Oxidative stress signaling in the pathogenesis of diabetic cardiomyopathy and the potential therapeutic role of antioxidant naringenin.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders that poses a global threat to human health. It can lead to complications in multiple organs and tissues, owing to its wide-ranging impact on the human body. Diabetic cardiomyopathy (DCM) is a specific cardiac manifestation of DM, which is characterized by heart failure in the absence of coronary heart disease, hypertension and valvular heart disease. Given that oxidative stress is a key factor in the pathogenesis of DCM, intervening to mitigate oxidative stress may serve as a therapeutic strategy for managing DCM. Naringenin is a natural product with anti-oxidative stress properties that can suppress oxidative damage by regulating various oxidative stress signaling pathways. In this review, we address the relationship between oxidative stress and its primary signaling pathways implicated in DCM, and explores the therapeutic potential of naringenin in DCM.

SGLT2 Inhibitors in Aging-Related Cardiovascular Disease: A Review of Potential Mechanisms.

Population aging combined with higher susceptibility to cardiovascular diseases in older adults is increasing the incidence of conditions such as atherosclerosis, myocardial infarction, heart failure, myocardial hypertrophy, myocardial fibrosis, arrhythmia, and hypertension. sodium-glucose cotransporter 2 inhibitors (SGLT2i) were originally developed as a novel oral drug for patients with type 2 diabetes mellitus. Unexpectedly, recent studies have shown that, beyond their effect on hyperglycemia, SGLT2i also have a variety of beneficial effects on cardiovascular disease. Experimental models of cardiovascular disease have shown that SGLT2i ameliorate the process of aging-related cardiovascular disease by inhibiting inflammation, reducing oxidative stress, and reversing endothelial dysfunction. In this review, we discuss the role of SGLT2i in aging-related cardiovascular disease and propose the use of SGLT2i to prevent and treat these conditions in older adults.

Pyroptosis-Related Inflammasome Pathway: A New Therapeutic Target for Diabetic Cardiomyopathy.

Pyroptosis is a highly specific type of inflammatory programmed cell death that is mediated by Gasdermine (GSDM). It is characterized by inflammasome activation, caspase activation, and cell membrane pore formation. Diabetic cardiomyopathy (DCM) is one of the leading diabetic complications and is a critical cause of fatalities in chronic diabetic patients, it is defined as a clinical condition of abnormal myocardial structure and performance in diabetic patients without other cardiac risk factors, such as hypertension, significant valvular disease, etc. There are no specific drugs in treating DCM despite decades of basic and clinical investigations. Although the relationship between DCM and pyroptosis is not well established yet, current studies provided the impetus for us to clarify the significance of pyroptosis in DCM. In this review, we summarize the recent literature addressing the role of pyroptosis and the inflammasome in the development of DCM and summary the potential use of approaches targeting this pathway which may be future anti-DCM strategies.

Exploring the substructural space of indole-3-carboxamide derivatives binding to renin: a novel active-site spatial partitioning approach.

Renin has recently attracted much attention in the antihypertensive community, since this enzyme starts the angiotensin-converting cascade and forms the rate-limiting step in this cascade. In the present study, we describe a new method called active-site spatial partitioning (ASSP) for quantitatively characterizing the nonbonding interaction profile between renin and the substructures of indole-3-carboxamide derivatives-a novel class of achiral renin inhibitors that exhibit both high affinity and strong specificity for renin, thus blocking its active state-on the basis of structural models of protein-ligand complexes. It is shown that the ASSP-derived potential parameters are highly correlated with the experimentally measured activities of indole-3-carboxamides; the statistical models linking the parameters and activities using a sophisticated partial least squares regression technique show much promise as an effective and powerful tool for generalizing and predicting the pharmaceutical potencies and the physicochemical properties of other modified derivatives. Furthermore, by visually examining substructure-color plots generated by the ASSP procedure, it is found that the relative importance of nonbonding contributions to the recognition and binding of a ligand by renin is as follows: steric < hydrophobic < electrostatic. The polar and charged moieties that float on the surface of the ligand molecule play a critical role in conferring electrostatic stability and specificity to renin-ligand complexes, whereas the aromatic rings embedded in the core region of the ligand are the main source of hydrophobic and steric potentials that lead to substantial stabilization of the complex architecture.

Expression of interleukin-15 and its receptor on the surface of stimulated human umbilical vein endothelial cells.

Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) to induce the production of human interleukin-15 (hIL-15) and IL-15 receptor (IL-15Ralpha) by human umbilical vein endothelial cells (HUVECs). The data are summarized as follows: 1. Northern blot revealed that IL-15 mRNA was up-regulated by IFN-gamma and TNF-alpha. 2. Intracellular IL-15 protein was visualized by fluorescence microscopy, whereas the expression of IL-15 on the surface of HUVECs was detected by fluorescence activated cell sorting (FACS), and no detectable IL-15 in the medium was verified by ELISA. 3. IL-15Ralpha was detected on the surface of HUVECs by FACS after IFN-gamma and TNF-alpha stimulation, whereas Western blotting revealed that the elevated expression on surface IL-15Ralpha was not due to the increased protein expression. The conclusion demonstrated from our results is that IFN-gamma and TNF-alpha play an important role in regulating the expression of IL-15 and IL-15Ralpha on the surface of HUVECs.

Expression of Interleukin-15 and Its Receptor on the Surface of Stimulated Human Umbilical Vein Endothelial Cells / 华中科技大学学报（医学）（英德文版）

Human interleukin-15 (hlL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-γ,(IFN-γ), and tumor necrosis factor-ct (TNF-α) to induce the production of human interleukin-15 (hlL-15)and IL-15 receptor (IL-15Rα) by human umbilical vein endothelial cells (HUVECs). The data are summarized as follows: 1. Northern blot revealed that IL-15 mRNA was up-regulated by IFN-γ and TNF-α. 2. lntracellular IL-15 protein was visualized by fluorescence microscopy, whereas the expres-sion of IL-15 on the surface of HUVECs was detected by fluorescence activated cell sorting (FACS),and no detectable IL-15 in the medium was verified by ELISA. 3. IL-15Rα was detected on the surface of HUVECs by FACS after IFN-γ and TNF-α stimulation, whereas Western blotting revealed that the elevated expression on surface IL-15Rα was not due to the increased protein expression. The conclusion demonstrated from our results is that IFN-γ and TNF-α play an important role in regulating the expres-sion of IL-15 and IL-15Rα on the surface of HUVECs.