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https://www.readbyqxmd.com/read/27915453/effects-of-chronic-nitric-oxide-synthase-inhibition-on-v-o2max-and-exercise-capacity-in-mice
#1
M Wojewoda, K Przyborowski, B Sitek, A Zakrzewska, L Mateuszuk, J A Zoladz, S Chlopicki
Acute inhibition of NOS by L-NAME (N(ω)-nitro-L-arginine methyl ester) is known to decrease maximal oxygen consumption (V'O2max) and impair maximal exercise capacity, whereas the effects of chronic L-NAME treatment on V'O2max and exercise performance have not been studied so far. In this study, we analysed the effect of L-NAME treatment, (LN2 and LN12, respectively) on V'O2max and exercise capacity (in maximal incremental running and prolonged sub-maximal incremental running tests), systemic NO bioavailability (plasma nitrite (NO2(-)) and nitrate (NO3(-))) and prostacyclin (PGI2) production in C57BL6/J mice...
December 3, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27915400/the-pathophysiological-role-of-nox2-in-hypertension-and-organ-damage
#2
REVIEW
Maurizio Forte, Cristina Nocella, Elena De Falco, Silvia Palmerio, Leonardo Schirone, Valentina Valenti, Giacomo Frati, Roberto Carnevale, Sebastiano Sciarretta
NADPH oxidases (NOXs) represent one of the major sources of reactive oxygen species in the vascular district. Reactive oxygen species are responsible for vascular damage that leads to several cardiovascular pathological conditions. Among NOX isoforms, NOX2 is widely expressed in many cells types, such as cardiomyocytes, endothelial cells, and vascular smooth muscle cells, confirming its pivotal role in vascular pathophysiology. Studies in mice models with systemic deletion of NOX2, as well as in transgenic mice overexpressing NOX2, have demonstrated the undeniable involvement of NOX2 in the development of hypertension, atherosclerosis, diabetes mellitus, cardiac hypertrophy, platelet aggregation, and aging...
December 3, 2016: High Blood Pressure & Cardiovascular Prevention: the Official Journal of the Italian Society of Hypertension
https://www.readbyqxmd.com/read/27915007/effect-of-the-oral-administration-of-nanoencapsulated-quercetin-on-a-mouse-model-of-alzheimer-s-disease
#3
Lina Clara Gayoso E Almendra Ibiapina, Elena Puerta, José Eduardo Suárez-Santiago, Nereide Stela Santos-Magalhães, Maria J Ramirez, Juan M Irache
Quercetin has been identified as a promising compound with a neuroprotective potential against age-related neurodegenerative diseases such as Alzheimer's disease (AD). Nevertheless, the clinical application of quercetin is hampered by its low oral bioavailability. The aim of this work was to evaluate the capability of nanoencapsulated quercetin in zein nanoparticles (NPQ), that significantly improves the oral absorption and bioavailability of the flavonoid, as potential oral treatment for AD. For this purpose, SAMP8 mice were orally treated for two months with either NPQ (25mg/kg every 48hours) or a solution of quercetin (Q; 25mg/kg daily)...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27914528/food-advanced-glycation-end-products-aggravate-the-diabetic-vascular-complications-via-modulating-the-ages-rage-pathway
#4
Xing Lv, Gao-Hong Lv, Guo-Ying Dai, Hong-Mei Sun, Hui-Qin Xu
The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27914197/young-adult-born-neurons-enhance-hippocampal-dependent-performance-via-influences-on-bilateral-networks
#5
Jia-Min Zhuo, Hua-An Tseng, Mitul Desai, Mark E Bucklin, Ali I Mohammed, Nick Tm Robinson, Edward S Boyden, Lara M Rangel, Alan P Jasanoff, Howard J Gritton, Xue Han
Adult neurogenesis supports performance in many hippocampal dependent tasks. Considering the small number of adult-born neurons generated at any given time, it is surprising that this sparse population of cells can substantially influence behavior. Recent studies have demonstrated that heightened excitability and plasticity may be critical for the contribution of young adult-born cells for certain tasks. What is not well understood is how these unique biophysical and synaptic properties may translate to networks that support behavioral function...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27913616/genetic-contributors-to-intergenerational-cag-repeat-instability-in-huntington-s-disease-knock-in-mice
#6
João Luís Neto, Jong-Min Lee, Ali Afridi, Tammy Gillis, Jolene R Guide, Stephani Dempsey, Brenda Lager, Isabel Alonso, Vanessa C Wheeler, Ricardo Mouro Pinto
Huntington's disease is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in Huntington's disease families, partly underlying the genetic anticipation seen in this disorder. Huntington's disease CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest Huntington's disease knock-in mouse model breeding datasets reported to date...
December 2, 2016: Genetics
https://www.readbyqxmd.com/read/27911782/egfr-signaling-is-critical-for-maintaining-the-superficial-layer-of-articular-cartilage-and-preventing-osteoarthritis-initiation
#7
Haoruo Jia, Xiaoyuan Ma, Wei Tong, Basak Doyran, Zeyang Sun, Luqiang Wang, Xianrong Zhang, Yilu Zhou, Farid Badar, Abhishek Chandra, X Lucas Lu, Yang Xia, Lin Han, Motomi Enomoto-Iwamoto, Ling Qin
Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox)...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911443/transient-mitochondrial-dna-double-strand-breaks-in-mice-cause-accelerated-aging-phenotypes-in-a-ros-dependent-but-p53-p21-independent-manner
#8
Milena Pinto, Alicia M Pickrell, Xiao Wang, Sandra R Bacman, Aixin Yu, Aline Hida, Lloye M Dillon, Paul D Morton, Thomas R Malek, Siôn L Williams, Carlos T Moraes
We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27911317/alzheimer-s-disease-histological-and%C3%A2-behavioral-manifestations-in%C3%A2-transgenic-mice-correlate-with%C3%A2-specific%C3%A2-gut-microbiome-state
#9
Liang Shen, Lu Liu, Hong-Fang Ji
Alzheimer's disease (AD) is a neurodegenerative brain disease and is the most common form of dementia. In recent years, many studies indicated the association of gut microbiota changes with metabolic diseases. However, the gut microbiota of AD has not been investigated. The present study aims to compare the gut microbiota in APP/PS1 transgenic mice of AD and C57/Bl6 wild-type (WT) mice by pyrosequencing the V3 and V4 regions of the bacterial 16S ribosomal RNA genes. The 3-, 6-, and 8-month-old APP/PS1 and WT mice were used to explore the effects of age on the gut microbiota...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911309/longitudinal-characterization-of-18f-fdg-and-18f-av45-uptake-in-the-double-transgenic-tastpm-mouse-model
#10
Ann-Marie Waldron, Leonie Wyffels, Jeroen Verhaeghe, Jill C Richardson, Mark Schmidt, Sigrid Stroobants, Xavier Langlois, Steven Staelens
We aimed to monitor the timing of amyloid-β deposition in relation to changes in brain function using in vivo imaging with [18F]-AV45 and [18F]-FDG in a mouse model of Alzheimer's disease. TASTPM transgenic mice and wild-type controls were scanned longitudinally with [18F]-AV45 and [18F]-FDG before (3 months of age) and at multiple time points after the onset of amyloid deposition (6, 9, 12, and 15 months of age). As expected with increasing amyloidosis, TASTPM mice demonstrated progressive age-dependent increases in [18F]-AV45 uptake that were significantly higher than for WT from 9 months onwards and correlated to ex vivo measures of amyloid burden...
November 25, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911305/nitrosylation-of-vesicular-transporters-in-brain-of-amyloid-precursor-protein-presenilin-1-double-transgenic-mice
#11
Ying Wang, Zhu Zhou, Hua Tan, Shenghua Zhu, Yiran Wang, Yingxia Sun, Xin-Min Li, Jun-Feng Wang
Nitric oxide can attack thiol groups of cysteine residues in proteins and induce protein cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer's disease. Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles, which is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and that S-nitrosylation of these transporters inhibits vesicular uptake of acetylcholine and glutamate...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27908889/microrna-146a-induces-lineage-negative-bone-marrow-cell-apoptosis-and-senescence-by-targeting-polo-like-kinase-2-expression
#12
Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, Dushyantha T Jayaweera, Derek M Dykxhoorn, Chunming Dong
OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27908750/mesenchymal-stromal-cell-based-therapies-reduce-obesity-and-metabolic-syndromes-induced-by-a-high-fat-diet
#13
Chien-Wei Lee, Wei-Ting Hsiao, Oscar K Lee
Obesity is an alarming global health problem that results in multiaspect metabolic syndromes in both genders and most age groups. The lack of effective therapies for obesity and its associated metabolic syndrome is an urgent societal issue. To elucidate whether mesenchymal stromal cell (MSC)-based therapies can ameliorate high-fat diet-induced obesity and compare the effectiveness of several methodological approaches, we transplanted human MSCs, MSC-derived brown adipocytes (M-BA), and MSC lysateinto obese mice...
November 12, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27908661/uniform-low-level-dystrophin-expression-in-the-heart-partially-preserved-cardiac-function-in-an-aged-mouse-model-of-duchenne-cardiomyopathy
#14
Nalinda B Wasala, Yongping Yue, Jenna Vance, Dongsheng Duan
Dystrophin deficiency results in Duchenne cardiomyopathy, a primary cause of death in Duchenne muscular dystrophy (DMD). Gene therapy has shown great promise in ameliorating the cardiac phenotype in mouse models of DMD. However, it is not completely clear how much dystrophin is required to treat dystrophic heart disease. We and others have shown that mosaic dystrophin expression at the wild-type level, depending on the percentage of dystrophin positive cardiomyocytes, can either delay the onset of or fully prevent cardiomyopathy in dystrophin-null mdx mice...
November 28, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27908425/copper-accumulation-in-rodent-brain-astrocytes-a-species-difference
#15
Brendan Sullivan, Gregory Robison, Yulia Pushkar, John K Young, Kebreten F Manaye
Changes in Cu homeostasis have been implicated in multiple neurodegenerative diseases. Factors controlling and regulating the distribution of Cu in the brain remain largely unknown. We have previously reported that a sub-set of astrocytes in the subventricular zone (SVZ) contain Cu-rich aggregates. Here we expand previous studies with detailed X-ray fluorescent imaging (XRF) analysis of the additional brain areas of hippocampus (HP) and rostral migratory stream (RMS). We also use conventional DAB (3,3'-diaminobenzidine) staining which accesses both peroxidase and pseudo-peroxidase activities...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27908291/muscle-pgc-1%C3%AE-modulates-satellite-cell-number-and-proliferation-by-remodeling-the-stem-cell-niche
#16
Ivana Dinulovic, Regula Furrer, Markus Beer, Arnaud Ferry, Bettina Cardel, Christoph Handschin
BACKGROUND: The myogenic capacity of satellite cells (SCs), adult muscle stem cells, is influenced by aging, exercise, and other factors. In skeletal muscle, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a key regulator of oxidative metabolism and endurance training adaptation. However, a link between PGC-1α and SC behavior remains unexplored. METHODS: We have now studied SC function in a PGC-1α fiber-specific gain-of-function animal model...
December 2, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27908170/high-resolution-digital-autoradiographic-and-dosimetric-analysis-of-heterogeneous-radioactivity-distribution-in-xenografted-prostate-tumors
#17
Oskar V Timmermand, Jenny Nilsson, Sven-Erik Strand, Jörgen Elgqvist
PURPOSE: The first main aim of this study was to illustrate the absorbed dose rate distribution from (177)Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of (90)Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using (177)Lu-h11B6, directed against the human kallikrein 2 antigen...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/27907249/grainyhead-like-3-grhl3-deficiency-in-brain-leads-to-altered-locomotor-activity-and-decreased-anxiety-like-behaviours-in-aged-mice
#18
Sebastian Dworkin, Alana Auden, Darren D Partridge, Maria Daglas, Robert L Medcalf, Theo Mantamadiotis, Smitha R Georgy, Charbel Darido, Stephen M Jane, Stephen B Ting
The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here we show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviours...
December 1, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/27906619/effects-of-4-pyridone-3-carboxamide-1%C3%AE-d-ribonucleoside-on-adenine-nucleotide-catabolism-in-the-aortic-wall-implications-for-atherosclerosis-in-apoe-ldlr-mice
#19
Magdalena Zabielska, Barbara Kutryb-Zajac, Paulina Żukowska, Ewa Slominska, Ryszard Smoleński
: 4-Pyridone-3-carboxamide-1-beta-D-ribonucleoside (4PYR) is an endogenously produced nucleoside that had been identified as a substrate for intracellular phosphorylation to form intracellular nucleotides. Previous studies demonstrated that 4PYR adversely affects metabolism of endothelial cells that is known risk factor for atherosclerosis. The purpose of this study was to evaluate effects of 4PYR on the progression of atherosclerosis and changes in extracellular nucleotides degradation on the surface of the vessel wall in the murine model...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906582/fiat-deletion-increases-bone-mass-but-does-not-prevent-high-fat-diet-induced-metabolic-complications
#20
Bahareh Hekmatnejad, Vionnie W C Yu, William Addison, Vice Mandic, Martin Pellicelli, Alice Arabian, René St-Arnaud
FIAT (Factor Inhibiting ATF4-mediated Transcription) interacts with ATF4 to repress its transcriptional activity. We performed a phenotypic analysis of Fiat-deficient male mice (Fiat(-/Y)) at 8 and 16 weeks of age. Fiat(-/Y) mice appeared normal at birth and weight gain was comparable between genotypes. μCT analysis of proximal femur demonstrated 46% and 13% age-dependent increases in trabecular bone volume and thickness, respectively, in Fiat(-/Y) mice. Cortical bone measurements at the femoral midshaft revealed a significant increase in cortical thickness in older Fiat(-/Y) mice...
December 1, 2016: Endocrinology
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