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BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.
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Perfilación de la Expresión Génica , Insuficiencia Cardíaca , Macrófagos , Análisis de la Célula Individual , Transcriptoma , Humanos , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Bases de Datos Genéticas , Microambiente Celular , Procesamiento Postranscripcional del ARN , Animales , Estudios de Casos y Controles , Regulación de la Expresión GénicaRESUMEN
INTRODUCTION: Preeclampsia is a pregnancy-specific disorder characterized by de novo development of hypertension and proteinuria over 20 weeks gestation that has been associated with the dysfunction of trophoblasts. Current evidence suggests that syncytin-1 plays an important role in the non-fusogenic biological activity of trophoblasts, except for specific fusogenic function. However, the underlying mechanism remains unclear. METHODS: The expression and location of syncytin-1 in normal and the late-onset preeclampsia placentas were detected by quantitative real-time PCR, western blotting and immunofluorescence. Morphological and apoptosis analysis were processed in placentas. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Real-time quantitative PCR and immunoblotting were used to calculate syncytin-1 levels in the trophoblast cells before and after syncytin-1 knockdown or overexpression. CCK-8 assay was used to detect the cell viability. TUNEL staining and immunoblotting were processed in trophoblast cells. Transwell assays and wound healing assays were utilize to assess the invasion and migration of trophoblastic cells. Conditional knockout of syncytin-a mouse model was conducted to present the change of placentas in vivo. The ex vivo extravillous explant culture model was used to explore the effect of syncytin-1 on EVT outgrowths. Western blotting was used to identify the key proteins of PI3K/Akt pathways and invasion-related proteins in trophoblast cells. RESULTS AND DISCUSSION: Here, reduced syncytin-1 was identified in the late-onset preeclampsia placentas. Reduced syncytin-1 may attenuates the EMT process by promoting apoptosis, inhibiting proliferation and invasion by suppressed PI3K/Akt pathway in trophoblast cells. Our findings provide novel insights into the non-fusogenic biological function of reduced syncytin-1 that may be involves in the pathogenesis of preeclampsia.
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Background: Cancer-associated fibroblasts (CAFs) represent the predominant stromal component within the tumour microenvironment (TME), exhibiting considerable heterogeneity and plasticity that significantly impact immune response and metabolic reprogramming within the TME, thereby influencing tumour progression. Consequently, investigating CAFs is of utmost importance. The objective of this study is to employ bibliometric analysis in order to evaluate the current state of research on CAFs and predict future areas of research and emerging trends. Methods: Conduct a comprehensive search for scholarly publications within the Web of Science Core Collection database, encompassing the time period from January 1, 2001, to December 31, 2022. Apply VOSviewer, CiteSpace, R software and Microsoft Excel for bibliometric analysis and visualisation. Results: This study involved a comprehensive analysis of 5,925 publications authored by 33,628 individuals affiliated with 4,978 institutions across 79 countries/regions. These publications were published in 908 journals, covering 14,495 keywords and 203,947 references. Notably, there was a significant increase in articles published between 2019 and 2022. China had the highest count of articles, while the United States emerged as the most frequently cited country. The primary research institutions in this field were Shanghai Jiao Tong University, Harvard University, and the University of Texas MD Anderson Cancer Center. Sotgia, Federica and Lisanti, Michael P from the University of Manchester, and Martinet, Wim from the University of Antwerp were the most prolific and highly cited authors. The journal Cancers had the highest number of publications, while Cancer Research was the most frequently cited journal. Molecular, biology, immunology, medicine and genetics were the main research disciplines in the field of CAFs. Key directions in CAFs research encompassed the study of transforming growth factor-ß, Fibroblast Activation Protein, breast cancer, as well as growth and metastasis. The findings from the analysis of keyword co-occurrence and literature co-citation have revealed several emerging hotspots and trends within the field of CAFs. These include STAT3, multidrug resistance, pancreatic ductal adenocarcinoma, pan-cancer analysis, preclinical evaluation, ionizing radiation, and gold nanoparticles. Conclusion: Targeting CAFs is anticipated to be a novel and effective strategy for cancer treatment. This study provides a comprehensive overview of the existing research on CAFs from 2001 to 2022, utilizing bibliometric analysis. The study identified the prominent areas of investigation and anticipated future research directions, with the aim of providing valuable insights and recommendations for future studies in the field of CAFs.