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https://www.readbyqxmd.com/read/28343228/focal-brain-injury-associated-with-a-model-of-severe-hypoxic-ischemic-encephalopathy-in-nonhuman-primates
#1
Ryan M McAdams, Ronald J McPherson, Raj P Kapur, Sandra E Juul
Worldwide, hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. To better understand the mechanisms contributing to brain injury and improve outcomes in neonates with HIE, better preclinical animal models that mimic the clinical situation following birth asphyxia in term newborns are needed. In an effort to achieve this goal, we modified our nonhuman primate model of HIE induced by in utero umbilical cord occlusion (UCO) to include postnatal hypoxic episodes, in order to simulate apneic events in human neonates with HIE...
March 25, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28343214/moderate-grade-germinal-matrix-haemorrhage-activates-cell-division-in-the-neonatal-mouse-subventricular-zone
#2
William J Dawes, Xinyu Zhang, Stephen P J Fancy, David Rowitch, Silvia Marino
Precise temporal and spatial control of the neural stem/progenitor cells within the subventricular zone (SVZ) germinal matrix of the brain is important for normal development in the third trimester and the early postnatal period. The high metabolic demands of proliferating germinal matrix precursors, coupled with the flimsy structure of the germinal matrix cerebral vasculature, are thought to account for the high rates of haemorrhage in extremely- and very-low-birth-weight preterm infants. Germinal matrix haemorrhage can commonly extend to intraventricular haemorrhage (IVH)...
March 25, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28342898/temperature-induces-significant-changes-in-both-glycolytic-reserve-and-mitochondrial-spare-respiratory-capacity-in-colorectal-cancer-cell-lines
#3
Mihail I Mitov, Jennifer W Harris, Michael C Alstott, Yekaterina Y Zaytseva, B Mark Evers, D Allan Butterfield
Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, in a microplate, label-free detection approach. This study investigate how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology...
March 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28342290/verapamil-treatment-induces-cytoprotective-autophagy-by-modulating-cellular-metabolism
#4
Elzbieta Kania, Beata Pajak, Jim O'Prey, Pablo Sierra Gonzalez, Anna Litwiniuk, Kaja Urbańska, Kevin M Ryan, Arkadiusz Orzechowski
Verapamil, an L-type calcium channel blocker, has been used successfully to treat cardiovascular diseases. Interestingly, we have recently shown that treatment of cancer cells with Verapamil causes an effect on autophagy. As autophagy is known to modulate chemotherapy responses, this prompted us to explore the impact of Verapamil on autophagy and cell viability in greater detail. We report here that Verapamil causes an induction of autophagic flux in a number or tumor cells and immortalized normal cells. Moreover, we found that inhibition of autophagy in COLO 205 cells, via treatment with the chloroquine or by CRISPR/Cas9-mediated disruption of the autophagy genes Atg7 and Atg5, causes an upregulation of apoptotic markers in response to Verapamil...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28338413/human-tissue-engineered-skeletal-muscle-myobundles-to-measure-oxygen-uptake-and-assess-mitochondrial-toxicity
#5
Brittany N J Davis, Jeffrey W Santoso, Michaela J Walker, Cindy S Cheng, Timothy R Koves, William E Kraus, George A Truskey
Mitochondrial dysfunction is responsible for the toxicity of a number of drugs. Current isolated mitochondria or cellular monoculture mitochondrial respiration measurement systems lack physiological relevance. Using a tissue engineering rather than cell- or mitochondria-based approach enables a more physiologically relevant detection of drug-induced mitochondrial impairment. To probe oxygen consumption and mitochondrial health, we assayed the bioenergetic profile of engineered three-dimensional human skeletal muscle myobundles derived from primary myoblasts...
March 24, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28337802/the-snf1-activating-kinase-sak1-is-a-key-regulator-of-metabolic-adaptation-and-in-vivo-fitness-of-candida-albicans
#6
Bernardo Ramírez-Zavala, Austin Mottola, Julia Haubenreißer, Sabrina Schneider, Stefanie Allert, Sascha Brunke, Knut Ohlsen, Bernhard Hube, Joachim Morschhäuser
The metabolic flexibility of the opportunistic fungal pathogen Candida albicans is important for colonisation and infection of different host niches. Complex regulatory networks, in which protein kinases play central roles, link metabolism and other virulence-associated traits, such as filamentous growth and stress resistance, and thereby control commensalism and pathogenicity. By screening a protein kinase deletion mutant library that was generated in the present work using an improved SAT1 flipper cassette, we found that the previously uncharacterised kinase Sak1 is a key upstream activator of the protein kinase Snf1, a highly conserved regulator of nutrient stress responses that is essential for viability in C...
March 23, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28335560/serum-amyloid-a-production-is-triggered-by-sleep-deprivation-in-mice-and-humans-is-that-the-link-between-sleep-loss-and-associated-comorbidities
#7
Edson M de Oliveira, Bruna Visniauskas, Sergio Tufik, Monica L Andersen, Jair R Chagas, Ana Campa
Serum amyloid A (SAA) was recently associated with metabolic endotoxemia, obesity and insulin resistance. Concurrently, insufficient sleep adversely affects metabolic health and is an independent predisposing factor for obesity and insulin resistance. In this study we investigated whether sleep loss modulates SAA production. The serum SAA concentration increased in C57BL/6 mice subjected to sleep restriction (SR) for 15 days or to paradoxical sleep deprivation (PSD) for 72 h. Sleep restriction also induced the upregulation of Saa1...
March 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28333097/effects-of-a-sativex-like-combination-of-phytocannabinoids-on-disease-progression-in-r6-2-mice-an-experimental-model-of-huntington-s-disease
#8
Sara Valdeolivas, Onintza Sagredo, Mercedes Delgado, Miguel A Pozo, Javier Fernández-Ruiz
Several cannabinoids afforded neuroprotection in experimental models of Huntington's disease (HD). We investigated whether a 1:1 combination of botanical extracts enriched in either ∆⁸-tetrahydrocannabinol (∆⁸-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex(®), is beneficial in R6/2 mice (a transgenic model of HD), as it was previously shown to have positive effects in neurotoxin-based models of HD. We recorded the progression of neurological deficits and the extent of striatal deterioration, using behavioral, in vivo imaging, and biochemical methods in R6/2 mice and their corresponding wild-type mice...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332630/pml-nuclear-bodies-contribute-to-the-basal-expression-of-the-mtor-inhibitor-ddit4
#9
Jayme Salsman, Alex Stathakis, Ellen Parker, Dudley Chung, Livia E Anthes, Kara L Koskowich, Sara Lahsaee, Daniel Gaston, Kimberly R Kukurba, Kevin S Smith, Ian C Chute, Daniel Léger, Laura D Frost, Stephen B Montgomery, Stephen M Lewis, Christopher Eskiw, Graham Dellaire
The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331986/renal-function-preservation-with-pioglitazone-or-with-basal-insulin-as-an-add-on-therapy-for-patients-with-type-2-diabetes-mellitus
#10
Yu-Hung Chang, Der-Wei Hwu, Dao-Ming Chang, Ling-Wang An, Chang-Hsun Hsieh, Yau-Jiunn Lee
AIMS: Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. METHODS: Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included...
March 22, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28329765/structural-insights-into-adiponectin-receptors-suggest-ceramidase-activity
#11
Ieva Vasiliauskaité-Brooks, Remy Sounier, Pascal Rochaix, Gaëtan Bellot, Mathieu Fortier, François Hoh, Luigi De Colibus, Chérine Bechara, Essa M Saied, Christoph Arenz, Cédric Leyrat, Sébastien Granier
Adiponectin receptors (ADIPORs) are integral membrane proteins that control glucose and lipid metabolism by mediating, at least in part, a cellular ceramidase activity that catalyses the hydrolysis of ceramide to produce sphingosine and a free fatty acid (FFA). The crystal structures of the two receptor subtypes, ADIPOR1 and ADIPOR2, show a similar overall seven-transmembrane-domain architecture with large unoccupied cavities and a zinc binding site within the seven transmembrane domain. However, the molecular mechanisms by which ADIPORs function are not known...
March 22, 2017: Nature
https://www.readbyqxmd.com/read/28329745/interleukin-6-and-hepcidin-levels-during-hormone-deplete-and-hormone-replete-phases-of-an-oral-contraceptive-cycle-a-pilot-study
#12
Marc Sim, Brian Dawson, Grant Landers, Dorine W Swinkels, Erwin Wiegerinck, Bu B Yeap, Debbie Trinder, Peter Peeling
BACKGROUND: In the past, elevated estradiol levels were reported to downregulate the iron regulatory hormone hepcidin, thereby potentially improving iron metabolism. As estrogen plays a role in regulating the menstrual cycle and can influence the cytokine interleukin-6 (IL-6; a hepcidin up-regulator), this investigation examined the effects of estradiol supplementation achieved by the use of a monophasic oral contraceptive pill (OCP) on IL-6, hepcidin levels and iron status during the hormone-deplete versus hormone-replete phases within an oral contraceptive cycle (OCC)...
March 23, 2017: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/28325801/insulin-and-glucagon-like-peptide-1-receptor-agonist-combination-therapy-in-type-2-diabetes-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#13
REVIEW
Maria Ida Maiorino, Paolo Chiodini, Giuseppe Bellastella, Annalisa Capuano, Katherine Esposito, Dario Giugliano
OBJECTIVE: The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA1c, proportion of patients at HbA1c target ≤7% (53 mmol/mol), hypoglycemia, and weight change...
April 2017: Diabetes Care
https://www.readbyqxmd.com/read/28324165/lipid-phenol-and-carotenoid-changes-in-bianca-grapevine-leaves-after-mechanical-wounding-a-case-study
#14
Giulia Chitarrini, Luca Zulini, Domenico Masuero, Urska Vrhovsek
Metabolic changes can occur in plants in response to abiotic stress. Extensive use of leaf discs (mechanical wounding) in studies regarding the effect on the biochemical response of the grapevine to different types of biotic stress makes it necessary to understand metabolic perturbation after injury. In this study, we investigate how mechanical wounding can affect the metabolism of grapevine leaf tissue using Bianca variety as case study. Two sizes of leaf discs (1.1 and 2.8 cm in diameter) were excised from leaves, and phenol, lipid and carotenoid perturbation were investigated 0, 6, 12, 24, 48, 96 and 120 h post cutting...
March 21, 2017: Protoplasma
https://www.readbyqxmd.com/read/28324109/sex-specific-life-course-changes-in-the-neuro-metabolic-phenotype-of-glut3-null-heterozygous-mice-ketogenic-diet-ameliorates-electroencephalographic-seizures-and-improves-sociability
#15
Yun Dai, Yuanzi Zhao, Masatoshi Tomi, Bo-Chul Shin, Shanthie Thamotharan, Andrey Mazarati, Raman Sankar, Elizabeth A Wang, Carlos Cepeda, Michael S Levine, Jingjing Zhang, Andrew Frew, Jeffry R Alger, Peter Clark, Monica Sondhi, Sudatip Kositamongkol, Leah Leibovitch, Sherin U Devaskar
We tested the hypothesis that exposure of glut3+/- mice to a ketogenic diet ameliorates autism-like features which includes aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma-CSF-brain metabolic profile, brain glucose transport/uptake, glucose and monocarboxylate transporter proteins, and ATP in the presence or absence of systemic insulin administration. Glut3+/- male but not female mice (5m of age) displayed reduced CSF glucose/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP...
January 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324055/substrate-metabolism-and-insulin-sensitivity-during-fasting-in-obese-human-subjects-impact-of-gh-blockade
#16
Morten Høgild Pedersen, Mads Vandsted Svart, Janne Lebeck, Martin Bidlingmaier, Hans Stødkilde-Jørgensen, Steen Bønløkke Pedersen, Niels Møller, Niels Jessen, Jens O L Jørgensen
Context: Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. GH secretion increases during fasting and GH causes insulin resistance. Objective: To study the metabolic effects of GH blockade during fasting in obese subjects. Subjects and Methods: Nine obese males were studied thrice in a randomized design: 1) After an overnight fast (Control), 2) After 72 h fasting (Fasting) and 3) After 72 h fasting with GH blockade (pegvisomant) (Fasting + GHA)...
January 18, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323916/acute-hypercortisolemia-exerts-depot-specific-effects-on-abdominal-and-femoral-adipose-tissue-function
#17
Konstantinos N Manolopoulos, Michael W O'Reilly, Iwona J Bujalska, Jeremy W Tomlinson, Wiebke Arlt
Context: Glucocorticoids have pleiotropic metabolic functions and acute glucocorticoid excess affects fatty acid metabolism, increasing systemic lipolysis. Whether glucocorticoids exert adipose tissue depot-specific effects remains unclear. Objective: In vivo assessment of femoral and abdominal adipose tissue responses to acute glucocorticoid administration. Design and outcome measures: Nine healthy male volunteers studied on two occasions, following a hydrocortisone infusion (0...
February 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28319890/one-year-follow-up-of-clinical-metabolic-and-oxidative-stress-profile-of-morbid-obese-patients-after-laparoscopic-sleeve-gastrectomy-8-oxo-dg-as-a-clinical-marker
#18
Lidia Monzo-Beltran, Antonio Vazquez-Tarragón, Concha Cerdà, Paula Garcia-Perez, Antonio Iradi, Carlos Sánchez, Benjamin Climent, Carmen Tormos, Antonio Vázquez-Prado, Javier Girbés, Nuria Estáñ, Sebastián Blesa, Raquel Cortés, Felipe J Chaves, Guillermo T Sáez
Obesity has grown worldwide over the last few decades. In its different degrees, obesity is accompanied by many clinical and biochemical alterations reflecting the pathological condition of various body tissues. Among the mechanisms underlying the pathogenesis of obesity and associated complications, oxidative stress (OS) may be playing an important role. In the present study, we have characterized at systemic level the degree of OS status in a group of morbid obese patients (BMI>40kg/m(2)) at basal sate and its modulation during one year after bariatric surgery using the laparoscopic sleeve gastrectomy (LSG) technique...
February 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/28319140/role-of-muscle-il-6-in-gender-specific-metabolism-in-mice
#19
Amalia Molinero, Antonio Fernandez-Perez, Aina Mogas, Mercedes Giralt, Gemma Comes, Olaya Fernandez-Gayol, Mario Vallejo, Juan Hidalgo
The aim of the present work was to further explore the physiological roles of muscle-derived IL-6. Adult-floxed and conditional skeletal muscle IL-6 knock out male and female mice were used to study energy expenditure (indirect calorimetry at rest and during treadmill exercise, and body temperature cycle during the light phase) and energy intake (response to fast/refeeding). We also evaluated the responses to leptin and the activity of the insulin signalling pathway in skeletal muscle and liver by phosphorylation of Akt at Ser 473...
2017: PloS One
https://www.readbyqxmd.com/read/28318687/protein-intake-distribution-pattern-does-not-affect-anabolic-response-lean-body-mass-muscle-strength-or-function-over-8-weeks-in-older-adults-a-randomized-controlled-trial
#20
Il-Young Kim, Scott Schutzler, Amy M Schrader, Horace J Spencer, Gohar Azhar, Robert R Wolfe, Arny A Ferrando
BACKGROUND & AIMS: In our recent acute metabolic study, we found no differences in the anabolic response to differing patterns of dietary protein intake. To confirm this in a chronic study, we investigated the effects of protein distribution pattern on functional outcomes and protein kinetics in older adults over 8 weeks. METHODS: To determine chronic effects of protein intake pattern at 1.1 g protein/kg/day in mixed meals on lean body mass (LBM), functional outcomes, whole body protein kinetics and muscle protein fractional synthesis rate (MPS) over 8-week respective dietary intervention, fourteen older subjects were randomly divided into either EVEN or UNVEN group...
March 3, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
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