Regulation of Gamma-Aminobutyric Acid Transaminase Expression and Its Clinical Significance in Hepatocellular Carcinoma.

Background: Gamma-aminobutyric acid transaminase (ABAT) catalyzes the conversion of gamma-aminobutyric acid (GABA) into succinic semialdehyde. Although some evidence supports a key role of ABAT in the progression of hepatocellular carcinoma (HCC), no systematic analysis is available. Thus, this study aimed to investigate the possible mechanisms related to low ABAT expression and the prognostic value and potential functions of ABAT in HCC. Methods: We obtained relevant datasets from the Encyclopedia of RNA Interactomes, MethSurv, cBioPortal, TISIDB and The Cancer Genome Atlas and used bioinformatic methods to analyze DNA methylation, copy number variation, gene mutation, and upstream microRNAs (miRNAs) of ABAT, exploring the potential relationship between ABAT expression and the prognosis, glycolysis, and immune infiltration in HCC. Results: The results indicated that ABAT expression was lower in HCC tumor tissues than in normal tissues or adjacent tissues. Low ABAT expression was related to patient age, T stage classification, pathologic stage, histological grade, and alpha-fetoprotein level of HCC. Kaplan-Meier survival analyses indicated that low ABAT expression was correlated with poor HCC prognosis. ABAT was also verified as an independent risk factor in HCC via Cox multivariate analysis. Gene set enrichment analysis showed enrichment in various signaling pathways. Furthermore, DNA methylation, copy number variation, and gene mutation potentially induced low ABAT expression; miR-135a-5p was a potential upstream miRNA of ABAT. Additionally, ABAT expression was associated with glycolysis-related genes, infiltrated immune cells, immunoinhibitors, and immunostimulators in HCC. Conclusions: Our study reveals that deficient ABAT expression is correlated with disease progression and poor prognosis in HCC because of its role in tumorigenesis and tumor immunity.

Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis.

BACKGROUND: Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secrete more exosomes, but little was known on MI repair. METHODS: Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization. RESULTS: Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs-Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF-κB signaling pathway and upregulated Nrf2/HO-1 Axis. CONCLUSIONS: FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI.

Regulation of Inflammatory Cytokine Storms by Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have been widely used in preclinical and clinical trials for various diseases and have shown great potential in the treatment of sepsis and coronavirus disease (COVID-19). Inflammatory factors play vital roles in the pathogenesis of diseases. The interaction between inflammatory factors is extremely complex. Once the dynamics of inflammatory factors are unbalanced, inflammatory responses and cytokine storm syndrome develop, leading to disease exacerbation and even death. Stem cells have become ideal candidates for the treatment of such diseases due to their immunosuppressive and anti-inflammatory properties. However, the mechanisms by which stem cells affect inflammation and immune regulation are still unclear. This article discusses the therapeutic mechanism and potential value of MSCs in the treatment of sepsis and the novel COVID-19, outlines how MSCs mediate innate and acquired immunity at both the cellular and molecular levels, and described the anti-inflammatory mechanisms and related molecular pathways. Finally, we review the safety and efficacy of stem cell therapy in these two diseases at the preclinical and clinical levels.