The oxidative damages are well-recognized factors in the pathogenesis of colorectal cancer (CRC). Increased levels of reactive oxygen species (ROS) can lead to oxidative DNA damage, which, if unrepaired, can be an underlying cause of cancerogenic transformation. To defend against these threats, cells have developed a range of defense mechanisms. One of the most important protection mechanisms is DNA repair systems, both nuclear and mitochondrial. Sirt3 is a mitochondrial protein involved in regulating NEIL1, NEIL2, MUTYH, APE1, and LIG3 proteins, which are involved in DNA repair, including mitochondrial repair through mtBER (mitochondrial Base Excision Repair). In this work, we show that NEIL1, NEIL2, MUTYH, APE1, and LIG3 are regulated by Sirt3 through deacetylation, and moreover, Sirt3 is directly involved in physical interaction with MUTYH, NEIL1, and APE1, which indicates the controlling role of Sirt3 over the mtBER mechanism. Also, if the cells deprived of Sirt3 are exposed to oxidative stress, altered levels of those proteins can be observed, which supports the theory of the regulatory role of Sirt3. Finally, to fully confirm the role of Sirt3 in DNA repair, we examined its role in apoptosis and found the impact of this protein on cell survival rate. Using the knowledge obtained in the course of conducted experiments, we postulate consideration of Sirt3 as a target in the rising vulnerability of cancer cells during therapy and therefore increasing the effectiveness of cancer treatment.
{"title":"Sirt3 Regulates Response to Oxidative Stress by Interacting with BER Proteins in Colorectal Cancer","authors":"J. Kabziński, A. Walczak, I. Majsterek","doi":"10.1155/2022/7299555","DOIUrl":"https://doi.org/10.1155/2022/7299555","url":null,"abstract":"The oxidative damages are well-recognized factors in the pathogenesis of colorectal cancer (CRC). Increased levels of reactive oxygen species (ROS) can lead to oxidative DNA damage, which, if unrepaired, can be an underlying cause of cancerogenic transformation. To defend against these threats, cells have developed a range of defense mechanisms. One of the most important protection mechanisms is DNA repair systems, both nuclear and mitochondrial. Sirt3 is a mitochondrial protein involved in regulating NEIL1, NEIL2, MUTYH, APE1, and LIG3 proteins, which are involved in DNA repair, including mitochondrial repair through mtBER (mitochondrial Base Excision Repair). In this work, we show that NEIL1, NEIL2, MUTYH, APE1, and LIG3 are regulated by Sirt3 through deacetylation, and moreover, Sirt3 is directly involved in physical interaction with MUTYH, NEIL1, and APE1, which indicates the controlling role of Sirt3 over the mtBER mechanism. Also, if the cells deprived of Sirt3 are exposed to oxidative stress, altered levels of those proteins can be observed, which supports the theory of the regulatory role of Sirt3. Finally, to fully confirm the role of Sirt3 in DNA repair, we examined its role in apoptosis and found the impact of this protein on cell survival rate. Using the knowledge obtained in the course of conducted experiments, we postulate consideration of Sirt3 as a target in the rising vulnerability of cancer cells during therapy and therefore increasing the effectiveness of cancer treatment.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45935219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Yang, Wu Zhang, Hua-jun Lu, Jinlong Liu, Yu Xia, S. Liao, Xiaohui Li, Xiaoshen Zhang, X. Fan, Chaojie Wang
Background Marfan syndrome (MFS) is a connective tissue disease involving multiple systems, with thoracic aortic aneurysm (TAA) as the most common life-threatening manifestation. Method A pedigree with TAA was investigated, and peripheral venous blood was extracted from six family members. After whole exome sequencing (WES) and chromosomal microarray analysis (CMA) in these individuals, bioinformatics and inheritance analyses were performed. Result WES revealed a novel, small, 0.76 Mb microdeletion in 15q21.1, which cosegregated with the disease phenotype in the family and led to the haploinsufficiency of the fibrillin 1 (FBN1) gene, which is associated with MFS. This small copy number variant (CNV) was confirmed by CMA. Conclusion Our study expands the phenotypic spectrum of the pathogenic CNV associated with MFS, thereby facilitating clinical genetic diagnosis and future genetic counseling for this family.
{"title":"Identification of a Novel 15q21.1 Microdeletion in a Family with Marfan Syndrome","authors":"R. Yang, Wu Zhang, Hua-jun Lu, Jinlong Liu, Yu Xia, S. Liao, Xiaohui Li, Xiaoshen Zhang, X. Fan, Chaojie Wang","doi":"10.1155/2022/3556302","DOIUrl":"https://doi.org/10.1155/2022/3556302","url":null,"abstract":"Background Marfan syndrome (MFS) is a connective tissue disease involving multiple systems, with thoracic aortic aneurysm (TAA) as the most common life-threatening manifestation. Method A pedigree with TAA was investigated, and peripheral venous blood was extracted from six family members. After whole exome sequencing (WES) and chromosomal microarray analysis (CMA) in these individuals, bioinformatics and inheritance analyses were performed. Result WES revealed a novel, small, 0.76 Mb microdeletion in 15q21.1, which cosegregated with the disease phenotype in the family and led to the haploinsufficiency of the fibrillin 1 (FBN1) gene, which is associated with MFS. This small copy number variant (CNV) was confirmed by CMA. Conclusion Our study expands the phenotypic spectrum of the pathogenic CNV associated with MFS, thereby facilitating clinical genetic diagnosis and future genetic counseling for this family.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47912772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maricela Aceves-Ramírez, Y. Valle, Fidel Casillas-Muñoz, Diana Emilia Martínez-Fernández, Brenda Parra-Reyna, Víctor Arturo López-Moreno, H. E. Flores-Salinas, Emmanuel Valdés-Alvarado, J. Muñóz-Valle, Texali C Garcia-Garduño, J. Padilla-Gutiérrez
Apolipoprotein B (APOB) is associated with the development of atherosclerosis and consequently in the acute coronary syndrome (ACS) physiopathology. Single number variants (SNVs) in apolipoprotein B gene (APOB) influence over the susceptibility for this syndrome. The aim of this study was to determine the impact of the rs1469513, rs673548, rs676210, and rs1042034 SNVs and serum levels of APOB in the risk of ACS in a population from western Mexico. We included 300 patients in the group of cases (ACSG) and 300 individuals in the control group (CG). APOB levels were evaluated by immunonephelometry, and SNVs were genotyped with TaqMan probes. We found significant allelic and genotypic differences between groups for rs673548 and rs676210 (OR = 1.33, p=0.030, OR = 2.69, p < 0.001) and rs1042034 (OR = 0.50, p=0.037) SNVs. We found a risk haplotype TAGT (OR: 2.14, IC 1.50–3.04, p < 0.001). Our findings support a significant risk association between rs673548 and rs676210 variants for ACS; meanwhile, rs1042034 could be considered protective factor in a western Mexican population. Also, in this population, haplotype TAGT may confer 2.14 times a higher risk. APOB serum levels were compared by genotype variants in both groups without any significant statistical difference.
{"title":"Analysis of the APOB Gene and Apolipoprotein B Serum Levels in a Mexican Population with Acute Coronary Syndrome: Association with the Single Nucleotide Variants rs1469513, rs673548, rs676210, and rs1042034","authors":"Maricela Aceves-Ramírez, Y. Valle, Fidel Casillas-Muñoz, Diana Emilia Martínez-Fernández, Brenda Parra-Reyna, Víctor Arturo López-Moreno, H. E. Flores-Salinas, Emmanuel Valdés-Alvarado, J. Muñóz-Valle, Texali C Garcia-Garduño, J. Padilla-Gutiérrez","doi":"10.1155/2022/4901090","DOIUrl":"https://doi.org/10.1155/2022/4901090","url":null,"abstract":"Apolipoprotein B (APOB) is associated with the development of atherosclerosis and consequently in the acute coronary syndrome (ACS) physiopathology. Single number variants (SNVs) in apolipoprotein B gene (APOB) influence over the susceptibility for this syndrome. The aim of this study was to determine the impact of the rs1469513, rs673548, rs676210, and rs1042034 SNVs and serum levels of APOB in the risk of ACS in a population from western Mexico. We included 300 patients in the group of cases (ACSG) and 300 individuals in the control group (CG). APOB levels were evaluated by immunonephelometry, and SNVs were genotyped with TaqMan probes. We found significant allelic and genotypic differences between groups for rs673548 and rs676210 (OR = 1.33, p=0.030, OR = 2.69, p < 0.001) and rs1042034 (OR = 0.50, p=0.037) SNVs. We found a risk haplotype TAGT (OR: 2.14, IC 1.50–3.04, p < 0.001). Our findings support a significant risk association between rs673548 and rs676210 variants for ACS; meanwhile, rs1042034 could be considered protective factor in a western Mexican population. Also, in this population, haplotype TAGT may confer 2.14 times a higher risk. APOB serum levels were compared by genotype variants in both groups without any significant statistical difference.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45294890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
X-chromosome inactivation (XCI) is the form of dosage compensation in mammalian female cells to balance X-linked gene expression levels of the two sexes. Many diseases are related to XCI due to inactivation escape and skewing, and the symptoms and severity of these diseases also largely depend on the status of XCI. They can be divided into 3 types: X-linked diseases, diseases that are affected by XCI escape, and X-chromosome aneuploidy. Here, we review representative diseases in terms of their definition, symptoms, and XCI's role in the pathogenesis of these diseases.
{"title":"X-Chromosome Inactivation and Related Diseases","authors":"Zhuo Sun, Jinbo Fan, Yang Wang","doi":"10.1155/2022/1391807","DOIUrl":"https://doi.org/10.1155/2022/1391807","url":null,"abstract":"X-chromosome inactivation (XCI) is the form of dosage compensation in mammalian female cells to balance X-linked gene expression levels of the two sexes. Many diseases are related to XCI due to inactivation escape and skewing, and the symptoms and severity of these diseases also largely depend on the status of XCI. They can be divided into 3 types: X-linked diseases, diseases that are affected by XCI escape, and X-chromosome aneuploidy. Here, we review representative diseases in terms of their definition, symptoms, and XCI's role in the pathogenesis of these diseases.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41953978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background As a part of a healthy lifestyle, exercise has been proven to be beneficial for the treatment of diseases and the prognosis of patients. Based on this, our research focuses on the impact of exercise on human health. Methods To study and analyze the samples in the GSE18966 gene expression profile, we first performed an analysis on the differential expressed genes (DEGs) through GEO2R, and then the DEGs enrichment in Gene Ontology functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways through the Database for Annotation, Visualization and Integrated Discovery database was conducted. Then, we delved into the gene set enrichment in KEGG through gene set enrichment analysis. After that, we achieved the construction of the protein-protein interaction (PPI) network of DEGs based on the Search Tool for the Retrieval of Interacting Genes online database, and the hub genes were screened and identified. Results We identified 433 upregulated DEGs and 186 downregulated DEGs from the samples before and after exercise in GSE18966. Through analysis, it was found that these DEGs-enriched pathways, such as the VEGF signaling pathway, the Wnt signaling pathway, and the insulin signaling pathway, were all involved in the regulation of various diseases. Then, GSEA analysis revealed that glycosaminoglycan biosynthesis chondroitin sulfate, type II diabetes mellitus, and basal cell carcinoma were related with exercise samples. The effects of these pathways on various diseases could be improved through exercise. Finally, 3 upregulated hub genes (VEGFA, POMC, and NRAS) and 3 downregulated hub genes (HRAS, NCOR1, and CAV1) were identified through the PPI network. Conclusions The bioinformatic analysis of samples before and after exercise provides key pathways and genes related to exercise to regulate various diseases, which confirms that exercise has an important influence on the treatment of many diseases.
{"title":"The Systematic Analysis of Exercise Mechanism in Human Diseases","authors":"Lei Pu, Peng Sun","doi":"10.1155/2022/8555020","DOIUrl":"https://doi.org/10.1155/2022/8555020","url":null,"abstract":"Background As a part of a healthy lifestyle, exercise has been proven to be beneficial for the treatment of diseases and the prognosis of patients. Based on this, our research focuses on the impact of exercise on human health. Methods To study and analyze the samples in the GSE18966 gene expression profile, we first performed an analysis on the differential expressed genes (DEGs) through GEO2R, and then the DEGs enrichment in Gene Ontology functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways through the Database for Annotation, Visualization and Integrated Discovery database was conducted. Then, we delved into the gene set enrichment in KEGG through gene set enrichment analysis. After that, we achieved the construction of the protein-protein interaction (PPI) network of DEGs based on the Search Tool for the Retrieval of Interacting Genes online database, and the hub genes were screened and identified. Results We identified 433 upregulated DEGs and 186 downregulated DEGs from the samples before and after exercise in GSE18966. Through analysis, it was found that these DEGs-enriched pathways, such as the VEGF signaling pathway, the Wnt signaling pathway, and the insulin signaling pathway, were all involved in the regulation of various diseases. Then, GSEA analysis revealed that glycosaminoglycan biosynthesis chondroitin sulfate, type II diabetes mellitus, and basal cell carcinoma were related with exercise samples. The effects of these pathways on various diseases could be improved through exercise. Finally, 3 upregulated hub genes (VEGFA, POMC, and NRAS) and 3 downregulated hub genes (HRAS, NCOR1, and CAV1) were identified through the PPI network. Conclusions The bioinformatic analysis of samples before and after exercise provides key pathways and genes related to exercise to regulate various diseases, which confirms that exercise has an important influence on the treatment of many diseases.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49312137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective Asthma is defined as a heterogeneous disease that is usually characterized by chronic airway inflammation. Long noncoding RNAs play important roles in various biological processes including inflammation. To know more about the relationships between lncRNAs and asthma, we sought to the role of LINC00847 in peripheral blood mononuclear cells (PBMCs) of children with asthma exacerbation or asthma remission. Methods Microarray analysis was performed on GSE143192 and GSE165934 datasets to screen differentially expressed lncRNAs (DElncRNAs) in human PBMCs between asthma patients and normal controls. LINC00847 was selected from DElncRNAs in human PBMCs between asthma patients and normal controls for further investigation. The expression levels of LINC00847 were quantified in PBMCs collected from 54 children with asthma exacerbation, 54 children with asthma remission, and 54 healthy children by real-time qPCR. The forced expiratory volume in the first second in percent predicted values (FEV1%), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), and peak expiratory flow rate (PEF%) were tested for evaluation of lung function. The concentration of immunoglobulin E (IgE) and eosinophil count was examined. The serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17A were determined by the ELISA method. Results The expression level of LINC00847 in PBMCs of asthma exacerbation children was remarkably higher than that in PBMCs of asthma remission children and healthy children (p < 0.001); the expression level of LINC00847 in PBMCs of asthma remission children was notably higher than that in PBMCs of healthy children (p < 0.001). Pearson correlation analysis revealed that the expression levels of LINC00847 in PBMCs of asthma children were negatively correlated with FEV1% (r = −0.489), FEV1/FVC (r = −0.436), PEF% (r = −0.626), and IFN-γ level (r = −0.614) of asthma children, but positively correlated with IgE concentration (r = 0.680), eosinophil count (r = 0.780), IL-4 (r = 0.524), and IL-17A (r = 0.622) levels. When LINC00847 expression was used to distinguish asthma exacerbation from asthma remission, a 0.871 AUC (95% CI: 0.805–0.936) was yielded with sensitivity of 79.63% and specificity of 77.78%. Conclusion The study demonstrates that increased LINC00847 expression may be associated with the development and progression of asthma, possibly serving as a novel biomarker for predicting asthma exacerbation from asthma remission.
{"title":"Expression of LINC00847 in Peripheral Blood Mononuclear Cells of Children with Asthma and Its Prediction between Asthma Exacerbation and Remission","authors":"Jiaying Hu, Zhike Wang, Suzhen Han, Kai Chen","doi":"10.1155/2022/5678257","DOIUrl":"https://doi.org/10.1155/2022/5678257","url":null,"abstract":"Objective Asthma is defined as a heterogeneous disease that is usually characterized by chronic airway inflammation. Long noncoding RNAs play important roles in various biological processes including inflammation. To know more about the relationships between lncRNAs and asthma, we sought to the role of LINC00847 in peripheral blood mononuclear cells (PBMCs) of children with asthma exacerbation or asthma remission. Methods Microarray analysis was performed on GSE143192 and GSE165934 datasets to screen differentially expressed lncRNAs (DElncRNAs) in human PBMCs between asthma patients and normal controls. LINC00847 was selected from DElncRNAs in human PBMCs between asthma patients and normal controls for further investigation. The expression levels of LINC00847 were quantified in PBMCs collected from 54 children with asthma exacerbation, 54 children with asthma remission, and 54 healthy children by real-time qPCR. The forced expiratory volume in the first second in percent predicted values (FEV1%), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), and peak expiratory flow rate (PEF%) were tested for evaluation of lung function. The concentration of immunoglobulin E (IgE) and eosinophil count was examined. The serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), and IL-17A were determined by the ELISA method. Results The expression level of LINC00847 in PBMCs of asthma exacerbation children was remarkably higher than that in PBMCs of asthma remission children and healthy children (p < 0.001); the expression level of LINC00847 in PBMCs of asthma remission children was notably higher than that in PBMCs of healthy children (p < 0.001). Pearson correlation analysis revealed that the expression levels of LINC00847 in PBMCs of asthma children were negatively correlated with FEV1% (r = −0.489), FEV1/FVC (r = −0.436), PEF% (r = −0.626), and IFN-γ level (r = −0.614) of asthma children, but positively correlated with IgE concentration (r = 0.680), eosinophil count (r = 0.780), IL-4 (r = 0.524), and IL-17A (r = 0.622) levels. When LINC00847 expression was used to distinguish asthma exacerbation from asthma remission, a 0.871 AUC (95% CI: 0.805–0.936) was yielded with sensitivity of 79.63% and specificity of 77.78%. Conclusion The study demonstrates that increased LINC00847 expression may be associated with the development and progression of asthma, possibly serving as a novel biomarker for predicting asthma exacerbation from asthma remission.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2022 1","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41446387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Wang, Huajing Zheng, Hui He, Shuying Meng, Yatian Han, Zhenping Su, H. Yan, Yanan Zhang
Background Endometrial cancer (EC) is a common tumor of the genital tract that affects the female reproductive system but with only limited treatment options. We aimed to discover new prognostic biomarkers for EC. Methods We used mRNA-seq data to detect differentially expressed genes (DEGs) between EC and control tissues. Detailed clinicopathological information was collected, and changes in the mRNA and protein levels of hub DEGs were analyzed in EC. Copy number variation (CNV) was also evaluated for its association with the pathogenesis of EC. Gene set enrichment analysis (GSEA) was conducted to enrich significant pathways driven by the hub genes. Cox regression analysis was used to select variables to create a nomogram. The nomogram was calibrated by applying the concordance index (C-index), and net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). Results Differential expression analysis identified 24 DEGs as potential risk factors for EC. Survival analysis revealed that TPX2 expression was related to worsening overall survival in patients with advanced EC. A high CNV was associated with the overexpression of TPX2; this suggested that modifications in the cell-cycle pathway might be crucial in the advancement of EC. Moreover, an individualized nomogram was developed for TPX2 incorporating clinical factors; this was also evaluated for its ability to predict EC. Calibration and DCA analyses confirmed the robustness and clinical usefulness of the nomogram. Conclusion We offer novel insights into the pathogenesis and molecular mechanisms of EC. The overexpression of TPX2 was related to a poorer prognosis and could serve as a biomarker for predicting prognostic outcomes in EC patients.
{"title":"TPX2 Serves as a Cancer Susceptibility Gene and Is Closely Associated with the Poor Prognosis of Endometrial Cancer","authors":"Jun Wang, Huajing Zheng, Hui He, Shuying Meng, Yatian Han, Zhenping Su, H. Yan, Yanan Zhang","doi":"10.1155/2022/5401106","DOIUrl":"https://doi.org/10.1155/2022/5401106","url":null,"abstract":"Background Endometrial cancer (EC) is a common tumor of the genital tract that affects the female reproductive system but with only limited treatment options. We aimed to discover new prognostic biomarkers for EC. Methods We used mRNA-seq data to detect differentially expressed genes (DEGs) between EC and control tissues. Detailed clinicopathological information was collected, and changes in the mRNA and protein levels of hub DEGs were analyzed in EC. Copy number variation (CNV) was also evaluated for its association with the pathogenesis of EC. Gene set enrichment analysis (GSEA) was conducted to enrich significant pathways driven by the hub genes. Cox regression analysis was used to select variables to create a nomogram. The nomogram was calibrated by applying the concordance index (C-index), and net benefits of the nomogram at different threshold probabilities were quantified using decision curve analysis (DCA). Results Differential expression analysis identified 24 DEGs as potential risk factors for EC. Survival analysis revealed that TPX2 expression was related to worsening overall survival in patients with advanced EC. A high CNV was associated with the overexpression of TPX2; this suggested that modifications in the cell-cycle pathway might be crucial in the advancement of EC. Moreover, an individualized nomogram was developed for TPX2 incorporating clinical factors; this was also evaluated for its ability to predict EC. Calibration and DCA analyses confirmed the robustness and clinical usefulness of the nomogram. Conclusion We offer novel insights into the pathogenesis and molecular mechanisms of EC. The overexpression of TPX2 was related to a poorer prognosis and could serve as a biomarker for predicting prognostic outcomes in EC patients.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42038076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Anjum, A. Nadeem, M. Javed, H. I. Ahmad, A. Riaz, W. Shehzad, Jahanzaib Azhar, Muhammad Fahad Bhutta
Transition nuclear proteins (TNPs), the principal proteins identified in the condensing spermatids chromatin, have been found to play a key role in histone displacement and chromatin condensation during mammalian spermatogenesis. One such gene belonging to the TNP family called TNP1 gene is abundantly expressed in the regulation of spermatogenesis, and its sequence is remarkably well conserved among mammals. Genomic analysis, by sequencing and computational approach, was used to identify the novel polymorphisms and to evaluate the molecular regulation of TNP1 gene expression in Sahiwal cattle breeding bulls. DNA samples were sequenced to identify novel single nucleotide polymorphisms (SNPs) in the TNP1 gene. Modern computational tools were used to predict putative transcription factor binding in the TNP1 promoter and CpG islands in the TNP1 promoter region. In the TNP1 gene, four SNPs, three TATA boxes, and one CAAT box were identified. One CAAT box was discovered at 89 bp upstream of start site ATG. The computational analyses indicated that the polymorphisms inside the promoter sequence results in an added HNF-1 transcription factor binding site. In contrast, the other variations may remove the naturally occurring SRF transcription factor binding site. The CpG islands in the TNP1 promoter region were predicted to be absent by the MethPrimer program before and after SNP site mutations. These findings pave the way for more research into the TNP1 gene's promoter activity and the links between these SNPs and reproductive attributes in the Sahiwal breeding bulls.
{"title":"Genomic and Computational Analysis of Novel SNPs in TNP1 Gene Promoter Region of Bos indicus Breeding Bulls","authors":"K. Anjum, A. Nadeem, M. Javed, H. I. Ahmad, A. Riaz, W. Shehzad, Jahanzaib Azhar, Muhammad Fahad Bhutta","doi":"10.1155/2022/9452234","DOIUrl":"https://doi.org/10.1155/2022/9452234","url":null,"abstract":"Transition nuclear proteins (TNPs), the principal proteins identified in the condensing spermatids chromatin, have been found to play a key role in histone displacement and chromatin condensation during mammalian spermatogenesis. One such gene belonging to the TNP family called TNP1 gene is abundantly expressed in the regulation of spermatogenesis, and its sequence is remarkably well conserved among mammals. Genomic analysis, by sequencing and computational approach, was used to identify the novel polymorphisms and to evaluate the molecular regulation of TNP1 gene expression in Sahiwal cattle breeding bulls. DNA samples were sequenced to identify novel single nucleotide polymorphisms (SNPs) in the TNP1 gene. Modern computational tools were used to predict putative transcription factor binding in the TNP1 promoter and CpG islands in the TNP1 promoter region. In the TNP1 gene, four SNPs, three TATA boxes, and one CAAT box were identified. One CAAT box was discovered at 89 bp upstream of start site ATG. The computational analyses indicated that the polymorphisms inside the promoter sequence results in an added HNF-1 transcription factor binding site. In contrast, the other variations may remove the naturally occurring SRF transcription factor binding site. The CpG islands in the TNP1 promoter region were predicted to be absent by the MethPrimer program before and after SNP site mutations. These findings pave the way for more research into the TNP1 gene's promoter activity and the links between these SNPs and reproductive attributes in the Sahiwal breeding bulls.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49207694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective The increase of hip fractures is related to the aging of the population, which has caused a huge medical burden in many countries. Hip replacement has been approved as a highly successful surgical intervention for the patients with hip fractures. Different anesthesia choices in the surgical intervention are associated with the prognosis of patients. This study focused on investigating the application of ultrasound-guided combined lumbar plexus-sciatic nerve block in elderly patients with hip fractures. Methods In this retrospective study, 62 elderly patients received combined spinal-epidural anesthesia and 58 elderly patients underwent ultrasound-guided combined lumbar plexus-sciatic nerve block during the surgery. Hemodynamic monitoring including pulse oxygen saturation (SpO2), heart rate and blood pressure, the assessment of pain intensity using Visual Analogue Scale (VAS), cognitive function assessment through Montreal Cognitive Assessment (MoCA) and biomarkers consisting of serum levels of neuron specific-enolase (NSE), S100 beta protein (S100-β), and amyloid beta protein (Aβ), as well as immune function by interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were detected in this study. Furthermore, length of hospital stay (LOS) and adverse reactions including hematoma, hypotension, nausea, and vomit were analyzed. Results The findings indicated that comparing with the patients receiving combined spinal-epidural anesthesia, those undergoing ultrasound-guided combined lumbar plexus-sciatic nerve block showed significantly lower level of heart rate, higher level of SpO2, and lower level of diastolic pressure and systolic pressure at 5 minutes and 30 minutes after anesthesia and after surgery (P < 0.05), indicated obviously lower VAS score at 12, 24, and 48 hours after surgery (P < 0.05), and revealed higher MoCA score at 12 days after surgery (P < 0.05). A significantly higher level of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP was revealed in the two groups receiving different anesthesia methods at 10 days after surgery compared with that before surgery (P < 0.05). However, the patients receiving ultrasound-guided combined lumbar plexus-sciatic nerve block had obviously lower expression of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP compared with the group accepting combined spinal-epidural anesthesia (P < 0.05). The two groups indicated no significant difference in incidence of hypotension and vomit, etc. (P < 0.05), but showed remarkable difference referring to total incidence of adverse reactions and LOS (P < 0.05). Conclusion The application of ultrasound-guided combined lumbar plexus-sciatic nerve block in hip replacement contributes to the stability of hemodynamics and alleviation of postoperative pain intensity. It can reduce cognitive and immune impairment of the elderly patients with hip fractures.
目的髋部骨折的增加与人口老龄化有关，人口老龄化在许多国家造成了巨大的医疗负担。髋关节置换术已被批准为髋部骨折患者的一种非常成功的手术干预。手术干预中麻醉选择的不同与患者的预后有关。本研究主要探讨超声引导下腰丛-坐骨神经联合阻滞在老年髋部骨折患者中的应用。方法回顾性分析62例老年患者行脊髓-硬膜外联合麻醉，58例老年患者行超声引导下腰丛-坐骨神经联合阻滞术。血流动力学监测包括脉搏血氧饱和度(SpO2)、心率和血压，视觉模拟量表(VAS)评估疼痛强度，蒙特利尔认知评估(MoCA)评估认知功能，血清神经元特异性烯醇化酶(NSE)、S100 β蛋白(S100-β)和β淀粉样蛋白(Aβ)水平，以及白细胞介素-6 (IL-6)、白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α)的免疫功能。高敏c反应蛋白(hs-CRP)。此外，还分析了住院时间(LOS)和包括血肿、低血压、恶心和呕吐在内的不良反应。结果超声引导腰丛-坐骨神经联合阻滞患者麻醉后5 min、30 min及术后舒张压、收缩压明显低于脊髓硬膜外联合麻醉患者(P < 0.05)，术后12、24、48 h VAS评分明显低于脊髓硬膜外联合麻醉患者(P < 0.05);术后12 d MoCA评分较高(P < 0.05)。两组患者术后10 d NSE、S100β、Aβ、IL-6、IL-1β、TNF-α、hs-CRP水平均显著高于术前(P < 0.05)。超声引导下腰丛-坐骨神经联合阻滞组患者NSE、S100β、Aβ、IL-6、IL-1β、TNF-α、hs-CRP表达明显低于脊髓-硬膜外联合麻醉组(P < 0.05)。两组患者在低血压、呕吐等方面的发生率差异无统计学意义(P < 0.05)，但在总不良反应发生率和LOS方面差异有统计学意义(P < 0.05)。结论超声引导腰丛-坐骨神经联合阻滞在髋关节置换术中的应用有助于稳定血流动力学，减轻术后疼痛强度。可减轻老年髋部骨折患者的认知和免疫功能损害。
{"title":"Reduced Concentrations of NSE, S100β, Aβ, and Proinflammatory Cytokines in Elderly Patients Receiving Ultrasound-Guided Combined Lumbar Plexus-Sciatic Nerve Block during Hip Replacement","authors":"Yi Zhang, Liya Jiang, Yang Han","doi":"10.1155/2022/1384609","DOIUrl":"https://doi.org/10.1155/2022/1384609","url":null,"abstract":"Objective The increase of hip fractures is related to the aging of the population, which has caused a huge medical burden in many countries. Hip replacement has been approved as a highly successful surgical intervention for the patients with hip fractures. Different anesthesia choices in the surgical intervention are associated with the prognosis of patients. This study focused on investigating the application of ultrasound-guided combined lumbar plexus-sciatic nerve block in elderly patients with hip fractures. Methods In this retrospective study, 62 elderly patients received combined spinal-epidural anesthesia and 58 elderly patients underwent ultrasound-guided combined lumbar plexus-sciatic nerve block during the surgery. Hemodynamic monitoring including pulse oxygen saturation (SpO2), heart rate and blood pressure, the assessment of pain intensity using Visual Analogue Scale (VAS), cognitive function assessment through Montreal Cognitive Assessment (MoCA) and biomarkers consisting of serum levels of neuron specific-enolase (NSE), S100 beta protein (S100-β), and amyloid beta protein (Aβ), as well as immune function by interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were detected in this study. Furthermore, length of hospital stay (LOS) and adverse reactions including hematoma, hypotension, nausea, and vomit were analyzed. Results The findings indicated that comparing with the patients receiving combined spinal-epidural anesthesia, those undergoing ultrasound-guided combined lumbar plexus-sciatic nerve block showed significantly lower level of heart rate, higher level of SpO2, and lower level of diastolic pressure and systolic pressure at 5 minutes and 30 minutes after anesthesia and after surgery (P < 0.05), indicated obviously lower VAS score at 12, 24, and 48 hours after surgery (P < 0.05), and revealed higher MoCA score at 12 days after surgery (P < 0.05). A significantly higher level of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP was revealed in the two groups receiving different anesthesia methods at 10 days after surgery compared with that before surgery (P < 0.05). However, the patients receiving ultrasound-guided combined lumbar plexus-sciatic nerve block had obviously lower expression of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP compared with the group accepting combined spinal-epidural anesthesia (P < 0.05). The two groups indicated no significant difference in incidence of hypotension and vomit, etc. (P < 0.05), but showed remarkable difference referring to total incidence of adverse reactions and LOS (P < 0.05). Conclusion The application of ultrasound-guided combined lumbar plexus-sciatic nerve block in hip replacement contributes to the stability of hemodynamics and alleviation of postoperative pain intensity. It can reduce cognitive and immune impairment of the elderly patients with hip fractures.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42719335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug delivery systems can be engineered to enhance the localization of therapeutics in specific tissues in response to externally applied stimuli and/or local environmental changes. In recent decades, efforts to improve drug delivery techniques at both nano- and macroscale have led to a new era of therapeutic efficacy. Such technological advancements resulted in improved drug delivery systems regularly entering the clinical setting. However, these delivery innovations are unfortunately not always readily applied to newly developed technologies. One of these new and exciting technologies that has been overlooked by drug delivery scientists is prime editing. Prime editing is a novel genome editing technology that exhibits the plug-and-play capability of CRISPR/Cas9 editors while avoiding double-strand DNA breaks throughout the entire process. This article focuses on describing the potential advantages and disadvantages of selecting nanomedicine technologies along with prime editing capabilities for the delivery of cargo.
{"title":"How Various Drug Delivery Methods Could Aid in the Translation of Genome Prime Editing Technologies","authors":"E. Ivanova","doi":"10.1155/2022/7301825","DOIUrl":"https://doi.org/10.1155/2022/7301825","url":null,"abstract":"Drug delivery systems can be engineered to enhance the localization of therapeutics in specific tissues in response to externally applied stimuli and/or local environmental changes. In recent decades, efforts to improve drug delivery techniques at both nano- and macroscale have led to a new era of therapeutic efficacy. Such technological advancements resulted in improved drug delivery systems regularly entering the clinical setting. However, these delivery innovations are unfortunately not always readily applied to newly developed technologies. One of these new and exciting technologies that has been overlooked by drug delivery scientists is prime editing. Prime editing is a novel genome editing technology that exhibits the plug-and-play capability of CRISPR/Cas9 editors while avoiding double-strand DNA breaks throughout the entire process. This article focuses on describing the potential advantages and disadvantages of selecting nanomedicine technologies along with prime editing capabilities for the delivery of cargo.","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47581386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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