p27 Protein Protects Metabolically Stressed Cardiomyocytes from Apoptosis by Promoting Autophagy

p27^Kip1 (p27), a key regulator of cell division, has been implicated in autophagy of cancer cells. However, its role in autophagy, the evolutionarily conserved catabolic process that enables cells to remove unwanted proteins and damaged organelles, had not been examined in the heart. Here we report that ectopic delivery of a p27 fusion protein (TAT-p27) was sufficient to induce autophagy in neonatal rat ventricular cardiomyocytes in vitro, under basal conditions and after glucose deprivation. Conversely, lentivirus-delivered shRNA against p27 successfully reduced p27 levels and suppressed basal and glucose-deprived levels of autophagy in cardiomyocytes in vitro. Glucose deprivation mimics myocardial ischemia and induces apoptosis in cardiomyocytes. During glucose deprivation, TAT-p27 inhibited apoptosis, whereas down-regulation of p27 decreased survival of cardiomyocytes. However, inhibition of autophagy by pharmacological (3-methyladenine, chloroquine, or bafilomycin A1) or genetic approaches (siRNA-mediated knockdown of Atg5) sensitized cardiomyocytes to glucose deprivation-induced apoptosis, even in the presence of TAT-p27. TAT-p27 was also able to provoke greater levels of autophagy in resting and fasting cardiomyocytes in vivo. Further, TAT-p27 enhanced autophagy and repressed cardiomyocytes apoptosis, improved cardiac function, and reduced infarct size following myocardial infarction. Again, these effects were lost when cardiac autophagy in vivo was blocked by chloroquine. Taken together, these data show that p27 positively regulates cardiac autophagy in vitro and in vivo, at rest and after metabolic stress, and that TAT-p27 inhibits apoptosis by promoting autophagy in glucose-deprived cardiomyocytes in vitro and in post-myocardial infarction hearts in vivo.     

Effects of Probiotic Bacteria Bacillus on Growth Performance,Digestive Enzyme Activity,and Hematological Parameters of Asian Sea Bass,Lates calcarifer (Bloch)

Probiotics and Antimicrobial Proteins - This study was conducted to evaluate different doses of two species of Bacillus (Bacillus licheniformis and Bacillus subtilis), on growth parameters,...     

Bioenergetic and functional consequences of stem cell-based VEGF delivery in pressure-overloaded swine hearts

In an established swine model of severe left ventricular (LV) hypertrophy (LVH), the bioenergetic and functional consequences of transplanting autologous mesenchymal stem cells (MSCs) overexpressing vascular endothelial growth factor (VEGF-MSCs) into the LV were evaluated; transplantation was accomplished by infusion of VEGF-MSCs into the interventricular cardiac vein. Specifically, the hypertrophic response to aortic banding was compared in seven pigs treated with 30 million VEGF-MSCs, eight pigs treated with 30 million MSCs without VEGF modification, and 19 untreated LVH pigs. Eight pigs without banding or cell transplantation (normal) were also studied. Four weeks postbanding, LV wall thickening (MRI), myocardial blood flow (MBF), high-energy phosphate levels ((31)P magnetic resonance spectroscopy), and hemodynamic measurements were obtained under basal conditions and during a catecholamine-induced high cardiac workstate (HCW). Although 9 of 19 untreated banded pigs developed clinical evidence of biventricular failure, no MSCs-treated animal developed heart failure. MSCs engraftment was present in both cell transplant groups, and both baseline and HCW MBF values were significantly increased in hearts receiving VEGF-MSCs compared with other groups (P < 0.05). During HCW, cardiac inotropic reserve (defined as the percent increase of rate pressure product at HCW relative to baseline) was normal in the VEGF-MSCs group and significantly decreased in all other banded groups. Additionally, during HCW, the myocardial energetic state [reflected by the phosphocreatine-to-ATP ratio (PCr/ATP)] of VEGF-MSCs-treated hearts remained stable, whereas in all other groups, PCr/ATP decreased significantly from baseline values (P < 0.05, each group). Myocardial von Willebrand factor and VEGF mRNA expressions and myocardial capillary density were significantly increased in VEGF-MSCs-treated hearts (P < 0.05). Hence, in the pressure-overloaded LV, transplantation of VEGF-MSCs prevents LV decompensation, induces neovascularization, attenuates hypertrophy, and improves MBF, myocardial bioenergetic characteristics, and contractile performance.     

Identifying people at high risk for developing sleep apnea syndrome (SAS): a cross-sectional study in a Pakistani population

Background  

Obstructive Sleep Apnea (OSA) is associated with many cardiovascular and psychiatric diseases. Day-time sleepiness is a common consequence of sleep apnea and correlates with road-traffic accidents (RTA). Pakistan has a high prevalence of factors which predispose an individual to OSA and death from RTAs are a huge burden. However there is a dearth of prevalence studies in this regard. We aim to understand local relevance of the disease and estimate the prevalence of individuals high-risk for OSA.     

The role of endothelin-1 in myocarditis and inflammatory cardiomyopathy: old lessons and new insights

Endothelin-1 has emerged as an important participant in the pathophysiology of a variety of cardiovascular diseases, where it may act on endocrine, paracrine and autocrine bases. Here we review its regulated biosynthesis, receptor-mediated signaling, and functional consequences in the heart, with particular emphasis on cardiac development and disease. Exploring published data employing molecular genetic mouse models of endothelin dysregulation, we highlight its heretofore underappreciated role as a pro-inflammatory cytokine. We also present novel micro-array data from one such mouse model, which implicate the specific downstream pathways that may mediate endothelin-1's effects.     

Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci

Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases. Mohammad Mahdi Motazacker and Masoud Garshasbi have contributed equally to this work.     

Essential trace and toxic element distribution in the scalp hair of Pakistani myocardial infarction patients and controls

The pathogenesis of heart disease has been associated with changes in the balance of certain trace elements. The aim of this study was to evaluate the Zn, Fe, Cu, Cr, Ni, Pb, and Cd contents in scalp hair samples of myocardial infarction (MCI) patients hospitalized in the cardiac ward of National Hospital in Hyderabad city (Pakistan). Scalp hair samples were collected from 193 patients (104 male, 89 female) of 3 age groups (46–60, 61–75, and 76–90 yr), for a comparative study, 200 normal, healthy subjects (103 male, 97 female) of the same age groups residing in the same city were selected. All metals in scalp hair samples were assessed by a flame/graphite furnace atomic absorption spectrophotometer, prior to microwave-assisted and conventional wet acid digestion methods. Results were calculated in micrograms per gram. The mean values of Fe and Zn of scalp hair samples of MCI patients were significantly reduced compared to the control subjects of both genders. The mean Fe concentrations in male patients were 19.42, 12.36, and 6.98 vs 30.69, 24.42, and 16.75 for the control patients in the three age groups (46–60, 61–75, and 76–90 yrs, respectively). The mean Zn concentration in male patients were 169.2, 149.4, and 107.7 μg/g vs 206.1, 188.0, and 154.4 μg/g for the control group (p<0.002, 0.004, and 0.001) in all three age groups, respectively. These differences were also observed in the female study groups. The mean values of Pb, Cd, and Ni were significantly high in patients compared to healthy subjects (mean Pb in male patients: 11.85, 12.89, and 14.52 those of female patients were 11.88, 12.73, and 14.21 vs the male controls patients (6.08, 7.56, and 8.56) and female controls (5.99, 7.41, and 8.25) for all three age groups, respectively. The concentration of Ni and Cd in the scalp hair samples of the heart patients of both sexes were significantly higher compared to the control; in the case of Ni the range of significant difference for males was found to be p<0.001–0.009 and for females to be p<0.0.002–0.007 and significantly high concentration of Cd were observed in hair samples of patients than in controls in the range for males (p<0.001–0.009) and in females (p<0.001–0.011). The Zn/Cu and Zn/Cd ratios in the scalp hair (p<0.01) of the diseased groups were significantly lower than that of the healthy groups. Deficiency of essential trace metals and high level of toxic metals might play a role in the development of heart disease in the subjects of this study. Toxic metals might also cause diminished absorption of essential elements.     

Effect of organic carbon sources and environmental factors on cell growth and lipid content of Pavlova lutheri

The present study aimed to investigate the effects of organic carbon sources, cultivation methods, and environmental factors on growth and lipid content of Pavlova lutheri for biodiesel production. In the 250-mL flask bioreactors, P. lutheri was cultivated in the modified artificial seawater (ASW) medium containing glucose, glycerol, sodium acetate, or sucrose as an organic carbon substrate. The effects of different growth conditions (phototrophic, mixotrophic, and heterotrophic) and environmental factors such as photoperiod, light intensity, and salinity were evaluated. Growth of P. lutheri was inhibited under heterotrophy but was enhanced in mixotrophy as compared to phototrophy. Biomass and lipid content of P. lutheri were significantly (p < 0.05) affected by changing photoperiod, light intensity, and salinity. Higher biomass concentration and lipid content were observed at a light intensity of 100 ± 2 μmol photons m−2 s−1, 18 h photoperiod, and 30% salinity, in a modified ASW medium supplemented with 10 mmol sucrose. An increase in biomass concentration from 320 ± 25.53 to 1106 ± 18.52 mg L−1 and high lipid content of 31.11 ± 1.65% (w/w) were observed with the optimized culture conditions, demonstrating a significant (p < 0.05) enhancement in biomass and lipid content due to the improved culture conditions. The present study emphasizes the possible use of sucrose for biomass and lipid production with P. lutheri under the optimized culture conditions. Using low-cost and relatively easy accessible feedstock such as sucrose would be a valuable alternative for growing microalgae with enhanced lipid content.