| INTRODUC TI ONCardiovascular diseases (CVD), including vascular remodelling diseases, are the leading cause of mortality among humans throughout the world. Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of many vascular remodelling diseases, including atherosclerosis, 1 hypertension 2 and vascular aneurysms. 3 The regulation of VSMC proliferation has been considered a key event due to its major implications for the prevention of pathological vascular conditions. 4 Non-coding RNAs (ncRNAs) form the dominant product of eukaryotic transcription, comprising over 73% of the human genome. 5 Circular RNAs (circRNAs) are a special novel type of endogenous ncRNAs, forming covalently closed-loop structures without 5′ caps Abstract Vascular smooth muscle cell (VSMC) proliferation is the pathological base of vascular remodelling diseases. Circular RNAs (circRNAs) are important regulators involved in various biological processes. However, the function of circRNAs in VSMC proliferation regulation remains largely unknown. This study was conducted to identify the key differentially expressed circRNAs (DEcircRNAs) and predict their functions in human aortic smooth muscle cell (HASMC) proliferation. To achieve this, DEcircRNAs between proliferative and quiescent HASMCs were detected using a microarray, followed by quantitative real-time RT-PCR validation. A DEcircRNA-miRNA-DEmRNA network was constructed, and functional annotation was performed using Gene Ontology (GO) and KEGG pathway analysis. The function of hsa_circ_0002579 in HASMC proliferation was analysed by Western blot. The functional annotation of the DEcircRNA-miRNA-DEmRNA network indicated that the four DEcircRNAs might play roles in the TGF-β receptor signalling pathway, Ras signalling pathway, AMPK signalling pathway and Wnt signalling pathway. Twenty-seven DEcircRNAs with coding potential were screened. Hsa_circ_0002579 might be a pro-proliferation factor of HASMC. Overall, our study identified the key DEcircRNAs between proliferative and quiescent HASMCs, which might provide new important clues for exploring the functions of circRNAs in vascular remodelling diseases. K E Y W O R D S circular RNAs, coding potential, HASMCs, microRNA sponge, proliferation | 4763 CHEN Et al.
Nuclear factor erythroid 2 like 2 (Nrf2) functions as a neuroprotective agent in Parkinson's disease (PD). This study aimed to investigate the key long non-coding RNAs (lncRNAs) correlated with Nrf2, which might provide valuable information for the exploration of pathogenesis of PD. The lncRNA and mRNA expression profiling of substantia nigra and corpus striatum of Nrf2 (-/-) mice model was obtained from microarray analysis. The animal experiments conducted for this study were approved by the ethics committee of Hebei Medical University. Bioinformatics analyses were conducted, including differentially expressed lncRNAs/mRNA (differentially expressed lncRNA, DEL/differentially expressed mRNA, DEM) identification, DEL-DEM coexpression network construction, and biological functions prediction. Quantitative real-time polymerase chain reaction (qRT-PCR) was subjected to validate abnormally expressed DELs and DEMs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice model. A total of 48 DELs (37 down-regulated and 11 up-regulated) were identified both in Nrf2 (-/-) substantia nigra and corpus striatum; 96 DEMs and 643 DEMs were identified in the substantia nigra and corpus striatum, respectively. DEL-DEM coexpressed network was constructed. LncRNA AK076880, AK036620, and AK020330 had high connectivity with DEMs both in the substantia nigra and corpus striatum. These DEMs were significantly enriched in signaling pathways such as the calcium signaling pathway, Huntington's disease, Alzheimer's disease, mitogen-activated protein kinase (MAPK) signaling pathway, and the Wnt signaling pathway. Generally, qRT-PCR validation results of selected DEMs and DELs were consistent with microarray data. The dysregulated DELs and DEMs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice were identified. Our results might provide useful information for further exploring the pathogenesis mechanism of PD.
The current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment.
The current diagnostic biomarkers of acute myocardial infarction (AMI), troponins, lack specificity and exist as false positives in other non-cardiac diseases. Previous studies revealed that cuproptosis, ferroptosis, and immune infiltration are all involved in the development of AMI. We hypothesize that combining the analysis of cuproptosis, ferroptosis, and immune infiltration in AMI will help identify more precise diagnostic biomarkers. The results showed that a total of 19 cuproptosis- and ferroptosis-related genes (CFRGs) were differentially expressed between the healthy and AMI groups. Functional enrichment analysis showed that the differential CFRGs were mostly enriched in biological processes related to oxidative stress and the inflammatory response. The immune infiltration status analyzed by ssGSEA found elevated levels of macrophages, neutrophils, and CCR in AMI. Then, we screened 6 immune-related CFRGs (CXCL2, DDIT3, DUSP1, CDKN1A, TLR4, STAT3) to construct a nomogram for predicting AMI and validated it in the GSE109048 dataset. Moreover, we also identified 5 pivotal miRNAs and 10 candidate drugs that target the 6 feature genes. Finally, RT-qPCR analysis verified that all 6 feature genes were upregulated in both animals and patients. In conclusion, our study reveals the significance of immune-related CFRGs in AMI and provides new insights for AMI diagnosis and treatment.
Objective: Crotonylation of histones is a recently discovered type of post-translational modification that can regulate gene expression. However, the function of crotonylation on nonhistone proteins in vascular smooth muscle cells (VSMC) is unclear. In this study, we aim to use modification and proteomic analysis to find the cellular characteristic of crotonylated nonhistone proteins for deep research.Methods: In this article, we performed modification and proteomic analysis of VSMCs before and after platelet-derived growth factor-BB (PDGF-BB) stimulation. The crotonylated pan-antibody was used to enrich the protein and then subjected to high-throughput mass spectrometry analysis. Results: As a result, there were 2138 crotonylation sites in 534 proteins. These proteins are widely distributed in the cytoplasm, nucleus, and mitochondria, and participate in the cell metabolism processes such as amino acid synthesis, glycolysis, and glycogen synthesis. Conclusions: In summary, our bioinformatics shows that nonhistone crotonylation plays an important role in the VSMC phenotypic transformation induced by PDGF-BB stimulation.
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