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1
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Thirunavukkarasu MK, Ramesh P, Karuppasamy R, Veerappapillai S. Transcriptome profiling and metabolic pathway analysis towards reliable biomarker discovery in early-stage lung cancer. J Appl Genet 2025; 66:115-126. [PMID: 38443694 DOI: 10.1007/s13353-024-00847-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 03/07/2024]
Abstract
Earlier diagnosis of lung cancer is crucial for reducing mortality and morbidity in high-risk patients. Liquid biopsy is a critical technique for detecting the cancer earlier and tracking the treatment outcomes. However, noninvasive biomarkers are desperately needed due to the lack of therapeutic sensitivity and early-stage diagnosis. Therefore, we have utilized transcriptomic profiling of early-stage lung cancer patients to discover promising biomarkers and their associated metabolic functions. Initially, PCA highlights the diversity level of gene expression in three stages of lung cancer samples. We have identified two major clusters consisting of highly variant genes among the three stages. Further, a total of 7742, 6611, and 643 genes were identified as DGE for stages I-III respectively. Topological analysis of the protein-protein interaction network resulted in seven candidate biomarkers such as JUN, LYN, PTK2, UBC, HSP90AA1, TP53, and UBB cumulatively for the three stages of lung cancers. Gene enrichment and KEGG pathway analyses aid in the comprehension of pathway mechanisms and regulation of identified hub genes in lung cancer. Importantly, the medial survival rates up to ~ 70 months were identified for hub genes during the Kaplan-Meier survival analysis. Moreover, the hub genes displayed the significance of risk factors during gene expression analysis using TIMER2.0 analysis. Therefore, we have reason that these biomarkers may serve as a prospective targeting candidate with higher treatment efficacy in early-stage lung cancer patients.
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Affiliation(s)
| | - Priyanka Ramesh
- Bioinformatics Core, College of Agriculture, Agriculture Research and Graduate Education, Purdue University, West Lafayette, IN, 47907, USA
| | - Ramanathan Karuppasamy
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India
| | - Shanthi Veerappapillai
- Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India.
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Zou E, Xu X, Chen L. Potential of plasma biomarkers for heart failure prediction, management, and prognosis: A multiomics perspective. Heart Fail Rev 2025; 30:55-67. [PMID: 39377997 DOI: 10.1007/s10741-024-10443-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/25/2024] [Indexed: 12/15/2024]
Abstract
Heart failure (HF) remains a major global health challenge, and more effective and comprehensive plasma biomarkers are needed to effectively treat HF patients. Multiomics studies have shown that DNA fragments, noncoding RNAs, proteins, and metabolites may be potential plasma biomarkers for HF. However, comprehensive reviews that focus on research on plasma biomarkers for HF from an omics perspective are lacking. This review summarizes the applications of various omics approaches in the exploration of biomarkers related to the risk assessment, diagnosis, subtype classification, medical management, and prognosis prediction of HF. Moreover, as heart transplantation and left ventricular assistant device (LVAD) implantation are terminal therapies for end-stage HF patients, this review also discusses the role of cell-free DNA as a biomarker for cardiac transplant rejection and omics studies of plasma biomarkers in patients who respond to LVAD therapy. Our findings suggest that future omics research on HF biomarkers should employ integrated multiomics methods and expand the sample size to increase the robustness of the results and that the identified biomarkers should be further validated in large cohorts.
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Affiliation(s)
- Erhou Zou
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinjie Xu
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liang Chen
- State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Han S, Xu Q, Du Y, Tang C, Cui H, Xia X, Zheng R, Sun Y, Shang H. Single-cell spatial transcriptomics in cardiovascular development, disease, and medicine. Genes Dis 2024; 11:101163. [PMID: 39224111 PMCID: PMC11367031 DOI: 10.1016/j.gendis.2023.101163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 10/17/2023] [Accepted: 10/29/2023] [Indexed: 09/04/2024] Open
Abstract
Cardiovascular diseases (CVDs) impose a significant burden worldwide. Despite the elucidation of the etiology and underlying molecular mechanisms of CVDs by numerous studies and recent discovery of effective drugs, their morbidity, disability, and mortality are still high. Therefore, precise risk stratification and effective targeted therapies for CVDs are warranted. Recent improvements in single-cell RNA sequencing and spatial transcriptomics have improved our understanding of the mechanisms and cells involved in cardiovascular phylogeny and CVDs. Single-cell RNA sequencing can facilitate the study of the human heart at remarkably high resolution and cellular and molecular heterogeneity. However, this technique does not provide spatial information, which is essential for understanding homeostasis and disease. Spatial transcriptomics can elucidate intracellular interactions, transcription factor distribution, cell spatial localization, and molecular profiles of mRNA and identify cell populations causing the disease and their underlying mechanisms, including cell crosstalk. Herein, we introduce the main methods of RNA-seq and spatial transcriptomics analysis and highlight the latest advances in cardiovascular research. We conclude that single-cell RNA sequencing interprets disease progression in multiple dimensions, levels, perspectives, and dynamics by combining spatial and temporal characterization of the clinical phenome with multidisciplinary techniques such as spatial transcriptomics. This aligns with the dynamic evolution of CVDs (e.g., "angina-myocardial infarction-heart failure" in coronary artery disease). The study of pathways for disease onset and mechanisms (e.g., age, sex, comorbidities) in different patient subgroups should improve disease diagnosis and risk stratification. This can facilitate precise individualized treatment of CVDs.
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Affiliation(s)
- Songjie Han
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Qianqian Xu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Yawen Du
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Chuwei Tang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Herong Cui
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Xiaofeng Xia
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Rui Zheng
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Yang Sun
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Hongcai Shang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
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Xie Z, Xie H, Xie C, Yang S, Feng Y, Su Z, Tang T, Zhang B, Yang J, Wang Y, Huang L, Zhu H, Cao J, Jiang R, Li T, Lu W. A combined analysis of bulk RNA-seq and scRNA-seq was performed to investigate the molecular mechanisms associated with the occurrence of myocardial infarction. BMC Genomics 2024; 25:921. [PMID: 39363266 PMCID: PMC11448016 DOI: 10.1186/s12864-024-10813-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 09/19/2024] [Indexed: 10/05/2024] Open
Abstract
BACKGROUND Myocardial infarction (MI) induces complex transcriptional changes across diverse cardiac cell types. Single-cell RNA sequencing (scRNA-seq) provides an unparalleled ability to discern cellular diversity during infarction, yet the veracity of these discoveries necessitates confirmation. This investigation sought to elucidate MI mechanisms by integrating scRNA-seq and bulk RNA-seq data. METHODS Publicly available scRNA-seq (GSE136088) and bulk RNA-seq (GSE153485) data from mice MI models were analyzed. Cell types were annotated, and differential expression analysis conducted. Bulk RNA-seq underwent quality control, principal component analysis, and differential expression analysis. RESULTS In scRNA-seq data, the comparison between MI and sham groups unveiled a reduction in endothelial cell populations, but macrophages and monocytes increased. Within fibroblast subgroups, three distinct categories were discerned, with two exhibiting upregulation in MI. Notably, endothelial cells exhibited an elevated expression of genes associated with apoptosis and ferroptosis. In bulk RNA-seq analysis, distinct patterns emerged when comparing MI and sham groups. Specifically, six genes linked to endothelial ferroptosis exhibited heightened expression in MI group, thereby corroborating the scRNA-seq findings. Moreover, the examination of isolated cardiac macrophages from mice MI model revealed increased expression of Spp1, Col1a2, Col3a1, Ctsd, and Lgals3 compared to sham group, thus substantiating the dysregulation of macrophage apoptosis-related proteins following MI. CONCLUSION MI altered the transcriptomic landscapes of cardiac cells with increased expression of apoptotic genes. Moreover, the upregulation of macrophage apoptosis marker was confirmed within MI models. The presence of endothelial cell depletion and ferroptosis in MI has been demonstrated.
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Affiliation(s)
- Zheng Xie
- Department of General Practice, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Huicong Xie
- Department of General Practice, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Chen Xie
- Department of General Practice, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Saichao Yang
- Department of General Practice, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Yun Feng
- Department of General Practice, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Zhaohai Su
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Tao Tang
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Bilong Zhang
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Jiangyong Yang
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Yueting Wang
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Ling Huang
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Hengqing Zhu
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Jun Cao
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Rengui Jiang
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China
| | - Tian Li
- School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China
| | - Weiling Lu
- Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital (Gannan Medical University Affiliated Municipal Hospital), 49 Dagong Road, Ganzhou, 341000, China.
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Yao J, Zhou Y, Yao Z, Meng Y, Yu W, Yang X, Zhou D, Yang X, Zhou Y. A novel machine learning-derived four-gene signature predicts STEMI and post-STEMI heart failure. BIOMOLECULES & BIOMEDICINE 2024; 24:423-433. [PMID: 37715537 PMCID: PMC10950350 DOI: 10.17305/bb.2023.9629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/05/2023] [Accepted: 09/15/2023] [Indexed: 09/17/2023]
Abstract
High mortality and morbidity rates associated with ST-elevation myocardial infarction (STEMI) and post-STEMI heart failure (HF) necessitate proper risk stratification for coronary artery disease (CAD). A prediction model that combines specificity and convenience is highly required. This study aimed to design a monocyte-based gene assay for predicting STEMI and post-STEMI HF. A total of 1,956 monocyte expression profiles and corresponding clinical data were integrated from multiple sources. Meta-results were obtained through the weighted gene co-expression network analysis (WGCNA) and differential analysis to identify characteristic genes for STEMI. Machine learning models based on the decision tree (DT), support vector machine (SVM), and random forest (RF) algorithms were trained and validated. Five genes overlapped and were subjected to the model proposal. The discriminative performance of the DT model outperformed the other two methods. The established four-gene panel (HLA-J, CFP, STX11, and NFYC) could discriminate STEMI and HF with an area under the curve (AUC) of 0.86 or above. In the gene set enrichment analysis (GSEA), several cardiac pathogenesis pathways and cardiovascular disorder signatures showed statistically significant, concordant differences between subjects with high and low expression levels of the four-gene panel, affirming the validity of the established model. In conclusion, we have developed and validated a model that offers the hope for accurately predicting the risk of STEMI and HF, leading to optimal risk stratification and personalized management of CAD, thereby improving individual outcomes.
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Affiliation(s)
- Jialu Yao
- Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Institute for Hypertension of Soochow University, Jiangsu Engineering Laboratory of Novel Functional Polymeric Materials of Soochow University, Suzhou, Jiangsu Province, China
| | - Yujia Zhou
- Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
- Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province, China
| | - Zhichao Yao
- Department of Vascular Surgery, Gusu School of Nanjing Medical University, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital (HQ), Suzhou, Jiangsu Province, China
| | - Ye Meng
- Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
- Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province, China
| | - Wangjianfei Yu
- Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
- Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province, China
| | - Xinyu Yang
- Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
- Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province, China
| | - Dayong Zhou
- Department of Vascular Surgery, Gusu School of Nanjing Medical University, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital (HQ), Suzhou, Jiangsu Province, China
| | - Xiaoqin Yang
- Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Institute for Hypertension of Soochow University, Jiangsu Engineering Laboratory of Novel Functional Polymeric Materials of Soochow University, Suzhou, Jiangsu Province, China
- Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China
- Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province, China
| | - Yafeng Zhou
- Department of Cardiology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Institute for Hypertension of Soochow University, Jiangsu Engineering Laboratory of Novel Functional Polymeric Materials of Soochow University, Suzhou, Jiangsu Province, China
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Zhu D, Wang C, Zhou Y, Che H, Wang R, Cheng L, Rao C, Zhong Q, Li Z, Duan Y, He K. The Associations of Two Novel Inflammation Biomarkers, SIRI and SII, with Mortality Risk in Patients with Chronic Heart Failure. J Inflamm Res 2024; 17:1255-1264. [PMID: 38415264 PMCID: PMC10898362 DOI: 10.2147/jir.s451190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 02/16/2024] [Indexed: 02/29/2024] Open
Abstract
Background The associations of two novel inflammation biomarkers, systemic inflammation response index (SIRI) and systemic immune inflammation index (SII), with mortality risk in patients with chronic heart failure (CHF) are not well-characterized. Methods This retrospective cohort study included patients with CHF in two medical centers of Chinese People's Liberation Army General Hospital, Beijing, China. The outcomes of this study included in-hospital mortality and long-term mortality. Associations of SIRI and SII with mortality were assessed using multivariable regressions and receiver operating characteristic (ROC) analyses. Results A total of 6232 patients with CHF were included in the present study. We documented 97 cases of in-hospital mortality and 1738 cases of long-term mortality during an average 5.01-year follow-up. Compared with patients in the lowest quartile of SIRI, those in the highest quartile exhibited 134% higher risk of in-hospital mortality (adjusted odds ratio, 2.34; 95% confidence interval [CI], 1.16-4.72) and 45% higher risk of long-term mortality (adjusted hazard ratio, 1.45; 95% CI, 1.25-1.67). Compared with patients in the lowest quartile of SII, those in the highest quartile exhibited 27% higher risk of long-term mortality (adjusted hazard ratio, 1.27; 95% CI, 1.11-1.46). In ROC analyses, SIRI showed better prognostic discrimination than C-reactive protein (area under the curve: 69.39 vs 60.91, P = 0.01, for in-hospital mortality; 61.82 vs 58.67, P = 0.03, for 3-year mortality), whereas SII showed similar prognostic value with C-reactive protein. Conclusion SIRI and SII were significantly associated with mortality risk in patients with CHF. SIRI may provide better prognostic discrimination than C-reactive protein.
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Affiliation(s)
- Di Zhu
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
- Graduate School of PLA General Hospital, Beijing, 100853, People's Republic of China
| | - Chi Wang
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
| | - You Zhou
- School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China
| | - Hebin Che
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
| | - Ruiqing Wang
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
- Graduate School of PLA General Hospital, Beijing, 100853, People's Republic of China
| | - Liting Cheng
- School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China
| | - Chongyou Rao
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
- Graduate School of PLA General Hospital, Beijing, 100853, People's Republic of China
| | - Qin Zhong
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
| | - Zongren Li
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
| | - Yongjie Duan
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
- Graduate School of PLA General Hospital, Beijing, 100853, People's Republic of China
| | - Kunlun He
- Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China
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Sansonetti M, Al Soodi B, Thum T, Jung M. Macrophage-based therapeutic approaches for cardiovascular diseases. Basic Res Cardiol 2024; 119:1-33. [PMID: 38170281 PMCID: PMC10837257 DOI: 10.1007/s00395-023-01027-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 12/08/2023] [Accepted: 12/08/2023] [Indexed: 01/05/2024]
Abstract
Despite the advances in treatment options, cardiovascular disease (CVDs) remains the leading cause of death over the world. Chronic inflammatory response and irreversible fibrosis are the main underlying pathophysiological causes of progression of CVDs. In recent decades, cardiac macrophages have been recognized as main regulatory players in the development of these complex pathophysiological conditions. Numerous approaches aimed at macrophages have been devised, leading to novel prospects for therapeutic interventions. Our review covers the advancements in macrophage-centric treatment plans for various pathologic conditions and examines the potential consequences and obstacles of employing macrophage-targeted techniques in cardiac diseases.
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Affiliation(s)
- Marida Sansonetti
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625, Hannover, Germany
| | - Bashar Al Soodi
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625, Hannover, Germany
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625, Hannover, Germany.
- REBIRTH-Center for Translational Regenerative Medicine, Hannover Medical School, 30625, Hannover, Germany.
- Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 30625, Hannover, Germany.
| | - Mira Jung
- Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625, Hannover, Germany.
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Zhou X, Chen Y, Zhang Z, Miao J, Chen G, Qian Z. Identification of differentially expressed genes, signaling pathways and immune infiltration in postmenopausal osteoporosis by integrated bioinformatics analysis. Heliyon 2024; 10:e23794. [PMID: 38205281 PMCID: PMC10777010 DOI: 10.1016/j.heliyon.2023.e23794] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 12/12/2023] [Accepted: 12/13/2023] [Indexed: 01/12/2024] Open
Abstract
Background Postmenopausal osteoporosis is a systemic metabolic disorder typified by an imbalance in bone turnover, where bone resorption supersedes bone formation. This imbalance primarily arises from a decline in bone mass induced by estrogen deficiency, and an elevated risk of fractures resulting from degradation of bone microstructure. Despite recognizing these changes, the precise causative factors and potential molecular pathways remain elusive. In this study, we aimed to identify differentially expressed genes (DEGs), associated pathways, and the role of immune infiltration in osteoporosis, leveraging an integrated bioinformatics approach to shed light on potential underlying molecular mechanisms. Methods We retrieved the expression profiles of GSE230665 from the Gene Expression Omnibus database, comprising 15 femur samples, including 12 postmenopausal osteoporosis samples and 3 normal controls. From the aggregated microarray datasets, we derived differentially expressed genes (DEGs) for further bioinformatics analysis. We used WGCNA, analyzed DEGs, PPI, and conducted GO analysis to identify pivotal genes. We then used the CIBERSORT method to explore the degree of immune cell infiltration within femur specimens affected by postmenopausal osteoporosis. To probe into the relationship between pivotal genes and infiltrating immune cells, we conducted correlation analysis. Results We identified a total of 12,204 DEGs. Among these, 12,157 were up-regulated, and 47 were down-regulated. GO and KEGG pathway analyses indicated that these DEGs predominantly targeted cellular protein localization activity and associated signaling pathways. The protein-protein interaction network highlighted four central hub-genes: RPL31, RPL34, EEF1G, and BPTF. Principal component analysis indicated a positive correlation between the expression of these genes and resting NK cells (as per CIBERSORT). In contrast, the expression of RPL31, RPL34, and EEF1G showed a negative correlation with T cells (gamma delta per CIBERSORT). Conclusions Immune infiltration plays a role in the development of osteoporosis.
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Affiliation(s)
- Xiaoli Zhou
- Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China
- Department of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China
| | - Yang Chen
- Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China
| | - Zepei Zhang
- Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China
| | - Jun Miao
- Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China
| | - Guangdong Chen
- Department of Orthopaedics, Cangzhou Central Hospital, Hebei 061001, China
| | - Zhiyong Qian
- Department of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China
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Chen J, Xu F, Mo X, Cheng Y, Wang L, Yang H, Li J, Zhang S, Zhang S, Li N, Cao Y. Exploratory Study of Differentially Expressed Genes of Peripheral Blood Monocytes in Patients with Carotid Atherosclerosis. Comb Chem High Throughput Screen 2024; 27:1344-1357. [PMID: 37608666 DOI: 10.2174/1386207326666230822122045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 06/15/2023] [Accepted: 07/13/2023] [Indexed: 08/24/2023]
Abstract
BACKGROUND The abundance of circulating monocytes is closely associated with the development of atherosclerosis in humans. OBJECTIVE This study aimed to further research into diagnostic biomarkers and targeted treatment of carotid atherosclerosis (CAS). METHODS We performed transcriptomics analysis through weighted gene co-expression network analysis (WGCNA) of monocytes from patients in public databases with and without CAS. Differentially expressed genes (DEGs) were screened by R package limma. Diagnostic molecules were derived by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms. NetworkAnalyst, miRWalk, and Star- Base databases assisted in the construction of diagnostic molecule regulatory networks. The Drug- Bank database predicted drugs targeting the diagnostic molecules. RT-PCR tested expression profiles. RESULTS From 14,369 hub genes and 61 DEGs, six differentially expressed monocyte-related hub genes were significantly associated with immune cells, immune responses, monocytes, and lipid metabolism. LASSO and SVM-RFE yielded five genes for CAS prediction. RT-PCR of these genes showed HMGB1 was upregulated, and CCL3, CCL3L1, CCL4, and DUSP1 were downregulated in CAS versus controls. Then, we constructed and visualized the regulatory networks of 9 transcription factors (TFs), which significantly related to 5 diagnostic molecules. About 11 miRNAs, 19 lncRNAs, and 39 edges centered on four diagnostic molecules (CCL3, CCL4, DUSP1, and HMGB1) were constructed and displayed. Eleven potential drugs were identified, including ibrutinib, CTI-01, roflumilast etc. Conclusion: A set of five biomarkers were identified for the diagnosis of CAS and for the study of potential therapeutic targets.
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Affiliation(s)
- Juhai Chen
- Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
- Internal Medicine Department Three Ward, Guiyang Public Health Clinical Center, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Fengyan Xu
- Comprehensive Ward, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Xiangang Mo
- Comprehensive Ward, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Yiju Cheng
- The Department of Respiratory and Critical Medicine, Guiyang Public Health Clinical Center, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Lan Wang
- Comprehensive Ward, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Hui Yang
- Comprehensive Ward, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Jiajing Li
- Comprehensive Ward, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Shiyue Zhang
- Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Shuping Zhang
- Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Nannan Li
- Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
| | - Yang Cao
- Guizhou Medical University, Guiyang, 550004, Guizhou Province, People's Republic of China
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10
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Zhan C, Tang T, Wu E, Zhang Y, He M, Wu R, Bi C, Wang J, Zhang Y, Shen B. From multi-omics approaches to personalized medicine in myocardial infarction. Front Cardiovasc Med 2023; 10:1250340. [PMID: 37965091 PMCID: PMC10642346 DOI: 10.3389/fcvm.2023.1250340] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 10/17/2023] [Indexed: 11/16/2023] Open
Abstract
Myocardial infarction (MI) is a prevalent cardiovascular disease characterized by myocardial necrosis resulting from coronary artery ischemia and hypoxia, which can lead to severe complications such as arrhythmia, cardiac rupture, heart failure, and sudden death. Despite being a research hotspot, the etiological mechanism of MI remains unclear. The emergence and widespread use of omics technologies, including genomics, transcriptomics, proteomics, metabolomics, and other omics, have provided new opportunities for exploring the molecular mechanism of MI and identifying a large number of disease biomarkers. However, a single-omics approach has limitations in understanding the complex biological pathways of diseases. The multi-omics approach can reveal the interaction network among molecules at various levels and overcome the limitations of the single-omics approaches. This review focuses on the omics studies of MI, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and other omics. The exploration extended into the domain of multi-omics integrative analysis, accompanied by a compilation of diverse online resources, databases, and tools conducive to these investigations. Additionally, we discussed the role and prospects of multi-omics approaches in personalized medicine, highlighting the potential for improving diagnosis, treatment, and prognosis of MI.
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Affiliation(s)
- Chaoying Zhan
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Tong Tang
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Erman Wu
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yuxin Zhang
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- KeyLaboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China
| | - Mengqiao He
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Rongrong Wu
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Cheng Bi
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- KeyLaboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China
| | - Jiao Wang
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yingbo Zhang
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- Tropical Crops Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou, China
| | - Bairong Shen
- Department of Cardiology and Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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11
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Schuurman AR, Butler JM, Michels EH, Otto NA, Brands X, Haak BW, Uhel F, Klarenbeek AM, Faber DR, Schomakers BV, van Weeghel M, de Vos AF, Scicluna BP, Houtkooper RH, Wiersinga WJ, van der Poll T. Inflammatory and glycolytic programs underpin a primed blood neutrophil state in patients with pneumonia. iScience 2023; 26:107181. [PMID: 37496676 PMCID: PMC10366455 DOI: 10.1016/j.isci.2023.107181] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 04/21/2023] [Accepted: 06/15/2023] [Indexed: 07/28/2023] Open
Abstract
Neutrophils are potent immune cells with key antimicrobial functions. Previous in vitro work has shown that neutrophil effector functions are mainly fueled by intracellular glycolysis. Little is known about the state of neutrophils still in the circulation in patients during infection. Here, we combined flow cytometry, stimulation assays, transcriptomics, and metabolomics to investigate the link between inflammatory and metabolic pathways in blood neutrophils of patients with community-acquired pneumonia. Patients' neutrophils, relative to neutrophils from age- and sex- matched controls, showed increased degranulation upon ex vivo stimulation, and portrayed distinct upregulation of inflammatory transcriptional programs. This neutrophil phenotype was accompanied by a high-energy state with increased intracellular ATP content, and transcriptomic and metabolic upregulation of glycolysis and glycogenolysis. One month after hospital admission, these metabolic and transcriptomic changes were largely normalized. These data elucidate the molecular programs that underpin a balanced, yet primed state of blood neutrophils during pneumonia.
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Affiliation(s)
- Alex R. Schuurman
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Joe M. Butler
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Erik H.A. Michels
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Natasja A. Otto
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Xanthe Brands
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Bastiaan W. Haak
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Fabrice Uhel
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Augustijn M. Klarenbeek
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Daniël R. Faber
- BovenIJ Hospital, Statenjachtstraat 1, 1034 CS Amsterdam, the Netherlands
| | - Bauke V. Schomakers
- Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics, Amsterdam Gastroenterology Endocrinology Metabolism, 1105 AZ Amsterdam, the Netherlands
- Core Facility Metabolomics, Amsterdam UMC, 1105 AZ Amsterdam, the Netherlands
| | - Michel van Weeghel
- Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Departments of Clinical Chemistry and Pediatrics, Amsterdam Gastroenterology Endocrinology Metabolism, 1105 AZ Amsterdam, the Netherlands
- Core Facility Metabolomics, Amsterdam UMC, 1105 AZ Amsterdam, the Netherlands
| | - Alex F. de Vos
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Brendon P. Scicluna
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
- Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei Hospital, University of Malta, Msida, Malta
| | - Riekelt H. Houtkooper
- Amsterdam Gastroenterology Endocrinology and Metabolism Institute, 1105 AZ Amsterdam, the Netherlands
- Amsterdam Cardiovascular Sciences Institute, 1105 AZ Amsterdam, the Netherlands
| | - W. Joost Wiersinga
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
- Division of Infectious Diseases, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
| | - Tom van der Poll
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
- Division of Infectious Diseases, Amsterdam University Medical Centers - Location AMC, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
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12
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Li L, Ma Q, Wang M, Mou J, Han Y, Wang J, Ye J, Sun G. Single-cell transcriptome sequencing of macrophages in common cardiovascular diseases. J Leukoc Biol 2023; 113:139-148. [PMID: 36822177 DOI: 10.1093/jleuko/qiac014] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Indexed: 01/18/2023] Open
Abstract
Macrophages are strategically located throughout the body at key sites in the immune system. A key feature in atherosclerosis is the uptake and accumulation of lipoproteins by arterial macrophages, leading to the formation of foam cells. After myocardial infarction, macrophages derived from monocytes infiltrate the infarcted heart. Macrophages are also closely related to adverse remodeling after heart failure. An in-depth understanding of the functions and characteristics of macrophages is required to study heart health and pathophysiological processes; however, the heterogeneity and plasticity explained by the classic M1/M2 macrophage paradigm are too limited. Single-cell sequencing is a high-throughput sequencing technique that enables the sequencing of the genome or transcriptome of a single cell. It effectively complements the heterogeneity of gene expression in a single cell that is ignored by conventional sequencing and can give valuable insights into the development of complex diseases. In the present review, we summarize the available research on the application of single-cell transcriptome sequencing to study the changes in macrophages during common cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure. This article also discusses the contribution of this knowledge to understanding the pathogenesis, development, diagnosis, and treatment of heart diseases.
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Affiliation(s)
- Lanfang Li
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Malianwa Road, Haidian District, Beijing, China
| | - Qiuxiao Ma
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Xiyuan Playground, Haidian District, Beijing, China
| | - Min Wang
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Malianwa Road, Haidian District, Beijing, China
| | - Junyu Mou
- School of Pharmacy, Harbin University of Commerce, Xuehai Street, Songbei District, Harbin, China
| | - Yanwei Han
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Waihuan East Road, Panyu District, Guangzhou, China
| | - Jialu Wang
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Malianwa Road, Haidian District, Beijing, China
| | - Jingxue Ye
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Malianwa Road, Haidian District, Beijing, China
| | - Guibo Sun
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Malianwa Road, Haidian District, Beijing, China
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13
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Dai YC, Qiao D, Fang CY, Chen QQ, Que RY, Xiao TG, Zheng L, Wang LJ, Zhang YL. Single-cell RNA-sequencing combined with bulk RNA-sequencing analysis of peripheral blood reveals the characteristics and key immune cell genes of ulcerative colitis. World J Clin Cases 2022; 10:12116-12135. [PMID: 36483809 PMCID: PMC9724533 DOI: 10.12998/wjcc.v10.i33.12116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/27/2022] [Accepted: 10/27/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response. Single-cell RNA sequencing (scRNA-seq) can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine, analyze the characteristics of cells with the same phenotype, and provide new insights into the growth and development of intestinal organs, the clonal evolution of cells, and immune cell changes. These findings can provide new ideas for the diagnosis and treatment of intestinal diseases. AIM To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC. METHODS Using the Gene Expression Omnibus (GEO) database, we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing (RNA-seq) to reveal the core genes of UC. We then combined weighted gene correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis to reveal diagnostic markers of UC. RESULTS After processing the scRNA-seq data, we obtained data from approximately 24340 cells and identified 17 cell types. Through intercellular communication analysis, we selected monocyte marker genes as the candidate gene set for the prediction model. Construction of a WGCNA coexpression network identified RhoB, cathepsin D (CTSD) and zyxin (ZYX) as core genes. Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells. Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses, which are associated with many challenges in the diagnosis and treatment of UC. CONCLUSION Through scRNA-seq analysis, LASSO diagnostic model building and WGCNA, we identified RhoB, CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.
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Affiliation(s)
- Yan-Cheng Dai
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Dan Qiao
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Chen-Ye Fang
- Department of Gastroenterology, Traditional Chinese Medicine Hospital of Ningbo, Ningbo 315000, Zhejiang Province, China
| | - Qiu-Qin Chen
- Department of Pathology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Ren-Ye Que
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Tie-Gang Xiao
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Lie Zheng
- Department of Gastroenterology, Traditional Chinese Medicine Hospital of Xi’an 730000, Shaanxi Province, China
| | - Li-Juan Wang
- Experimental Education Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ya-Li Zhang
- Institute of Digestive Diseases, LongHua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
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14
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Xu Z, Lu D, Yuan J, Wang L, Wang J, Lei Z, Liu S, Wu J, Wang J, Huang L. Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R-Ankrd1-P53 Signaling Pathway. Int J Mol Sci 2022; 23:13161. [PMID: 36361958 PMCID: PMC9657855 DOI: 10.3390/ijms232113161] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 10/17/2022] [Accepted: 10/26/2022] [Indexed: 02/05/2023] Open
Abstract
Myocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosis and cardiac function. The AMI rat model was established by subcutaneous injection of Isoproterenol hydrochloride (ISO). Storax (0.1, 0.2, 0.4 g/kg) was administered by gavage once/d for 7 days. Electrocardiogram, echocardiography, hemodynamic and cardiac enzyme in AMI rats were measured. HE, Masson, immunofluorescence and TUNEL staining were used to observe the degree of pathological damage, fibrosis and cardiomyocyte apoptosis in myocardial tissue, respectively. Expression of AT1R, CARP and their downstream related apoptotic proteins were detected by WB. The results demonstrated that storax could significantly improve cardiac electrophysiology and function, decrease serum cardiac enzyme activity, reduce type I and III collagen contents to improve fibrosis and alleviate myocardial pathological damage and cardiomyocyte apoptosis. It also found that storax can significantly down-regulate expression of AT1R, Ankrd1, P53, P-p53 (ser 15), Bax and cleaved Caspase-3 and up-regulate expression of Mdm2 and Bcl-2. Taken together, these findings indicated that storax effectively protected cardiomyocytes against myocardial fibrosis and cardiac dysfunction by inhibiting the AT1R-Ankrd1-P53 signaling pathway.
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Affiliation(s)
- Zhuo Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Danni Lu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jianmei Yuan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Liying Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jiajun Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Ziqin Lei
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Si Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Junjie Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jian Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Lihua Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
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15
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Hwang N, Huh Y, Bu S, Seo KJ, Kwon SH, Kim JW, Yoon BK, Ahn HS, Fang S. Single-cell sequencing of PBMC characterizes the altered transcriptomic landscape of classical monocytes in BNT162b2-induced myocarditis. Front Immunol 2022; 13:979188. [PMID: 36225942 PMCID: PMC9549039 DOI: 10.3389/fimmu.2022.979188] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/08/2022] [Indexed: 11/13/2022] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dangerous threat to public health worldwide for the last few years, which led to the development of the novel mRNA vaccine (BNT162b2). However, BNT162b2 vaccination is known to be associated with myocarditis. Here, as an attempt to determine the pathogenesis of the disease and to develop biomarkers to determine whether subjects likely proceed to myocarditis after vaccination, we conducted a time series analysis of peripheral blood mononuclear cells of a patient with BNT162b2-induced myocarditis. Single-cell RNA sequence analysis identified monocytes as the cell clusters with the most dynamic changes. To identify distinct gene expression signatures, we compared monocytes of BNT162b2-induced myocarditis with monocytes under various conditions, including SARS-CoV-2 infection, BNT162b2 vaccination, and Kawasaki disease, a disease similar to myocarditis. Representative changes in the transcriptomic profile of classical monocytes include the upregulation of genes related to fatty acid metabolism and downregulation of transcription factor AP-1 activity. This study provides, for the first time, the importance of classical monocytes in the pathogenesis of myocarditis following BNT162b2 vaccination and presents the possibility that vaccination affects monocytes, further inducing their differentiation and infiltration into the heart.
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Affiliation(s)
- Nahee Hwang
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea
- Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - Yune Huh
- Department of Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Seonghyeon Bu
- Divison of Cardiology, Department of Internal medicine, The Catholic University of Korea, Uijeongbu St. Mary’s Hospital, Seoul, South Korea
- Catholic Research Institute for Intractable Cardiovascular Disease (CRID), College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Kyung Jin Seo
- Department of Hospital Pathology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Se Hwan Kwon
- Department of Radiology, Kyung Hee University Medical Center, Seoul, South Korea
| | - Jae-woo Kim
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea
- Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
| | - Bo Kyung Yoon
- Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Bo Kyung Yoon, ; Hyo-Suk Ahn, ; Sungsoon Fang,
| | - Hyo-Suk Ahn
- Divison of Cardiology, Department of Internal medicine, The Catholic University of Korea, Uijeongbu St. Mary’s Hospital, Seoul, South Korea
- Catholic Research Institute for Intractable Cardiovascular Disease (CRID), College of Medicine, The Catholic University of Korea, Seoul, South Korea
- *Correspondence: Bo Kyung Yoon, ; Hyo-Suk Ahn, ; Sungsoon Fang,
| | - Sungsoon Fang
- Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
- Severance Biomedical Science Institute, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Bo Kyung Yoon, ; Hyo-Suk Ahn, ; Sungsoon Fang,
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16
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Wu J, Fu YS, Lin K, Huang X, Chen YJ, Lai D, Kang N, Huang L, Weng CF. A narrative review: The pharmaceutical evolution of phenolic syringaldehyde. Biomed Pharmacother 2022; 153:113339. [PMID: 35780614 DOI: 10.1016/j.biopha.2022.113339] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/15/2022] [Accepted: 06/24/2022] [Indexed: 12/11/2022] Open
Abstract
To better understand the pharmacological characters of syringaldehyde (SA), which is a key-odorant compound of whisky and brandy, this review article is the first to compile the published literature for molecular docking that were subsequently validated by in vitro and in vivo assays to predict and develop insights into the medicinal properties of SA in terms of anti-oxidation, anti-inflammation, and anti-diabetes. The molecular docking displayed significantly binding affinity for SA towards tumor necrosis factor-α, interleukin-6, and antioxidant enzymes when inflammation from myocardial infarction and spinal cord ischemia. Moreover, SA nicely docked with dipeptidyl peptidase-IV, glucagon-like peptide 1 receptor, peroxisome proliferator-activated receptor, acetylcholine M2 receptor, and acetylcholinesterase in anti-diabetes investigations. These are associated with (1) an increase glucose utilization and insulin sensitivity to an anti-hyperglycemic effect; and (2) to potentiate intestinal contractility to abolish the α-amylase reaction when concurrently reducing retention time and glucose absorption of the intestinal tract to achieve a glucose-lowering effect. In silico screening of multi-targets concomitantly with preclinical tests could provide a potential exploration for new indications for drug discovery and development.
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Affiliation(s)
- Jingyi Wu
- Anatomy and Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Yaw-Syan Fu
- Anatomy and Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Kaihuang Lin
- Anatomy and Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Xin Huang
- Anatomy and Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Yi-Jing Chen
- Anatomy and Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Dong Lai
- Medical Research Center, the Second Affiliated Hospital of Xiamen Medical College, Xiamen 361021, Fujian, China.
| | - Ning Kang
- Department of Otorhinolaryngology, the Second Affiliated Hospital of Xiamen Medical College, Xiamen 361021, Fujian, China.
| | - Liyue Huang
- Anatomy and Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
| | - Ching-Feng Weng
- Anatomy and Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen 361023, Fujian, China.
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17
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Abstract
The immune system is fundamental to tissue homeostasis and is the first line of defense following infection, injury or disease. In the damaged heart, large numbers of immune cells are recruited to the site of injury. These cells play an integral part in both repair by scar formation and the initiation of tissue regeneration. They initially assume inflammatory phenotypes, releasing pro-inflammatory cytokines and removing dead and dying tissue, before entering a reparative stage, replacing dead muscle tissue with a non-contractile scar. In this Review, we present an overview of the innate and adaptive immune response to heart injury. We explore the kinetics of immune cell mobilization following cardiac injury and how the different innate and adaptive immune cells interact with one another and with the damaged tissue. We draw on key findings from regenerative models, providing insight into how to support a robust immune response permissible for cardiac regeneration. Finally, we consider how the latest technological developments can offer opportunities for a deeper and unbiased functional understanding of the immune response to heart disease, highlighting the importance of such knowledge as the basis for promoting regeneration following cardiac injury in human patients.
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Affiliation(s)
- Filipa C. Simões
- MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford,Oxford, OxfordshireOX3 9DS, UK
- Institute of Developmental and Regenerative Medicine, Old Road Campus, Oxford, OxfordshireOX3 7DQ, UK
| | - Paul R. Riley
- Institute of Developmental and Regenerative Medicine, Old Road Campus, Oxford, OxfordshireOX3 7DQ, UK
- Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OxfordshireOX1 3PT, UK
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18
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Diaz-Riera E, García-Arguinzonis M, López L, Garcia-Moll X, Badimon L, Padro T. Urinary Proteomic Signature in Acute Decompensated Heart Failure: Advances into Molecular Pathophysiology. Int J Mol Sci 2022; 23:2344. [PMID: 35216460 PMCID: PMC8875709 DOI: 10.3390/ijms23042344] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 02/17/2022] [Accepted: 02/18/2022] [Indexed: 11/16/2022] Open
Abstract
Acute decompensated heart failure (ADHF) is a life-threatening clinical syndrome involving multi-organ function deterioration. ADHF results from multifaceted, dysregulated pathways that remain poorly understood. Better characterization of proteins associated with heart failure decompensation is needed to gain understanding of the disease pathophysiology and support a more accurate disease phenotyping. In this study, we used an untargeted mass spectrometry (MS) proteomic approach to identify the differential urine protein signature in ADHF patients and examine its pathophysiological link to disease evolution. Urine samples were collected at hospital admission and compared with a group of healthy subjects by two-dimensional electrophoresis coupled to MALDI-TOF/TOF mass spectrometry. A differential pattern of 26 proteins (>1.5-fold change, p < 0.005), mostly of hepatic origin, was identified. The top four biological pathways (p < 0.0001; in silico analysis) were associated to the differential ADHF proteome including retinol metabolism and transport, immune response/inflammation, extracellular matrix organization, and platelet degranulation. Transthyretin (TTR) was the protein most widely represented among them. Quantitative analysis by ELISA of TTR and its binding protein, retinol-binding protein 4 (RBP4), validated the proteomic results. ROC analysis evidenced that combining RBP4 and TTR urine levels highly discriminated ADHF patients with renal dysfunction (AUC: 0.826, p < 0.001) and significantly predicted poor disease evolution over 18-month follow-up. In conclusion, the MS proteomic approach enabled identification of a specific urine protein signature in ADHF at hospitalization, highlighting changes in hepatic proteins such as TTR and RBP4.
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Affiliation(s)
- Elisa Diaz-Riera
- Cardiovascular-Program ICCC, Research Institute—Hospital Santa Creu i Sant Pau, IIB-Sant Pau, 08041 Barcelona, Spain; (E.D.-R.); (M.G.-A.); (L.B.)
- Faculty of Medicine, Universtitat de Barcelona, 08036 Barcelona, Spain
| | - Maísa García-Arguinzonis
- Cardiovascular-Program ICCC, Research Institute—Hospital Santa Creu i Sant Pau, IIB-Sant Pau, 08041 Barcelona, Spain; (E.D.-R.); (M.G.-A.); (L.B.)
| | - Laura López
- Cardiology Department, Hospital Santa Creu i Sant Pau, 08025 Barcelona, Spain; (L.L.); (X.G.-M.)
| | - Xavier Garcia-Moll
- Cardiology Department, Hospital Santa Creu i Sant Pau, 08025 Barcelona, Spain; (L.L.); (X.G.-M.)
- Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Lina Badimon
- Cardiovascular-Program ICCC, Research Institute—Hospital Santa Creu i Sant Pau, IIB-Sant Pau, 08041 Barcelona, Spain; (E.D.-R.); (M.G.-A.); (L.B.)
- Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain
- Cardiovascular Research Chair, UAB, 08025 Barcelona, Spain
| | - Teresa Padro
- Cardiovascular-Program ICCC, Research Institute—Hospital Santa Creu i Sant Pau, IIB-Sant Pau, 08041 Barcelona, Spain; (E.D.-R.); (M.G.-A.); (L.B.)
- Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Wu M, Wei B, Duan SL, Liu M, Ou-Yang DJ, Huang P, Chang S. Methylation-Driven Gene PLAU as a Potential Prognostic Marker for Differential Thyroid Carcinoma. Front Cell Dev Biol 2022; 10:819484. [PMID: 35141223 PMCID: PMC8818873 DOI: 10.3389/fcell.2022.819484] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 01/07/2022] [Indexed: 11/16/2022] Open
Abstract
Purpose: Aberrant DNA methylation plays a crucial role in the tumorigenesis of differentiated thyroid cancer (DTC); nevertheless, the factors leading to the local and regional recurrence of DTC are not well understood. This study aimed to establish the connection between DNA methylation-driven genes and the recurrence of DTC. Methods: RNA sequencing profiles and DNA methylation profiles of DTC were downloaded from The Cancer Genome Atlas (TCGA) database. Combined application of the methylmix R package and univariate Cox regression analyses were used to screen and distinguish prognosis-related methylation-driven genes. Multivariate Cox regression analyses were utilized to identify the target genes that were closely associated with the recurrence of DTC. Then, correlations between the expression levels of the target genes and the clinicopathological features were verified, as well as their potential biological functions. Results: A total of 168 Methylation-driven genes were differentially expressed in thyroid cancer, among which 10 genes (GSTO2, GSTM5, GSTM1, GPX7, FGF2, LIF, PLAU, BCL10, SHARPIN and TNFRSF1A) were identified as Hub genes. We selected PLAU for further analysis because PLAU was most strongly correlated with DTC recurrence and the DNA methylation levels of PLAU were closely associated with multiple clinicopathological features of DTC. PLAU was significantly upregulated in DTC, and patients with a high expression level of PLAU had a higher risk of recurrence (p < 0.05). Functional predictions suggested that PLAU-related genes were mainly involved in the regulation of immune-related signaling pathways. Moreover, the mRNA level of PLAU was found to be positively correlated with the cell markers of neutrophils and dendritic cells. In addition, we found that two DNA methylation sites (cg06829584, cg19399285) were associated with abnormal expression of PLAU in DTC. Conclusion: The methylation-driven gene PLAU is an independent risk factor for the recurrence of DTC and it functions as an oncogene through the regulation of immune-related signaling pathways, which offers new insight into the molecular mechanisms of thyroid cancer and provides new possibilities for individualized treatment of thyroid cancer patients.
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Affiliation(s)
- Min Wu
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Bo Wei
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Sai-Li Duan
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Mian Liu
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Deng-Jie Ou-Yang
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Peng Huang
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
- *Correspondence: Peng Huang,
| | - Shi Chang
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
- Clinical Research Center for Thyroid Disease in Hunan Province, Changsha, China
- Hunan Provincial Engineering Research Center for Thyroid and Related Diseases Treatment Technology, Changsha, China
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The Identification and Validation of Hub Genes Associated with Acute Myocardial Infarction Using Weighted Gene Co-Expression Network Analysis. J Cardiovasc Dev Dis 2022; 9:jcdd9010030. [PMID: 35050240 PMCID: PMC8778825 DOI: 10.3390/jcdd9010030] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/08/2022] [Accepted: 01/12/2022] [Indexed: 02/06/2023] Open
Abstract
Acute myocardial infarction (AMI), one of the most severe and fatal cardiovascular diseases, remains the main cause of mortality and morbidity worldwide. The objective of this study is to investigate the potential biomarkers for AMI based on bioinformatics analysis. A total of 2102 differentially expressed genes (DEGs) were screened out from the data obtained from the gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) explored the co-expression network of DEGs and determined the key module. The brown module was selected as the key one correlated with AMI. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses demonstrated that genes in the brown module were mainly enriched in ‘ribosomal subunit’ and ‘Ribosome’. Gene Set Enrichment Analysis revealed that ‘TNFA_SIGNALING_VIA_NFKB’ was remarkably enriched in AMI. Based on the protein–protein interaction network, ribosomal protein L9 (RPL9) and ribosomal protein L26 (RPL26) were identified as the hub genes. Additionally, the polymerase chain reaction (PCR) results indicated that the expression levels of RPL9 and RPL26 were both downregulated in AMI patients compared with controls, in accordance with the bioinformatics analysis. In summary, the identified DEGs, modules, pathways, and hub genes provide clues and shed light on the potential molecular mechanisms of AMI.
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