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Serum tsncRNAs Reveals Novel Potential Therapeutic Targets of Salvianolic Acid B on Atherosclerosis

ABSTRACT: Serum tsncRNAs Reveals Novel Potential Therapeutic Targets of Salvianolic Acid B on Atherosclerosis

PROVIDER: PRJNA884351 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21710559.fastq.gz	Fastqsanger.gz
	SRR21710560.fastq.gz	Fastqsanger.gz
	SRR21710561.fastq.gz	Fastqsanger.gz
	SRR21710562.fastq.gz	Fastqsanger.gz
	SRR21710563.fastq.gz	Fastqsanger.gz

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Serum tsncRNAs Reveals Novel Potential Therapeutic Targets of Salvianolic Acid B on Atherosclerosis

Project description:Objective: Salvianolic Acid B (SalB) extracted from the roots and rhizomes of Salvia Miltiorrhiza Bunge has been utilized to delay the progression of atherosclerosis (AS). Its therapeutic mechanisms remain unclear. Pre-transfer RNA and mature transfer RNA (tsncRNAs) is a novel class of short non-coding RNA possessing potential regulating functions. In this study the novel therapeutic targets of SalB by tsncRNAs-sequencing were explored. Methods: Mice were randomly divided into three groups: control group (CON) AS model group (MOD) and SalB-treated group (SAB). The weight change aortic sinus plaque and inflammatory cytokines (IL-6 IL-10 TNF-) were assessed. Total RNA was extracted from serum to obtain tsncRNAs followed expression profiling by the Illumina NextSeq instrument. Subsequently tRNAscan and TargetScan were used to predict tsncRNAs targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to predict the bioinformatics analysis. Quantitative real-time PCR (qPCR) was the method to validate potential tsncRNAs and related targets. Results: A total of 8 tsncRNAs (fold change >1.5 and P-value <0.05) were significantly decreased in MOD group compared to CON group. Among them tRNA-Glu-CTC-014 and tRNA-Gly-GCC-074 were markedly increased by SalB treatment and validated with quantitative real-time PCR. GO analysis revealed that the altered target genes of the selected tsncRNAs were most enriched in protein binding and cellular process. Moreover KEGG pathway analysis demonstrated that altered target genes of tsncRNAs were most enriched in mitogen-activated protein kinase (MAPK) signaling pathway. Conclusion: In conclusion tRNA-Glu-CTC-014 and tRNA-Gly-GCC-074 were the potential therapeutic targets of SalB on AS treatment.

2023-08-31 | GSE214198 | GEO

Single-cell genomics reveals a novel cell state during smooth muscle cell phenotypic switching and potential therapeutic targets for atherosclerosis in mouse and human [human]

Project description:Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration and transdifferentiation into other cell types. Yet, how SMC contribute to pathophysiology of atherosclerosis remains elusive. To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques.

2020-10-06 | GSE155512 | GEO

Single-cell genomics reveals a novel cell state during smooth muscle cell phenotypic switching and potential therapeutic targets for atherosclerosis in mouse and human [mouse]

2020-10-06 | GSE155513 | GEO

Ligustilide targets SMAD3, obstructing vascular fibrosis process in preventing atherosclerosis

Project description:Atherosclerosis is a persistent inflammatory state accompanied by lipid overload. Vascular fibrosis is one of the primary causes of atherosclerosis development. Although ligustilide (Lig) was shown to exert obvious antiatherogenic effects in previous studies, its precise mechanism has not been comprehensively discussed. In this paper, pharmacologic studies were performed to explore the pharmacodynamic effects of Lig on protecting aorta vascular wall structures and modulating serum inflammatory factors in ApoE-/- mice. Chemical proteomics based on a Lig-derived photoaffinity labelling (Lig-PAL) probe were applied to identify potential therapeutic targets. Mothers against decapentaplegic homologue 3 (SMAD3), which is closely related to the development of vascular fibrosis and atherosclerosis, was identified as a potential target of Lig. Lig suppressed the phosphorylation and nuclear translocation of SMAD3 by blocking the interaction between SMAD3 and transforming growth factor-β (TGF-β) receptor 1, thereby inhibiting the collagen synthesis process, preventing vascular fibrosis and improving atherosclerosis. The quantitative proteomics results from Lig-treated atherosclerotic ApoE-/- mice also indicated that Lig inhibits the expression of collagens I and III, interferes with collagen fibril organization processes and protects the aorta from vascular fibrosis. Hence, developing a novel SMAD3 inhibitor may present another therapeutic option for preventing atherosclerosis.

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Identification of Potential Gene targets and Pathways Shared by Diabetes and Atherosclerosis

Project description:Identification of Potential Gene targets and Pathways Shared by Diabetes and Atherosclerosis

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Unraveling the immunological roles of murine serum amyloid A3 in aortic immune cell subsets during atherosclerosis progression

Project description:Atherosclerosis is a growing concern in developed nations, necessitating the identification of therapeutic targets for advancing personalized medicine. Serum amyloid A3 (Saa3) has been linked to accelerated plaque progression by affecting cholesterol metabolism and modulation of inflammation. We hypothesize that knocking out Saa3 (Saa3-/-) could mitigate plaque development by regulating aortic immune cell subsetscompositions during atherosclerosis progression. Using a murine model, we induced atherosclerosis via a gain-of-function mutant PCSK9-encoding adeno-associated viral vector (AAVmPCSK9) in wild-type (WT) and Saa3-/- mice. Single-cell RNA sequencing revealed that Saa3-/- mice developed smaller plaques than WT mice, with and single-cell RNA sequencing revealed significant differences in aortic immune cell populations, particularly among aortic macrophages. Saa3-/-Trem2hi macrophages, characterized by high Gpnmb, Lpl, and Spp1 expressions, predominated over the typical resident foamy macrophages in WT mice.Saa3-/- compared to WT mice. SAA3 regulates cholesterol metabolism and inflammatory responses in foamy macrophages. Notably, aortic immune cells in atherosclerotic Saa3-/- mice also showed enhanced intercellular immune communication and increased signaling interactions, suggesting a shift towards an anti-inflammatory and tissue-repairing phenotype. Our study highlights the potential of Saa3 as a therapeutic target forkey modulator of aortic immune cells that impact atherosclerosis progression.

2025-06-27 | GSE270922 | GEO

Pyelonephritis decreases serum cholesterol and mitigates atherosclerosis severity despite systemic inflammation

Project description:Pyelonephritis decreases serum cholesterol and mitigates atherosclerosis severity despite systemic inflammation

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Bioinformation and deep-learning based model reveals norepinephrine inhibiting PRDX1 aggravates atherosclerosis

Project description:The regulation of metabolites comprises the fundamental biological processes of human. More new phenotypes of classic metabolites were revealed, while the devolution of functional targets and mechanisms of them still have many gaps due to diversity in structures and functions. Here, we report a bioinformation and attention mechanism based deep learning model leveraging abundant bioinformation of metabolites for functional target prediction of specific phenotypes. Taking advantage of this model, the potential target database of 3,382 common human metabolites were resourced publicly. Norepinephrine was identified as a selective peroxidase inhibitor of peroxiredoxin 1 (PRDX1) for atherosclerosis aggravation in model validation experiments. Salvianolic acid A (SAA) was screened out as PRDX1 exogenous stabilization compound for rescuing norepinephrine’s aggravation effects in vivo. Besides, bulk RNA-Sequencing analysis indicated norepinephrine aggravates atherosclerosis through activating transcriptional activity of SREBP2 in a ROS dependent manner. Overall, our research provides a new computational regime for metabolites target identification besides experimental chemical proteomics and PRDX1 stabilization was validated a potential druggable target for cardiovascular diseases intervention.

2025-05-07 | GSE282003 | GEO

Microarray analysis of the therapeutic effects of the mixture of salvianolic acids from Salvia miltiorrhiza and total flavonoids from Anemarrhena asphodeloides on sulfur mustard-induced damages

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