Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well as genetic and environmental factors. Liraglutide has been used to control blood sugar. But the impact of liraglutide on T2DM-associated NAFLD remains unclear. In this study, we investigated the impact and potential molecular mechanisms of inhibiting ferroptosis for liraglutide improves T2DM-associated NAFLD. Methods: Mice were fed on high-fat-diet and injected with streptozotocin to mimic T2DM-associated NAFLD and gene expression in liver was analysed by RNA-seq. The fast blood glucose was measured during the period of liraglutide and ferrostatin-1 administration. Hematoxylin and eosin staining was used to evaluate the pathological changes in the liver. The occurrence of hepatic ferroptosis was measured by lipid peroxidation in vivo. The mechanism of liraglutide inhibition ferroptosis was investigated by in vitro cell culture. Results: Liraglutide not only improved glucose metabolism, but also ameliorated tissue damage in the livers. Transcriptomic analysis indicated that liraglutide regulates lipid metabolism related signaling including AMPK and ACC. Furthermore, ferroptosis inhibitor rather than other cell death inhibitors rescued liver cell viability in the presence of high glucose. Mechanistically, liraglutide-induced activation of AMPK phosphorylated ACC, while AMPK inhibitor compound C blocked the liraglutide-mediated suppression of ferroptosis. Moreover, ferroptosis inhibitor restored liver function in T2DM mice in vivo. Conclusions: These findings indicate that liraglutide ameliorates the T2DM-associated NAFLD, which possibly through the activation of AMPK/ACC pathway and inhibition of ferroptosis.

Biomass waste treatment and detrimental dye adsorption are two of the crucial environmental issues nowadays. In this study, we investigate to simultaneously resolve the aforementioned issues by synthesizing chitosan sponges as adsorbents toward rose bengal (RB) dye adsorption. Through a temperature-controlled freeze-casting process, robust and recyclable chitosan sponges are fabricated with hierarchical porosities resulted from the control of concentrations of chitosan solutions. Tested as the adsorbents for RB, to the best of our knowledge, the as-prepared chitosan sponge in this work reports the highest adsorption capacity of RB (601.5 mg/g) ever. The adsorption mechanism, isotherm, kinetics, and thermodynamics are comprehensively studied by employing statistical analysis. Importantly and desirably, the sponge type of chitosan adsorbents exceedingly facilitates the retrieving and elution of chitosan sponges for recyclable uses. Therefore, the chitosan sponge adsorbent is demonstrated to possess dramatically squeezable capability with durability for 10,000 cycles and recyclable adsorption for at least 10 cycles, which provides an efficient and economical way for both biomass treatment and water purification.

Canagliflozin, an inhibitor of sodium glucose co-transporter (SGLT) 2, has been shown to reduce body weight during the treatment of type 2 diabetes mellitus (T2DM). In this study, we sought to determine the role of canagliflozin in body weight loss and liver injury in obesity. C57BL/6J mice were fed a high-fat diet to simulate diet-induced obesity (DIO). Canagliflozin (15 and 60 mg/kg) was administered to DIO mice for 4 weeks. Orlistat (10 mg/kg) was used as a positive control. The body weight, liver weight, liver morphology, total cholesterol (TC) and triglyceride (TG) levels were examined. Signaling molecules, including diacylgycero1 acyltransferase-2 (DGAT2), peroxisome proliferation receptor alpha-1 (PPARα1), PPARγ1, PPARγ2 mRNA levels and the protein expression of SGLT2 were evaluated. Canagliflozin reduced body weight, especially the high-dose canagliflozin, and resulted in increased body weight loss compared with orlistat. Moreover, canagliflozin reduced the liver weight and the ratio of liver weight to body weight, lowered the serum levels of TC and TG, and ameliorated liver steatosis. During the canagliflozin treatment, SGLT2, DGAT2, PPARγ1 and PPARγ2 were inhibited, and PPARα1 was elevated in the liver tissues. This finding may explain why body weight was reduced and secondary liver injury was ameliorated in response to canagliflozin. Together, the results suggest that canagliflozin may be a potential anti-obesity strategy.

Ulcerative colitis (UC) is defined by persistent inflammatory processes within the gastrointestinal tract of uncertain etiology. Current therapeutic approaches are limited in their ability to address oxidative stress, inflammation, barrier function restoration, and modulation of gut microbiota in a coordinated manner to maintain intestinal homeostasis. This study involves the construction of a metal-phenolic nanozyme (Cur-Fe) through a ferric ion-mediated oxidative coupling of curcumin. Cur-Fe nanozyme exhibits superoxide dismutase (SOD)-like and •OH scavenging activities, demonstrating significant anti-inflammatory and anti-oxidant properties for maintaining intracellular redox balance in vitro. Drawing inspiration from Escherichia coli Nissle 1917 (EcN), a biomimetic Cur-Fe nanozyme (CF@EM) is subsequently developed by integrating Cur-Fe into the EcN membrane (EM) to improve the in vivo targeting ability and therapeutic effectiveness of the Cur-Fe nanozyme. When orally administered, CF@EM demonstrates a strong ability to colonize the inflamed colon and restore intestinal redox balance and barrier function in DSS-induced colitis models. Importantly, CF@EM influences the gut microbiome towards a beneficial state by enhancing bacterial diversity and shifting the compositional structure toward an anti-inflammatory phenotype. Furthermore, analysis of intestinal microbial metabolites supports the notion that the therapeutic efficacy of CF@EM is closely associated with bile acid metabolism. Inspired by gut microbes, we have successfully synthesized a biomimetic Cur-Fe nanozyme with the ability to inhibit inflammation and restore intestinal homeostasis. Collectively, without appreciable systemic toxicity, this work provides an unprecedented opportunity for targeted oral nanomedicine in the treatment of ulcerative colitis.

Diabetic nephropathy (DN), one of the most detrimental microvascular complications of diabetes, is the leading cause of end-stage renal disease. The pathogenesis of DN is complicated, including hemodynamic changes, inflammatory response, oxidative stress, among others. Recently, many studies have demonstrated that mitophagy, especially PINK1/Parkin-mediated mitophagy, plays an important role in the pathogenesis of DN. Erythropoietin (EPO), a glycoprotein hormone mainly secreted by the kidney, regulates the production of erythrocytes. This research intends to explore the beneficial effects of EPO on DN and investigate related mechanisms. In in vitro experiments, we found that EPO promoted autophagic flux and alleviated mitochondrial dysfunction in terms of mitochondrial fragmentation, elevated mitochondrial ROS as well as the loss of mitochondrial potential, and lowered the apoptosis level in high-glucose-treated mesangial cells. Moreover, EPO increased protein expressions of PINK1 and Parkin, enhanced the co-localization of LC3 with mitochondria, Parkin with mitochondria as well as LC3 with Parkin, and increased the number of GFP-LC3 puncta, resulting in increased level of PINK1/Parkin-mediated mitophagy in mesangial cells. The knockdown of PINK1 abrogated the effect of EPO on mitophagy. In addition, in vivo experiments demonstrated that EPO attenuated renal injury, reduced oxidative stress, and promoted expressions of genes related to PINK1/Parkin-mediated mitophagy in the kidneys of DN mice. In summary, these results suggest that PINK1/Parkin-mediated mitophagy is involved in the development of DN and EPO mitigates DN by restoring PINK1/Parkin-mediated mitophagy.