Heat shock factor 1-mediated transcription activation of Omi/HtrA2 induces myocardial mitochondrial apoptosis in the aging heart.

BACKGROUND: Increased cardiac apoptosis is a hallmark of the elderly, which in turn increases the risk for developing cardiac disease. The overexpression of Omi/HtrA2 mRNA and protein contributes to apoptosis in the aged heart. Heat shock factor 1 (HSF1) is a transcription factor that binds to the promoter of Omi/HtrA2 in the aging myocardium. However, whether HSF1 participates in cardiomyocyte apoptosis via transcriptional regulation of Omi/HtrA2 remains unclear. The present study was designed to investigate whether HSF1 plays a role in Omi/HtrA2 transcriptional regulation and myocardial apoptosis. METHODS AND RESULTS: Assessment of the hearts of mice of different ages was performed, which indicated a decrease in cardiac function reserve and an increase in mitochondrial apoptosis. Omi/HtrA2 overexpression in the elderly was negatively correlated with left ventricular function after exercise overload and positively correlated with myocardial Caspase-9 apoptosis. Chromatin immunoprecipitation (ChIP) of aging hearts and plasmid transfection/RNA interference of H9C2 cells revealed that enhancement of HSF1 expression promotes Omi/HtrA2 expression by inducing the promoter activity of Omi/HtrA2 while also increasing mitochondrial apoptosis by upregulating Omi/HtrA2 expression. CONCLUSIONS: HSF1 acts as a transcriptional factor that induces Omi/HtrA2 expression and Caspase-9 apoptosis in aged cardiomyocytes, while also decreasing cardiac function reserve

Effects of Dietary Supplementation with Fermented Ginkgo Leaves on Innate Immunity, Antioxidant Capability, Lipid Metabolism, and Disease Resistance Against Aeromonas hydrophila Infection in Blunt Snout Bream (Megalobrama amblycephala)

This study was conducted to investigate the effect of Candida utilis and Aspergillus niger, combined with fermented Ginkgo biloba leaves (FGB) on immunity, antioxidant capability, lipid metabolism, and disease resistance against Aeromonas hydrophila infection in juvenile blunt snout bream (Megalobrama amblycephala). Fish were fed basal diets supplemented with fermented Ginkgo biloba leaves FGB1(0.125%), FGB2(0.25%), FGB3(0.5%), FGB4(1.0%), or Control (0.00%) respectively. At the end of the 60-day feeding trial, fish were challenged by A. hydrophila and mortality rate was recorded for the next 7 days. Results showed that, compared with the control, serum myeloperoxidase (MPO) activity of groups FGB1 and FGB2, alkaline phosphatase (AKP) and lysozyme (LZM) activity of group FGB2 increased significantly (P0.05). After A. hydrophila challenge, the relative mortality of group FGB1 and FGB2 were significantly lower than the control (P<0.05), however the highest rate was in group FGB4. Results of this study indicate that dietary supplementation of 0.125%~0.25% fermented G. biloba leaves can significantly enhance immunity, antioxidant capability, and lipid metabolism of blunt snout bream, as well as improve its disease resistance

An Improved Frequency-Adaptive Virtual Variable Sampling-Based Repetitive Control for an Active Power Filter

To eliminate the harmonics caused by nonlinear loads, repetitive controllers are widely applied as current controllers for active power filters (APF). In practice, a variation in grid frequency leads to the appearance of a fractional-order delay filter. As a result, the resonant frequency of the repetitive controller will deviate from the fundamental frequency and the controller cannot compensate for harmonics accurately. To solve this problem, an improved frequency-adaptive repetitive controller based on virtual variable sampling (IMFA-VVS-RC) for APF is proposed in this paper. To enhance the system stability margin, the proposed RC introduces an infinite impulse response (IIR) low-pass filter. The proposed RC has a high stability margin at high frequencies due to the low gain of the IIR low-pass filter in the region above the cutoff frequency. In this way, the influence of model uncertainty and parameter uncertainty on system stability are reduced at high frequencies. At the same time, compared with the conventional repetitive controller (CRC), the proposed RC for APF has a better harmonic suppression ability when the frequency varies. Experiments have verified the effectiveness of the scheme adopted for APF

An Improved Frequency-Adaptive Virtual Variable Sampling-Based Repetitive Control for an Active Power Filter

To eliminate the harmonics caused by nonlinear loads, repetitive controllers are widely applied as current controllers for active power filters (APF). In practice, a variation in grid frequency leads to the appearance of a fractional-order delay filter. As a result, the resonant frequency of the repetitive controller will deviate from the fundamental frequency and the controller cannot compensate for harmonics accurately. To solve this problem, an improved frequency-adaptive repetitive controller based on virtual variable sampling (IMFA-VVS-RC) for APF is proposed in this paper. To enhance the system stability margin, the proposed RC introduces an infinite impulse response (IIR) low-pass filter. The proposed RC has a high stability margin at high frequencies due to the low gain of the IIR low-pass filter in the region above the cutoff frequency. In this way, the influence of model uncertainty and parameter uncertainty on system stability are reduced at high frequencies. At the same time, compared with the conventional repetitive controller (CRC), the proposed RC for APF has a better harmonic suppression ability when the frequency varies. Experiments have verified the effectiveness of the scheme adopted for APF

Functional Characterization and Screening of Promiscuous Kinases and Isopentenyl Phosphate Kinases for the Synthesis of DMAPP via a One-Pot Enzymatic Cascade

Dimethylallyl diphosphate (DMAPP) is a key intermediate metabolite in the synthesis of isoprenoids and is also the prenyl donor for biosynthesizing prenylated flavonoids. However, it is difficult to prepare DMAPP via chemical and enzymatic methods. In this study, three promiscuous kinases from Shigella flexneri (SfPK), Escherichia coli (EcPK), and Saccharomyces cerevisiae (ScPK) and three isopentenyl phosphate kinases from Methanolobus tindarius (MtIPK), Methanothermobacter thermautotrophicus str. Delta H (MthIPK), and Arabidopsis thaliana (AtIPK) were cloned and expressed in Escherichia coli. The enzymatic properties of recombinant enzymes were determined. The Kcat/Km value of SfPK for DMA was 6875 s&minus;1 M&minus;1, which was significantly higher than those of EcPK and ScPK. The Kcat/Km value of MtIPK for DMAP was 402.9 s&minus;1 M&minus;1, which was ~400% of that of MthIPK. SfPK was stable at pH 7.0&ndash;9.5 and had a 1 h half-life at 65 &deg;C. MtIPK was stable at pH 6.0&ndash;8.5 and had a 1 h half-life at 50 &deg;C. The stability of SfPK and MtIPK was better than that of the other enzymes. Thus, SfPK and MtIPK were chosen to develop a one-pot enzymatic cascade for producing DMAPP from DMA because of their catalytic efficiency and stability. The optimal ratio between SfPK and MtIPK was 1:8. The optimal pH and temperature for the one-pot enzymatic cascade were 7.0 and 35 &deg;C, respectively. The optimal concentrations of ATP and DMA were 10 and 80 mM, respectively. Finally, maximum DMAPP production reached 1.23 mM at 1 h under optimal conditions. Therefore, the enzymatic method described herein for the biosynthesis of DMAPP from DMA can be widely used for the synthesis of isoprenoids and prenylated flavonoids

Quantitative estimation for the impact of mining activities on vegetation phenology and identifying its controlling factors from Sentinel-2 time series

International audienc

Study on Synergistic Antioxidant Effect of Typical Functional Components of Hydroethanolic Leaf Extract from Ginkgo Biloba In Vitro

The predicted anti-oxidation is related to apoptosis, proliferation, lipid metabolism, cell differentiation, and immune response. There are some differences in the antioxidant capacity of the four typical components of ginkgo biloba extract (EGb) including ginkgo flavone (GF), ginkgolide (G), procyanidins (OPC), and organic acids (OA), and any two members of them can exhibit apparent synergistic effects. The order of DPPH scavenging ability was: OPC > GF > OA > G. The scavenging ability of procyanidins was close to that of VC; the scavenging capacity of ABTS was GF > OPC > OA > G. The GF:OPC (1:9) showed the best synergism in scavenging DPPH and ABTS radicals. The 193 kinds of small molecules reported in EGb were obtained by analyzing the properties of EGb. In order to construct a corresponding biological activity target set, molecular docking and the network pharmacology method were employed to build the molecular action mechanism network of a compound target, and the main biological functions and signaling pathways involved with their antioxidant activities were predicted. The results displayed that the top ten compounds which belonged to the two broad categories, ginkgo flavonoids and proanthocyanidins, could interact closely with several important target proteins (CASP3, SOD2, MAPK1, HSPA4, and NQO1). This would be expected to lay a theoretical foundation for the deep development of Ginkgo biloba extract

Corticosterone rather than ethanol epigenetic programmed testicular dysplasia caused by prenatal ethanol exposure in male offspring rats

Prenatal ethanol exposure (PEE) could affect offspring’s testicular development. This study aimed to illuminate its intrauterine origin and the programming mechanism caused by PEE. Pregnant Wistar rats were given ethanol (4 g/kg.d) by gavage administration during gestational days (GD) 9–20. Serum samples and testes of male offspring rats were collected on GD20, postnatal week (PW) 6, and PW12. We found that PEE induced testicular morphological abnormality, low serum testosterone levels, expressive suppression of 3β-hydroxysteroid dehydrogenase (3β-HSD), and low acetylation levels of histone 3 lysine 14 (H3K14ac) of 3β-HSD before and after birth. In utero, when fetal rats were overexposed to corticosterone by PEE, the expression levels of testicular glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) were increased, while that of steroidogenic factor 1 (SF1) was decreased. In vitro, corticosterone (rather than ethanol) at 500 to 2,000 nM concentration decreased testosterone production and 3β-HSD expression in a concentration-dependent manner. Moreover, corticosterone downregulated SF1 and upregulated HDAC2 via activating GR, accompanied by a low H3K14ac level of 3β-HSD; SF1 overexpression could reverse the increased HDAC2 expression, and knockdown of HDAC2 could partially reverse the inhibitory effects of corticosterone on H3K14ac level and 3β-HSD expression but not on SF1 expression. Taken together, PEE caused testicular dysplasia in male offspring rats, which was associated with corticosterone-induced low-functional programming of 3β-HSD through the GR/SF1/HDAC2/H3K14ac pathway. This study provides new academic perspectives to illuminate the theory of ‘Developmental Origins of Health and Disease.