Myricetin alleviates diabetic cardiomyopathy by regulating gut microbiota and their metabolites.

BACKGROUND: The gut microbiota is involved in the pathogenesis of diabetic cardiomyopathy (DCM). Myricetin protects cardiac function in DCM. However, the low bioavailability of myricetin fails to explain its pharmacological mechanisms thoroughly. Research has shown that myricetin has a positive effect on the gut microbiota. We hypothesize that myricetin improves the development of DCM via regulating gut microbiota. METHODS: DCM mice were induced with streptozotocin and fed a high-fat diet, and then treated with myricetin by gavage and high-fat diet for 16 weeks. Indexes related to gut microbiota composition, cardiac structure, cardiac function, intestinal barrier function, and inflammation were detected. Moreover, the gut contents were transplanted to DCM mice, and the effect of fecal microbiota transplantation (FMT) on DCM mice was assessed. RESULTS: Myricetin could improve cardiac function in DCM mice by decreasing cardiomyocyte hypertrophy and interstitial fibrosis. The composition of gut microbiota, especially for short-chain fatty acid-producing bacteria involving Roseburia, Faecalibaculum, and Bifidobacterium, was more abundant by myricetin treatment in DCM mice. Myricetin increased occludin expression and the number of goblet cells in DCM mice. Compared with DCM mice unfed with gut content, the cardiac function, number of goblet cells, and expression of occludin in DCM mice fed by gut contents were elevated, while cardiomyocyte hypertrophy and TLR4/MyD88 pathway-related proteins were decreased. CONCLUSIONS: Myricetin can prevent DCM development by increasing the abundance of beneficial gut microbiota and restoring the gut barrier function.

6-Gingerol Alleviates Ferroptosis and Inflammation of Diabetic Cardiomyopathy via the Nrf2/HO-1 Pathway.

Background: Diabetes mellitus (DM) can induce cardiomyocyte injury and lead to diabetic cardiomyopathy (DCM) which presently has no specific treatments and consequently increase risk of mortality. Objective: To characterize the therapeutic effect of 6-gingerol (6-G) on DCM and identify its potential mechanism. Methods: In vivo streptozotocin- (STZ-) induced DM model was established by using a high-fat diet and STZ, followed by low-dose (25 mg/kg) and high-dose (75 mg/kg) 6-G intervention. For an in vitro DCM model, H9c2 rat cardiomyoblast cells were stimulated with high glucose (glucose = 33 mM) and palmitic acid (100 µM) and then treated with 6-G (100 µM). Histological and echocardiographic analyses were used to assess the effect of 6-G on cardiac structure and function in DCM. Western blotting, ELISA, and real-time qPCR were used to assess the expression of ferroptosis, inflammation, and the Nrf2/HO-1 pathway-related proteins and RNAs. Protein expression of collagen I and collagen III was assessed by immunohistochemistry, and kits were used to assay SOD, MDA, and iron levels. Results: The results showed that 6-G decreased cardiac injury in both mouse and cell models of DCM. The cardiomyocyte hypertrophy and interstitial fibrosis were attenuated by 6-G treatment in vivo and resulted in an improved heart function. 6-G inhibited the expression of ferroptosis-related protein FACL4 and the content of iron and enhanced the expression of anti-ferroptosis-related protein GPX4. In addition, 6-G also diminished the secretion of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. 6-G treatment activated the Nrf2/HO-1 pathway, enhanced antioxidative stress capacity proved by increased activity of SOD, and decreased MDA production. Compared with in vivo, 6-G treatment of H9c2 cells treated with high glucose and palmitic acid could produce a similar effect. Conclusion: These findings suggest that 6-G could protect against DCM by the mechanism of ferroptosis inhibition and inflammation reduction via enhancing the Nrf2/HO-1 pathway.

Electrolyte Concentration Regulation Boosting Zinc Storage Stability of High-Capacity K0.486V2O5 Cathode for Bendable Quasi-Solid-State Zinc Ion Batteries.

Vanadium-based cathodes have attracted great interest in aqueous zinc ion batteries (AZIBs) due to their large capacities, good rate performance and facile synthesis in large scale. However, their practical application is greatly hampered by vanadium dissolution issue in conventional dilute electrolytes. Herein, taking a new potassium vanadate K0.486V2O5 (KVO) cathode with large interlayer spacing (~ 0.95 nm) and high capacity as an example, we propose that the cycle life of vanadates can be greatly upgraded in AZIBs by regulating the concentration of ZnCl2 electrolyte, but with no need to approach "water-in-salt" threshold. With the optimized moderate concentration of 15 m ZnCl2 electrolyte, the KVO exhibits the best cycling stability with ~ 95.02% capacity retention after 1400 cycles. We further design a novel sodium carboxymethyl cellulose (CMC)-moderate concentration ZnCl2 gel electrolyte with high ionic conductivity of 10.08 mS cm-1 for the first time and assemble a quasi-solid-state AZIB. This device is bendable with remarkable energy density (268.2 Wh kg-1), excellent stability (97.35% after 2800 cycles), low self-discharge rate, and good environmental (temperature, pressure) suitability, and is capable of powering small electronics. The device also exhibits good electrochemical performance with high KVO mass loading (5 and 10 mg cm-2). Our work sheds light on the feasibility of using moderately concentrated electrolyte to address the stability issue of aqueous soluble electrode materials.

Surface and Interface Engineering of Nanoarrays toward Advanced Electrodes and Electrochemical Energy Storage Devices.

The overall performance of electrochemical energy storage devices (EESDs) is intrinsically correlated with surfaces and interfaces. As a promising electrode architecture, 3D nanoarrays (3D-NAs) possess relatively ordered, continuous, and fully exposed active surfaces of individual nanostructures, facilitating mass and electron transport within the electrode and charge transfer across interfaces and providing an ideal platform for engineering. Herein, a critical overview of the surface and interface engineering of 3D-NAs, from electrode and interface designs to device integration, is presented. The general merits of 3D-NAs and surface/interface engineering principles of 3D-NA hybrid electrodes are highlighted. The focus is on the use of 3D-NAs as a superior platform to regulate the interface nature and unveiling new mechanism/materials without the interference of binders. The engineering and utilization of the surface of 3D-NAs to develop flexible/solid-state EESDs with 3D integrated electrode/electrolyte interfaces, or 3D triphase interfaces involving other active species, which are characteristic of (quasi-)solid-state electrolyte infiltration into the entire device, are also considered. Finally, the challenges and future directions of surface/interface engineering of 3D-NAs are outlined. In particular, potential strategies to obtain electrode charge balance, optimize the multiphase solid-state interface, and attain 3D solid electrolyte infiltration are proposed.