Edaravone Maintains AQP4 Polarity Via OS/MMP9/ß-DG Pathway in an Experimental Intracerebral Hemorrhage Mouse Model.

Oxidative stress (OS) is the main cause of secondary damage following intracerebral hemorrhage (ICH). The polarity expression of aquaporin-4 (AQP4) has been shown to be important in maintaining the homeostasis of water transport and preventing post-injury brain edema in various neurological disorders. This study primarily aimed to investigate the effect of the oxygen free radical scavenger, edaravone, on AQP4 polarity expression in an ICH mouse model and determine whether it involves in AQP4 polarity expression via the OS/MMP9/ß-dystroglycan (ß-DG) pathway. The ICH mouse model was established by autologous blood injection into the basal nucleus. Edaravone or the specific inhibitor of matrix metalloproteinase 9 (MMP9), MMP9-IN-1, called MMP9-inh was administered 10 min after ICH via intraperitoneal injection. ELISA detection, neurobehavioral tests, dihydroethidium staining (DHE staining), intracisternal tracer infusion, hematoxylin and eosin (HE) staining, immunofluorescence staining, western blotting, Evans blue (EB) permeability assay, and brain water content test were performed. The results showed that OS was exacerbated, AQP4 polarity was lost, drainage function of brain fluids was damaged, brain injury was aggravated, expression of AQP4, MMP9, and GFAP increased, while the expression of ß-DG decreased after ICH. Edaravone reduced OS, restored brain drainage function, reduced brain injury, and downregulated the expression of AQP4, MMP9. Both edaravone and MMP9-inh alleviated brain edema, maintained blood-brain barrier (BBB) integrity, mitigated the loss of AQP4 polarity, downregulated GFAP expression, and upregulated ß-DG expression. The current study suggests that edaravone can maintain AQP4 polarity expression by inhibiting the OS /MMP9/ß-DG pathway after ICH.

Copper chaperone antioxidant 1: multiple roles and a potential therapeutic target.

Copper (Cu) was recently demonstrated to play a critical role in cellular physiological and biochemical processes, including energy production and maintenance, antioxidation and enzymatic activity, and signal transduction. Antioxidant 1 (ATOX1), a chaperone of Cu previously named human ATX1 homologue (HAH1), has been found to play an indispensable role in maintaining cellular Cu homeostasis, antioxidative stress, and transcriptional regulation. In the past decade, it has also been found to be involved in a variety of diseases, including numerous neurodegenerative diseases, cancers, and metabolic diseases. Recently, increasing evidence has revealed that ATOX1 is involved in the regulation of cell migration, proliferation, autophagy, DNA damage repair (DDR), and death, as well as in organism development and reproduction. This review summarizes recent advances in the research on the diverse physiological and cytological functions of ATOX1 and the underlying mechanisms of its action in human health and diseases. The potential of ATOX1 as a therapeutic target is also discussed. This review aims to pose unanswered questions related to ATOX1 biology and explore the potential use of ATOX1 as a therapeutic target.

Copper enhances genotoxic drug resistance via ATOX1 activated DNA damage repair.

Copper is involved in various biochemical and physiological processes. The absorbed copper ions are transported to the intracellular destination via copper chaperones, such as ATOX1. Previous studies have demonstrated that neoplastic cells have a high demand for copper; however, its role in cancer cells has not been fully elucidated. Here, we reveal that the high level of copper contributes to drug resistance and repair of damaged DNA in cancer cells at least partially via ATOX1-induced expression of MDC1, a crucial protein involved in double-strand DNA damage repair. Specifically, ATOX1 enters into nuclear to target MDC1 promoter after treatments of various genotoxic agents, thus promoting the transcription of MDC1 in a copper-dependent manner. Therefore, knockout or blockage of ATOX1 conferred sensitivity to Gemcitabine in transplanted tumor mouse models. Together, our findings gain new insight into the role of copper in DNA damage repair and provide a novel strategy for clinical cancer therapy of drug-resistance cancers.

Efficient peroxymonosulfate (PMS) activation by visible-light-driven formation of polymorphic amorphous manganese oxides.

Heterogeneous sulfate radical-based advanced oxidation processes (SR-AOPs) have been widely reported over the last decade as a promising technology for pollutant removal from wastewater. In this study, a novel peroxymonosulfate (PMS) activator was obtained by visible-light-driven Mn(II) oxidation in the presence of nitrate. The photochemically synthesized manganese oxides (PC-MnOx) were polymorphic amorphous nanoparticles and nanorods, with an average oxidation state of approximately 3.0. It possesses effective PMS activation capacity and can remove 20 mg L-1 acid organic II (AO7) within 30 min. The AO7 removal performance of PC-MnOx was slightly decreased in natural waterbodies and in the presence of CO32-, while it showed an anti-interference capacity for Cl-, NO3- and humic acid. Chemical quenching, reactive oxygen species (ROS) trapping, X-ray photoelectric spectroscopy (XPS), in-situ Raman spectroscopy, and electrochemical experiments supported a nonradical mechanism, i.e., electron transfer from AO7 to the metastable PC-MnOx-PMS complex, which was responsible for AO7 oxidation. The PC-MnOx-PMS system also showed substrate preferences based on their redox potentials. Moreover, PC-MnOx could activate periodate (PI) but not peroxydisulfate (PDS) or H2O2. Overall, this study provides a new catalyst for PMS activation through a mild and green synthesis approach.

Catalytic performance and periodate activation mechanism of anaerobic sewage sludge-derived biochar.

Periodate (PI)-based advanced oxidation processes are a newly discovered approach for effective pollutant elimination. In this study, we demonstrated that biochar obtained from pyrolysis of anaerobic sewage sludge without any pretreatment can be used for PI activation. The biochar obtained at 800 °C (SBC-800) exhibited the best PI activation capacity using acid organic II (AO7) as substrate. The PI activation was strongly dependent on pH and exhibited the highest AO7 removal rate at pH 3.0. Meanwhile, the anti-interference capacity with common wastewater components and reusability of the SBC-800/PI system were confirmed. Combined with the results of chemical quenching, reactive oxygen species (ROS) trapping, X-ray photoelectric spectroscopy (XPS), electrochemical and density function theory (DFT)-based calculations, singlet oxygen production and electron transfer mediated by the SBC-800-PI complex were the dominant AO7 oxidation mechanisms. This study provides easily prepared catalysts for PI activation and paves the way for solid waste recycling and reuse.

Highly selective colorimetric determination of catechol based on the aggregation-induced oxidase-mimic activity decrease of δ-MnO2.

Multiple enzyme-like activities of manganese oxides (MnO2) have been reported and applied in catalysis, biosensors, and cancer therapy. Here, we report that catechol can be determined colorimetrically based on the 3,3',5,5'-tetramethylbenzidine (TMB) oxidase-like activity of δ-MnO2. The detection was based on pre-incubation of catechol containing water samples with δ-MnO2, and then the residual TMB oxidase-like activity of reacted δ-MnO2 was linearly dependent on the catechol concentration in the range of 0.5 to 10 µM. This determination method was stable at pH 3.73-6.00 and was not affected by ion strength up to 200 µM. Common co-solutes in water bodies (50 µM) have negligible effects and excellent selectivity of catechol among various phenolic compounds (15 µM) was facilitated. Both reduction and aggregation of δ-MnO2 were observed during the incubation process with catechol, and aggregation-induced TMB oxidase-mimic activity decrease was the main factor for this colorimetric determination.