Rationale: The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. However, whether and how GDM exposure induces fetal programming of adult cardiac dysfunctional phenotype, especially the underlying epigenetic molecular mechanisms and theranostics remain unclear. To address this problem, we developed a late GDM rat model. Methods: Pregnant rats were made diabetic on day 12 of gestation by streptozotocin (STZ). Experiments were conducted in 6 weeks old offspring. Results: There were significant increases in ischemia-induced cardiac infarction and gender-dependent left ventricular (LV) dysfunction in male offspring in GDM group as compared to controls. Exposure to GDM enhanced ROS level and caused a global DNA methylation in offspring cardiomyocytes. GDM attenuated cardiac Sirt 1 protein and p-Akt/Akt levels, but enhanced autophagy-related proteins expression (Atg 5 and LC3 II/LC3 I) as compared to controls. Ex-vivo treatment of DNA methylation inhibitor, 5-Aza directly inhibited Dnmt3A and enhanced Sirt 1 protein expression in fetal hearts. Furthermore, treatment with antioxidant, N-acetyl-cysteine (NAC) in offspring reversed GDM-mediated DNA hypermethylation, Sirt1 repression and autophagy-related gene protein overexpression in the hearts, and rescued GDM-induced deterioration in heart ischemic injury and LV dysfunction. Conclusion: Our data indicated that exposure to GDM induced offspring cardiac oxidative stress and DNA hypermethylation, resulting in an epigenetic down-regulation of Sirt1 gene and aberrant development of heart ischemia-sensitive phenotype, which suggests that Sirt 1-mediated signaling is the potential therapeutic target for the heart ischemic disease in offspring.
Interconversion between CO 2 + H 2 and FA/formate is the most promising strategy for the fixation of carbon dioxide and reversible hydrogen storage; however, FA dehydrogenation and CO 2 hydrogenation are usually studied separately using different catalysts for each reaction. This report describes of the catalysis of [Cp*Ir(N∧N)(X)] n+ (Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl; X = Cl, n = 0; X = H 2 O, n = 1) bearing a proton-responsive N∧N pyridylpyrrole ligand for both reactions. Complex 2-H 2 O catalyzes FA dehydrogenation at 90 °C with a TOF max of 45 900 h −1 . Its catalysis is more active in aqueous solution than in neat solution under base-free conditions. These complexes also catalyze CO 2 hydrogenation in the presence of base to formate under atmospheric pressure (CO 2 /H 2 = 0.05 MPa/0.05 MPa) at 25 °C with a TOF value of 4.5 h −1 in aqueous solution and with a TOF value of 29 h −1 in a methanol/H 2 O mixture solvent. The possible mechanism is proposed by intermediate characterization and KIE experiments. The extraordinary activity of these complexes are mainly attributed to the metal−ligand cooperative effect of the the pyrrole group to accept a proton in the dehydrogenation of formic acid and assist cooperative heterolytic H−H bond cleavage in CO 2 hydrogenation.
Background: Radix isatidis has been used in China and other Asian countries for its antiviral and anti-inflammatory effects for thousands of years. However, the antiviral effect of Radix isatidis polysaccharide against pseudorabies virus (PRV) is still unknown. Methods: The polysaccharide were isolated from extract of the roots of Radix isatidis. MTT assays were used to determine the preventive effect, inhibitory effect and antiviral effect of Radix isatidis polysaccharide on PRV in vitro.Results: This study found that different concentrations of polysaccharides from this plant can inhibit PRV replication by 14.674-30.840%, prevent infection at rates of 6.668-14.923%, and kill this virus at rates of 32.214-67.422%.
Conclusion:These results broaden the understanding of this traditional Chinese herb and provide a theoretical basis for further research. Moreover, Radix isatidis polysaccharide could be used for antiviral therapy.
The results suggest that gestational HAH exposure induces in utero programming of the hypoxia/ischemia-sensitive gene expression pattern in the developing heart and increases cardiac susceptibility to I/R injury.
Long non-coding RNA (lncRNA) DANCR has been reported to participate in key processes such as stem cell differentiation and tumorigenesis. In a high throughput screening for lncRNAs involved in Doxorubicin-induced apoptosis, we found DANCR was suppressed by Doxorubicin and it acted as an important repressor of apoptosis in colorectal cancer. Further studies demonstrated that DANCR promoted the oncogenic lncRNA MALAT1 expression via enhancing the RNA stability of MALAT1 to suppress apoptosis. MALAT1 could efficiently mediate the suppressive function of DANCR on apoptosis. Mechanistic studies found the RNA-binding protein QK served as an interacting partner of both DANCR and MALAT1, and the protein level of QK was subjected to the regulation by DANCR. Furthermore, QK was able to modulate the RNA stability of MALAT1, and the interaction between QK and MALAT1 was controlled by DANCR. In addition, QK could mediate the function of DANCR in regulating the expression of MALAT1 and suppressing apoptosis. These results revealed DANCR played a critical role in Doxorubicin-induced apoptosis in colorectal cancer cells, which was achieved by the interaction between DANCR and QK to enhance the expression of MALAT1.
Smectite illitization is an important diagenetic phenomenon of mudstones, but only rarely has the influence of organic matter (OM) on this process been examined. In the present study, hydrothermal experiments were conducted with smectite (M1, total organic carbon (TOC) <0.3%) and a smectite and N,N-dimethylhexadecylamine (16DMA) complex (M2, TOC >1%). X-ray diffraction (XRD), infrared, X-ray fluorescence (XRF), and organic carbon analyses were employed to characterize the mineralogy and OM of the samples and the effect of OM on smectite illitization. The XRD patterns showed changes in clay mineral parameters with increased temperature. These changes varied in both M1 and M2 and indicated a difference in the degree of smectite illitization. Moreover, the OM in M2 was mainly adsorbed in smectite interlayers, the OM was largely desorbed/decomposed at temperatures above 350°C, and the OM was the main reason for differences in the degree of smectite illitization between M1 and M2. Bulk mineral composition, elemental content, and infrared absorption band intensities were changed with increased temperature (especially above 350°C). This indicated the formation of new minerals (e.g., ankerite). Overall, OM entered the interlayer space of smectite in M2 and delayed the exchange of K+ by interlayer cations, and thus, suppressed the transformation of smectite to illite and resulted in differences in smectite illitization of M1 and M2. In particular, the formation of CO2 after the decomposition of OM at temperatures above 300°C led to the formation of ankerite in M2. This demonstrated the effect of organic-inorganic interactions on smectite illitization and mineral formation. The disparities in smectite illitization between M1 andM2, therefore, were linked to differences in the mineral formation mechanisms of a water-rock system (M1) and a water-rock-OM system (M2) in natural environments. The insights obtained in the present study should be of high importance in understanding organic-mineral interactions, hydrocarbon generation, and the carbon cycle.
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