Bone Marrow-Derived Mesenchymal Stem Cell-Derived Exosomes Containing Gli1 Alleviate Microglial Activation and Neuronal Apoptosis In Vitro and in a Mouse Parkinson Disease Model by Direct Inhibition of Sp1 Signaling.

This study investigated possible therapeutic effect mechanisms of exosomes from bone marrow-derived mesenchymal stem cells (BMSC) in neuronal and microglial cells and in a Parkinson disease (PD) model. Neuronal SH-SY5Y cells and microglial HMC3 cells were subjected to 1-methyl-4-phenylpyridinium (MPP+) or LPS, respectively. The mRNA and protein expression was assessed using qRT-PCR, Western blotting, and enzyme-linked immunosorbent assay. Cell viability and apoptosis of SH-SY5Y cells were examined using the MTT assay and flow cytometry. Chromatin immunoprecipitation assays were performed to assess the binding relationship between glioma-associated oncogene homolog 1 (Gli1) and the Sp1 transcription factor promoter. BMSC-derived exosomes promoted cell proliferation and inhibited apoptosis in MPP+-treated SH-SY5Y cells and suppressed inflammatory markers in LPS-treated HMC3 cells. Sp1 knockdown decreased SH-SY5Y cell damage and HMC3 immune activation. Gli1 carried by BMSC exosomes directly bound with Sp1 to inhibit Sp1-mediated LRRK2 activation whereas exosomes secreted by Gli1-knockdown in BMSC did not. In a PD mouse model induced with MPTP, BMSC exosomes decreased neuron loss injury and the inflammatory response by inhibiting Sp1 signaling. Thus, BMSC-derived exosomal Gli1 alleviates inflammatory damage and neuronal apoptosis by inhibiting Sp1 in vitro and in vivo. These findings provide the basis for the potential clinical use of BMSC-derived exosomes in PD.

A comparative study of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma: A protocol for systematic review and meta-analysis.

BACKGROUND: Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma. METHODS: Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) were used to search for studies related to the utilization of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma. Literature screening, extraction of data, and evaluation of high standard studies were conducted by 2 independent researchers. The robustness and strength of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic methodology for recurrent high-grade glioma was assessed based on the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). RevMan 5.3 software was used for carrying out the statistical analysis. RESULTS: These results obtained in this study will be published in a peer-reviewed journal. CONCLUSION: Evidently, the conclusion of this study will provide an assessment on whether combined procarbazine, lomustine, and vincristine provides an effective and safe form of treatment for recurrent high-grade glioma. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202080078.

Supercritical water oxidation and process enhancement of nitrogen-containing organics and ammonia.

Supercritical water oxidation (SCWO), as a promising technology for treating organic wastewater and sludge, has attracted the attention of many scholars. Nitrogen-containing organics are refractory substances that widely exist in industrial waste, and their effective degradation is of great significance to the environment. In this paper, the treatment effects, reaction kinetics, and migration and transformation pathways of various nitrogen-containing organics (amino group, nitro group, mixed group, and nitrogen heteroatom) under SCWO conditions are summarized, and the influences of the reaction temperature, oxidant type and concentration, residence time, and initial concentration of organics on the degradation of organics are also discussed. NH3-N is the primary intermediate product produced during the oxidation process of the amino group and nitrogen heteroatom organics, and the further degradation of NH3-N is the limiting step for the whole reaction. This paper focuses on the relevant strengthening technologies used to enhance the degradation of NH3-N, including heterogeneous catalytic oxidation with reactor wall or metal oxides; co-oxidation with auxiliary fuels such as methanol, ethanol, isopropanol, and glycol; strong oxidation with NO3- or NO2-; and segmented oxidation by multi-injection of oxidants or fuels. In addition, in order to achieve the complete removal of NH3-N and COD synergistically under relatively mild SCWO conditions, avoid the formation of NOx, NO3-, and NO2-, and convert organic nitrogen into environmentally friendly products such as N2 and N2O, further research requirements and challenges are introduced.

Supercritical water oxidation of semi-coke wastewater: Effects of operating parameters, reaction mechanism and process enhancement.

Semi-coke wastewater is a kind of industrial wastewater with complex composition, high concentration of organic pollutants and high chroma, seriously threatening the ecological environment and requiring to be effectively degraded. Supercritical water oxidation (SCWO), as for a promising environmental technology, was applied to treat semi-coke wastewater in this work. The influences of key operating parameters such as reaction temperature (400-600 °C), oxidation coefficient (1.0-4.0) and residence time (0.5-10 min), the reaction mechanism for organics in semi-coke wastewater and the process enhancement methods like catalytic oxidation and segmented oxidation were systematically investigated. Experimental results showed that the removal efficiency of COD and NH3-N both significantly increased with the increasing of temperature, oxidation coefficient and residence time, the COD removal efficiency and NH3-N removal efficiency could be 99.02% and 63.94% obtained under the condition of 600 °C, 25 MPa, 1.3 times oxidation coefficient and 10 min. The residual organics in liquid products were mainly phenols, ketones, imidazoles, esters and pyridines, which produced from the cyclization and esterification reaction between intermediate products such as alcohols, aldehydes, acids and NH3-N, etc. What's more, NH3-N was proved to have inhibitory effect on the degradation of phenol by generating more stubborn nitrogen-containing compounds with that. Besides, compared with single catalyst, the composite catalyst of MnO2/CeO2 exhibited the highest catalytic activity, which could synergistically degrade 98.52% COD and 67.18% NH3-N under a relatively mild reaction condition (550 °C, 25 MPa, 1.3 times oxidation coefficient, 2 min). Moreover, the segmented oxidation, combining the pre-oxidation in preheater and oxidation in reactor, was firstly observed and analyzed here, could achieve a higher COD removal efficiency with a shorter length of the reactor. The results obtained in this paper proved the technical feasibility and could provide basic data support for the industrialization of semi-coke wastewater treatment by SCWO.