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Cerebral ischaemiareperfusion injury is an important pathological process in nervous system diseases during which neurons undergo oxygenglucose deprivation and reoxygenation (OGD/R) injury. No study has used epitranscriptomics to explore the characteristics and mechanism of injury. N6methyladenosine (m6A) is the most abundant epitranscriptomic RNA modification. However, little is known about m6A modifications in neurons, especially during OGD/R. m6A RNA immunoprecipitation sequencing (MeRIPseq) and RNA-sequencing data for normal and OGD/R-treated neurons were analysed by bioinformatics. MeRIP quantitative real-time polymerase chain reaction was used to determine the m6A modification levels on specific RNAs. We report the m6A modification profiles of the mRNA and circRNA transcriptomes of normal and OGD/R-treated neurons. Expression analysis revealed that the m6A levels did not affect m6A mRNA or m6A circRNA expression. We found crosstalk between m6A mRNAs and m6A circRNAs and identified three patterns of m6A circRNA production in neurons; thus, distinct OGD/R treatments induced the same genes to generate different m6A circRNAs. Additionally, m6A circRNA biogenesis during distinct OGD/R processes was found to be time specific. These results expand our understanding of m6A modifications in normal and OGD/R-treated neurons, providing a reference to explore epigenetic mechanisms and potential treatments for OGD/R-related diseases. [ABSTRACT FROM AUTHOR]

Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury. The aim of this study was to investigate the role of the factor erythroid 2-related factor 2 pathway in the protective effects of LE and MIG against triptolide-induced hepatotoxicity. Hepatotoxicity models were established in L-02 cells and rats using triptolide, and the protective effects of LE and MIG were investigated in vitro and in vivo, respectively. LE and MIG significantly protected against triptolide-induced cytotoxicity. Additionally, triptolide decreased the mRNA and protein levels of Nrf2 and down-regulated Nrf2 target genes, including UGT1A, BSEP, and MRP2, while pretreatment with LE and MIG reversed these effects. Finally, Nrf2-involved antioxidant responses were activated in the presence of LE and MIG. [ABSTRACT FROM AUTHOR]

Background and purpose: Spinal cord injury (SCI) involves serious damage that can result in abnormal or absent motor and sensory functions and a disruption of autonomic function, and a series of pathological reactions occur after the injury. As a type of small non-coding RNA, microRNAs (miRNAs) have been verified to inhibit gene expression via post-transcriptional regulation. This review mainly focuses on recent advances regarding the roles of miRNAs following SCI.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. The studies regarding the roles of miRNAs following SCI were identified through PubMed, Embase and Web of Science. We summarise the changes in expression levels of miRNAs and discuss the roles of miRNAs after SCI.Results: A total of 77 empirical studies meeting the inclusion criteria were identified. Existing studies showed that miRNAs were temporally altered and had effects on apoptosis, inflammation, angiogenesis, astrogliosis, oligodendrocyte development, axonal regeneration and remyelination after SCI. The alteration of miRNAs and the regulative action of pathological reactions can also provide opportunities for potential therapeutic interventions. “miRNA replacement therapy” aims to transfer miRNAs into diseased cells via delivery techniques and improve targeting effectiveness in cells, and this novel therapeutic tool provides a promising technique to promote the repair of SCI and reduces functional deficits.Conclusions: This review is helpful for understanding the underlying mechanisms of SCI and the potential clinical value of miRNAs. miRNAs have the potential to be attractive tools and targets for novel diagnostic and therapeutic approaches of SCI. [ABSTRACT FROM PUBLISHER]

Our previous work proved that sequence specific double strand RNA (dsRNA-p21) effectively activated p21 gene expression of colorectal cancer (CRC) cells and consequently suppressed CRC growth. However, efficient delivery system is a significant challenge to achieve sufficient therapy. In this study, a self-assembled HA/PEI/dsRNA-p21 ternary complex (TC-dsRNA-p21) was developed for the tumor-target delivery of dsRNA-p21 into CRC cells. Hyaluronic acid (HA) was introduced to shield the PEI/dsRNA-p21 binary complexes (BC-dsRNA-p21) for reducing the cytotoxicity of PEI and for increasing the tumor-targeted intracellular uptake by cancer cells through HA-CD44 mediated endocytosis. Comparing to the BC-dsRNA-p21, the TC-dsRNA-p21 showed increase in size, decrease in zeta potential, low cytotoxicity as well as high stability in physiological conditions due to the anionic shielding. Confocal microscopy analysis and flow cytometry confirmed that TC-dsRNA-p21 had high transfection efficiency in the CD44-abundant Lovo cells, as compared with binary complex.In vitrophysiological experiment showed that, comparing to the control group, the TC-dsRNA-p21 effectively activated the expression of p21 mRNA and P21 protein, causing blockage of cell cycle atG0/G1phase and suppression of cancer cell proliferation as well as colony formation. Furthermore,in vivodistribution experiment demonstrated that the TC-dsRNA-p21 could effectively accumulate at rectal wall for up to 10 h, followingin situapplication. These findings indicated that TC-dsRNA-p21 might hold great potential for delivering dsRNA-p21 to treat CRC. [ABSTRACT FROM AUTHOR]

Secreted frizzled related protein 5 (SFRP5), an anti-inflammatory adipokine, is relevant to the adipocyte differentiation. In order to clarify its role in regulating intramuscular fat (IMF) deposition in Tibetan chicken, the full-length sequence of the Tibetan chicken SFRP5 gene was cloned. The relative expression ofSFRP5gene was detected using quantitative RT-PCR in various tissues of 154 days old Tibetan chicken, as well as in breast muscle, thigh muscle, and adipose tissue at different growth stages. The results showed thatSFRP5gene was expressed in all examined tissues but highly enriched in adipose tissue. Temporal expression profile showed that the expression ofSFRP5was gradually decreased in breast muscle, but was fluctuated in thigh muscle and adipose tissue with the growth of Tibetan chicken. Furthermore, correlation analysis demonstrated that the expression ofSFRP5in breast muscle, thigh muscle and adipose tissue was correlated with IMF content at different levels. The results indicated that Tibetan chicken SFRP5 is involved in IMF deposition. [ABSTRACT FROM AUTHOR]

Previous studies have revealed that the subunit α 2 (Gabra2) of the γ-aminobutyric acid receptor plays a critical role in the stress response. However, little is known about the gentetic regulatory network for Gabra2 and the stress response. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Gabra2 expression in the hippocampus of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Gabra2 exhibited much variation in the hippocampus across the BXD RI strains and between the parental strains, C57BL/6J, and DBA/2J. Expression QTL (eQTL) mapping showed three microarray probe sets of Gabra2 to have highly significant linkage likelihood ratio statistic (LRS) scores. Gene co-regulatory network analysis showed that 10 genes, including Gria3, Chka, Drd3, Homer1, Grik2, Odz4, Prkag2, Grm5, Gabrb1, and Nlgn1 are directly or indirectly associated with stress responses. Eleven genes were implicated as Gabra2 downstream genes through mapping joint modulation. The genetical genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to complex traits, such as stress responses. [ABSTRACT FROM AUTHOR]