Nucleic acid drug and delivery techniques for disease therapy: Present situation and future prospect

Wang, Tianjiao; Tang, Youhong; Tao, Yuandong; Zhou, Huixia; Ding, Dan

doi:10.1002/inmd.20230041

Cited by 11 publications

(2 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…miRNAs are closely associated with many significant diseases. The advancement and cost reduction of gene sequencing technologies, along with the development of RNA modification techniques and breakthroughs in delivery systems, have made miRNAs a focal point in disease treatment [ 56 , 57 ]. Employing the miEAA 2.1 analysis platform, we screened DEMs with extensive regulatory effects after SCI and conducted a comprehensive multi-omics analysis.…”

Section: Discussionmentioning

confidence: 99%

miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1

Ou,

Cheng,

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Background Spinal cord injury (SCI) is characterized by extensive demyelination and inflammatory responses. Facilitating the clearance of lipid droplets (LDs) within microglia contributes to creating a microenvironment that favors neural recovery and provides essential materials for subsequent remyelination. Therefore, investigating MicroRNAs (miRNAs) that regulate lipid homeostasis after SCI and elucidating their potential mechanisms in promoting LDs clearance in microglia have become focal points of SCI research. Methods We established a subacute C5 hemicontusion SCI model in mice and performed transcriptomic sequencing on the injury epicenter to identify differentially expressed genes and associated pathways. Confocal imaging was employed to observe LDs accumulation. Multi-omics analyses were conducted to identify differentially expressed mRNA and miRNA post-SCI. Pathway enrichment analysis and protein-protein interaction network construction were performed using bioinformatics methods, revealing miR-223-Abca1 as a crucial miRNA-mRNA pair in lipid metabolism regulation. BV2 microglia cell lines overexpressing miR-223 were engineered, and immunofluorescence staining, western blot, and other techniques were employed to assess LDs accumulation, relevant targets, and inflammatory factor expression, confirming its role in regulating lipid homeostasis in microglia. Results Histopathological results of our hemicontusion SCI model confirmed LDs aggregation at the injury epicenter, predominantly within microglia. Our transcriptomic analysis during the subacute phase of SCI in mice implicated ATP-binding cassette transporter A1 (Abca1) as a pivotal gene in lipid homeostasis, cholesterol efflux and microglial activation. Integrative mRNA-miRNA multi-omics analysis highlighted the crucial role of miR-223 in the neuroinflammation process following SCI, potentially through the regulation of lipid metabolism via Abca1. In vitro experiments using BV2 cells overexpressing miR-223 demonstrated that elevated levels of miR-223 enhance ABCA1 expression in myelin debris and LPS-induced BV2 cells. This promotes myelin debris degradation and LDs clearance, and induces a shift toward an anti-inflammatory M2 phenotype. Conclusions In summary, our study unveils the critical regulatory role of miR-223 in lipid homeostasis following SCI. The mechanism by which this occurs involves the upregulation of ABCA1 expression, which facilitates LDs clearance and myelin debris degradation, consequently alleviating the lipid burden, and inhibiting inflammatory polarization of microglia. These findings suggest that strategies to enhance miR-223 expression and target ABCA1, thereby augmenting LDs clearance, may emerge as appealing new clinical targets for SCI treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1

Ou,

Cheng,

et al. 2024

J Transl Med

View full text Add to dashboard Cite

show abstract

“…Previous study have demonstrated a significant increase in IL-6, TNF-α, and iNOS expression in astrocytes following OGD, with iNOS(+) reactive astrocytes leading to increased neuronal apoptosis (10), suggesting the involvement of A1 astrocytes in post-IS inflammation and oxidative stress. Moreover, it has been found that edaravone inhibits the transformation of A1 astrocytes by suppressing the expression of inflammatory cytokines and chemokines (11). Additionally, astrocytes play a critical role in the redox homeostasis during ischemic stroke, as evidenced by the significantly higher glutathione (GSH) content in astrocytes compared to neurons during OGD, with mitochondrial transfer from astrocytes to neurons aiding in maintaining neuronal mitochondrial function (12).…”

Section: Introductionmentioning

confidence: 99%

MiR-122 overexpression alleviates oxygen–glucose deprivation-induced neuronal injury by targeting sPLA2-IIA

Yu,

Li,

Chen

et al. 2024

Front. Neurol.

View full text Add to dashboard Cite

BackgroundIschemic stroke (IS) is a neurological disease with significant disability and mortality. MicroRNAs were proven to be associated with cerebral ischemia. Previous studies have demonstrated miR-122 downregulation in both animal models of IS and the blood of IS patients. Nonetheless, the role and mechanism of miR-122-5p in IS remain unclear.MethodsWe established primary human and mouse astrocytes, along with HT22 mouse hippocampal neuronal cells, through oxygen–glucose deprivation/reoxygenation (OGD/R) treatment. To assess the impact of miR-122, we employed CCK8 assays, flow cytometry, RT-qPCR, western blotting, and ELISA to evaluate cell viability, apoptosis, reactive oxygen species (ROS) generation, and cytokine expression. A dual-luciferase reporter gene assay was employed to investigate the interaction between miR-122 and sPLA2-IIA.ResultsOverexpression of miR-122 resulted in decreased apoptosis, reduced cleaved caspase-3 expression, and increased cell viability in astrocytes and HT22 cells subjected to OGD/R. RT-qPCR and ELISA analyses demonstrated a decrease in mRNA and cytokine levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in both astrocytes and HT22 cells following miR-122 overexpression. Moreover, miR-122 overexpression reversed OGD/R-induced ROS levels and 8-OHdG formation in astrocytes. Additionally, miR-122 overexpression decreased the mRNA and protein expression of inducible nitric oxide synthase (iNOS). Furthermore, we found that miR-122 attaches to the 3′-UTR of sPLA2-IIA, thereby downregulate its expression.ConclusionOur study demonstrates that miR-122-mediated inhibition of sPLA2-IIA attenuates OGD/R-induced neuronal injury by suppressing apoptosis, alleviating post-ischemic inflammation, and reducing ROS production. Thus, the miR-122/sPLA2-IIA axis may represent a promising target for IS treatment.

show abstract

Photochemical regulatory strategies for nucleic acid function and their biomedical applications

Hu,

Wang,

Zhou

2024

Interdisciplinary Medicine

View full text Add to dashboard Cite

Nucleic acids are not only essential biomolecules that drive critical life processes such as growth, development, reproduction, inheritance, and mutation, but also serve as significant markers for disease diagnosis, pathogen identification, and cancer screening. Nevertheless, several challenges have hindered the widespread use of nucleic acids in biomedicine, such as susceptibility to degradation, limited cellular uptake efficiency, potential toxicity, and uncontrollable activity. Photo‐regulation offers an effective solution to address these challenges. It allows for the precise control of nucleic acid structure and function and enhances the stability and safety of their application in biomedicine. In this review, we systematically review the structural characteristics of the three primary photosensitive groups commonly used in the regulation of nucleic acid molecules (i.e., photocleavable molecules, photoisomerization molecules, and photo‐crosslinking molecules) under light irradiation. Subsequently, recent research advances in the development and application of photo‐modulation strategies based on these photosensitive molecules in antisense oligonucleotides, RNA interference, nucleic acid amplification, and CRISPR/Cas systems are outlined. Finally, we discuss the challenges faced in the widespread application of these photo‐regulatory strategies and outline potential future directions for their development.

show abstract

Nucleic acid drug and delivery techniques for disease therapy: Present situation and future prospect

Cited by 11 publications

References 61 publications

miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1

miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1

MiR-122 overexpression alleviates oxygen–glucose deprivation-induced neuronal injury by targeting sPLA2-IIA

Photochemical regulatory strategies for nucleic acid function and their biomedical applications

Contact Info

Product

Resources

About