ABSTRACT
Background: Myocardial infarction (MI) is one of the leading threats to human health. N6-methyladenosine (m6A) modification, as a pivotal regulator of messenger RNA stability, protein expression, and cellular processes, exhibits important roles in the development of cardiac remodeling and cardiomyocyte contractile function. Methods: The expression levels of m6A regulators were analyzed using the GSE5406 database. We analyzed genome-wide association study data and single-cell sequencing data to confirm the functional importance of m6A regulators in MI. Three molecular subtypes with different clinical characteristics were established to tailor treatment strategies for patients with MI. We applied pathway analysis and differentially expressed gene (DEG) analysis to study the changes in gene expression and identified four common DEGs. Furthermore, we constructed the protein-protein interaction network and confirmed several hub genes in three clusters of MI. To lucubrate the potential functions, we performed a ClueGO analysis of these hub networks. Results: In this study, we identified that the levels of FTO, YTHDF3, ZC3H13, and WTAP were dramatically differently expressed in MI tissues compared with controls. Bioinformatics analysis showed that DEGs in MI were significantly related to modulating calcium signaling and chemokine signaling, and m6A regulators were related to regulating glucose measurement and elevated blood glucose levels. Furthermore, genome-wide association study data analysis showed that WTAP single-nucleotide polymorphism was significantly related to the progression of MI. In addition, single-cell sequencing found that WTAP is widely expressed in the heart tissues. Moreover, we conducted consensus clustering for MI in view of the dysregulated m6A regulators' expression in MI. According to the expression levels, we found MI patients could be clustered into three subtypes. Pathway analysis showed the DEGs among different clusters in MI were assigned to HIF-1, IL-17, MAPK, PI3K-Akt signaling pathways, etc. The module analysis detected several genes, including BAG2, BAG3, MMP2, etc. We also found that MI-related network was significantly related to positive and negative regulation of angiogenesis and response to heat. The hub networks in MI clusters were significantly related to antigen processing and ubiquitin-mediated proteolysis, RNA splicing, and stability, indicating that these processes may contribute to the development of MI. Conclusion: Collectively, our study could provide more information for understanding the roles of m6A in MI, which may provide a novel insight into identifying biomarkers for MI treatment and diagnosis.
ABSTRACT
Owing to the high mortality rates of heart failure (HF), a more detailed description of the HF becomes extremely urgent. Since the pathogenesis of HF remain elusive, a thorough identification of the genetic factors will provide novel insights into the molecular basis of this cardiac dysfunction. In our research, we performed publicly available transcriptome profiling datasets, including non-failure (NF), dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) hearts tissues. Through principal component analysis (PCA), gene differential expression analysis, gene set enrichment analysis (GSEA), and gene Set Variation Analysis (GSVA), we figured out the candidate genes noticeably altered in HF, the specific biomarkers of endothelial cell (EC) and cardiac fibrosis, then validated the differences of the inflammation-related cell adhesion molecules (CAMs), extracellular matrix (ECM) genes, and immune responses. Taken together, our results suggested the EC and fibroblast could be activated in response to HF. DCM and ICM had both commonality and specificity in the pathogenesis of HF. Higher inflammation in ICM might related to autocrine CCL3/CCL4-CCR5 interaction induced chemokine signaling activation. Furthermore, the activities of neutrophil and macrophage were higher in ICM than DCM. These findings identified features of the landscape of previously underestimated cellular, transcriptomic heterogeneity between ICM and DCM.
ABSTRACT
BACKGROUND: In spite of increasing knowledge of allelopathic rice as an efficient component involved in paddy weed management, relatively little is known about its reproduction in response to competing weeds. Reproduction allocation of individual allelopathic rice plants in relation to monoculture and mixed culture with competing barnyardgrass in a paddy field was studied, along with analyses of soil nutrients and microbial communities to understand the potential mechanism. RESULTS: At a 1:1 barnyardgrass and rice mixture proportion identified from a replacement series study, biomass, grain yield and major parameters of individual allelopathic rice plants at the mature stage were increased by competing barnyardgrass. There was no difference in allelopathic rice root-zone soil ammonium N and Olsen P between monoculture and mixed culture. However, mixed culture altered soil microbial biomass C and communities. When mixed with barnyardgrass, allelopathic rice root zone had an 87% increase in soil microbial biomass C. Phospholipid fatty acid (PLFA) profiling indicated that the signature lipid biomarkers of bacteria, actinobacteria and fungi were affected by mixed culture. Principal component analysis clearly identified differences in the composition of PLFA in different soil samples. CONCLUSION: Allelopathic rice specific changes in soil microbial communities may generate a positive feedback on its own growth and reproduction in the presence of competing barnyardgrass in a given paddy system.
