Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns.

AIMS/HYPOTHESIS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) are antihyperglycaemic drugs that protect the kidneys of individuals with type 2 diabetes mellitus. However, the underlying mechanisms mediating the renal benefits of SGLT2i are not fully understood. Considering the fuel switches that occur during therapeutic SGLT2 inhibition, we hypothesised that SGLT2i induce fasting-like and aestivation-like metabolic patterns, both of which contribute to the regulation of metabolic reprogramming in diabetic kidney disease (DKD). METHODS: Untargeted and targeted metabolomics assays were performed on plasma samples from participants with type 2 diabetes and kidney disease (n=35, 11 women) receiving canagliflozin (CANA) 100 mg/day at baseline and 12 week follow-up. Next, a systematic snapshot of the effect of CANA on key metabolites and pathways in the kidney was obtained using db/db mice. Moreover, the effects of glycine supplementation in db/db mice and human proximal tubular epithelial cells (human kidney-2 [HK-2]) cells were studied. RESULTS: Treatment of DKD patients with CANA for 12 weeks significantly reduced HbA1c from a median (interquartile range 25-75%) of 49.0 (44.0-57.0) mmol/mol (7.9%, [7.10-9.20%]) to 42.2 (39.7-47.7) mmol/mol (6.8%, [6.40-7.70%]), and reduced urinary albumin/creatinine ratio from 67.8 (45.9-159.0) mg/mmol to 47.0 (26.0-93.6) mg/mmol. The untargeted metabolomics assay showed downregulated glycolysis and upregulated fatty acid oxidation. The targeted metabolomics assay revealed significant upregulation of glycine. The kidneys of db/db mice undergo significant metabolic reprogramming, with changes in sugar, lipid and amino acid metabolism; CANA regulated the metabolic reprogramming in the kidneys of db/db mice. In particular, the pathways for glycine, serine and threonine metabolism, as well as the metabolite of glycine, were significantly upregulated in CANA-treated kidneys. Glycine supplementation ameliorated renal lesions in db/db mice by inhibiting food intake, improving insulin sensitivity and reducing blood glucose levels. Glycine supplementation improved apoptosis of human proximal tubule cells via the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. CONCLUSIONS/INTERPRETATION: In conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.

High-capacity removal of oxytetracycline hydrochloride from wastewater via Mikania micrantha Kunth-derived biochar modified by Zn/Fe-layered double hydroxide.

Antibiotic contamination in water has been an increasing global concern, and how to effectively remove antibiotics (e.g., oxytetracycline [OTC] hydrochloride) from wastewater becomes imperative. In this study, the biochar derived from an invasive plant (Mikania micrantha Kunth) was synthesized with Zn/Fe- layered double hydroxide (LDH) by co-precipitation method (ZnFe-LDH/MBC) to remove OTC from water. ZnFe-LDH/MBC posed the highest OTC removal performance of 426.61 mg/g. ZnFe-LDH/MBC exhibited stability and efficiency in OTC adsorption at different pH levels and under interfering conditions with co-existing ions, as well as outstanding regeneration capabilities during adsorption-desorption cycles. Furthermore, the removal of OTC by ZnFe-LDH/MBC was mediated by several processes including pore filling, hydrogen bonding force, electrostatic interaction, π-π interaction, as well as complexation. Consequently, ZnFe-LDH/MBC has excellent potential for the purification of OTC pollutants that is low-cost, efficient, and environmentally friendly.

Morphology-controlled electrochemical sensing amaranth at nanomolar levels using alumina.

Different-shaped aluminas were readily prepared via hydrothermal reaction. It was found that the morphology and the electrochemical sensing properties of alumina were heavily dependent on the reaction time. When extending the reaction time from 6 h to 24 h, the obtained alumina samples changed from amorphous bumps to regular microfibers in diameter of 200 nm, as confirmed by scanning electron microscopy. Transmission electron microscopy observation revealed that longer reaction time was beneficial for the formation of porous and uniform fiber-like structures. Electrochemical tests proved that alumina microfibers were more active for the oxidation of amaranth and exhibited much higher enhancement effect, compared with alumina bumps. On the surface of alumina microfibers, the oxidation peak currents of amaranth increased remarkably. The influences of pH value, amount of alumina microfibers, and accumulation time on the signal enhancement of amaranth were discussed. As a result, a novel electrochemical method was developed for the detection of amaranth. The linear range was from 1 to 150 nM, and the detection limit was 0.75 nM after 1-min accumulation. The analytical application in drink samples was investigated, and the results consisted with the values that obtained by high-performance liquid chromatography.

A disposable electrochemical sensor for the determination of indole-3-acetic acid based on poly(safranine T)-reduced graphene oxide nanocomposite.

A disposable electrochemical sensor for the determination of indole-3-acetic acid (IAA) based on nanocomposites of reduced graphene oxide (rGO) and poly(safranine T) (PST) was reported. The sensor was prepared by coating a rGO film on a pre-anodized graphite electrode (AGE) through dipping-drying and electrodepositing a uniform PST layer on the rGO film. Scanning electron microscopic (SEM) and infrared spectroscopic (IR) characterizations indicated that PST-rGO formed a rough and crumpled composite film on AGE, which exhibited high sensitive response for the oxidation of IAA with 147-fold enhancement of the current signal compared with bare AGE. The voltammetric current has a good linear relationship with IAA concentration in the range 1.0×10(-7)-7.0×10(-6)M, with a low detection limit of 5.0×10(-8)M. This sensor has been applied to the determination of IAA in the extract samples of several plant leaves and the recoveries varied in the range of 97.71-103.43%.