Type 2 diabetes mellitus patients often suffer from kidney damage, which is more serious than in ordinary people. The insulin-like growth factor (IGF) system has synergistic effects with other hormonal axes and has an essential role in glucose metabolism and type 2 diabetes. The study aimed to observe the association of IGF-1 and IGF factor-binding protein-3 (IGFBP-3) with estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus. We recruited 521 patients with type 2 diabetes from the Endocrinology Department of the First Affiliated Hospital of Xinjiang Medical University from March 1, 2021, to December 20, 2021. The clinical data we collected were analyzed to determine the association of IGF-1 and IGFBP-3 with eGFR in patients with type 2 diabetes. Spearman correlation analysis showed that eGFR was positively correlated with IGF-1 and IGFBP-3 in all subjects (P = 0.044 and P = 0.004, respectively). We developed a linear regression model. In the multiple linear regression model, serum IGF-1 and IGFBP-3 were positively correlated with eGFR (β = 0.03, 95% CI = 0.01 – 0.06; P = 0.009 and β = 1.29, 95% CI = 0.09 – 2.49; P = 0.035). The results of the correlations were further validated. This preliminary study demonstrated positive associations of serum IGF-1 and IGFBP-3 levels with eGFR in patients with type 2 diabetes.
{"title":"Association of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 with estimated glomerular filtration rate in patients with type 2 diabetes mellitus","authors":"Sheng Jiang, Jing Yang","doi":"10.36922/gtm.v1i2.62","DOIUrl":"https://doi.org/10.36922/gtm.v1i2.62","url":null,"abstract":"Type 2 diabetes mellitus patients often suffer from kidney damage, which is more serious than in ordinary people. The insulin-like growth factor (IGF) system has synergistic effects with other hormonal axes and has an essential role in glucose metabolism and type 2 diabetes. The study aimed to observe the association of IGF-1 and IGF factor-binding protein-3 (IGFBP-3) with estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus. We recruited 521 patients with type 2 diabetes from the Endocrinology Department of the First Affiliated Hospital of Xinjiang Medical University from March 1, 2021, to December 20, 2021. The clinical data we collected were analyzed to determine the association of IGF-1 and IGFBP-3 with eGFR in patients with type 2 diabetes. Spearman correlation analysis showed that eGFR was positively correlated with IGF-1 and IGFBP-3 in all subjects (P = 0.044 and P = 0.004, respectively). We developed a linear regression model. In the multiple linear regression model, serum IGF-1 and IGFBP-3 were positively correlated with eGFR (β = 0.03, 95% CI = 0.01 – 0.06; P = 0.009 and β = 1.29, 95% CI = 0.09 – 2.49; P = 0.035). The results of the correlations were further validated. This preliminary study demonstrated positive associations of serum IGF-1 and IGFBP-3 levels with eGFR in patients with type 2 diabetes.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89318842","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}
Cardiovascular disease (CVD) refers to a class of diseases related to the heart or blood vessels that have high global incidence. Succinate is generally considered an important intermediate product of the tricarboxylic acid cycle. Recent studies have shown that succinate is related to the pathophysiology of CVD, such as atherosclerosis, acute aortic dissection, hypertension, myocardial ischemia-reperfusion injury, and heart failure. It may represent a potential target or biomarker for CVD. It has been demonstrated that succinate not only participates in various energy metabolic pathways but also plays an important role in various pathophysiological activities as a signaling molecule. Given the significance of metabolism in CVD, it is important to focus on the metabolic regulation mechanism of succinate in CVD. This review outlines the latest evidence pointing to the potential role of succinate in CVD, along with its mechanisms, and updates the current understanding on the role of succinate in CVD. Further studies may focus on identifying succinate, its receptor, and its downstream signaling molecules as new targets for the prevention and treatment of CVD.
{"title":"Succinate metabolism in cardiovascular diseases","authors":"Wenxin Shan, Hongtu Cui, Yangkai Xu, Jing Xue, Lemin Zheng","doi":"10.36922/gtm.v1i2.160","DOIUrl":"https://doi.org/10.36922/gtm.v1i2.160","url":null,"abstract":"Cardiovascular disease (CVD) refers to a class of diseases related to the heart or blood vessels that have high global incidence. Succinate is generally considered an important intermediate product of the tricarboxylic acid cycle. Recent studies have shown that succinate is related to the pathophysiology of CVD, such as atherosclerosis, acute aortic dissection, hypertension, myocardial ischemia-reperfusion injury, and heart failure. It may represent a potential target or biomarker for CVD. It has been demonstrated that succinate not only participates in various energy metabolic pathways but also plays an important role in various pathophysiological activities as a signaling molecule. Given the significance of metabolism in CVD, it is important to focus on the metabolic regulation mechanism of succinate in CVD. This review outlines the latest evidence pointing to the potential role of succinate in CVD, along with its mechanisms, and updates the current understanding on the role of succinate in CVD. Further studies may focus on identifying succinate, its receptor, and its downstream signaling molecules as new targets for the prevention and treatment of CVD.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85041332","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}
In patients with obesity or type 2 diabetes, the accumulation of lipotoxic by-products in cardiomyocytes leads to apoptosis and contractile dysfunction, eventually resulting in metabolic cardiomyopathy (MC). However, the underlying mechanisms remain unclear. Inb this study, a comparative proteome analysis was conducted to evaluate the differentially expressed proteins (DEPs) in the hearts of normal mice on standard diet (control group) and of high-fat diet (HFD)-induced MC mice (HFD group). We identified 90 DEPs unique to the control group and 18 DEPs unique to the HFD group. In 90 DEPs unique to the control group, only 74 DEPs were annotated in the gene ontology (GO) database. These annotated DEPs are involved in 114 biological processes, 68 molecular functions, and 174 cellular components. In 18 DEPs unique to the HFD group, only 14 DEPs were annotated in the GO database. These annotated DEPs are involved in 24 biological processes, 22 molecular functions, and six cellular components. Protein levels of two fatty acid metabolism-related enzymes, carnitine palmitoyltransferase 1B (CPT1B) and acetyl-CoA acyltransferase 2 (ACAA2), in the hearts of the mice in control group and HFD group were analyzed by immunostaining and Western blot. The results showed that the protein levels of CPT1B and ACAA2 were elevated in hearts of the mice in HFD group, which were consistent with the proteomic analysis. Our results reveal the differentially expressed proteome related to the progression of MC, providing a series of potential therapeutic targets for MC.
{"title":"Comparative proteomic analysis of hearts from mice with high-fat diet-induced metabolic cardiomyopathy","authors":"Zong-zhe Jiang, Mingyang Pang, Wei Huang","doi":"10.36922/gtm.v1i2.137","DOIUrl":"https://doi.org/10.36922/gtm.v1i2.137","url":null,"abstract":"In patients with obesity or type 2 diabetes, the accumulation of lipotoxic by-products in cardiomyocytes leads to apoptosis and contractile dysfunction, eventually resulting in metabolic cardiomyopathy (MC). However, the underlying mechanisms remain unclear. Inb this study, a comparative proteome analysis was conducted to evaluate the differentially expressed proteins (DEPs) in the hearts of normal mice on standard diet (control group) and of high-fat diet (HFD)-induced MC mice (HFD group). We identified 90 DEPs unique to the control group and 18 DEPs unique to the HFD group. In 90 DEPs unique to the control group, only 74 DEPs were annotated in the gene ontology (GO) database. These annotated DEPs are involved in 114 biological processes, 68 molecular functions, and 174 cellular components. In 18 DEPs unique to the HFD group, only 14 DEPs were annotated in the GO database. These annotated DEPs are involved in 24 biological processes, 22 molecular functions, and six cellular components. Protein levels of two fatty acid metabolism-related enzymes, carnitine palmitoyltransferase 1B (CPT1B) and acetyl-CoA acyltransferase 2 (ACAA2), in the hearts of the mice in control group and HFD group were analyzed by immunostaining and Western blot. The results showed that the protein levels of CPT1B and ACAA2 were elevated in hearts of the mice in HFD group, which were consistent with the proteomic analysis. Our results reveal the differentially expressed proteome related to the progression of MC, providing a series of potential therapeutic targets for MC.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91333729","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}
Yanna Liu, X. Qian, Congying Wu, Weidong Pan, Jingmin Zhao, Xiangmei Chen, F. Lu
Liver cirrhosis has been a well-known risk factor for the development of hepatocellular carcinoma (HCC). However, this view has recently been challenged. This study aimed to investigate the potential association of cirrhosis with hepatitis B virus (HBV)-related HCC. In this study, two independent multicenter clinical cohorts that included 1,431 HCC patients with chronic HBV infection were retrospectively studied. The first cohort consisted of 334 HCC patients undergoing curative resection and cirrhosis, who have been pathologically diagnosed. The second cohort consisted of 1,087 HCC patients, who have been diagnosed for the presence of cirrhosis based on clinical evidence. Patients of each cohort were further divided into different subgroups according to the presence of cirrhosis and the severity of the cirrhosis. In both cohorts, patients with cirrhosis had smaller tumor size compared to those without cirrhosis (P < 0.05) and a relatively lower proportion of large tumor, defined as tumor size > 5 cm in diameter (P < 0.05). Patients with decompensated cirrhosis had the highest rate of vascular invasion and/or extrahepatic metastases compared with compensated cirrhosis and non-cirrhosis (53.0% vs. 24.8% vs. 26.9%, P < 0.001). In the first cohort, globulin (odds ratio [OR] = 1.096, P = 0.001) and vascular invasion (OR = 4.013, P = 0.013) were independent risk predictors of HCC tumor size >5 cm, while cirrhosis stage Laennec 4B/C was a protective factor (OR = 0.372, P = 0.002). Similar results were observed in the second cohort. In conclusion, this study implied that HCC patients with compensated cirrhosis tend to harbor smaller tumor, but severe cirrhosis favors tumor vascular invasion and metastasis.
肝硬化是肝细胞癌(HCC)发展的一个众所周知的危险因素。然而，这一观点最近受到了挑战。本研究旨在探讨肝硬化与乙型肝炎病毒(HBV)相关HCC的潜在关联。在这项研究中，回顾性研究了两个独立的多中心临床队列，包括1431例慢性HBV感染的HCC患者。第一组包括334例接受根治性切除和肝硬化的HCC患者，他们已被病理诊断。第二组包括1087例HCC患者，他们根据临床证据被诊断为存在肝硬化。每个队列的患者根据肝硬化的存在和肝硬化的严重程度进一步分为不同的亚组。在两个队列中，肝硬化患者的肿瘤大小均小于无肝硬化患者(P < 0.05)，大肿瘤(定义为肿瘤直径> 5 cm)的比例相对较低(P < 0.05)。与代偿性肝硬化和非肝硬化患者相比，失代偿性肝硬化患者的血管侵犯和/或肝外转移率最高(53.0%比24.8%比26.9%，P < 0.001)。在第一个队列中，球蛋白(比值比[OR] = 1.096, P = 0.001)和血管侵犯(OR = 4.013, P = 0.013)是肝癌肿瘤大小>5 cm的独立危险预测因素，而肝硬化阶段Laennec 4B/C是保护因素(OR = 0.372, P = 0.002)。在第二组中也观察到类似的结果。综上所述，本研究提示HCC代偿性肝硬化患者肿瘤倾向于较小，而重度肝硬化则有利于肿瘤血管的侵袭和转移。
{"title":"The status of compensated cirrhosis might be negatively associated with the tumor size in patients with hepatitis B virus-related hepatocellular carcinoma","authors":"Yanna Liu, X. Qian, Congying Wu, Weidong Pan, Jingmin Zhao, Xiangmei Chen, F. Lu","doi":"10.36922/gtm.v1i2.94","DOIUrl":"https://doi.org/10.36922/gtm.v1i2.94","url":null,"abstract":"Liver cirrhosis has been a well-known risk factor for the development of hepatocellular carcinoma (HCC). However, this view has recently been challenged. This study aimed to investigate the potential association of cirrhosis with hepatitis B virus (HBV)-related HCC. In this study, two independent multicenter clinical cohorts that included 1,431 HCC patients with chronic HBV infection were retrospectively studied. The first cohort consisted of 334 HCC patients undergoing curative resection and cirrhosis, who have been pathologically diagnosed. The second cohort consisted of 1,087 HCC patients, who have been diagnosed for the presence of cirrhosis based on clinical evidence. Patients of each cohort were further divided into different subgroups according to the presence of cirrhosis and the severity of the cirrhosis. In both cohorts, patients with cirrhosis had smaller tumor size compared to those without cirrhosis (P < 0.05) and a relatively lower proportion of large tumor, defined as tumor size > 5 cm in diameter (P < 0.05). Patients with decompensated cirrhosis had the highest rate of vascular invasion and/or extrahepatic metastases compared with compensated cirrhosis and non-cirrhosis (53.0% vs. 24.8% vs. 26.9%, P < 0.001). In the first cohort, globulin (odds ratio [OR] = 1.096, P = 0.001) and vascular invasion (OR = 4.013, P = 0.013) were independent risk predictors of HCC tumor size >5 cm, while cirrhosis stage Laennec 4B/C was a protective factor (OR = 0.372, P = 0.002). Similar results were observed in the second cohort. In conclusion, this study implied that HCC patients with compensated cirrhosis tend to harbor smaller tumor, but severe cirrhosis favors tumor vascular invasion and metastasis.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72986323","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}
G. Korytina, Y. G. Aznabaeva, T. Nasibullin, O. Kochetova, N. N. Khusnutdinova, T. Viktorova, N. Zagidullin
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that is characterized by partly reversible airflow limitation, chronic inflammation, fibrosis of small airways, and destruction of lung parenchyma. We aimed to assess the association of the inflammatory gene loci singly and in combinations with COPD in smokers and non-smokers in ethnic Tatar from Russia to evaluate the gene-gene and gene-environment interactions in COPD development. Eleven loci of inflammatory genes, including IL19, IL20, IL24, PPBP, IL4, IL4RA, С5, FAS, FASLG, and TGFb1, were genotyped in 484 smoking COPD patients, 517 healthy smokers, 117 non-smoking COPD patients, and 100 healthy non-smokers. Significant associations with COPD in smokers were identified for IL19 (rs2243193), IL4 (rs2243250), IL4 (rs2070874), and PPBP (rs352010). In non-smokers, associations were established for IL24 (rs291107), IL4 (rs2070874), and PPBP (rs352010). Associations of inflammatory genes loci IL19 (rs2243193), IL4 (rs2070874), TGFb1 (rs1800469), PPBP (rs352010), and FASLG (rs763110) and smoking index were determined. Associations of FAS (rs1800682), FASLG (rs763110), IL4 (rs2243250), IL4RA (rs1805010), and PPBP (rs352010) loci with pulmonary function variables were observed. The results of gene-gene interactions analysis showed distinctive patterns of association of inflammatory gene loci with COPD in groups stratified by smoking status. The combination of A allele of IL19 (rs2243193), C allele of IL4 (rs2243250), and T allele of PPBP (rs352010) was the main component of the majority of protective gene-gene combination associated with COPD in smokers. The highest risk of COPD was conferred by TT genotype of PPBP (rs352010) in combination with A allele of FAS (rs1800682). While in non-smokers, the most commonly featured was IL24 (rs291107) C allele in protective patterns and IL24 (rs291107) T allele in predisposing combinations. The highest risk of COPD in non-smokers was detected in a gene-gene combination consisting of A allele of IL12RB2 (rs3762317) together with G allele of IL12A (rs2243115), C allele of IL4 (rs2070874), and A allele of IL4RA (rs1805010).
{"title":"Gene-gene and gene-environment interactions of the inflammatory gene variants in the development of chronic obstructive pulmonary disease","authors":"G. Korytina, Y. G. Aznabaeva, T. Nasibullin, O. Kochetova, N. N. Khusnutdinova, T. Viktorova, N. Zagidullin","doi":"10.36922/gtm.v1i1.91","DOIUrl":"https://doi.org/10.36922/gtm.v1i1.91","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that is characterized by partly reversible airflow limitation, chronic inflammation, fibrosis of small airways, and destruction of lung parenchyma. We aimed to assess the association of the inflammatory gene loci singly and in combinations with COPD in smokers and non-smokers in ethnic Tatar from Russia to evaluate the gene-gene and gene-environment interactions in COPD development. Eleven loci of inflammatory genes, including IL19, IL20, IL24, PPBP, IL4, IL4RA, С5, FAS, FASLG, and TGFb1, were genotyped in 484 smoking COPD patients, 517 healthy smokers, 117 non-smoking COPD patients, and 100 healthy non-smokers. Significant associations with COPD in smokers were identified for IL19 (rs2243193), IL4 (rs2243250), IL4 (rs2070874), and PPBP (rs352010). In non-smokers, associations were established for IL24 (rs291107), IL4 (rs2070874), and PPBP (rs352010). Associations of inflammatory genes loci IL19 (rs2243193), IL4 (rs2070874), TGFb1 (rs1800469), PPBP (rs352010), and FASLG (rs763110) and smoking index were determined. Associations of FAS (rs1800682), FASLG (rs763110), IL4 (rs2243250), IL4RA (rs1805010), and PPBP (rs352010) loci with pulmonary function variables were observed. The results of gene-gene interactions analysis showed distinctive patterns of association of inflammatory gene loci with COPD in groups stratified by smoking status. The combination of A allele of IL19 (rs2243193), C allele of IL4 (rs2243250), and T allele of PPBP (rs352010) was the main component of the majority of protective gene-gene combination associated with COPD in smokers. The highest risk of COPD was conferred by TT genotype of PPBP (rs352010) in combination with A allele of FAS (rs1800682). While in non-smokers, the most commonly featured was IL24 (rs291107) C allele in protective patterns and IL24 (rs291107) T allele in predisposing combinations. The highest risk of COPD in non-smokers was detected in a gene-gene combination consisting of A allele of IL12RB2 (rs3762317) together with G allele of IL12A (rs2243115), C allele of IL4 (rs2070874), and A allele of IL4RA (rs1805010).","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84884848","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}
Dilated cardiomyopathy (DCM) is a common cause of heart failure. However, genetic-level treatments are not available for this condition. In this study, we searched for biological markers and therapeutic targets for DCM from a genetic perspective. We chose microarray datasets of idiopathic DCM with heart failure tissues and normal function (NF) heart tissues, which were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were analyzed by the GEO2R tool. Gene ontology (GO) and gene set enrichment analysis were used to analyze the functions of DEGs and the pathways in which they are involved. Next, protein-protein interaction networks were built to filter out the hub genes from DEGs. The expression of hub gene was validated by other GEO datasets. Receiver operating characteristic (ROC) curves were plotted to verify the accuracy of the genetic diagnosis. In the end, the mRNA-miRNA-lncRNA network was built to find potentially correlative genes. Twenty-eight common DEGs in total were screened, and GO analysis showed that DEGs were mainly associated with neutrophil degranulation and activation, regulation of Wnt signaling pathway and the development of cardiac cell and tissue. Five hub genes (asporin [ASPN], osteoglycin [OGN], secreted frizzled-related protein 4 [SFRP4], membrane metalloendopeptidase [MME], and natriuretic peptide gene [NPPA]) were shown to be highly expressed in the validation sets and accurate in distinguish between DCM and NF by ROC curves. miRNA prediction of the hub genes revealed that hsa-mir-28b-5p was associated with SFRP4, ASPN, and MME. All of them may serve as biological diagnostic indicators and provide direction for treatment at the genetic level.
扩张型心肌病(DCM)是心力衰竭的常见原因。然而，基因水平的治疗还不能用于这种情况。在本研究中，我们从遗传学角度寻找DCM的生物学标记和治疗靶点。我们选择了特发性DCM合并心衰组织和正常功能(NF)心脏组织的微阵列数据集，这些数据集从Gene Expression Omnibus (GEO)数据库下载。用GEO2R工具分析差异表达基因(DEGs)。基因本体(GO)和基因集富集分析用于分析deg的功能及其参与的途径。接下来，构建蛋白-蛋白相互作用网络，从deg中过滤出中心基因。hub基因的表达通过其他GEO数据验证。绘制受试者工作特征(ROC)曲线以验证遗传诊断的准确性。最后，构建mRNA-miRNA-lncRNA网络，寻找潜在相关基因。共筛选出28个常见的deg，通过GO分析发现，deg主要与中性粒细胞脱粒活化、Wnt信号通路调控以及心脏细胞和组织的发育有关。5个中心基因(抗菌肽[ASPN]、骨溶素[OGN]、分泌卷曲相关蛋白4 [SFRP4]、膜金属内肽酶[MME]、利钠肽基因[NPPA])在验证集中高表达，且通过ROC曲线能准确区分DCM和NF。枢纽基因的miRNA预测显示，hsa-mir-28b-5p与SFRP4、ASPN、mme相关，可作为生物学诊断指标，在遗传水平上为治疗提供指导。
{"title":"Identification of potential hub genes for the diagnosis and therapy of dilated cardiomyopathy with heart failure through bioinformatics analysis","authors":"Xin Zhuang, Mengyue Tian, Liming Li, Shurong Xu, Meiling Cai, Xiaojie Yang, Zhihuang Qiu, Tianci Chai, L. Chen","doi":"10.36922/gtm.v1i1.104","DOIUrl":"https://doi.org/10.36922/gtm.v1i1.104","url":null,"abstract":"Dilated cardiomyopathy (DCM) is a common cause of heart failure. However, genetic-level treatments are not available for this condition. In this study, we searched for biological markers and therapeutic targets for DCM from a genetic perspective. We chose microarray datasets of idiopathic DCM with heart failure tissues and normal function (NF) heart tissues, which were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were analyzed by the GEO2R tool. Gene ontology (GO) and gene set enrichment analysis were used to analyze the functions of DEGs and the pathways in which they are involved. Next, protein-protein interaction networks were built to filter out the hub genes from DEGs. The expression of hub gene was validated by other GEO datasets. Receiver operating characteristic (ROC) curves were plotted to verify the accuracy of the genetic diagnosis. In the end, the mRNA-miRNA-lncRNA network was built to find potentially correlative genes. Twenty-eight common DEGs in total were screened, and GO analysis showed that DEGs were mainly associated with neutrophil degranulation and activation, regulation of Wnt signaling pathway and the development of cardiac cell and tissue. Five hub genes (asporin [ASPN], osteoglycin [OGN], secreted frizzled-related protein 4 [SFRP4], membrane metalloendopeptidase [MME], and natriuretic peptide gene [NPPA]) were shown to be highly expressed in the validation sets and accurate in distinguish between DCM and NF by ROC curves. miRNA prediction of the hub genes revealed that hsa-mir-28b-5p was associated with SFRP4, ASPN, and MME. All of them may serve as biological diagnostic indicators and provide direction for treatment at the genetic level.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77313837","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}
Circulating tumor DNA (ctDNA) is DNA fragment shed from tumor cells and can be isolated from peripheral blood. ctDNA carries genomic information of cancer and is the most widely utilized indicator in liquid biopsy. The application of ctDNA is gaining traction due to its reproducible, non-invasive, and easy-to-obtain characteristics. With the development of detection approaches, ctDNA plays an important role in the management of patients with cancers. In this review, we summarize the basic ctDNA detection measurements and review its application in early screening, prognosis evaluation after the surgery, and efficacy prediction of different therapies in non-small cell lung cancer.
{"title":"Role of circulating tumor DNA in the management of patients with non-small cell lung cancer","authors":"Yi Jin, Manfeng Wu, Kezhong Chen, Jun Wang","doi":"10.36922/gtm.v1i1.96","DOIUrl":"https://doi.org/10.36922/gtm.v1i1.96","url":null,"abstract":"Circulating tumor DNA (ctDNA) is DNA fragment shed from tumor cells and can be isolated from peripheral blood. ctDNA carries genomic information of cancer and is the most widely utilized indicator in liquid biopsy. The application of ctDNA is gaining traction due to its reproducible, non-invasive, and easy-to-obtain characteristics. With the development of detection approaches, ctDNA plays an important role in the management of patients with cancers. In this review, we summarize the basic ctDNA detection measurements and review its application in early screening, prognosis evaluation after the surgery, and efficacy prediction of different therapies in non-small cell lung cancer.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87035645","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}
A. Vijayalakshmi, Venkateshwaran Anitha, Tawfia M. Mustafa Al-Antary
The aim of the present study was to investigate the effect of Solanum xanthocarpum on KB human oral cancer cells by analyzing its anti-proliferative and apoptotic properties as well as its inhibitory effect on cell adhesion. In this study, the leaves extract of S. xanthocarpum was prepared using the maceration method. Cytotoxic effect of different doses of the S. xanthocarpum extract was assessed using MTT assay. Measurements of reactive oxygen species (ROS), lipid peroxidation and antioxidant enzymes were also performed. In addition, we also studied the impacts of S. xanthocarpum on the apoptosis and mitochondrial membrane potential of KB cells. Determination of antioxidant enzymes and lipid peroxidation was performed using biochemical methods. The S. xanthocarpum showed cytotoxic activity against KB cells with IC50 (200 μg/mL). Besides, DCFH-DA staining and acridine orange/ethidium bromide staining results demonstrated that S. xanthocarpum induced the generation of ROS and apoptosis in KB cells, respectively. Based on the Rh-123 staining results, S. xanthocarpum decreased mitochondrial depolarization in KB cells. Furthermore, the S. xanthocarpum treatment contributed to increased lipid peroxidation, accompanied by reduced activities of superoxide dismutase and catalase, as well as decreased glutathione content. Taken together, these findings indicate that S. xanthocarpum extract might comprise bioactive compounds of therapeutic significance, which can inhibit the growth of KB cells.
{"title":"Inhibitory effect of Solanum xanthocarpum on the growth of KB human oral cancer cell line in vitro through ROS-induced mitochondrial pathway","authors":"A. Vijayalakshmi, Venkateshwaran Anitha, Tawfia M. Mustafa Al-Antary","doi":"10.36922/gtm.v1i1.68","DOIUrl":"https://doi.org/10.36922/gtm.v1i1.68","url":null,"abstract":"The aim of the present study was to investigate the effect of Solanum xanthocarpum on KB human oral cancer cells by analyzing its anti-proliferative and apoptotic properties as well as its inhibitory effect on cell adhesion. In this study, the leaves extract of S. xanthocarpum was prepared using the maceration method. Cytotoxic effect of different doses of the S. xanthocarpum extract was assessed using MTT assay. Measurements of reactive oxygen species (ROS), lipid peroxidation and antioxidant enzymes were also performed. In addition, we also studied the impacts of S. xanthocarpum on the apoptosis and mitochondrial membrane potential of KB cells. Determination of antioxidant enzymes and lipid peroxidation was performed using biochemical methods. The S. xanthocarpum showed cytotoxic activity against KB cells with IC50 (200 μg/mL). Besides, DCFH-DA staining and acridine orange/ethidium bromide staining results demonstrated that S. xanthocarpum induced the generation of ROS and apoptosis in KB cells, respectively. Based on the Rh-123 staining results, S. xanthocarpum decreased mitochondrial depolarization in KB cells. Furthermore, the S. xanthocarpum treatment contributed to increased lipid peroxidation, accompanied by reduced activities of superoxide dismutase and catalase, as well as decreased glutathione content. Taken together, these findings indicate that S. xanthocarpum extract might comprise bioactive compounds of therapeutic significance, which can inhibit the growth of KB cells.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91308390","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}
Structural variants, including chromosomal rearrangements and translocations, may result in the formation of fusion genes. Glioma is the most frequent brain tumor among adults. Due to complex tumor classifications, characterization of recurrence, inadequate sample size and controversial mechanisms of tumor malignancy, clinical strategies have not been developed for almost 30 years. Fusion gene is one of the strong driver events in glioma tumorigenesis and has provided fundamental insights into the disease mechanisms. This review elucidates the literature on the discovery of fusion genes, the development of detection techniques, and their clinical implementations. In conclusion, fusion genes are important diagnostic and predictive biomarkers for brain tumors.
{"title":"Fusion genes as diagnostic and predictive biomarkers for tumor","authors":"Z. Bao, Ruichao Chai, Xing Liu, Jiayi Wang","doi":"10.36922/gtm.v1i1.54","DOIUrl":"https://doi.org/10.36922/gtm.v1i1.54","url":null,"abstract":"Structural variants, including chromosomal rearrangements and translocations, may result in the formation of fusion genes. Glioma is the most frequent brain tumor among adults. Due to complex tumor classifications, characterization of recurrence, inadequate sample size and controversial mechanisms of tumor malignancy, clinical strategies have not been developed for almost 30 years. Fusion gene is one of the strong driver events in glioma tumorigenesis and has provided fundamental insights into the disease mechanisms. This review elucidates the literature on the discovery of fusion genes, the development of detection techniques, and their clinical implementations. In conclusion, fusion genes are important diagnostic and predictive biomarkers for brain tumors.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73183118","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}
S. Subramaniyan, Yoganathan Kamaraj, Veenayohini Kumaresan, Muthulakshmi Kannaiyan, E. David, Babujanarthanam Ranganathan, Vijayanand Selvaraj, Agilan Balupillai
This study aimed to assess the apoptosis-inducing mechanism of zinc oxide nanoparticles (ZnO NPs) stabilized by Solanum xanthocarpum plant extract in human osteosarcoma MG63 cells. In the present study, we synthesized ZnO NPs from S. xanthocarpum extract and evaluated its anticancer mechanism on MG 63 cells. The synthesized ZnO NPs were characterized by ultraviolet spectroscopy, X-ray crystallography, transmission electron microscopy, energy dispersive X-ray, and Fourier-transform infrared spectroscopy analysis. The mean size of the synthesized ZnO NPs was 21.62 ± 7.45 nm and spherical in shape. The cytotoxicity of ZnO NPs on MG63 cells was determined by MTT assay. The Western blot analysis was carried out to examine the expression of apoptotic and autophagy-related proteins in MG63 cells. The findings of the study reveal that ZnO NPs treatment showed concentration-dependent cytotoxicity, increased lipid peroxidation, decreased antioxidant activity, increased reactive oxygen species generation, and increased DNA damage. In addition, ZnO NPs treatment increased the expression of apoptotic members such as p53, Bax, caspase-3, -8, and -9 while downregulating Bcl-2 expression in MG63 cells. Furthermore, ZnO NPs treatment suppressed the P13K/AKT/mTOR signaling pathway and increased the expression of LC3 and beclin-1 in MG63 cells. The present study demonstrated that ZnO NPs induced apoptosis and autophagy in MG63 cells through modifying apoptotic and autophagy-related proteins.
{"title":"Green synthesized zinc oxide nanoparticles induce apoptosis by suppressing PI3K/Akt/mTOR signaling pathway in osteosarcoma MG63 cells","authors":"S. Subramaniyan, Yoganathan Kamaraj, Veenayohini Kumaresan, Muthulakshmi Kannaiyan, E. David, Babujanarthanam Ranganathan, Vijayanand Selvaraj, Agilan Balupillai","doi":"10.36922/gtm.v1i1.34","DOIUrl":"https://doi.org/10.36922/gtm.v1i1.34","url":null,"abstract":"This study aimed to assess the apoptosis-inducing mechanism of zinc oxide nanoparticles (ZnO NPs) stabilized by Solanum xanthocarpum plant extract in human osteosarcoma MG63 cells. In the present study, we synthesized ZnO NPs from S. xanthocarpum extract and evaluated its anticancer mechanism on MG 63 cells. The synthesized ZnO NPs were characterized by ultraviolet spectroscopy, X-ray crystallography, transmission electron microscopy, energy dispersive X-ray, and Fourier-transform infrared spectroscopy analysis. The mean size of the synthesized ZnO NPs was 21.62 ± 7.45 nm and spherical in shape. The cytotoxicity of ZnO NPs on MG63 cells was determined by MTT assay. The Western blot analysis was carried out to examine the expression of apoptotic and autophagy-related proteins in MG63 cells. The findings of the study reveal that ZnO NPs treatment showed concentration-dependent cytotoxicity, increased lipid peroxidation, decreased antioxidant activity, increased reactive oxygen species generation, and increased DNA damage. In addition, ZnO NPs treatment increased the expression of apoptotic members such as p53, Bax, caspase-3, -8, and -9 while downregulating Bcl-2 expression in MG63 cells. Furthermore, ZnO NPs treatment suppressed the P13K/AKT/mTOR signaling pathway and increased the expression of LC3 and beclin-1 in MG63 cells. The present study demonstrated that ZnO NPs induced apoptosis and autophagy in MG63 cells through modifying apoptotic and autophagy-related proteins.","PeriodicalId":73176,"journal":{"name":"Global translational medicine","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85158425","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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