Accumulated evidence shows that tumor microenvironment plays crucial roles in predicting clinical outcomes of lung adenocarcinoma (LUAD). The current study aimed to identify some potentially prognostic signatures by systematically revealing the transcriptome characteristics in LUADs with differing immune phenotypes. LUAD gene expression data were retrieved from the public TCGA and GEO databases, and the transcriptome characteristics were systematically revealed using a comprehensive bioinformatics method including single-sample gene set enrichment analysis, differentially expressed gene (DEG) analysis, protein and protein interaction (PPI) network construction, competitive endogenous RNA (ceRNA) network construction, weighted gene coexpression network analysis and prognostic model establishment. Finally, 1169 key DEGs associated with LUAD immune phenotype, including 88 immune DEGs, were excavated. Five essential and eight immune essential DEGs were separately identified by constructing two PPI networks based on the above DEGs. Totals of 1085 key DElncRNAs and 45 key DEmiRNAs were excavated and one ceRNA network consisting of 26 DEmRNAs, 3 DEmiRNAs and 57 DElncRNAs were established. The most significant gene coexpression module (cor=0.63 and p=3e-55) associated with LUAD immune phenotypes and three genes (FGR, BTK, SPI1) related to the immune cell infiltration were identified. Three robust prognostic signatures including a 9-lncRNA, an 8-lncRNA and an 8-mRNA were established. The areas under the curves of 5-year correlated with overall survival rate were separately 0.7319, 0.7228 and 0.713 in the receiver operating characteristic curve. The findings provide novel insights into the immunological mechanism in LUAD biology and in predicting the prognosis of LUAD patients.
{"title":"Identification of prognostic candidate signatures by systematically revealing transcriptome characteristics in lung adenocarcinoma with differing tumor microenvironment immune phenotypes","authors":"Qiang Chen, Jiakang Ma, Xiaoyi Wang, Xiangqing Zhu","doi":"10.18632/aging.204112","DOIUrl":"https://doi.org/10.18632/aging.204112","url":null,"abstract":"Accumulated evidence shows that tumor microenvironment plays crucial roles in predicting clinical outcomes of lung adenocarcinoma (LUAD). The current study aimed to identify some potentially prognostic signatures by systematically revealing the transcriptome characteristics in LUADs with differing immune phenotypes. LUAD gene expression data were retrieved from the public TCGA and GEO databases, and the transcriptome characteristics were systematically revealed using a comprehensive bioinformatics method including single-sample gene set enrichment analysis, differentially expressed gene (DEG) analysis, protein and protein interaction (PPI) network construction, competitive endogenous RNA (ceRNA) network construction, weighted gene coexpression network analysis and prognostic model establishment. Finally, 1169 key DEGs associated with LUAD immune phenotype, including 88 immune DEGs, were excavated. Five essential and eight immune essential DEGs were separately identified by constructing two PPI networks based on the above DEGs. Totals of 1085 key DElncRNAs and 45 key DEmiRNAs were excavated and one ceRNA network consisting of 26 DEmRNAs, 3 DEmiRNAs and 57 DElncRNAs were established. The most significant gene coexpression module (cor=0.63 and p=3e-55) associated with LUAD immune phenotypes and three genes (FGR, BTK, SPI1) related to the immune cell infiltration were identified. Three robust prognostic signatures including a 9-lncRNA, an 8-lncRNA and an 8-mRNA were established. The areas under the curves of 5-year correlated with overall survival rate were separately 0.7319, 0.7228 and 0.713 in the receiver operating characteristic curve. The findings provide novel insights into the immunological mechanism in LUAD biology and in predicting the prognosis of LUAD patients.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"18 1","pages":"4786 - 4818"},"PeriodicalIF":0.0,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79820698","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}
Bin Wang, He Xiao, Xin Yang, Ying Zeng, Zhimin Zhang, Rui Yang, Hang Chen, Chuan Chen, Junxia Chen
Introduction: Immune microenvironment and microRNAs serve as common predictors for diagnosis and prognosis of tumors. Methods: Expression of 122 genes and 126 microRNAs in thymoma was obtained from TCGA database. The proportion of tumor-infiltrating cells was calculated, and IMRS was constructed. TREM2hi score was calculated before functional enrichment analysis on gene sets. Results: IMRS3, TREM2hi score, and CD8+ T lymphocyte abundance were significantly different among WHO classifications. WHO classification, Masaoka staging, and miR-130b-5p, miR-1307-3p, miR-425-5p, CD8, CD68, and CCL18 expression were prognostic factors for relapse-free survival and overall survival. IMRS3 upregulation polarized macrophages into M2, which rejected CD8+ T and other effector lymphocytes to promote thymoma malignant progression. Conclusions: BRRS may present a novel immune-related microRNA signature for TET prognosis.
{"title":"A novel immune-related microRNA signature for prognosis of thymoma","authors":"Bin Wang, He Xiao, Xin Yang, Ying Zeng, Zhimin Zhang, Rui Yang, Hang Chen, Chuan Chen, Junxia Chen","doi":"10.18632/aging.204108","DOIUrl":"https://doi.org/10.18632/aging.204108","url":null,"abstract":"Introduction: Immune microenvironment and microRNAs serve as common predictors for diagnosis and prognosis of tumors. Methods: Expression of 122 genes and 126 microRNAs in thymoma was obtained from TCGA database. The proportion of tumor-infiltrating cells was calculated, and IMRS was constructed. TREM2hi score was calculated before functional enrichment analysis on gene sets. Results: IMRS3, TREM2hi score, and CD8+ T lymphocyte abundance were significantly different among WHO classifications. WHO classification, Masaoka staging, and miR-130b-5p, miR-1307-3p, miR-425-5p, CD8, CD68, and CCL18 expression were prognostic factors for relapse-free survival and overall survival. IMRS3 upregulation polarized macrophages into M2, which rejected CD8+ T and other effector lymphocytes to promote thymoma malignant progression. Conclusions: BRRS may present a novel immune-related microRNA signature for TET prognosis.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"27 1","pages":"4739 - 4754"},"PeriodicalIF":0.0,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89561109","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}
Qi Zhang, Yanan Li, Jiaxu Yu, Chunping Yin, Junfei Guo, Juan Zhao, Qiujun Wang
This research aimed to explore the influence of TLR deletion on sevoflurane-induced postoperative cognitive dysfunction in neonatal mice. Herein, WT and TLR3 KO neonatal mice, each with 24, were randomly divided into control group, sevoflurane group, and TLR3−/−+sevoflurane group. The hippocampal neurons of WT, TLR3 KO and RIP3 KO neonatal mice in C group, SEV group, TLR3−/−+SEV group and RIP3−/−+SEV group were extracted for in vitro experiments. The results revealed the degeneration and necrosis of nerve cells in SEV group. Microscopic findings indicated that nerve cells showed shrinkage and nuclear hyperchromatism, along with lessening or even disappearance of nuclei and enlargement of cell spaces, and apoptotic cells in the brain tissues were evidently increased. Compared with SEV group, TLR3−/−+SEV group displayed reductions in these phenomena. Additionally, SEV group showed the reduced SHP2 expression and the increased expressions of proteins associated with TLR signaling pathway and apoptosis. Furthermore, there were no obvious differences in the expressions of such proteins in hippocampal neurons between RIP3−/−+SEV and TLR3−/−+SEV groups. The results confirmed that inhibiting RIP3 phosphorylation and suppressing TLR3 expressions exerted the same influence on the expressions of these proteins in the hippocampus of neonatal mice with sevoflurane-induced cognitive dysfunction. Based on these, it is speculated that TLR3 influences neonatal mice with sevoflurane-induced cognitive dysfunction probably by regulating RIP3 phosphorylation.
{"title":"TLR3 deletion inhibits programmed necrosis of brain cells in neonatal mice with sevoflurane-induced cognitive dysfunction","authors":"Qi Zhang, Yanan Li, Jiaxu Yu, Chunping Yin, Junfei Guo, Juan Zhao, Qiujun Wang","doi":"10.18632/aging.204092","DOIUrl":"https://doi.org/10.18632/aging.204092","url":null,"abstract":"This research aimed to explore the influence of TLR deletion on sevoflurane-induced postoperative cognitive dysfunction in neonatal mice. Herein, WT and TLR3 KO neonatal mice, each with 24, were randomly divided into control group, sevoflurane group, and TLR3−/−+sevoflurane group. The hippocampal neurons of WT, TLR3 KO and RIP3 KO neonatal mice in C group, SEV group, TLR3−/−+SEV group and RIP3−/−+SEV group were extracted for in vitro experiments. The results revealed the degeneration and necrosis of nerve cells in SEV group. Microscopic findings indicated that nerve cells showed shrinkage and nuclear hyperchromatism, along with lessening or even disappearance of nuclei and enlargement of cell spaces, and apoptotic cells in the brain tissues were evidently increased. Compared with SEV group, TLR3−/−+SEV group displayed reductions in these phenomena. Additionally, SEV group showed the reduced SHP2 expression and the increased expressions of proteins associated with TLR signaling pathway and apoptosis. Furthermore, there were no obvious differences in the expressions of such proteins in hippocampal neurons between RIP3−/−+SEV and TLR3−/−+SEV groups. The results confirmed that inhibiting RIP3 phosphorylation and suppressing TLR3 expressions exerted the same influence on the expressions of these proteins in the hippocampus of neonatal mice with sevoflurane-induced cognitive dysfunction. Based on these, it is speculated that TLR3 influences neonatal mice with sevoflurane-induced cognitive dysfunction probably by regulating RIP3 phosphorylation.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"46 1","pages":"4714 - 4727"},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91231739","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}
B. Cortez, Nadine Bahour, Cristina Aguayo-Mazzucato
susceptibility to disease, physical and cognitive impairment, and death [1]. The mainstream use of age describes chronological age (CA), the years lived since birth. CA can directly impact biological age (BA) which specifically measures the rate of cellular decline or physiological breakdown of cells and organs within the body. While CA and BA can change at the same rate, we found that in Diabetes mellitus, BA is accelerated when compared to CA [2].
{"title":"Biological age in diabetes and precision medicine","authors":"B. Cortez, Nadine Bahour, Cristina Aguayo-Mazzucato","doi":"10.18632/aging.204123","DOIUrl":"https://doi.org/10.18632/aging.204123","url":null,"abstract":"susceptibility to disease, physical and cognitive impairment, and death [1]. The mainstream use of age describes chronological age (CA), the years lived since birth. CA can directly impact biological age (BA) which specifically measures the rate of cellular decline or physiological breakdown of cells and organs within the body. While CA and BA can change at the same rate, we found that in Diabetes mellitus, BA is accelerated when compared to CA [2].","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"42 1","pages":"4622 - 4623"},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78713390","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}
Ryota Imai, Keita Mizuno, Y. Omiya, K. Mizoguchi, Y. Maejima, K. Shimomura
The ventral tegmental area (VTA), substantia nigra pars compacta (SNpc) and nucleus accumbens (NAc) are involved in the regulation of appetite and motivational behaviors. A traditional Japanese (Kampo) medicine, ninjin’yoeito (NYT), has been reported to improve decreased motivation and anorexia in patients with Alzheimer’s disease and apathy-like model mice. Thus, NYT may affect the activities of neurons in the VTA, SNpc and NAc. However, little is known about the underlying mechanisms of NYT. Here, we investigated the effects of NYT on the electrophysiological properties of dopaminergic neurons in the VTA and SNpc, as well as on those of medium spiny neurons (MSNs) in the NAc (core and shell subregions), by applying the patch-clamp technique in the brain slices. NYT reduced the resting membrane potential of VTA and SNpc dopaminergic neurons. In contrast, NYT increased the firing frequency of NAc MSNs accompanied by shortened first spike latency and interspike interval. Furthermore, NYT attenuated the inward rectification and sustained outward currents. In conclusion, NYT may directly influence the excitability of dopaminergic neurons in the VTA and SNpc, as well as MSNs in the NAc (core and shell). NYT may modulate dopamine signals in appetite and motivational behaviors.
{"title":"The effects of ninjin’yoeito on the electrophysiological properties of dopamine neurons in the ventral tegmental area/substantia nigra pars compacta and medium spiny neurons in the nucleus accumbens","authors":"Ryota Imai, Keita Mizuno, Y. Omiya, K. Mizoguchi, Y. Maejima, K. Shimomura","doi":"10.18632/aging.204109","DOIUrl":"https://doi.org/10.18632/aging.204109","url":null,"abstract":"The ventral tegmental area (VTA), substantia nigra pars compacta (SNpc) and nucleus accumbens (NAc) are involved in the regulation of appetite and motivational behaviors. A traditional Japanese (Kampo) medicine, ninjin’yoeito (NYT), has been reported to improve decreased motivation and anorexia in patients with Alzheimer’s disease and apathy-like model mice. Thus, NYT may affect the activities of neurons in the VTA, SNpc and NAc. However, little is known about the underlying mechanisms of NYT. Here, we investigated the effects of NYT on the electrophysiological properties of dopaminergic neurons in the VTA and SNpc, as well as on those of medium spiny neurons (MSNs) in the NAc (core and shell subregions), by applying the patch-clamp technique in the brain slices. NYT reduced the resting membrane potential of VTA and SNpc dopaminergic neurons. In contrast, NYT increased the firing frequency of NAc MSNs accompanied by shortened first spike latency and interspike interval. Furthermore, NYT attenuated the inward rectification and sustained outward currents. In conclusion, NYT may directly influence the excitability of dopaminergic neurons in the VTA and SNpc, as well as MSNs in the NAc (core and shell). NYT may modulate dopamine signals in appetite and motivational behaviors.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"12 1","pages":"4634 - 4652"},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89231672","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}
Bing-Heng Yang, Hsing-Yi Chung, L. Kao, M. Jian, Chih-Kai Chang, Jung‐Chung Lin, Kuo‐Ming Yeh, Chien-Wen Chen, Ya-Sung Yang, Shan-Shan Hsieh, Sheng-Hui Tang, C. Perng, F. Chang, Hung-Sheng Shang
Since the late 2020, the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has been characterized by the emergence of spike protein mutations, and these variants have become dominant worldwide. The gold standard SARS-CoV-2 diagnosis protocol requires two complex processes, namely, RNA extraction and real-time reverse transcriptase polymerase chain reaction (RT-PCR). There is a need for a faster, simpler, and more cost-effective detection strategy that can be utilized worldwide, especially in developing countries. We propose the novel use of direct RT-qPCR, which does not require RNA extraction or a preheating step. For the detection, retrospectively, we used 770 clinical nasopharyngeal swabs, including positive and negative samples. The samples were subjected to RT-qPCR in the N1 and E genes using two different thermocyclers. The limit of detection was 30 copies/reaction for N1 and 60 copies/reaction for E. Analytical sensitivity was assessed for the developed direct RT-qPCR; the sensitivity was 95.69%, negative predictive value was 99.9%, accuracy of 99.35%, and area under the curve was 0.978. This novel direct RT-qPCR diagnosis method without RNA extraction is a reliable and high-throughput alternative method that can significantly save cost, labor, and time during the coronavirus disease 2019 pandemic.
{"title":"Emergency SARS-CoV-2 variants of concern: rapidly direct RT-qPCR detection without RNA extraction, clinical comparison, cost-effective, and high-throughput","authors":"Bing-Heng Yang, Hsing-Yi Chung, L. Kao, M. Jian, Chih-Kai Chang, Jung‐Chung Lin, Kuo‐Ming Yeh, Chien-Wen Chen, Ya-Sung Yang, Shan-Shan Hsieh, Sheng-Hui Tang, C. Perng, F. Chang, Hung-Sheng Shang","doi":"10.18632/aging.204095","DOIUrl":"https://doi.org/10.18632/aging.204095","url":null,"abstract":"Since the late 2020, the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has been characterized by the emergence of spike protein mutations, and these variants have become dominant worldwide. The gold standard SARS-CoV-2 diagnosis protocol requires two complex processes, namely, RNA extraction and real-time reverse transcriptase polymerase chain reaction (RT-PCR). There is a need for a faster, simpler, and more cost-effective detection strategy that can be utilized worldwide, especially in developing countries. We propose the novel use of direct RT-qPCR, which does not require RNA extraction or a preheating step. For the detection, retrospectively, we used 770 clinical nasopharyngeal swabs, including positive and negative samples. The samples were subjected to RT-qPCR in the N1 and E genes using two different thermocyclers. The limit of detection was 30 copies/reaction for N1 and 60 copies/reaction for E. Analytical sensitivity was assessed for the developed direct RT-qPCR; the sensitivity was 95.69%, negative predictive value was 99.9%, accuracy of 99.35%, and area under the curve was 0.978. This novel direct RT-qPCR diagnosis method without RNA extraction is a reliable and high-throughput alternative method that can significantly save cost, labor, and time during the coronavirus disease 2019 pandemic.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"12 1","pages":"4624 - 4633"},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81305507","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}
Xiulin Jiang, Xi Chen, Xiaobin Huang, Chunyan Wang, Chenyang Wang, Chenglong Pan, W. C. Cho, Zhi Nie, Jun Pu, Weixiang Wang
Background: Glioma is a lethal malignant brain tumor, it comprises about 80% of all malignant brain tumours. Mounting evidence has reported that YTHDF2 plays a significant role in the cancer progression. However, the effects of YTHDF2 on the prognosis of low-grade gliomas (LGGs) and its correlation with tumor immune infiltration are unclear. The present study was designed to determine the biological functions of YTHDF2 in glioma and to evaluate the association of YTHDF2 expression with glioma progression. Methods: Clinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), as well as the Rembrandt and Gravendeel databases. The correlations among YTHDF2 expression, pathological characteristics, glioma progression and clinical outcome were evaluated. In addition, the correlation of YTHDF2 expression with immune cell infiltration was analyzed too. Results: We found that YTHDF2 was significantly up-regulated in LGGs which correlated with tumor grade and poor prognosis. Interestingly, we showed that YTHDF2 expression in LGG was associated with copy number variation, DNA hypomethylation, and induced transcription factor YY1. Besides, KEGG pathway analysis shows that YTHDF2 mainly participates in the immune response and oncogenic signaling pathway. Additionally, YTHDF2 is positively associated with diverse immune cells infiltration, immune cells, and multiple immune checkpoint molecules. Finally, we confirmed that YTHDF2 was highly expressed in LGGs tissues and correlated with the tumor grade with immunohistochemistry assay. More importantly, our results demonstrated that YTHDF2 was elevated in GBM cells. Knockdown of YTHDF2 significantly inhibits the proliferation and migration of GBM cells. Conclusion: YTHDF2 correlates with glioma progression and immune cell infiltration, suggesting that YTHDF2 may be a useful prognostic biomarker for glioma.
{"title":"DNA methylation-regulated YTHDF2 correlates with cell migration and immune cell infiltration in glioma","authors":"Xiulin Jiang, Xi Chen, Xiaobin Huang, Chunyan Wang, Chenyang Wang, Chenglong Pan, W. C. Cho, Zhi Nie, Jun Pu, Weixiang Wang","doi":"10.18632/aging.204104","DOIUrl":"https://doi.org/10.18632/aging.204104","url":null,"abstract":"Background: Glioma is a lethal malignant brain tumor, it comprises about 80% of all malignant brain tumours. Mounting evidence has reported that YTHDF2 plays a significant role in the cancer progression. However, the effects of YTHDF2 on the prognosis of low-grade gliomas (LGGs) and its correlation with tumor immune infiltration are unclear. The present study was designed to determine the biological functions of YTHDF2 in glioma and to evaluate the association of YTHDF2 expression with glioma progression. Methods: Clinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), as well as the Rembrandt and Gravendeel databases. The correlations among YTHDF2 expression, pathological characteristics, glioma progression and clinical outcome were evaluated. In addition, the correlation of YTHDF2 expression with immune cell infiltration was analyzed too. Results: We found that YTHDF2 was significantly up-regulated in LGGs which correlated with tumor grade and poor prognosis. Interestingly, we showed that YTHDF2 expression in LGG was associated with copy number variation, DNA hypomethylation, and induced transcription factor YY1. Besides, KEGG pathway analysis shows that YTHDF2 mainly participates in the immune response and oncogenic signaling pathway. Additionally, YTHDF2 is positively associated with diverse immune cells infiltration, immune cells, and multiple immune checkpoint molecules. Finally, we confirmed that YTHDF2 was highly expressed in LGGs tissues and correlated with the tumor grade with immunohistochemistry assay. More importantly, our results demonstrated that YTHDF2 was elevated in GBM cells. Knockdown of YTHDF2 significantly inhibits the proliferation and migration of GBM cells. Conclusion: YTHDF2 correlates with glioma progression and immune cell infiltration, suggesting that YTHDF2 may be a useful prognostic biomarker for glioma.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"29 9","pages":"7774 - 7793"},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72622058","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}
Yuan Xiang, Hui Liu, Hao Hu, Leping Li, Qiang Zong, Tangwei Wu, Xiaoyi Li, Shiqiang Fang, Yi-Wen Liu, Y. Zhan, Hui Wang, Zhongxin Lu
The endocrine therapy resistance of breast cancer is the difficulty and challenge to be urgently solved in the current treatment. In this study, we examined the effects of noncoding RNA LINC00094 and miR-19a-3p on breast cancer in vivo and in vitro by RT-QPCR, Western Blot, luciferase assay, immunofluorescence and drug sensitivity tests. The plasma level of CYP19A1 in patients with breast cancer resistance was lower than that in drug sensitive patients. Compared with normal subjects, miR-19a-3p was highly expressed in plasma of patients with breast cancer. miR-19a-3p is highly expressed in estrogen receptor positive breast cancer cells. The expression of miR-19a-3p promoted the migration and EMT of breast cancer cells and reduced the sensitivity of breast cancer to Letrozole. LINC00094 sponge adsorbed miR-19a-3p. LINC00094 promotes the expression of CYP19A1, the target gene of miR-19a-3p, and inhibits the EMT process of breast cancer, ultimately promoting the sensitivity of ER-positive breast cancer cells to Letrozole. This study found a new mechanism of Letrozole sensitivity in ER positive breast cancer.
{"title":"LINC00094/miR-19a-3p/CYP19A1 axis affects the sensitivity of ER positive breast cancer cells to Letrozole through EMT pathway","authors":"Yuan Xiang, Hui Liu, Hao Hu, Leping Li, Qiang Zong, Tangwei Wu, Xiaoyi Li, Shiqiang Fang, Yi-Wen Liu, Y. Zhan, Hui Wang, Zhongxin Lu","doi":"10.18632/aging.204110","DOIUrl":"https://doi.org/10.18632/aging.204110","url":null,"abstract":"The endocrine therapy resistance of breast cancer is the difficulty and challenge to be urgently solved in the current treatment. In this study, we examined the effects of noncoding RNA LINC00094 and miR-19a-3p on breast cancer in vivo and in vitro by RT-QPCR, Western Blot, luciferase assay, immunofluorescence and drug sensitivity tests. The plasma level of CYP19A1 in patients with breast cancer resistance was lower than that in drug sensitive patients. Compared with normal subjects, miR-19a-3p was highly expressed in plasma of patients with breast cancer. miR-19a-3p is highly expressed in estrogen receptor positive breast cancer cells. The expression of miR-19a-3p promoted the migration and EMT of breast cancer cells and reduced the sensitivity of breast cancer to Letrozole. LINC00094 sponge adsorbed miR-19a-3p. LINC00094 promotes the expression of CYP19A1, the target gene of miR-19a-3p, and inhibits the EMT process of breast cancer, ultimately promoting the sensitivity of ER-positive breast cancer cells to Letrozole. This study found a new mechanism of Letrozole sensitivity in ER positive breast cancer.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"25 1","pages":"4755 - 4768"},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81061351","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}
Premature aging diseases, also called ‘progeroid syndrome’, display signs and features of normal aging in early life, ultimately leading to premature death. Although progeroid syndromes do not perfectly mimic chronological aging they can be excellent model systems to study characteristics of normal aging. Werner syndrome (WS) is one of the rare autosomal recessive progeroid syndromes, characterized by accelerated in vivo/in vitro aging [2]. WRN is suggested to play a central role in maintaining genome stability and rapidly recruits to the DNA damage sites to take part in DNA repair, including base excision DNA repair (BER), classical/alternative non-homologous end joining (NHEJ), homologous recombination (HR), and replication re-start after DNA damage.
{"title":"WRNing for the right DNA repair pathway choice","authors":"Jong-Hyuk Lee, D. Croteau, V. Bohr","doi":"10.18632/aging.204120","DOIUrl":"https://doi.org/10.18632/aging.204120","url":null,"abstract":"Premature aging diseases, also called ‘progeroid syndrome’, display signs and features of normal aging in early life, ultimately leading to premature death. Although progeroid syndromes do not perfectly mimic chronological aging they can be excellent model systems to study characteristics of normal aging. Werner syndrome (WS) is one of the rare autosomal recessive progeroid syndromes, characterized by accelerated in vivo/in vitro aging [2]. WRN is suggested to play a central role in maintaining genome stability and rapidly recruits to the DNA damage sites to take part in DNA repair, including base excision DNA repair (BER), classical/alternative non-homologous end joining (NHEJ), homologous recombination (HR), and replication re-start after DNA damage.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"77 1","pages":"4620 - 4621"},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83486650","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}
Haixiao Wu, Guijun Xu, Zhijun Li, Yao Xu, Yile Lin, V. Chekhonin, K. Peltzer, Jun Wang, Shu Li, Hui-yan Li, Jin Zhang, Yuan Xue, Wenjuan Ma, Xin Wang, Chao Zhang
Purpose: To explore the trends of plasma drug concentration changes after high-dose methotrexate (MTX) treatment of osteosarcoma (OS), analyse the risk factors for leukopenia (LP) after MTX treatment, and establish a LP prediction nomogram. Methods: A total of 35 OS patients at Tianjin Medical University Cancer Institute and Hospital between 2017 and 2021 were collected (the construction cohort). Another 12 OS patients between 2019 and 2021 in P.A. Hertsen Moscow Oncology Research Center were involved (the external validation cohort). Peripheral venous blood MTX concentration (CMTX) was monitored at 0h, 6h, 24h, 48h and 72h after MTX administration. The characteristics were collected: age, sex, body surface area, lesion site, pathological subtype, pathological fractures, American Joint Committee on Cancer (AJCC) clinical stage, MTX dose, tumour necrosis, Ki-67 index, erythrocyte count, haemoglobin count, white blood cell count, platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, albumin concentration, creatinine, alkaline phosphatase, and lactate dehydrogenase. Logistic regression analysis was used to determine the risk factors for LP occurrence. Significant factors were used to construct the prediction nomogram. Results: A total of 128 MTX chemotherapy cycles from 35 OS patients were included. Female, Ki-67>20%, CMTX>112μmol/L at 6h, PLT, and AST were risk factors for post-chemotherapy LP occurrence. The LP prediction nomogram was created and validated. Conclusions: Female, CMTX at 6h, Ki-67 index, AST and PLT before MTX treatment were risk factors for LP in OS patients who received MTX treatment. The established nomogram can guide personalized LP prediction in OS patients receiving MTX chemotherapy.
{"title":"Nomogram predicting leukopenia in osteosarcoma after high-dose methotrexate chemotherapy","authors":"Haixiao Wu, Guijun Xu, Zhijun Li, Yao Xu, Yile Lin, V. Chekhonin, K. Peltzer, Jun Wang, Shu Li, Hui-yan Li, Jin Zhang, Yuan Xue, Wenjuan Ma, Xin Wang, Chao Zhang","doi":"10.18632/aging.203978","DOIUrl":"https://doi.org/10.18632/aging.203978","url":null,"abstract":"Purpose: To explore the trends of plasma drug concentration changes after high-dose methotrexate (MTX) treatment of osteosarcoma (OS), analyse the risk factors for leukopenia (LP) after MTX treatment, and establish a LP prediction nomogram. Methods: A total of 35 OS patients at Tianjin Medical University Cancer Institute and Hospital between 2017 and 2021 were collected (the construction cohort). Another 12 OS patients between 2019 and 2021 in P.A. Hertsen Moscow Oncology Research Center were involved (the external validation cohort). Peripheral venous blood MTX concentration (CMTX) was monitored at 0h, 6h, 24h, 48h and 72h after MTX administration. The characteristics were collected: age, sex, body surface area, lesion site, pathological subtype, pathological fractures, American Joint Committee on Cancer (AJCC) clinical stage, MTX dose, tumour necrosis, Ki-67 index, erythrocyte count, haemoglobin count, white blood cell count, platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, albumin concentration, creatinine, alkaline phosphatase, and lactate dehydrogenase. Logistic regression analysis was used to determine the risk factors for LP occurrence. Significant factors were used to construct the prediction nomogram. Results: A total of 128 MTX chemotherapy cycles from 35 OS patients were included. Female, Ki-67>20%, CMTX>112μmol/L at 6h, PLT, and AST were risk factors for post-chemotherapy LP occurrence. The LP prediction nomogram was created and validated. Conclusions: Female, CMTX at 6h, Ki-67 index, AST and PLT before MTX treatment were risk factors for LP in OS patients who received MTX treatment. The established nomogram can guide personalized LP prediction in OS patients receiving MTX chemotherapy.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"288 1","pages":"5023 - 5033"},"PeriodicalIF":0.0,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77481596","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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