Although previous studies have shown that cardiac myosin heavy chain (MHC) composition undergoes a switch from the alpha- to beta-isoform in the heart during adult aging, the underlying mechanisms responsible for this switch are unknown. Cardiac MHC gene expression is regulated, in part, by thyroid hormone responsive elements present in the regulatory control regions of the alpha- and beta-MHC genes. Age-associated changes in the expression of thyroid hormone receptors (THRs) and/or retinoid X receptors (RXRs), the heterodimeric partner for THRs, could explain the age-associated changes in MHC expression. Accordingly, we measured mRNA levels for the cardiac muscle MHCs and the rat THR and RXR genes in the left ventricles of Wistar rats at 2, 6, and 24 months of age. Although there were no significant changes in RXR alpha or RXR beta mRNA levels with age, both alpha 1 and alpha 2 THR mRNA levels decreased significantly between 2 and 6 months of age. During this same time period, the mRNA levels for alpha-MHC declined by more than half, whereas beta-MHC mRNA levels remained low and unchanged. On the other hand, between 6 and 24 months, when mRNA levels for beta-MHC increased and alpha-MHC continued to decrease, there was a significant decline in THR beta 1 and RXR gamma mRNA levels accompanied by a reduction in the THR beta 1 and RXR gamma protein levels. These data show a pattern of change that suggests that the decline in alpha-MHC gene expression may be biphasic and due to a decline in alpha 1 (and possibly alpha 2) THR levels between 2 and 6 months of age and a decline in THR beta 1 and RXR gamma levels at later stages. In contrast, the increase in beta-MHC gene expression was associated only with the changes in THR beta 1 and RXR gamma mRNA and protein levels.

Background:Since 2010, two versions of National Guidelines aimed at promoting the management of ST-segment elevation myocardial infarction (STEMI) have been formulated by the Chinese Society of Cardiology. However, little is known about the changes in clinical characteristics, management, and in-hospital outcomes in rural areas.Methods:In the present multicenter, cross-sectional study, participants were enrolled from rural hospitals located in Liaoning province in Northeast China, during two different periods (from June 2009 to June 2010 and from January 2015 to December 2015). Data collection was conducted using a standardized questionnaire. In total, 607 and 637 STEMI patients were recruited in the 2010 and 2015 cohorts, respectively.Results:STEMI patients in rural hospitals were older in the second group (63 years vs. 65 years, P = 0.039). We found increases in the prevalence of hypertension, prior percutaneous coronary intervention (PCI), and prior stroke. Over the past 5 years, the cost during hospitalization almost doubled. The proportion of STEMI patients who underwent emergency reperfusion had significantly increased from 42.34% to 54.47% (P < 0.0001). Concurrently, the proportion of primary PCI increased from 3.62% to 10.52% (P < 0.0001). The past 5 years have also seen marked increases in the use of guideline-recommended drugs and clinical examinations. However, in-hospital mortality and major adverse cardiac events did not significantly change over time (13.01% vs. 10.20%, P = 0.121; 13.34% vs. 13.66%, P = 0.872).Conclusions:Despite the great progress that has been made in guideline-recommended therapies, in-hospital outcomes among rural STEMI patients have not significantly improved. Therefore, there is still substantial room for improvement in the quality of care.

A b s t r a c tIntroduction: This study aimed to explore the bio-function of miR-210 in the pathogenesis of pre-eclampsia and provide new insights into the diagnosis and treatment of pre-eclampsia. Material and methods: A JAR cell line cultured in standard or hypoxic conditions was used in this study. Expression levels of miR-210 and PTPN2 were determined using real-time polymerase chain reaction (RT-PCR). Protein and phosphorylation levels were assessed using western blotting. Proliferation of JAR cells was evaluated using MTT assay. Migration and invasion were measured using transwell assay. Results: Expression of miR-210 increased significantly in a time-dependent manner after hypoxia treatment within 36 h (p < 0.05). miR-210 inhibitor significantly decreased the cell proliferation, migration, and invasion (p < 0.05), while miR-210 mimic reversed these findings (p < 0.05). Hypoxia significantly suppressed the expression of PTPN2; however, this elevation was abolished by miR-210 inhibitor (p < 0.05). Inhibition of PTPN2 or hypoxia significantly increased the proliferation, migration, and invasion of JAR cells, while miR-210 inhibitor significantly reversed these changes (p < 0.05). The phosphorylation levels of PDGFR, Akt, and Erk were markedly upregulated by hypoxia or si-PTPN2, but this effect was abolished by miR-210 inhibitor (p < 0.05). Conclusions: miR-210 can promote proliferation, migration, and invasion via downregulating PTPN2 in the PDGFR-Akt pathway.

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Background: Cadmium (Cd) is a common heavy metal pollutant. Prenatal exposure to Cd results in adverse effects on fetal development. Placental apoptosis, inflammation, and epigenetic disruption have been implicated in Cdinduced placental toxicity. Resveratrol (Res) is a naturally occurring polyphenol with anti-apoptotic, anti-inflammatory, and epigenetic regulatory activities. In present study, the effects of Res on placental toxicity induced by Cd were evaluated. Methods: Pregnant CD-1 mice were fed with base diet containing 0.2% Res started on gestational day 0 (GD0), and intraperitoneally injected with 4.5 mg/kg CdCl 2 or saline once on GD9. JEG-3 cells were treated with 20 μM Res for 24 hr in the absence or presence of 20 μM CdCl 2 for the second 12 hr. The fetal outcomes, the apoptosis in placenta and JEG-3 cells, the expression of inflammatory cytokines and chemokines including tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein-2 (MIP-2) and chemokine (C-X-C motif) ligand 1 (KC), and expression of endoplasmic reticulum (ER) stress markers were evaluated. The expression and activities of DNA methyltransferase (DNMT), and the activation of Akt signaling pathway were detected. Results: Cd exposure resulted in decreased fetal weight and crown-rump length while Res ameliorated these outcomes. Res suppressed Cd-induced apoptosis in placenta and JEG-3 cells, and decreased Cd-induced expression of TNF-α, IFN-γ, MCP-1, MIP-2, and KC in placenta. Cd greatly increased ER stress in placenta in mice, which was partially ameliorated by Res treatment. Res decreased Cd-induced upregulation of DNMT activity and suppressed Cdinduced expression of DNMT3B. Res restored estradiol secretion, enhances activity and protein levels of SIRT1 and inhibited Cd-induced activation of Akt signaling pathway. Conclusion: Res ameliorated Cd-induced placental toxicity and regulated DNMT3 expression and PI3K/Akt pathway activation.