RESUMEN

The predictive value of non-invasive electrocardiographic examination findings for the risk of sudden cardiac death (SCD) in populations with structurally normal hearts remains unclear. This study aimed to investigate the characteristics of the QRS vectorcardiography of surface electrocardiography in patients with structurally normal hearts who experienced SCD. We consecutively enrolled patients who underwent vectorcardiography between March 2017 and December 2018 in a tertiary referral medical center. These patients didn't have structural heart diseases, histories of congestive heart failure, or reduced ejection fraction, and they were classified into SCD (with aborted SCD history and cerebral performance category score of 1) and control groups (with an intervention for atrioventricular node reentrant tachycardia and without SCD history). A total of 162 patients (mean age, 54.3±18.1 years; men, 75.9%), including 59 in the SCD group and 103 in the control group, underwent propensity analysis. The baseline demographic variables, underlying diseases, QRS loop descriptors (the percentage of the loop area, loop dispersion, and inter-lead QRS dispersion), and other electrocardiographic parameters were compared between the two groups. In the univariate and multivariate analyses, a smaller percentage of the loop area (odds ratio, 0.0003; 95% confidence interval, 0.00-0.02; p<0.001), more significant V4-5 dispersion (odds ratio, 1.04; 95% confidence interval, 1.02-1.07; p = 0.002), and longer QRS duration (odds ratio, 1.05; 95% confidence interval, 1.00-1.10; p = 0.04) were associated with SCD. In conclusion, the QRS loop descriptors of surface electrocardiography could be used as non-invasive markers to identify patients experiencing aborted SCD from a healthy population. A decreased percentage of loop area and elevated V4-5 QRS dispersion values assessed using vectorcardiography were associated with an increased risk of SCD in patients with structurally normal hearts.

Asunto(s)

Muerte Súbita Cardíaca/etiología , Electrocardiografía/métodos , Corazón/fisiopatología , Medición de Riesgo/métodos , Vectorcardiografía/métodos , Estudios de Casos y Controles , Muerte Súbita Cardíaca/patología , Femenino , Corazón/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo

RESUMEN

Adhesives that can stick to multiple surface types in underwater and high moisture conditions are critical for various applications such as marine coatings, sealants, and medical devices. The analysis of natural underwater adhesives shows that L-3,4-dihydroxyphenylalanine (DOPA) and functional amyloid nanostructures are key components that contribute to the adhesive powers of these natural glues. The combination of DOPA and amyloid-forming peptides into DOPA-amyloid(-forming peptide) conjugates provides a new approach to design generic underwater adhesives. However, it remains unclear how the DOPA monomers may interact with amyloid-forming peptides and how these interactions may influence the adhesive ability of the conjugates. In this paper, we investigate the behavior of DOPA monomers, (glycine-DOPA)3 chains, and a KLVFFAE and DOPA-glycine chain conjugate in aqueous environments using molecular simulations. The DOPA monomers do not aggregate significantly at concentrations lower than 1.0M. Simulations of (glycine-DOPA)3 chains in water were done to examine the intra-molecular interactions of the chain, wherein we found that there were unlikely to be interactions detrimental to the adhesion process. After combining the alternating DOPA-glycine chain with the amyloid-forming peptide KLVFFAE into a single chain conjugate, we then simulated the conjugate in water and saw the possibility of both intra-chain folding and no chain folding in the conjugate.

RESUMEN

Whey proteins (WPI) were polymerized with transglutaminase (TGase) before and after partially hydrolyzing the protein with thermolysin to produce protein nanoparticles/polymers. Electrophoresis and atomic force microscopy (AFM) were used to determine the size and structural characteristics of the polymers. The foaming and emulsifying properties of these nanoparticles were studied. The polymerized WPI (WPI-TG) produced more stable foams than the repolymerized WPI hydrolysate (WPIH-TG). In contrast, WPIH-TG produced better emulsions with better storage stability than WPI-TG emulsions. These differences were due to their structure and electrostatic properties: The WPI-TG particles were linear, less than 100 nm in size with lower net negative charge, whereas the WPIH-TG polymers were much larger and were highly negatively charged as judged from zeta potential. This suggested that while protein nanoparticles may provide Pickering stability to both emulsions and foams, strong lateral electrostatic repulsion between nanoparticles within the adsorbed film destabilizes foams but not emulsions.

Asunto(s)

Nanoestructuras/química , Transglutaminasas/química , Proteína de Suero de Leche/química , Suero Lácteo/química , Animales , Biocatálisis , Bovinos , Emulsiones/química , Polimerizacion , Hidrolisados de Proteína/química , Electricidad Estática

RESUMEN

Wild lowbush blueberries (Vaccinium angustifolium Ait) are a rich source of anthocyanins and other flavonoids with anti-inflammatory activities; however, their individual effects on cellular signaling remain to be elucidated. This study determined the capacity of blueberry bioactives to protect murine RAW 264.7 macrophages from lipopolysaccharide-induced inflammation. Fractionation of the crude extract (CE) into polyphenol-rich (PPR), anthocyanin-rich (ANC), and proanthocyanidin-rich (PAC) fractions and an ethyl acetate fraction (EA) revealed that PPR, ANC, and PAC components most effectively suppressed mRNA biomarkers of acute inflammation (Cox-2, iNOS, and IL-1ß). Among major polyphenols found in the wild blueberries, malvidin-3-glucoside was significantly more effective than epicatechin or chlorogenic acid in reducing the expression of pro-inflammatory genes in vitro.

Asunto(s)

Antocianinas/farmacología , Biomarcadores/metabolismo , Arándanos Azules (Planta)/química , Inflamación/metabolismo , Enfermedad Aguda , Animales , Secuencia de Bases , Línea Celular , Cromatografía Líquida de Alta Presión , Enfermedad Crónica , Cartilla de ADN , Técnicas In Vitro , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Reacción en Cadena de la Polimerasa

RESUMEN

Salinity is among the environmental factors that affect plant growth and development and constrain agricultural productivity. Salinity stress triggers increases in cytosolic free Ca(2+) concentration ([Ca(2+)]i) via Ca(2+) influx across the plasma membrane. Salinity stress, as well as other stresses, induces the production of reactive oxygen species (ROS). It is well established that ROS also triggers increases in [Ca(2+)]i. However, the relationship and interaction between salinity stress-induced [Ca(2+)]i increases and ROS-induced [Ca(2+)]i increases remain poorly understood. Using an aequorin-based Ca(2+) imaging assay we have analyzed [Ca(2+)]i changes in response to NaCl and H2O2 treatments in Arabidopsis thaliana. We found that NaCl and H2O2 together induced larger increases in [Ca(2+)]i in Arabidopsis seedlings than either NaCl or H2O2 alone, suggesting an additive effect on [Ca(2+)]i increases. Following a pre-treatment with either NaCl or H2O2, the subsequent elevation of [Ca(2+)]i in response to a second treatment with either NaCl or H2O2 was significantly reduced. Furthermore, the NaCl pre-treatment suppressed the elevation of [Ca(2+)]i seen with a second NaCl treatment more than that seen with a second treatment of H2O2. A similar response was seen when the initial treatment was with H2O2; subsequent addition of H2O2 led to less of an increase in [Ca(2+)]i than did addition of NaCl. These results imply that NaCl-gated Ca(2+) channels and H2O2-gated Ca(2+) channels may differ, and also suggest that NaCl- and H2O2-evoked [Ca(2+)]i may reduce the potency of both NaCl and H2O2 in triggering [Ca(2+)]i increases, highlighting a feedback mechanism. Alternatively, NaCl and H2O2 may activate the same Ca(2+) permeable channel, which is expressed in different types of cells and/or activated via different signaling pathways.

Asunto(s)

Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Calcio/metabolismo , Citosol/efectos de los fármacos , Citosol/metabolismo , Peróxido de Hidrógeno/farmacología , Cloruro de Sodio/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

Flue gas from power plants can promote algal cultivation and reduce greenhouse gas emissions(1). Microalgae not only capture solar energy more efficiently than plants(3), but also synthesize advanced biofuels(2-4). Generally, atmospheric CO2 is not a sufficient source for supporting maximal algal growth(5). On the other hand, the high concentrations of CO2 in industrial exhaust gases have adverse effects on algal physiology. Consequently, both cultivation conditions (such as nutrients and light) and the control of the flue gas flow into the photo-bioreactors are important to develop an efficient "flue gas to algae" system. Researchers have proposed different photobioreactor configurations(4,6) and cultivation strategies(7,8) with flue gas. Here, we present a protocol that demonstrates how to use models to predict the microalgal growth in response to flue gas settings. We perform both experimental illustration and model simulations to determine the favorable conditions for algal growth with flue gas. We develop a Monod-based model coupled with mass transfer and light intensity equations to simulate the microalgal growth in a homogenous photo-bioreactor. The model simulation compares algal growth and flue gas consumptions under different flue-gas settings. The model illustrates: 1) how algal growth is influenced by different volumetric mass transfer coefficients of CO2; 2) how we can find optimal CO2 concentration for algal growth via the dynamic optimization approach (DOA); 3) how we can design a rectangular on-off flue gas pulse to promote algal biomass growth and to reduce the usage of flue gas. On the experimental side, we present a protocol for growing Chlorella under the flue gas (generated by natural gas combustion). The experimental results qualitatively validate the model predictions that the high frequency flue gas pulses can significantly improve algal cultivation.

Asunto(s)

Reactores Biológicos , Microalgas/crecimiento & desarrollo , Modelos Biológicos , Dióxido de Carbono/química , Chlorella/crecimiento & desarrollo , Simulación por Computador , Gases/química , Centrales Eléctricas

RESUMEN

Ghrelin is a unique peptide gut hormone that requires post-translational modification to stimulate both feeding and growth hormone release. Ghrelin O-acyltransferase (GOAT) was identified as a specific acyl-transferase for ghrelin, and recent genetic deletion studies of the Goat gene (Goat(-/-)) uncovered the role of ghrelin in the regulation of glucose homeostasis. To further understand the physiological functions of the GOAT/ghrelin system, we have conducted a metabolomic and microarray profile of Goat-null mice, as well as determined Goat expression in different tissues using the lacZ reporter gene. Serum metabolite profile analysis revealed that Goat(-/-) mice exhibited increased secondary bile acids >2.5-fold. This was attributed to increased mRNA and protein expression of the ileal sodium-dependent bile acid transporter (ISBT) in the intestinal and biliary tract. Increased expression of additional solute carrier proteins, including Slc5a12 (>10-fold) were also detected in the small intestine and bile duct. Goat staining was consistently observed in the pituitary glands, stomach, and intestines, and to a lesser extent in the gallbladder and pancreatic duct. This is the first report that the GOAT/ghrelin system regulates bile acid metabolism, and these findings suggest a novel function of GOAT in the regulation of intestinal bile acid reabsorption..

Asunto(s)

Aciltransferasas/genética , Aciltransferasas/metabolismo , Ácidos y Sales Biliares/metabolismo , Absorción Intestinal/fisiología , Metaboloma/genética , Acilación , Tejido Adiposo/anatomía & histología , Tejido Adiposo/metabolismo , Animales , Sistema Biliar/metabolismo , Línea Celular , Cromosomas Artificiales Bacterianos/genética , Ingestión de Alimentos/fisiología , Vesícula Biliar/metabolismo , Perfilación de la Expresión Génica , Ghrelina/metabolismo , Íleon/metabolismo , Operón Lac/genética , Masculino , Proteínas de la Membrana , Ratones , Ratones Mutantes , Adenohipófisis/metabolismo

RESUMEN

Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis), a major cause of which is the loss of outer hair cells (OHCs) and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC) efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP), under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

RESUMEN

Thioredoxin-interacting protein (Txnip) inhibits thioredoxin NADPH-dependent reduction of protein disulfides. Total Txnip knockout (TKO) mice adapted inappropriately to prolonged fasting by shifting fuel dependence of skeletal muscle and heart from fat and ketone bodies to glucose. TKO mice exhibited increased Akt signaling, insulin sensitivity, and glycolysis in oxidative tissues (skeletal muscle and hearts) but not in lipogenic tissues (liver and adipose tissue). The selective activation of Akt in skeletal muscle and hearts was associated with impaired mitochondrial fuel oxidation and the accumulation of oxidized (inactive) PTEN, whose activity depends on reduction of two critical cysteine residues. Whereas muscle- and heart-specific Txnip knockout mice recapitulated the metabolic phenotype exhibited by TKO mice, liver-specific Txnip knockout mice were similar to WT mice. Embryonic fibroblasts derived from knockout mice also accumulated oxidized (inactive) PTEN and had elevated Akt phosphorylation. In addition, they had faster growth rates and increased dependence on anaerobic glycolysis due to impaired mitochondrial fuel oxidation, and they were resistant to doxorubicin-facilitated respiration-dependent apoptosis. In the absence of Txnip, oxidative inactivation of PTEN and subsequent activation of Akt attenuated mitochondrial respiration, resulting in the accumulation of NADH, a competitive inhibitor of thioredoxin NADPH-reductive activation of PTEN. These findings indicate that, in nonlipogenic tissues, Txnip is required to maintain sufficient thioredoxin NADPH activity to reductively reactivate oxidized PTEN and oppose Akt downstream signaling.

Asunto(s)

Proteínas Portadoras/metabolismo , Disulfuros/metabolismo , Fosfohidrolasa PTEN/metabolismo , Transducción de Señal , Tiorredoxinas/metabolismo , Animales , Dieta , Embrión de Mamíferos/citología , Embrión de Mamíferos/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Eliminación de Gen , Glucólisis/efectos de los fármacos , Homeostasis/efectos de los fármacos , Insulina/farmacología , Resistencia a la Insulina , Lípidos/administración & dosificación , Lípidos/sangre , Lípidos/farmacología , Ratones , Ratones Noqueados , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias/patología , Especificidad de Órganos/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Fenotipo , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

Unlike the livers of humans and mice, and most hepatoma cells, which accumulate triglycerides when treated with microsomal triglyceride transfer protein (MTP) inhibitors, L35 rat hepatoma cells do not express MTP and cannot secrete very low density lipoprotein (VLDL), yet they do not accumulate triglyceride. In these studies we show that transcriptional co-repression of the two lipid transfer proteins, liver fatty acid-binding protein (L-FABP) and MTP, which cooperatively shunt fatty acids into de novo synthesized glycerolipids and the transfer of lipids into VLDL, respectively, act together to maintain hepatic lipid homeostasis. FAO rat hepatoma cells express L-FABP and MTP and demonstrate the ability to assemble and secrete VLDL. In contrast, L35 cells, derived as a single cell clone from FAO cells, do not express L-FABP or MTP nor do they assemble and secrete VLDL. We used these hepatoma cells to elucidate how a conserved DR1 promoter element present in the promoters of L-FABP and MTP affects transcription, expression, and VLDL production. In FAO cells, the DR1 elements of both L-FABP and MTP promoters are occupied by peroxisome proliferator-activated receptor alpha-retinoid X receptor alpha (RXRalpha), with which PGC-1beta activates transcription. In contrast, in L35 cells the DR1 elements of both L-FABP and MTP promoters are occupied by chicken ovalbumin upstream promoter transcription factor II, and transcription is diminished. The combined findings indicate that peroxisome proliferator-activated receptor alpha-RXRalpha and PGC-1beta coordinately up-regulate L-FABP and MTP expression, by competing with chicken ovalbumin upstream promoter transcription factor II for the DR1 sites in the proximal promoters of each gene. Additional studies show that ablation of L-FABP prevents hepatic steatosis caused by treating mice with an MTP inhibitor. Our findings show that reducing both L-FABP and MTP is an effective means to reduce VLDL secretion without causing hepatic steatosis.

Asunto(s)

Proteínas Portadoras/genética , Proteínas de Unión a Ácidos Grasos/genética , Lipoproteínas VLDL/metabolismo , Hígado/metabolismo , Transcripción Genética/genética , Animales , Apolipoproteínas B/metabolismo , Secuencia de Bases , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/metabolismo , Línea Celular , Dimerización , Proteínas de Unión a Ácidos Grasos/deficiencia , Proteínas de Unión a Ácidos Grasos/metabolismo , Hígado Graso/genética , Hígado Graso/metabolismo , Expresión Génica/genética , Genes Reporteros/genética , Factor Nuclear 1-beta del Hepatocito/metabolismo , Masculino , Ratones , Ratones Noqueados , PPAR alfa/agonistas , PPAR alfa/metabolismo , Regiones Promotoras Genéticas/genética , Unión Proteica , ARN Mensajero/genética , Ratas , Receptores X Retinoide/agonistas , Receptores X Retinoide/metabolismo , Transcripción Genética/efectos de los fármacos

RESUMEN

OBJECTIVES: The purpose of the present study was to assess whether preoperative and postoperative B-type natriuretic peptide (BNP) levels could be used as predictors of postoperative complications and outcomes in patients after open-heart surgery. BACKGROUND: A variety of multifactor indexes have been proposed for preoperative risk assessment of patients undergoing cardiac surgery, but they have shown limited ability and utility in accurately predicting postoperative complications, hospital stay, and mortality. METHODS: Subjects consisted of 98 male patients (63 +/- 9.1 years) undergoing open-heart surgery at the San Diego Veterans Administration Health System during a 19-month period. B-type natriuretic peptide levels were analyzed, and postoperative data recorded. RESULTS: There was a higher preoperative BNP level in patients requiring the use of intra-aortic balloon pumps (IABPs) (mean BNP = 387 +/- 112 pg/ml vs. 181 +/- 25 pg/ml), in patients who died within one year (357 +/- 93 pg/ml vs. 184 +/- 26 pg/ml), and in patients with postoperative hospital stays of 10 days or more (307 +/- 68 pg/ml vs. 179 +/- 27 pg/ml). Receiver operating characteristic curves demonstrated preoperative BNP levels as predictors of postoperative IABP use, hospital stay 385 pg/ml predict the postoperative complications and one-year mortality after heart surgery. Postoperatively, elevated peak BNP levels and elevated change to peak BNP levels were associated with prolonged hospital stay and mortality within one year.

Asunto(s)

Procedimientos Quirúrgicos Cardíacos/mortalidad , Cardiopatías/cirugía , Péptido Natriurético Encefálico/sangre , Complicaciones Posoperatorias , Anciano , Cardiopatías/sangre , Cardiopatías/mortalidad , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Atención Perioperativa , Valor Predictivo de las Pruebas , Medición de Riesgo , Resultado del Tratamiento