], P < 0.0001; OR = 1.85 [1.51, 2.26], P < 0.0001). Conclusion: Due to the lack of robust evidence, this meta-analysis may not support the preventive effect of beta blockers on stroke associated infection. But beta blockers treatment may be associated with development of post-stroke urinary tract infection and stroke associated pneumonia in some stroke patients.
背景:过度交感神经兴奋可导致卒中相关感染。抑制交感神经兴奋可降低卒中后感染风险。因此，本研究旨在通过系统回顾和荟萃分析来确定-受体阻滞剂对卒中相关感染的保护作用。方法:系统检索截至2022年2月的多个数据库。纳入的研究要求对中风患者进行-受体阻滞剂治疗，并评估卒中相关感染的发生率。研究结果包括感染、肺炎、尿路感染和败血症。采用随机效应模型分析。异质性采用I2统计量评估，发表偏倚采用漏斗图评估。结果:在最初的搜索中，总共发现了83篇可能相关的出版物。6项研究符合meta分析的纳入标准。纳入文章的偏倚风险满足meta分析的质量要求。未发现-受体阻滞剂治疗与预防脑卒中相关感染、脑卒中相关肺炎和败血症之间存在显著相关性，但亚组分析显示-受体阻滞剂治疗与部分脑卒中患者脑卒中后尿路感染或脑卒中相关肺炎风险增加存在相关性(or = 1.69 [1.33, 2.14]， P < 0.0001;Or = 1.85 [1.51, 2.26]， p < 0.0001)。结论:由于缺乏强有力的证据，本荟萃分析可能不支持-受体阻滞剂对卒中相关感染的预防作用。但在一些中风患者中，受体阻滞剂治疗可能与卒中后尿路感染和卒中相关性肺炎的发生有关。
{"title":"Are beta blockers effective in preventing stroke-associated infections? - a systematic review and meta-analysis","authors":"Li Yang, Wen-ping Xiang, Jinfeng Zhang, Jiangxia Pang, Jingbo Wang, Baojun Wang","doi":"10.18632/aging.204086","DOIUrl":"https://doi.org/10.18632/aging.204086","url":null,"abstract":"Background: Excessive sympathoexcitation could lead to stroke associated infection. Inhibiting sympathetic excitation may reduce the infection risk after stroke. Thus, the present study aimed to determine the protective effect of beta blockers on stroke associated infection through systematic review and meta-analysis. Methods: A systematic search of multiple databases were performed up to February 2022. The included studies required beta blockers therapy in stroke patients and assessed the incidence of stroke-associated infections. Outcomes of interest included infections, pneumonia, urinary tract infection and sepsis. Random-effects model was used for analysis. Heterogeneity was evaluated using I2 statistics and publication bias was evaluated by the funnel plot. Result: A total of 83 potentially relevant publications was identified in the initial search. Six studies met the inclusion criteria for meta-analysis. The risk of bias in the included articles satisfies the quality requirement of meta-analysis. No significant associations between beta blockers therapy and the prevention of stroke associated infection, stroke associated pneumonia and septicemia were found, However, subgroup analyses revealed an association between beta blockers treatment and the increased risk of post-stroke urinary tract infection or stroke associated pneumonia in some stroke patients (OR = 1.69 [1.33, 2.14], P < 0.0001; OR = 1.85 [1.51, 2.26], P < 0.0001). Conclusion: Due to the lack of robust evidence, this meta-analysis may not support the preventive effect of beta blockers on stroke associated infection. But beta blockers treatment may be associated with development of post-stroke urinary tract infection and stroke associated pneumonia in some stroke patients.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"104 1","pages":"4459 - 4470"},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77381438","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}
Qing Zhang, Yao Guo, Wan-Lin Zhang, H. Lian, Natasha Iranzad, Endi Wang, Ying-Chun Li, Hai Tong, Le-Yao Li, Ling-Yun Dong, Lian-He Yang, Shuang Ma
Gliomas are the most common malignant tumor in the brain. As with other tumors, the progression of glioma depends on intra-tumoral angiogenesis. However, the effect of angiogenesis on gliomas is still not fully understood. In this study, we developed an angiogenesis pathway score using Gene Set Variation Analysis (GSAV) in R to assess the status of intra-glioma angiogenesis in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA mRNAseq_325, CGGA mRNA-array), and GSE16011 datasets. We found that the angiogenesis pathway score not only accurately predicted the prognosis of glioma patients, but also accurately distinguished the malignant phenotype and immune characteristics of gliomas. In addition, as an independent prognostic factor, the score could predict glioma sensitivity to radiotherapy and chemotherapy. In summary, we used the angiogenesis pathway score to reveal the relationship between glioma angiogenesis and the malignant phenotype, immune characteristics, and prognosis of glioma.
{"title":"Intra-tumoral angiogenesis correlates with immune features and prognosis in glioma","authors":"Qing Zhang, Yao Guo, Wan-Lin Zhang, H. Lian, Natasha Iranzad, Endi Wang, Ying-Chun Li, Hai Tong, Le-Yao Li, Ling-Yun Dong, Lian-He Yang, Shuang Ma","doi":"10.18632/aging.204079","DOIUrl":"https://doi.org/10.18632/aging.204079","url":null,"abstract":"Gliomas are the most common malignant tumor in the brain. As with other tumors, the progression of glioma depends on intra-tumoral angiogenesis. However, the effect of angiogenesis on gliomas is still not fully understood. In this study, we developed an angiogenesis pathway score using Gene Set Variation Analysis (GSAV) in R to assess the status of intra-glioma angiogenesis in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA mRNAseq_325, CGGA mRNA-array), and GSE16011 datasets. We found that the angiogenesis pathway score not only accurately predicted the prognosis of glioma patients, but also accurately distinguished the malignant phenotype and immune characteristics of gliomas. In addition, as an independent prognostic factor, the score could predict glioma sensitivity to radiotherapy and chemotherapy. In summary, we used the angiogenesis pathway score to reveal the relationship between glioma angiogenesis and the malignant phenotype, immune characteristics, and prognosis of glioma.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"57 1","pages":"4402 - 4424"},"PeriodicalIF":0.0,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88570723","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}
Zhenlong Zheng, Xianglan Zhang, Bong-Kyeong Oh, Ki-Yeol Kim
Osteoporosis is a severe chronic skeletal disorder that affects older individuals, especially postmenopausal women. However, molecular biomarkers for predicting the risk of osteoporosis are not well characterized. The aim of this study was to identify combined biomarkers for predicting the risk of osteoporosis using machine learning methods. We merged three publicly available gene expression datasets (GSE56815, GSE13850, and GSE2208) to obtain expression data for 6354 unique genes in postmenopausal women (45 with high bone mineral density and 45 with low bone mineral density). All machine learning methods were implemented in R, with the GEOquery and limma packages, for dataset download and differentially expressed gene identification, and a nomogram for predicting the risk of osteoporosis was constructed. We detected 378 significant differentially expressed genes using the limma package, representing 15 major biological pathways. The performance of the predictive models based on combined biomarkers (two or three genes) was superior to that of models based on a single gene. The best predictive gene set among two-gene sets included PLA2G2A and WRAP73. The best predictive gene set among three-gene sets included LPN1, PFDN6, and DOHH. Overall, we demonstrated the advantages of using combined versus single biomarkers for predicting the risk of osteoporosis. Further, the predictive nomogram constructed using combined biomarkers could be used by clinicians to identify high-risk individuals and in the design of efficient clinical trials to reduce the incidence of osteoporosis.
{"title":"Identification of combined biomarkers for predicting the risk of osteoporosis using machine learning","authors":"Zhenlong Zheng, Xianglan Zhang, Bong-Kyeong Oh, Ki-Yeol Kim","doi":"10.18632/aging.204084","DOIUrl":"https://doi.org/10.18632/aging.204084","url":null,"abstract":"Osteoporosis is a severe chronic skeletal disorder that affects older individuals, especially postmenopausal women. However, molecular biomarkers for predicting the risk of osteoporosis are not well characterized. The aim of this study was to identify combined biomarkers for predicting the risk of osteoporosis using machine learning methods. We merged three publicly available gene expression datasets (GSE56815, GSE13850, and GSE2208) to obtain expression data for 6354 unique genes in postmenopausal women (45 with high bone mineral density and 45 with low bone mineral density). All machine learning methods were implemented in R, with the GEOquery and limma packages, for dataset download and differentially expressed gene identification, and a nomogram for predicting the risk of osteoporosis was constructed. We detected 378 significant differentially expressed genes using the limma package, representing 15 major biological pathways. The performance of the predictive models based on combined biomarkers (two or three genes) was superior to that of models based on a single gene. The best predictive gene set among two-gene sets included PLA2G2A and WRAP73. The best predictive gene set among three-gene sets included LPN1, PFDN6, and DOHH. Overall, we demonstrated the advantages of using combined versus single biomarkers for predicting the risk of osteoporosis. Further, the predictive nomogram constructed using combined biomarkers could be used by clinicians to identify high-risk individuals and in the design of efficient clinical trials to reduce the incidence of osteoporosis.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"107 1","pages":"4270 - 4280"},"PeriodicalIF":0.0,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81470323","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}
The sperm chromatin structure assay (SCSA) is crucial for assessing male fertility. However, the predictive value of the SCSA parameters, including the DNA fragment indices (DFI) and the percentages of high DNA stainability (HDS), for outcomes of artificial insemination by husband (AIH) remains controversial. This study aims to evaluate the correlations between SCSA parameters and male aging as well as other routine semen parameters, and explore their prognostic powers on AIH outcomes of the Chinese infertile couples. A total of 809 AIH cycles were retrospectively analyzed. The results showed that DFI in the age groups < 35 years were significantly lower than that in the age groups ≥ 35 years (P < 0.001). Meanwhile, there was no statistical difference in HDS between the age groups (P = 0.063). DFI and HDS are negatively correlated with most routine semen parameters (all P < 0.05). The chi-square and generalized linear model tests indicated that neither DFI nor HDS influenced the clinical pregnancy rate of AIH. In summary, this study found that aging is a critical factor leading to increased sperm DFI but not HDS. DFI and HDS are negatively correlated with most semen parameters but do not significantly influence AIH outcomes.
{"title":"Sperm DNA integrity is critically impacted by male age but does not influence outcomes of artificial insemination by husband in the Chinese infertile couples","authors":"Yumei Luo, Shunhong Wu, Mimi Zhang, Hua Zhou, Jingru Yuan, Yiying Yang, Yufang Zhong, Qing Li, Xiaofang Sun, Xia Xu, Detu Zhu","doi":"10.18632/aging.204058","DOIUrl":"https://doi.org/10.18632/aging.204058","url":null,"abstract":"The sperm chromatin structure assay (SCSA) is crucial for assessing male fertility. However, the predictive value of the SCSA parameters, including the DNA fragment indices (DFI) and the percentages of high DNA stainability (HDS), for outcomes of artificial insemination by husband (AIH) remains controversial. This study aims to evaluate the correlations between SCSA parameters and male aging as well as other routine semen parameters, and explore their prognostic powers on AIH outcomes of the Chinese infertile couples. A total of 809 AIH cycles were retrospectively analyzed. The results showed that DFI in the age groups < 35 years were significantly lower than that in the age groups ≥ 35 years (P < 0.001). Meanwhile, there was no statistical difference in HDS between the age groups (P = 0.063). DFI and HDS are negatively correlated with most routine semen parameters (all P < 0.05). The chi-square and generalized linear model tests indicated that neither DFI nor HDS influenced the clinical pregnancy rate of AIH. In summary, this study found that aging is a critical factor leading to increased sperm DFI but not HDS. DFI and HDS are negatively correlated with most semen parameters but do not significantly influence AIH outcomes.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"121 1","pages":"4326 - 4335"},"PeriodicalIF":0.0,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76706211","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}
Ryan Wallis, Deborah A. Milligan, Bethany K Hughes, Hannah Mizen, J. López-Domínguez, Ugochim Eduputa, E. Tyler, M. Serrano, C. Bishop
Senescence occurs in response to a number of damaging stimuli to limit oncogenic transformation and cancer development. As no single, universal senescence marker has been discovered, the confident classification of senescence induction requires the parallel assessment of a series of hallmarks. Therefore, there is a growing need for “first-pass” tools of senescence identification to streamline experimental workflows and complement conventional markers. Here, we utilise a high content, multidimensional phenotypic profiling-based approach, to assess the morphological profiles of senescent cells induced via a range of stimuli. In the context of senescence, we refer to these as senescence-associated morphological profiles (SAMPs), as they facilitate distinction between senescent and proliferating cells. The complexity of the profiles generated also allows exploration of the heterogeneity both between models of senescence and within an individual senescence model, providing a level of insight at the single cell level. Furthermore, we also demonstrate that these models are applicable to the assessment of senescence in vivo, which remains a key challenge for the field. Therefore, we believe SAMPs has the potential to serve as a useful addition in the repertoire of senescence researchers, either as a first-pass tool or as part of the established senescence hallmarks.
{"title":"Senescence-associated morphological profiles (SAMPs): an image-based phenotypic profiling method for evaluating the inter and intra model heterogeneity of senescence","authors":"Ryan Wallis, Deborah A. Milligan, Bethany K Hughes, Hannah Mizen, J. López-Domínguez, Ugochim Eduputa, E. Tyler, M. Serrano, C. Bishop","doi":"10.18632/aging.204072","DOIUrl":"https://doi.org/10.18632/aging.204072","url":null,"abstract":"Senescence occurs in response to a number of damaging stimuli to limit oncogenic transformation and cancer development. As no single, universal senescence marker has been discovered, the confident classification of senescence induction requires the parallel assessment of a series of hallmarks. Therefore, there is a growing need for “first-pass” tools of senescence identification to streamline experimental workflows and complement conventional markers. Here, we utilise a high content, multidimensional phenotypic profiling-based approach, to assess the morphological profiles of senescent cells induced via a range of stimuli. In the context of senescence, we refer to these as senescence-associated morphological profiles (SAMPs), as they facilitate distinction between senescent and proliferating cells. The complexity of the profiles generated also allows exploration of the heterogeneity both between models of senescence and within an individual senescence model, providing a level of insight at the single cell level. Furthermore, we also demonstrate that these models are applicable to the assessment of senescence in vivo, which remains a key challenge for the field. Therefore, we believe SAMPs has the potential to serve as a useful addition in the repertoire of senescence researchers, either as a first-pass tool or as part of the established senescence hallmarks.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"89 1","pages":"4220 - 4246"},"PeriodicalIF":0.0,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83868106","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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