Dynamin-related protein 1 (Drp1) is a cytosolic GTPase protein that when activated translocates to the mitochondria, meditating mitochondrial fission and increasing reactive oxygen species (ROS) in cardiomyocytes. Drp1 has shown promise as a therapeutic target for reducing cardiac ischemia/reperfusion (IR) injury; however, the lack of specificity of some small molecule Drp1 inhibitors and the reliance on the use of Drp1 haploinsufficient hearts from older mice have left the role of Drp1 in IR in question. Here, we address these concerns using two approaches, using: (a) short-term (3 weeks), conditional, cardiomyocyte-specific, Drp1 knockout (KO) and (b) a novel, highly specific Drp1 GTPase inhibitor, Drpitor1a.
View Article and Find Full Text PDFMyocardial infarction (MI) significantly compromises the integrity of the cardiac microvascular endothelial barrier, leading to enhanced leakage and inflammation that contribute to the progression of heart failure. While HIF2α is highly expressed in cardiac endothelial cells (ECs) under hypoxic conditions, its role in regulating microvascular endothelial barrier function during MI is not well understood. In this study, we utilized mice with a cardiac-specific deletion of HIF2α, generated through an inducible Cre (Cdh5Cre-ERT2) recombinase system.
View Article and Find Full Text PDFManganese deficiency critically impairs the function and stability of photosystem II (PSII) and negatively impacts crop growth and yield. However, the response mechanisms of carbon and nitrogen metabolism to Mn deficiency in different genotypes of maize and the differences in Mn deficiency tolerance are unclear. Herein, three different genotypes of maize seedlings (sensitive genotype: Mo17, tolerant genotype: B73, and B73 × Mo17) were exposed to Mn deficiency treatment for 16 days using liquid culture with different concentrations of MnSO [0.
View Article and Find Full Text PDFThe research aimed to assess the contribution of fertilizer, density, and row spacing in integrated cultivation measures and identify their regulation mechanism on canopy architecture and factors in biomass accumulation in spring maize. Zhengdan 958 was used as the experimental material, and the optimum mode (OM) was identified based on a preliminary experiment, including the optimal fertilizer management, suitable plant density and wide-narrow row spacing, and dramatic yield performance (11,445.16 kg ha in 2017).
View Article and Find Full Text PDFCadmium (Cd) stress is one of the principal abiotic stresses that inhibit maize growth. The research was to explore (hemin chloride) Hemin (100 μmol L) on photosynthesis, ascorbic acid (AsA)-glutathione (GSH) cycle system, and polyamine metabolism of maize under Cd stress (85 mg L) using nutrient solution hydroponics, with Tiannong 9 (Cd tolerant) and Fenghe 6 (Cd sensitive) as experimental materials. The results showed that Hemin can increase leaf photosynthetic pigment content and ameliorate the ratio of Chlorophyll a/chlorophyll b (/) under Cd stress.
View Article and Find Full Text PDFBackground: Neurological injury following successful resuscitation from sudden cardiac arrest (CA) is common. The pathophysiological basis of this injury remains poorly understood, and treatment options are limited. Microglial activation and neuroinflammation are established contributors to many neuropathologies, such as Alzheimer disease and traumatic brain injury, but their potential role in post-CA injury has only recently been recognized.
View Article and Find Full Text PDFLoss-of-function (LOF) variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are linked to human diseases with high risk of sudden death, including developmental and epileptic encephalopathy and cardiac arrhythmia. β1 Subunits modulate the cell-surface localization, gating, and kinetics of sodium channel pore-forming α subunits. They also participate in cell-cell and cell-matrix adhesion, resulting in intracellular signal transduction, promotion of cell migration, calcium handling, and regulation of cell morphology.
View Article and Find Full Text PDFBackground: Cardiac arrest (CA) patients who survived by cardiopulmonary resuscitation (CPR) can present different levels of neurological deficits ranging from minor cognitive impairments to persistent vegetative state and brain death. The pathophysiology of the resulting brain injury is poorly understood, and whether changes in post-CA brain metabolism contribute to the injury are unknown. Here we utilized [F]fluorodeoxyglucose (FDG)-Positron emission tomography (PET) to study in vivo cerebral glucose metabolism 72 h following CA in a murine CA model.
View Article and Find Full Text PDFObjectives: Cardiogenic shock following cardiopulmonary resuscitation for sudden cardiac arrest is common, occurring even in the absence of acute coronary artery occlusion, and contributes to high rates of postcardiopulmonary resuscitation mortality. The pathophysiology of this shock is unclear, and effective therapies for improving clinical outcomes are lacking.
Design: Laboratory investigation.
Exercise is commonly prescribed to improve lipid profile and glucose levels in people living with HIV (PLWH). This systematic review was performed in order to examine the effects of exercise interventions on lipid profile and glucose levels on PLWH. Randomized controlled trials (RCTs) investigating the effects of exercise on blood glucose, triglycerides (TG), total cholesterol (TC), HDL and LDL published up to November 2017 were reviewed.
View Article and Find Full Text PDFJ Prim Care Community Health
June 2020
The purpose of this study was to determine the validity and reliability of the Exercise Vital Sign (EVS) questionnaire in an ethnically diverse sample. Participants (N = 39) were asked to wear an accelerometer at the hip for at least 7 days and to complete the EVS at the beginning (T1) and end (T2) of the wear period. The EVS questionnaire validity was determined against accelerometry, and bias was calculated as the mean difference between measures.
View Article and Find Full Text PDFThe alpha subunit of the voltage gated human ether-a-go-go-related (hERG) potassium channel regulates cell excitability in a broad range of cell lines. HERG channels are also expressed in a variety of cancer cells and control cell proliferation and apoptosis. Hypoxia, a common feature of tumors, alters gating properties of hERG currents in SH-SY5Y neuroblastoma cells.
View Article and Find Full Text PDFA ship in bottle nanocomposite was fabricated as a novel adsorbent for lanthanides by immobilizing a lanthanide-sensitive polymer into mesocellular siliceous foam (MCF). The MCF was used as a novel carrier for immobilization of the polymer, and the polymer was synthesized via in situ ring-opening polymerization of 2-methyl-2-oxazoline (MOL) and divinylbenzene (DVB) in the presence of MCFs. The substantially physically modified MCF-based composite exhibited superior adsorptivity and selectivity to lanthanides due to its exceptional properties, which was employed for lanthanide adsorption from aqueous solution by a facile solid-liquid separation procedure.
View Article and Find Full Text PDFRationale: Post-ischemic changes in cellular metabolism alter myocardial and neurological function. Pyruvate dehydrogenase (PDH), the limiting step in mitochondrial glucose oxidation, is inhibited by increased expression of PDH kinase (PDK) during ischemia/reperfusion injury. This results in decreased utilization of glucose to generate cellular ATP.
View Article and Find Full Text PDFCross-correlation between pairs of variables takes multi-time scale characteristic, and it can be totally different on different time scales (changing from positive correlation to negative one), e.g., the associations between mean air temperature and relative humidity over regions to the east of Taihang mountain in China.
View Article and Find Full Text PDFIn this study, relations between winter-time Pacific-Northern America pattern (PNA)/East Pacific wave-train (EPW) and winter-time drought in the west United States over the period of 1951-2010 are analyzed. Considering traditional Pearson's Correlation Coefficient can be influenced by non-stationarity and nonlinearity, a recently proposed method, Detrended Partial-Cross-Correlation Analysis (DPCCA) is applied. With DPCCA, we analyzed the "intrinsic" correlations between PNA/EPW and the winter drought with possible effects of ENSO and PDO removed.
View Article and Find Full Text PDFIn this paper, a new method, detrended partial-cross-correlation analysis (DPCCA), is proposed. Based on detrended cross-correlation analysis (DCCA), this method is improved by including partial-correlation technique, which can be applied to quantify the relations of two non-stationary signals (with influences of other signals removed) on different time scales. We illustrate the advantages of this method by performing two numerical tests.
View Article and Find Full Text PDFObjectives: Survival following sudden cardiac arrest is poor despite advances in cardiopulmonary resuscitation and the use of therapeutic hypothermia. Dynamin-related protein 1, a regulator of mitochondrial fission, is an important determinant of reactive oxygen species generation, myocardial necrosis, and left ventricular function following ischemia/reperfusion injury, but its role in cardiac arrest is unknown. We hypothesized that dynamin-related protein 1 inhibition would improve survival, cardiac hemodynamics, and mitochondrial function in an in vivo model of cardiac arrest.
View Article and Find Full Text PDFUnlabelled: The rapid growth of cancer cells is permitted by metabolic changes, notably increased aerobic glycolysis and increased glutaminolysis. Aerobic glycolysis is also evident in the hypertrophying myocytes in right ventricular hypertrophy (RVH), particularly in association with pulmonary arterial hypertension (PAH). It is unknown whether glutaminolysis occurs in the heart.
View Article and Find Full Text PDFPulmonary arterial hypertension (PAH) is a syndrome in which pulmonary vascular cross sectional area and compliance are reduced by vasoconstriction, vascular remodeling, and inflammation. Vascular remodeling results in part from increased proliferation and impaired apoptosis of vascular cells. The resulting increase in afterload promotes right ventricular hypertrophy (RVH) and RV failure.
View Article and Find Full Text PDFRationale: Pulmonary arterial hypertension (PAH) is a lethal, female-predominant, vascular disease. Pathologic changes in PA smooth muscle cells (PASMC) include excessive proliferation, apoptosis-resistance, and mitochondrial fragmentation. Activation of dynamin-related protein increases mitotic fission and promotes this proliferation-apoptosis imbalance.
View Article and Find Full Text PDFPyruvate dehydrogenase kinase (PDK) is activated in right ventricular hypertrophy (RVH), causing an increase in glycolysis relative to glucose oxidation that impairs right ventricular function. The stimulus for PDK upregulation, its isoform specificity, and the long-term effects of PDK inhibition are unknown. We hypothesize that FOXO1-mediated PDK4 upregulation causes bioenergetic impairment and RV dysfunction, which can be reversed by dichloroacetate.
View Article and Find Full Text PDFBackground: The cause and consequences of impaired adrenergic signaling in right ventricular failure/hypertrophy (RVH) are poorly understood. We hypothesized that G protein-coupled receptor kinase-2 (GRK2)-mediated uncoupling of β-adrenergic receptor signaling impairs inotropic reserve. The implications of right ventricular (RV) adrenergic remodeling for inotrope selection and the therapeutic benefit of interrupting Gβγ-GRK2 interaction, using gallein, were tested.
View Article and Find Full Text PDFRationale: Pulmonary arterial hypertension (PAH) is a lethal syndrome characterized by pulmonary vascular obstruction caused, in part, by pulmonary artery smooth muscle cell (PASMC) hyperproliferation. Mitochondrial fragmentation and normoxic activation of hypoxia-inducible factor-1α (HIF-1α) have been observed in PAH PASMCs; however, their relationship and relevance to the development of PAH are unknown. Dynamin-related protein-1 (DRP1) is a GTPase that, when activated by kinases that phosphorylate serine 616, causes mitochondrial fission.
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