Systematic analysis of tRNA-derived small RNAs reveals therapeutic targets of Xuefu Zhuyu decoction in the cortexes of experimental traumatic brain injury

Yang, Zhaoyu; Tang, Tao; Li, Pengfei; Li, Xuexuan; Wu, Yi-Ming; Feng, Dandan; Hu, Mingrui; Dai, Feng; Zheng, Fei; Zhang, Wei; Wang, Yang

doi:10.1016/j.phymed.2022.154168

Cited by 17 publications

(5 citation statements)

References 52 publications

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“…Developing effective treatments to promote cognitive rehabilitation in TBI patients during the subacute phase is of high clinical importance [110]. The bioinformatics analyses and experimental validation performed in this study mainly focused on the subacute phase (14 days), which was important for assessing cognitive function in the rodent model of TBI [13,113]. Notably, there was some evidence that several potential biomarkers were significantly upregulated in the acute phase.…”

Section: Discussionmentioning

confidence: 99%

“…TBI differs from other diseases in that it involves different periods after the injury. However, subacute phase studies of TBI functional recovery have received substantially less attention than acute phase studies [12,13]. Since effective therapeutic strategies for the subacute phase of TBI are limited, it is essential to explore optimal therapeutic targets at this stage [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Identification of Key Genes and Pathways in the Hippocampus after Traumatic Brain Injury: Bioinformatics Analysis and Experimental Validation

Zeng¹,

Zhao²,

Zhao³

et al. 2023

J. Integr. Neurosci.

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Background: Traumatic brain injury (TBI) is a common brain injury with a high morbidity and mortality. The complex injury cascade triggered by TBI can result in permanent neurological dysfunction such as cognitive impairment. In order to provide new insights for elucidating the underlying molecular mechanisms of TBI, this study systematically analyzed the transcriptome data of the rat hippocampus in the subacute phase of TBI. Methods: Two datasets (GSE111452 and GSE173975) were downloaded from the Gene Expression Omnibus (GEO) database. Systematic bioinformatics analyses were performed, including differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) network construction, and hub gene identification. In addition, hematoxylin and eosin (HE), Nissl, and immunohistochemical staining were performed to assess the injured hippocampus in a TBI rat model. The hub genes identified by bioinformatics analyses were verified at the mRNA expression level. Results: A total of 56 DEGs were shared in the two datasets. GSEA results suggested significant enrichment in the MAPK and PI3K/Akt pathways, focal adhesion, and cellular senescence. GO and KEGG analyses showed that the common DEGs were predominantly related to immune and inflammatory processes, including antigen processing and presentation, leukocyte-mediated immunity, adaptive immune response, lymphocyte-mediated immunity, phagosome, lysosome, and complement and coagulation cascades. A PPI network of the common DEGs was constructed, and 15 hub genes were identified. In the shared DEGs, we identified two transcription co-factors and 15 immune-related genes. The results of GO analysis indicated that these immune-related DEGs were mainly enriched in biological processes associated with the activation of multiple cells such as microglia, astrocytes, and macrophages. HE and Nissl staining results demonstrated overt hippocampal neuronal damage. Immunohistochemical staining revealed a marked increase in the number of Iba1-positive cells in the injured hippocampus. The mRNA expression levels of the hub genes were consistent with the transcriptome data. Conclusions: This study highlighted the potential pathological processes in TBI-related hippocampal impairment. The crucial genes identified in this study may serve as novel biomarkers and therapeutic targets, accelerating the pace of developing effective treatments for TBI-related hippocampal impairment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of Key Genes and Pathways in the Hippocampus after Traumatic Brain Injury: Bioinformatics Analysis and Experimental Validation

Zeng¹,

Zhao²,

Zhao³

et al. 2023

J. Integr. Neurosci.

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“…RNA therapies involve the use of RNA-based molecules to treat or prevent diseases and hold significance in disease diagnosis and treatment [ 178 ]. Yang et al [ 179 ] explored the expression profiles of tsRNAs in experimental traumatic brain injury (TBI) mice. These mice were treated with a Chinese herbal formula, Xuefu Zhuyu Decoction (XFZYD).…”

Section: Clinical Application Value Of Tsrnas In Cancersmentioning

confidence: 99%

tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application

Zhou,

He,

Zhang

et al. 2024

Mol Cancer

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Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent studies have shown that tsRNAs play an important role in tumorigenesis by regulating biological behaviors such as malignant proliferation, invasion and metastasis, angiogenesis, immune response, tumor resistance, and tumor metabolism reprogramming. These may be new potential targets for tumor treatment. Furthermore, tsRNAs can exist abundantly and stably in various bodily fluids (e.g., blood, serum, and urine) in the form of free or encapsulated extracellular vesicles, thereby affecting intercellular communication in the tumor microenvironment (TME). Meanwhile, their abnormal expression is closely related to the clinicopathological features of tumor patients, such as tumor staging, lymph node metastasis, and poor prognosis of tumor patients; thus, tsRNAs can be served as a novel type of liquid biopsy biomarker. This review summarizes the discovery, production, and expression of tsRNAs and analyzes their molecular mechanisms in tumor development and potential applications in tumor therapy, which may provide new strategies for early diagnosis and targeted therapy of tumors.

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“…For HE staining, 3-mm-thick brain tissue sections were taken, with the trauma foci as the center. Standard protocols for hematoxylin and eosin staining were followed, and the stained sections were observed under a light microscope to assess the histopathological damage caused by TBI [15] .…”

Section: He and Tunel Stainingmentioning

confidence: 99%

Network pharmacology and molecular docking–based investigation of monocyte locomotion inhibitory factor attenuates traumatic brain injury by regulating aquaporin 4 expression

Li,

Ma,

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Traumatic brain injury (TBI) is a significant cause of disability and mortality worldwide, and effective treatment options are currently limited. Monocyte locomotion inhibitor factor (MLIF), a small molecular pentapeptide, has demonstrated a protective effect against cerebral ischemia. This study aimed to investigate the protective effects of MLIF on TBI and explore its underlying mechanism of action. In animal experiments, we observed that administration of MLIF after TBI reduced brain water content and improved brain edema, suggesting a certain degree of protection against TBI. By utilizing of network pharmacology methodologies, we employed target screening techniques to identify the potential targets of MLIF in the context of TBI. As a result, we successfully enriched 10 signaling pathways that are closely associated with TBI. Furthermore, using molecular docking techniques, we identified AQP4 as one of the top 10 central genes discovered in this study.

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Systematic analysis of tRNA-derived small RNAs reveals therapeutic targets of Xuefu Zhuyu decoction in the cortexes of experimental traumatic brain injury

Cited by 17 publications

References 52 publications

Identification of Key Genes and Pathways in the Hippocampus after Traumatic Brain Injury: Bioinformatics Analysis and Experimental Validation

Identification of Key Genes and Pathways in the Hippocampus after Traumatic Brain Injury: Bioinformatics Analysis and Experimental Validation

tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application

Network pharmacology and molecular docking–based investigation of monocyte locomotion inhibitory factor attenuates traumatic brain injury by regulating aquaporin 4 expression

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