Thiyl Radical Trapped by Cobalt Catalysis: An Approach to Markovnikov Thiol-Ene Reaction.

In the presence of a thiyl radical species, the catalytic Markovnikov thiol-ene reaction is challenging because it prefers to proceed via a radical pathway, thereby leading to anti-Markovnikov selectivity. In this work, a rare example of thiyl radical engaged in Markovnikov thiol-ene reaction enabled by cobalt catalysis is reported. This protocol features the avoidance of unique oxidants, exclusive regioselectivity, and broad substrate scope. Scalable synthesis and late-stage modification of complex molecules demonstrate the practicability of the protocol.

Knockdown of miR-372-3p Inhibits the Development of Diabetic Cardiomyopathy by Accelerating Angiogenesis via Activating the PI3K/AKT/mTOR/HIF-1α Signaling Pathway and Suppressing Oxidative Stress.

Background: DCM is the most common and malignant complication of diabetes. It is characterized by myocardial dilatation, hypertrophy, fibrosis, ventricular remodeling, and contractile dysfunction. Although many studies have demonstrated the function of miRNAs in the progression of DCM, but the specific role of miR-372-3p in DCM remains unknown. Methods: C57/BL6J mice were used to construct mouse models of DCM by intraperitoneal injection of STZ (50 mg/kg/d) for 5 consecutive days. Then the mice were randomly divided into model group (intramyocardial injection of empty lentivirus) and miR-372-3p KD group (intramyocardial injection of miR-372-3p KD lentivirus at 109/mouse). Besides, the control group (injection of 0.9% normal saline) was also set up. LY294002, a PI3K inhibitor, was employed in the current study. Western blotting, immunofluorescence staining, quantitative ultrasound method, Masson's trichrome staining, and bioinformatics analysis were performed. Results: It was found that miR-372-3p KD significantly improved left ventricular dysfunction and cardiac hypertrophy in DCM mice. Furthermore, it also improved myocardial interstitial fibrosis and remodeling in DCM mice. Immunofluorescence staining and RT-qPCR revealed that miR-372-3p KD might accelerate cardiac remodeling by increasing angiogenesis in DCM mice. Western blotting results revealed that miR-372-3p was an upstream target of the PI3K/AKT-mTOR and HIF-1α signals, as well as NOX2, NOX4, which were responsible for angiogenesis in DCM mice. Besides, the in vitro experiment showed that LY294002 markedly diminished the increased expression levels of p-PI3K, AKT, p-mTOR, p-P70S6K, HIF-1α, NOX2, and NOX4 in the model group and the miR-372-3p KD group, suggesting that PI3K signaling pathway and oxidative stress are involved in miR-372-3p KD-induced angiogenesis in HG-stimulated C166 cells. Conclusions: MiR-372-3p KD inhibits the development of DCM via activating the PI3K/AKT/mTOR/HIF-1α signaling pathway or suppressing oxidative stress. This offers an applicable biomarker for DCM treatment.

Correction: A novel electrochemical sensor based on microporous polymeric nanospheres for measuring peroxynitrite anion released by living cells and studying the synergistic effect of antioxidants.

Correction for 'A novel electrochemical sensor based on microporous polymeric nanospheres for measuring peroxynitrite anion released by living cells and studying the synergistic effect of antioxidants' by Fuxin Liu et al., Analyst, 2019, 144, 6905-6913, https://doi.org/10.1039/C9AN01693G.

A novel electrochemical sensor based on microporous polymeric nanospheres for measuring peroxynitrite anion released by living cells and studying the synergistic effect of antioxidants.

Peroxynitrite anion (ONOO-) is a crucial reactive nitrogen species (RNS), which has aroused immense research interest in the biological and biomedical fields because aberrant expression levels of ONOO- are related to many diseases. In this work, a novel electrochemical sensor is described for the detection of peroxynitrite anion (ONOO-) released from living cells. It is constructed with a glassy carbon electrode (GCE) decorated with a nanocomposite (CTS-MPNS) synthesized from chitosan (CTS) functionalized microporous polymeric nanospheres (MPNS). The prepared CTS-MPNS/GCE sensor shows a supernormal manifestation in measuring ONOO- in a wide range of concentrations from 3.83 nM to 0.104 mM, and the detection limit is as low as 1.28 nM (S/N = 3), which makes it possible to detect trace amounts of ONOO- released from U87 cells. Significantly, the synergistic effect of different antioxidants on scavenging ONOO- in biological systems is further studied by an electrochemical method for the first time, which provides an efficient strategy for protecting cells against oxidative stress. The developed platform and the efficient strategy may pave the way for their future applications in the field of biomedicine and the treatment of cancer diseases.

Metal-organic framework derived carbon-based sensor for monitoring of the oxidative stress of living cell and assessment of antioxidant activity of food extracts.

A novel non-enzymatic superoxide anion radical (O2•-) sensor was prepared by silver nanoparticles (AgNPs) decorated organic frameworks (MOFs) compound-derived metal oxide coated carbon material. Transmission electron microscopy (TEM) was employed to characterize morphologies and structures of the as-prepared samples AgNPs/Co3O4@C. Electrochemical studies indicated that the AgNPs/Co3O4@C/GCE exhibited excellent detection ability to O2•-. It offered a linear range of 8 orders of magnitude and a super low detection limits of 0.0564 pM. The sensor was successfully adapted to detection of O2•- released from living cells. Furthermore, the capacities of scavenging O2•- of food antioxidants were also studied by electrochemical method at cellular milieu. Accordingly, this work provided tremendous potential for reduction incidence of oxidative stress by intaking food antioxidants.

Protective effects of Schisandrin on high glucose-induced changes of RhoA and eNOS activity in human umbilical vein endothelial cells.

Schisandrin, derived from the Chinese medicinal herb Schisandra chinensis, has been found to confer protective effects on circulation systems. But the underlying molecular mechanisms remain unclear. The aim of this study was to investigate the effects of a high level of glucose on RhoA and eNOS activity in human umbilical vein endothelial cells(HUVECs) and how Schisandrin plays a role in mediating these effects. To find the optimal treatment time, HUVECs were cultured at a high glucose concentration (30 mM) for different lengths of time (0, 12, 24, and 48 h). Subsequently, the cells were randomized into five groups: a normal group, a high glucose group, and three high glucose groups that were given different doses (5, 10, and 20 µM) of Schisandrin. The cells were pretreated with Schisandrin for 24 h before stimulation with high glucose. The morphology of HUVECs in the various groups was assessed under a light microscope. Immunocytochemical staining was used to detect the level of p-MYPT1 expression. The levels of RhoA activity were determined using the RhoA Activation Assay Biochem Kit. The levels of eNOS activity were examined using a nitrate reduction test. The results showed that in the high glucose group, the activity of RhoA was increased and the activity of eNOS was reduced, thus decreasing the secretion of NO. However, after pretreatment with Schisandrin (10, 20 µM), the activity of RhoA was inhibited and the activity of eNOS increased, which led to an increase in NO production compared with the high glucose group. There was no evident difference between the 5 µM Schisandrin group and the high glucose group. Taken together, these findings indicate that Schisandrin can improve the function of endothelial cells by lowering the activity of RhoA/Rho kinase and raising both the activity of eNOS and the production of NO.

Comparative pharmacokinetics and bioavailability of four alkaloids in different formulations from Corydalis decumbens.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis decumbens, a Traditional Chinese Medicine listed in Chinese Pharmacopoeia, is clinically used for the treatment of paralytic stroke, headache, rheumatic arthritis and sciatica in China. AIM OF THE STUDY: This study was aimed to compare the pharmacokinetics and bioavailability of protopine, tetrahydropalmatine, bicuculline, and egenine in three formulations prepared from the rhizomes of Corydalis decumbens. MATERIALS AND METHODS: Alkaloid extract (CDAs-SFE) was prepared from the rhizomes of Corydalis decumbens by supercritical CO2 fluid extraction; CDAs-SFE/HPßCD (hydroxypropyl-ß-cyclodextrin inclusion complex), and CDAs-SFE/HCl (hydrochloride freeze-dried powder) were resulted from CDAs-SFE through complexation with HPßCD and hydrochloride, respectively. An UFLC-MS/MS method was developed for quantitative analysis of protopine, tetrahydropalmatine, bicuculline and egenine simultaneously in rat plasma after oral administration. The differences of pharmacokinetics and bioavailability of the four alkaloids in three formulations were determined by pharmacokinetics analyses. RESULTS AND CONCLUSIONS: The Cmax, AUC and bioavailability of protopine and tetrahydropalamatine (bioactive components) in CDAs-SFE/HCl were significantly higher than in CDAs-SFE and in CDAs-SFE/HPßCD. In contrast, in CDAs-SFE/HPßCD, AUC and bioavailability of tetrahydropalamatine were significantly lower, while those of bicuculline (toxic compound) appeared to be higher than both in CDAs-SFE and in CDAs-SFE/HCl. The results indicated that CDAs-SFE/HCl was the best beneficial formulation among the three formulations for the alkaloid extract prepared from the rhizomes of Corydalis decumbens, in which protopine and tetrahydropalamatine displayed higher bioavailability, but lower for bicuculline.