Bile duct ligation enhances AZT CNS toxicity partly by impairing the expression and function of BCRP in rat brain.

Breast cancer resistance protein (BCRP) is one of ATP-binding cassette (ABC) transporters in brain microvessel endothelial cells that transport their substrates from brain to blood, thus limiting substrates to crossing into brain through blood-brain barrier. Our previous works show that bile duct ligation (BDL) impairs expression and function of brain BCRP in rats. Since zidovudine (AZT) is BCRP substrate, we investigated whether impaired expression and function of BCRP increased brain distribution and toxicity of AZT in BDL-D7 rats. After administration of AZT (10 mg/kg, i.v.), BDL markedly increased brain AZT concentrations, compared with sham-operated (SO) rats. The ratio of AZT brain-to-plasma area under concentration curve (AUC) in BDL rats was increased to 1.6-folds of SO rats. After treatment with AZT (100 mg/kg every day, i.v.) for 7 days, BDL significantly impaired cognitive functions compared with SO rats, evidenced by the significantly decreased percentage of alternation in Y-maze test and prolonged escaped latency in two-way passive avoidance trial. Furthermore, AZT treatment caused significant decrease in copies of mitochondrial DNA and mitochondrial membrane potential in hippocampus of BDL rats. Moreover, AZT treatment caused a significant decrease of cortex microtubule-associated protein 2 and hippocampus synaptophysin levels in BDL rats. AZT-induced CNS adverse alterations in BDL rats were not observed in SO rats treated with AZT. In conclusion, BDL decreases the function and expression of brain BCRP in rats, leading to increased brain distribution of AZT, which in turn enhances AZT CNS toxicity, leading to mitochondrial dysfunction, neuronal damage, and ultimately cognitive dysfunction.

In-situ Electrochemical Transformed Cu Oxide from Cu Sulfide for Efficient Upgrading of Biomass Derived 5-Hydroxymethylfurfural in Anion Exchange Membrane Electrolyzer.

The electrochemical transformation of biomass to high value-added products is attractive. Herein, Cu sulfide-mediated in-situ synthesis of Cu oxide was achieved for efficient electro-oxidation of biomass derived 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). The copper foam-supported Cu sulfide (Cu-S/CF) was in-situ converted to Cu oxide during the electro-oxidation process. The in-situ formed Cu oxide presented high HMF conversion, FDCA yield, and faradaic efficiency in 1 m KOH with HMF concentration up to 100 mm. The oxidation of HMF on Cu oxide started with the formation of high-valence Cu species with the assistance of OH- , which then oxidized HMF spontaneously. An anion exchange membrane (AEM) electrolyzer with Cu-S/CF as the anode was assembled to continuously produce FDCA with H2 generation at the cathode. The AEM electrolyzer ran stably for 60 h with FDCA content higher than 85 % at a cell voltage between 1.50 and 1.60 V.

Effectiveness of neuromuscular electrical stimulation for endometriosis-related pain: A protocol of systematic review and meta-analysis.

BACKGROUND: This study will assess the effectiveness and safety of neuromuscular electrical stimulation (NMES) for endometriosis-related pain (ERP). METHODS: Seven electronic databases of Cochrane Library, PUBMED, EMBASE, WANGFANG, VIP, CBM, and CNKI will be searched. We will search all electronic databases related the randomized controlled trials (RCTs) on the effectiveness and safety of NMES for ERP up to the March 31, 2020 without restrictions of language. RevMan 5.3 software will be used for risk of bias assessment, related data analysis and meta-analysis. RESULTS: This systematic review and meta-analysis will summarize current high-quality RCTs on the effectiveness and safety of NMES for ERP. Results of this study will provide the basis for both clinician and further research. CONCLUSION: This study will investigate whether NMES is effective and safety for the treatment of ERP. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040191.