Monoclofenamic Acid

In recent decades, climate change and global warming have intensified water scarcity, while the growing global population demands have increased. Reclaimed water (RW) has become essential, offering a viable alternative for crop irrigation in line with circular economy principles. However, although RW reuse is crucial for addressing water shortages, the presence of micropollutants still poses a challenge. The potential for micropollutants to be taken up by crops and enter the food chain still raises significant scientific concern. This work studies RW treated by conventional activated sludge followed by sand filtration and chlorination (CAS+SFC-RW) and membrane-bioreactor-treated RW (MBR-RW) in terms of micropollutant concentrations, providing insights into the differences in micropollutant profiles between the two treatments. The results demonstrate that MBR-RW generally exhibits lower cumulative concentrations of target analytes. However, the study also indicates that the storage of RW for irrigation significantly affects the presence of micropollutants, contributing to their degradation, increase or persistence. Soil analysis revealed fewer detectable micropollutants in the topsoil (0-20 cm) compared to RW, likely attributed to attenuation processes, and more micropollutants (both with respect to concentration and number) compared to deeper soil layers. Carbamazepine, 10,11-epoxide-carbamazepine, and telmisartan were found to migrate to deeper soil levels. The analysis revealed 13 micropollutants in lettuce irrigated with CAS+SFC-RW and 8 with MBR-RW, with carbamazepine and sulfamethoxazole being the most abundant. These differences are likely driven by the physicochemical properties of the compounds and plant-specific factors. Leachates examination showed the potential for contaminants to leach through soil, posing a risk for groundwater contamination. The study showed that the presence of micropollutants in RW is not directly associated with their presence in soil or lettuce, underscoring the need for regulatory policies that address not only their presence in RW but their eventual fate within the agricultural and environmental context.

Podocyte injury associated with albuminuria and diabetic nephropathy (DN) progression. N6-methyladenosine (m6A) is a common form of epigenetic modification in eukaryotic cells and is known to be associated with a variety of disease processes. Its role in podocyte injury of DN remains poorly studied. We observed a higher expression of fat mass and obesity-associated protein (FTO) both in diabetic mice and human kidneys and DN podocytes in vitro, and the level of FTO was correlated with lipid accumulation. Furthermore, we confirmed that two selective FTO demethylation inhibitors meclofenamic acid (MA) and diacerein (DIA) administration effectively ameliorated lipotoxicity-induced podocyte injury, evidenced by restored autophagy, inhibition of apoptosis and inflammation, as well as mitigating endoplasmic reticulum stress (ERS) and mitochondrial damage both in vitro and vivo model of DN. Mechanistically, FTO demethylation inhibitors downregulated Acetyl-CoA-carboxylase 1 (ACC1) levels in db/db mice and advanced glycation end product (AGE)-treated podocytes, subsequently decreased podocyte fatty acid accumulation. ACC1 was identified as a direct FTO target in which FTO stabilizes ACC1 mRNA with the mediation of YTH domain-containing family protein 2 (YTHDF2) in an m6A-dependent manner using m6A RNA immunoprecipitation-quantitative real-time PCR (MeRIP-qPCR) and dual-luciferase reporter gene assays. Collectively, our findings demonstrate an important role of FTO mediated-m6A modification of ACC1 contributed to s lipotoxicity-mediated injury of DN podocytes, which provide fresh insights into the therapeutic strategies for DN.