Exosomal miR-23b from bone marrow mesenchymal stem cells alleviates oxidative stress and pyroptosis after intracerebral hemorrhage

Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.

A multi-omics study on cutaneous and uveal melanoma

AIM:To present the multi-omics landscape of cutaneous melanoma(CM)and uveal melanoma(UM)from The Cancer Genome Atlas(TCGA).METHODS:The differentially expressed genes(DEGs)between CM and UM were found and integrated into a gene ontology enrichment analysis.Besides,the differentially expressed miRNAs were also identified.We also compared the methylation level of CM with UM and identified the differentially methylated regions to integrate with the DEGs to display the relationship between the gene expression and DNA methylation.The differentially expressed transcription factors(TFs)were identified.RESULTS:Though CM had more mutational burden than UM,they shared several similarities such as the same rankings in diverse variant types.Except GNAQ and GNA11,the other top 18 mutated genes of the combined group were mostly detected in CM instead of UM.On the transcriptomic level,4610 DEGs were found and integrated into a gene ontology enrichment analysis.We also identified 485 differentially expressed miRNAs.The methylation analysis showed that UM had a significantly higher methylation level than CM.The integration of differentially methylated regions and DEGs demonstrated that most DEGs were downregulated in UM and the hypo-and hypermethylation presented no obvious difference within these DEGs.Finally,116 hypermethylated TFs and 114 hypomethylated TFs were identified as differentially expressed TFs in CM when compared with UM.CONCLUSION:This multi-omics study on comparing CM with UM confirms that they differ in all analyzed levels.Of notice,the results also offer new insights with implications for elucidating certain unclear problems such as the distinct role of epithelial mesenchymal transition in two melanomas,the different metastatic routes of CM and UM and the liver tropism of metastatic UM.

A rare porous zinc phosphonocarboxylate framework with high thermal stability and interesting structural transformation

A rare porous zinc-organic framework with ultrahigh thermal stability over 500℃ was obtained, which exhibits a CaF2-type topology formed by 8-connected tetranuclear Zn4 clusters and 4-connected phosphonocarboxylate ligands. Interestingly, the similar reactions to the 2 zinc-organic framework but in the absence of H2 O or by the replacement of Zn2＋with Co2＋can yield three different 3 D cluster-based frameworks but with the same CaF2-type topology.