Hypervalent Iodine-Mediated Synthesis of Sulfinimidate Esters from Sulfenamides.

In this study, we present a novel and efficient approach for the oxidative esterification of sulfenamides using phenyliodonium diacetate, enabling the synthesis of sulfinimidate esters and sulfilimines under mild and metal-free conditions, with yields reaching up to 99%. The protocol is readily scalable and compatible with a diverse range of substrates and functional groups, and we demonstrate its potential for late-stage functionalization of pharmacologically relevant molecules. Furthermore, we propose a plausible reaction mechanism to account for the observed sequence of events.

miR-92a regulates the expression levels of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 3 via sirtuin 1 signaling in hydrogen peroxide-induced vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) exhibit a notably increased rate of migration, which is one of the most common pathological changes in atherosclerosis. Investigations into the role of micro (mi)RNAs in the regulation of VSMC migration are beginning to emerge and additional miRNAs involved in VSMC migration modulation require identification. In the current study, VSMCs were primarily cultured from rat thoracic aortas, transfected with miR­92a mimics and induced by hydrogen peroxide (H2O2) for 24 h. Total mRNA and protein were collected for quantitative polymerase chain reaction and western blot analysis. In addition, the sirtuin 1 (SIRT1) gene was detected by luciferase reporter assay and VSMC migration was detected by Transwell migration assay. The current results demonstrated that reduced expression of miR­92a and overexpression of SIRT1 at the mRNA level were observed in H2O2­induced VSMCs. Furthermore, luciferase reporter assay demonstrated that the activity of the SIRT1 3'­untranslated region was reduced by miR­92a mimics. The upregulation of MMP9 and the downregulation of TIMP3 in H2O2­induced VSMCs were observed to be reversed by miR­92a mimics in addition to SIRT1 siRNA. Finally, Transwell migration assay revealed that miR­92a overexpression and silencing SIRT1 mitigated VSMC migration following H2O2 treatment. The present study indicated that miR­92a prevented the migration of H2O2­induced VSMCs by repressing the expression of SIRT1, and also provided a novel therapy to protect against the phenotypic change of VSMCs in atherosclerosis.

Activation of nuclear ß-catenin/c-Myc axis promotes oxidative stress injury in streptozotocin-induced diabetic cardiomyopathy.

Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/ß-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with ß-catenin in DCM remains elusive. This study intended to explore the effect of ß-catenin on oxidative damage of DCM by establishing streptozotocin (STZ)-induced diabetic mouse model and hydrogen peroxide (H2O2)-treated myocardial cell model. Cardiac oxidative stress in DCM was detected by measurements of lipid peroxidation and anti-oxidative enzyme activities as well as DHE staining. Nuclear ß-catenin activity and oxidative damage degree were measured by western blotting, qPCR, MTT assay and TUNEL staining. Cardiac function and morphology were evaluated by echocardiography and histopathology. Under diabetic oxidative stress or H2O2 stimulation, nuclear ß-catenin accumulation upregulated downstream c-Myc and further facilitated DNA damage and p53-mediated apoptosis as well as cell viability reduction, followed by phenotypic changes of cardiac dysfunction, interstitial fibrosis deposition and myocardial atrophy. Conversely, through directly inhibiting nuclear ß-catenin/c-Myc axis, not only did siRNA knockdown of ß-catenin or c-Myc attenuate cell injury in H2O2-stimulated cardiomyocytes, but also diabetic cardiac-specific ß-catenin-knockout mice displayed the same prevention of heart injury as insulin-treated diabetic mice. The present study demonstrated that activated nuclear ß-catenin/c-Myc axis was responsible for oxidative cardiac impairment of DCM. Therefore, repressing functional nuclear ß-catenin may provide a hopeful therapeutic strategy for DCM.