Paraoxonase-2 agonist vutiglabridin promotes autophagy activation and mitochondrial function to alleviate non-alcoholic steatohepatitis.

BACKGROUND AND PURPOSE: Only limited therapeutic agents have been developed for non-alcoholic steatohepatitis (NASH). Glabridin, a promising anti-obesity candidate, has only limited druggability due to its low in vivo chemical stability and bioavailability. Therefore, we developed vutiglabridin (VUTI), which is based on a glabridin backbone, and investigated its mechanism of action in treating NASH in animal models. EXPERIMENTAL APPROACH: Anti-NASH effects of VUTI were determined in in vitro fatty liver models, spheroids of primary human hepatocytes and L02 normal liver cell lines. To identify VUTI possible cellular target/s, biotin-labelled VUTI was synthesized and underwent chemical proteomic analysis. Further, the evaluation of VUTI therapeutic efficacy was carried out using an amylin-NASH and high-fat (HF) diet-induced obese (DIO) mouse models. This was carried out using transcriptomic, lipidomic and proteomic analyses of the livers from the amylin-NASH mouse model. KEY RESULTS: VUTI treatment markedly reduces hepatic steatosis, fibrosis and inflammation by promoting lipid catabolism, activating autophagy and improving mitochondrial dysfunction, all of which are hallmarks of effective NASH treatment. The cellular target of VUTI was identified as paraoxonase 2 (PON2), a newly proposed protein target for the treatment of NASH, VUTI enhanced PON2 activity. The results using PON2 knockdown cells demonstrated that PON2 is important for VUTI- activation of autophagy, promoting mitochondrial function, decreasing oxidative stress and alleviating lipid accumulation under lipotoxic condition. CONCLUSION AND IMPLICATIONS: Our data demonstrated that VUTI is a promising therapeutic for NASH. Targeting PON2 may be important for improving liver function in various immune-metabolic diseases including NASH.

Surface-tuning TiO2 NR photoanodes using CoOx interlayers and NiFe-LDH cocatalysts for photoelectrochemical wastewater treatment.

Increasing multidrug-resistant pathogenic microbial around the world become a global problem, making it imperative to develop effective methods for bacterial inactivation in wastewater. In this study, we propose a multifunctional photoelectrochemical (PEC) system to successfully disinfect microbial cells and degrade orange (II) dyes. CoOx NP were synthesized by spin-coating onto hydrothermally synthesized TiO2 nanorod arrays followed by electrodeposited NiFe-LDH to develop the NiFe-LDH/CoOx NP-TiO2 NRs. Interestingly, spin-coated CoOx NP-TiO2 NRs exhibited a 1.5-fold enhancement in photocurrent (1.384 mA/cm2) than pristine TiO2 NRs (0.92 mA/cm2). A NiFe-layered double hydroxide (LDH) cocatalysts layer further exhibits the maximum photocurrent density of 1.64 mA/cm2 with IPCE of 84.5% at 1.0 VAg/AgCl at 380 nm. Furthermore, NiFe-LDH/CoOx-TiO2 NR photoanodes were effectually employed for photoelectrochemical bacteria disinfection and organic pollutant removals. With NiFe-LDH/CoOx-TiO2 NR, 99% (120 min) bacterial inactivation and 99% (60 min) orange II dye decomposition efficiency was achieved. Superoxide radicals (-O2•), hydroxyl radicals (HO•), and holes (h+) played a critical role in the PEC degradation systems. Due to the synergy between NiFe-LDH cocatalyst and CoOx interlayer, surface water oxidation reactions were accelerated over NiFe-LDH/CoOx NP-TiO2 NRs. The charge transport process in NiFe-LDH/CoOx NP-TiO2 NRs photoanode-based PEC system was proposed in detail.

Bio-electrochemical degradation of carbamazepine (CBZ): A comprehensive study on effectiveness, degradation pathway, and toxicological assessment.

Recent attention on the detrimental effects of pharmaceutically active compounds (PhACs) in natural water has spurred researchers to develop advanced wastewater treatment methods. Carbamazepine (CBZ), a widely recognized anticonvulsant, has often been a primary focus in numerous studies due to its prevalence and resistance to breaking down. This study aims to explore the effectiveness of a bio-electrochemical system in breaking down CBZ in polluted water and to assess the potential harmful effects of the treated wastewater. The results revealed bio-electro degradation process demonstrated a collaborative effect, achieving the highest CBZ degradation compared to electrodegradation and biodegradation techniques. Notably, a maximum CBZ degradation efficiency of 92.01% was attained using the bio-electrochemical system under specific conditions: Initial CBZ concentration of 60 mg/L, pH level at 7, 0.5% (v/v) inoculum dose, and an applied potential of 10 mV. The degradation pathway established by identifying intermediate products via High-Performance Liquid Chromatography-Mass Spectrometry, revealed the complete breakdown of CBZ without any toxic intermediates or end products. This finding was further validated through in vitro and in vivo toxicity assays, confirming the absence of harmful remnants after the degradation process.

In-situ Hf/Zr co-doped Fe2O3 nanorod decorated with CuOx/CoOx: Enhanced photocatalytic performance for antibacterial and organic pollutants.

Herein, we successfully synthesized Hf/Zr co-doping on Fe2O3 nanorod photocatalyst by a hydrothermal process and quenching methods. The synergistic roles of Hf and Zr double-doping on the bacteria inactivation test and decomposition of organic pollutants were investigated in detail for the 1 wt% CoOx loaded Hf/Zr-Fe2O3 NRs and CuOx/CoOx loaded Hf/Zr-Fe2O3 NRs photocatalyst. Initially, the rod-like porous morphology of the Hf/Zr-doped Fe2O3 NRs was produced via a hydrothermal method at various Hf co-doping (0, 2, 4, 7 and 10)%. Further, CoOx and CuOx loaded by a wet impregnation approach on the Hf/Zr-Fe2O3 NRs and a highly photoactive Hf(4)/Zr-Fe2O3 [CoOx/CuOx] NRs photocatalyst were developed. After the Hf(4)/Zr-Fe2O3 [CoOx/CuOx] NRs photocatalyst treatment, the Bio-TEM imagery of bacterial cells showed extensive morphological deviations in cell membranes. Hf(4)/Zr-Fe2O3 NR achieved 84.1% orange II degradation upon 3 h illumination, which is higher than that of Hf-Fe2O3 and Zr-Fe2O3 (68.7 and 73.5%, respectively). Additionally, the optimum sample, Hf(4)/Zr-Fe2O3 [CoOx/CuOx] photocatalyst, exhibited 95.5% orange II dye degradation after light radiation for 3 h. Optimized Hf(4)/Zr-Fe2O3 [CoOx/CuOx] catalysts exhibited 99.9% and 99.7% inactivation of E. coli and S. aureus with 120 min, respectively. Further, scavenger experiments revealed that the electrons are the primary responsible species for photocatalytic kinetics. This work will provide a rapid method for the development of high photocatalytic performance materials for bacterial disinfection and organic degradation.