Mitochondrial ROS-Mediated Metabolic and Cytotoxic Effects of Isoproterenol on Cardiomyocytes Are p53-Dependent and Reversed by Curcumin

Acute β-adrenergic stimulation contributes to heart failure. Here, we investigated the role of p53 in isoproterenol (ISO)-mediated metabolic and oxidative stress effects on cardiomyocytes and explored the direct protective effects offered by the antioxidant nutraceutical curcumin. Differentiated H9C2 rat cardiomyocytes treated with ISO were assayed for glucose uptake, lactate release, and mitochondrial reactive oxygen species (ROS) generation. Survival was assessed by sulforhodamine B assays. Cardiomyocytes showed significantly decreased glucose uptake and lactate release, as well as increased cellular toxicity by ISO treatment. This was accompanied by marked dose-dependent increases of mitochondria-derived ROS. Scavenging with N-acetyl-L-cysteine (NAC) effectively lowered ROS levels, which completely recovered glycolytic metabolism and survival suppressed by ISO. Mechanistically, ISO reduced extracellular-signal-regulated kinase (ERK) activation, whereas it upregulated p53 expression in an ROS-dependent manner. Silencing of p53 with siRNA blocked the ability of ISO to stimulate mitochondrial ROS and suppress glucose uptake, and partially recovered cell survival. Finally, curcumin completely reversed the metabolic and ROS-stimulating effects of ISO. Furthermore, curcumin improved survival of cardiomyocytes exposed to ISO. Thus, ISO suppresses cardiomyocyte glycolytic metabolism and survival by stimulating mitochondrial ROS in a p53-dependent manner. Furthermore, curcumin can efficiently rescue cardiomyocytes from these adverse effects.     

Exploring Helical Folding in Oligomers of Cyclopentane‐Based ϵ‐Amino Acids: A Computational Study

Invited for this month''s cover picture is the group of Young Kee Kang at Chungbuk National University (Republic of Korea). The cover picture shows the preferred conformation of the hexamer of ϵ‐amino acid Amc₅a with a cyclopentane substituent in the backbone investigated using DFT methods in chloroform and water. The Amc₅a hexamer adopted a stable left‐handed conformation with a rise of 4.8 Å per turn both in chloroform and water. However, the hexamer of Ampa (an analogue of Amc₅a with replacing cyclopentane by pyrrolidine) adopted different conformations in chloroform and in water. Read the full text of their Research Article at 10.1002/open.202100253.

“…Finding the appropriate protocol is a crucial step for conformational prediction of peptides and peptide foldamers in solution…” Find out more about the story behind the front cover research at 10.1002/open.202100253.     

Human cardiac stem cells rejuvenated by modulating autophagy with MHY-1685 enhance the therapeutic potential for cardiac repair

Stem cell-based therapies with clinical applications require millions of cells. Therefore, repeated subculture is essential for cellular expansion, which is often complicated by replicative senescence. Cellular senescence contributes to reduced stem cell regenerative potential as it inhibits stem cell proliferation and differentiation as well as the activation of the senescence-associated secretory phenotype (SASP). In this study, we employed MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, and examined its long-term priming effect on the activities of senile human cardiac stem cells (hCSCs) and the functional benefits of primed hCSCs after transplantation. In vitro experiments showed that the MHY-1685‒primed hCSCs exhibited higher viability in response to oxidative stress and an enhanced proliferation potential compared to that of the unprimed senile hCSCs. Interestingly, priming MHY-1685 enhanced the expression of stemness-related markers in senile hCSCs and provided the differentiation potential of hCSCs into vascular lineages. In vivo experiment with echocardiography showed that transplantation of MHY-1685‒primed hCSCs improved cardiac function than that of the unprimed senile hCSCs at 4 weeks post-MI. In addition, hearts transplanted with MHY-1685-primed hCSCs exhibited significantly lower cardiac fibrosis and higher capillary density than that of the unprimed senile hCSCs. In confocal fluorescence imaging, MHY-1685‒primed hCSCs survived for longer durations than that of the unprimed senile hCSCs and had a higher potential to differentiate into endothelial cells (ECs) within the infarcted hearts. These findings suggest that MHY-1685 can rejuvenate senile hCSCs by modulating autophagy and that as a senescence inhibitor, MHY-1685 can provide opportunities to improve hCSC-based myocardial regeneration.Subject terms: Heart stem cells, Stem-cell therapies     

Highly Chemoselective Esterification from O-Aminoallylation of Carboxylic Acids: Metal- and Reagent-Free Hydrocarboxylation of Allenamides

Metal-free hydrocarboxylation of allenamides with various functionalized carboxylic acids were achieved with complete regio- and stereocontrol (>49:1). This environmentally compatible transformation affords γ-acyloxyenamides with exclusive E-selectivity. Electron rich, electron poor, aliphatic, aryl, and heterocyclic carboxylic acids all gave excellent yields (avg. 89 %, 47 examples). We demonstrate the synthetic potential of this transformation in the late-stage modification of complex natural carboxylic acids and simple modification of the products to three-carbon synthons with ample opportunity for further diversification. DFT studies revealed that the reaction occurs in a stepwise manner through the intermediacy of a conjugated iminum species, which is rapidly captured by the carboxylate ion, resulting in the observed linear selectivity.     

Effects of dielectric barrier discharge plasma on pathogen inactivation and the physicochemical and sensory characteristics of pork loin

This study aimed to evaluate the use of a dielectric barrier discharge (DBD) plasma system to improve the safety of pork loins. When pork loin was exposed to DBD plasma with the input gases He and He + O₂, the population of Escherichia coli was reduced by 0.26 and 0.50 log cycles following a 5-min treatment and by 0.34 and 0.55 log units following a 10-min treatment, respectively. That of Listeria monocytogenes was also reduced from 0.17 to 0.35 and 0.43 to 0.59 log cycles when the samples were exposed to DBD for 5 and 10 min using He and He + O₂, respectively. The pH and L*-values (lightness) of the samples decreased significantly with DBD plasma treatment, but a*- (redness) and b*-values (yellowness) exhibited no obvious changes. Lipid oxidation, measured by TBARS values, was greater in samples with He + O₂ than in other samples. Significant reductions in sensory quality parameters (appearance, color, odor, acceptability, etc.) were observed in DBD-treated samples. These results indicate that the DBD plasma system has potential for use in sanitizing pork loins by inactivation of foodborne pathogens, although the effect was limited. In order to meet market requirements, however, a method to overcome sensory deterioration of pork loins should be developed and applied.     

Effects of annealing on ion-implanted Si for interdigitated back contact solar cell

Effects of annealing on the properties of P- and B-implanted Si for interdigitated back contact (IBC) solar cells were investigated with annealing temperature of from 950 to 1050 °C. P-implanted samples annealed at 950 °C were enough to activate dopants and recover the damage by implantation. As the annealing temperature was increased, the diode properties of P-implanted samples were degraded, while that of B-implanted samples were improved. However, in order to activate an implanted B ion, B-implanted samples needed an annealing of above 1000 °C. The implied V_oc of lifetime samples by quasi-steady-state photoconductance decay followed the trend of diode properties on annealing temperature. Finally, IBC cell was fabricated with a two-step annealing at 1050 °C for B of the emitter and 950 °C for P of the front and back surface fields. The IBC cell had V_oc of 618 mV, J_sc of 35.1 mA/cm², FF of 78.8%, and the efficiency of 17.1% without surface texturing.     

Flavonoid profiling in three citrus varieties native to the Republic of Korea using liquid chromatography coupled with tandem mass spectrometry: contribution to overall antioxidant activity

A mixture of flavonoid components was isolated from the fruit peel of three varieties of citrus native to Republic of Korea, Citrus leiocarpa Hort. ex Tanaka (CLHT), Citrus aurantium L. (CAL) and Citrus erythrosa Hort. (CEH), via 70% methanol extraction followed by ethyl acetate elution over a silica gel cartridge. The flavonoid components of the mixture were analyzed via high‐performance liquid chromatography–tandem mass spectrometry (HPLC‐MS/MS) in positive‐ion mode and a comparison of the reported data. Among 17 characterized components, two flavanones, four flavones and two coumarin derivatives in the fruit peel of the three varieties were identified for the first time. The individual characterized components were quantified via HPLC‐UV. The flavanones dominated in CAL, whereas the flavones prevailed in CLHT and CEH. The antioxidant activity of the flavonoid mixture of the fruit peel was determined via DPPH^?, ABTS^?+ and reducing power assays. The antioxidant activity of CEH and CAL was greater than that of CLHT. Copyright © 2011 John Wiley & Sons, Ltd.     

Design of piezoelectric energy harvesting devices subjected to broadband random vibrations by applying topology optimization

Converting ambient vibration energy into electrical energy by using piezoelectric energy harvester has attracted a lot of interest in the past few years.In this paper,a topology optimization based method is applied to simultaneously determine the optimal layout of the piezoelectric energy harvesting devices and the optimal position of the mass loading.The objective function is to maximize the energy harvesting performance over a range of vibration frequencies.Pseudo excitation method (PEM) is adopted to analyze structural stationary random responses,and sensitivity analysis is then performed by using the adjoint method.Numerical examples are presented to demonstrate the validity of the proposed approach.