DNA methylation is known to regulate the expression of numerous genes but its role in the pathogenesis of thoracic aortic dissection (TAD) has remained largely elusive. In the present study, the DNA methylome of patients with TAD was analyzed using a methylation microarray and bisulfite pyrosequencing was used to determine whether the hypermethylation of matrix metalloproteinase 2 (MMP2) specifically is associated with TAD. Chip-based whole-DNA methylome analysis was performed on 4 male patients with TAD and 4 male healthy controls using an Illumina HumanMethylation EPIC 850K BeadChip. The resulting data were analyzed by clustering and principal component analysis, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the differentially methylated genes to interrogate their biological functions. Compared to the healthy controls, 3,362 loci were differentially methylated in the patients with TAD with a statistical significance of P<0.05, while 1,223 loci had a significance of P<0.01. Among these loci, 2,019 were hypermethylated and 1,343 were hypomethylated. From GO analysis within the biological process category, the MMP2, MMP14 and WNT2B genes were identified. enrichment was observed for loci involved in cellular component organization, enzyme-linked receptor protein signaling pathways (potentially having a key role in the development of cardiopulmonary function disorders) and vascular reconstruction. Bisulfite pyrosequencing of plasma samples indicated significantly increased methylation (P<0.01) of the CpG site at position 2 in the promoter of MMP2 in the TAD group relative to the healthy controls, and the mean methylation level of four CpG sites on the MMP2 gene in the TAD group was slightly higher than that in the control group, but not significantly. Hypermethylation of the MMP2 promoter may be a promising novel diagnostic and prognostic biomarker for TAD. Future studies on the epigenetics of biomarkers linked to vascular reconstruction and immune function may provide further insight into the pathogenesis and progression of TAD.

No abstract

Background: Several studies demonstrated a connection between human leukocyte antigen (HLA)-B∗1502 and lamotrigine (LTG)-induced cutaneous adverse drug reactions (cADRs). The correlation between the HLA-A∗24:02 and LTG-cADRs remains controversial. To examine the associations between HLA-A∗24:02 and LTG-cADRs, we conducted a systematic review and meta-analysis. Methods: We performed a comprehensive search of the literature in several electronic database systems including Cochrane Library, EMBASE and PubMed from inception to January 2020. Review Manager was used to compare the frequencies of HLA-A∗24:02 carriers between the subgroups. Results: A total of 5 studies were eligible, including 197 LTD-cADRs, 396 LTD-tolerant controls, and 2068 population controls. Compared with the LTG-tolerant controls, there was a statistically significant association between the HLA-A∗24:02 allele and LTG-induced cADRs (odds ratios: 1.94, 95% confidence intervals 1.06–3.54; P = .03). Compared with the general population, the relationship between the HLA-A∗24:02 genotype and LTG-induced cADRs was statistically significant (summary odds ratios: 2.12, 95% confidence intervals 1.04–4.30; P = .04). Conclusions: HLA-A∗24:02 may be a risk factor for LTG-cADRs.

Phellinus igniarius (PI) has various kinds of biological activities, such as antitumour activities, and polysaccharides are one of its main components. In this study, polysaccharides from PI (PIP) were prepared, purified, analysed for their structure and investigated for their antitumour activity and mechanism in vitro. PIP consists of 12138 kDa of carbohydrates containing 90.5±1.6% neutral carbohydrates. PIP consists of glucose, galactose , mannose , xylose, D-fructose , L-guluronic acid, glucosamine hydrochloride , rhamnose , arabinose and D-mannoturonic acid . PIP can significantly inhibit HepG2 cell proliferation, induce cell apoptosis and also inhibited migration and invasion in a concentration-dependent manner. PIP increased reactive oxygen species (ROS), reduced mitochondrial membrane potential, increased the expression of p53, and induced cytochrome c release into the cytoplasm to activate caspase-3. PIP is a promising potential candidate for the therapeutic treatment of hepatic carcinoma via the ROS-mediated mitochondrial apoptosis pathway.

Background: Spinal cord injury (SCI) is recognized as a severe traumatic disease because of its complications and multiorgan dysfunction. After the injury, microenvironment stability disruption in the lesion will rapidly demolish the surrounding healthy tissues and cells via various pathways. Regulating the microenvironment is an effective strategy to mitigate the rigorous condition, which is beneficial for subsequent neural restoration and functional recovery. Nevertheless, sustained release, cellular uptake, and long-term retention in the impaired site of therapeutic molecules are insufficient.Results: Herein, a local-implantation system is constructed for SCI treatment by encapsulating exosomes derived from Flos Sophorae Immaturus (so-exos) in a polydopamine (pDA) modified hydrogel (pDA-Gel). So-exos are applied as nano-scale natural vehicles of rutin, a flavonoid phytochemical that has been confirmed effective in microenvironment mitigation and nerve regeneration. pDA-Gel not only enables the long-term retention and sustainable release of so-exos in the lesion but also offers a nutritional and suitable microenvironment for nerve regeneration at the same time.Conclusion: The pDA-Gel encapsulating so-exos exhibits rapid restoration of the nervous system and preservation of downstream urinary system by modulating the inflammatory and oxidative condition. The oxidative sophora exosome encapsulated hydrogel exhibits a potential SCI treatment via plant exosomes combinational delivery.