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https://www.readbyqxmd.com/read/28315453/defects-in-mitochondrial-energetic-function-compels-fanconi-anemia-cells-to-glycolytic-metabolism
#1
Enrico Cappelli, Paola Cuccarolo, Giorgia Stroppiana, Maurizio Miano, Roberta Bottega, Vanessa Cossu, Paolo Degan, Silvia Ravera
Energetic metabolism plays an essential role in the differentiation of haematopoietic stem cells (HSC). In Fanconi Anaemia (FA), DNA damage is accumulated during HSC differentiation, an event that is likely associated with bone marrow failure (BMF). One of the sources of the DNA damage is altered mitochondrial metabolism and an associated increment of oxidative stress. Recently, altered mitochondrial morphology and a deficit in the energetic activity in FA cells have been reported. Considering that mitochondria are the principal site of aerobic ATP production, we investigated FA metabolism in order to understand what pathways are able to compensate for this energy deficiency...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28302504/mitochondrial-nudix-hydrolases-a-metabolic-link-between-nad-catabolism-gtp-and-mitochondrial-dynamics
#2
Aaron Long, Nina Klimova, Tibor Kristian
NAD(+) catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD(+) catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism...
March 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28283797/influence-of-nrf2-activators-on-subcellular-skeletal-muscle-protein-and-dna-synthesis-rates-after-6%C3%A2-weeks-of-milk-protein-feeding-in-older-adults
#3
Adam R Konopka, Jaime L Laurin, Robert V Musci, Christopher A Wolff, Justin J Reid, Laurie M Biela, Qian Zhang, Fredrick F Peelor, Christopher L Melby, Karyn L Hamilton, Benjamin F Miller
In older adults, chronic oxidative and inflammatory stresses are associated with an impaired increase in skeletal muscle protein synthesis after acute anabolic stimuli. Conjugated linoleic acid (CLA) and Protandim have been shown to activate nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor for the antioxidant response element and anti-inflammatory pathways. This study tested the hypothesis that compared to a placebo control (CON), CLA and Protandim would increase skeletal muscle subcellular protein (myofibrillar, mitochondrial, cytoplasmic) and DNA synthesis in older adults after 6 weeks of milk protein feeding...
March 10, 2017: Geroscience
https://www.readbyqxmd.com/read/28278478/abnormality-detection-in-correlated-gaussian-molecular-nano-networks-design-and-analysis
#4
Siavash Ghavami, Farshad Lahouti
A nano abnormality detection scheme (NADS) in molecular nano-networks is studied. This is motivated by the fact that early detection of diseases such as cancer play a crucial role in their successful treatment. The proposed NADS is in fact a two-tier network of sensor nano-machines (SNMs) in the first tier and a data-gathering node (DGN) at the sink. The SNMs detect the presence of competitor cells (abnormality) by variations in input and/or parameters of a nano-communications channel (NCC). The noise of SNMs as their nature suggest is considered correlated in time and space and herein assumed additive Gaussian...
March 2, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28261868/in-vivo-assessment-of-intracellular-redox-state-in-rat-liver-using-hyperpolarized-1-13-c-alanine
#5
Jae Mo Park, Chalermchai Khemtong, Shie-Chau Liu, Ralph E Hurd, Daniel M Spielman
PURPOSE: The intracellular lactate to pyruvate concentration ratio is a commonly used tissue assay biomarker of redox, being proportional to free cytosolic [NADH]/[NAD(+) ]. In this study, we assessed the use of hyperpolarized [1-(13) C]alanine and the subsequent detection of the intracellular products of [1-(13) C]pyruvate and [1-(13) C]lactate as a useful substrate for assessing redox levels in the liver in vivo. METHODS: Animal experiments were conducted to measure in vivo metabolism at baseline and after ethanol infusion...
March 5, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28259765/evaluating-the-transport-kinetics-of-a-model-compound-released-from-cellulosic-coacervate-compositions-into-artificial-sebum
#6
Nada H Baalbaki, Gerald B Kasting
Complex coacervates of cationic polymers and anionic surfactants, which are produced spontaneously during the use of rinse-off formulations, represent an important delivery vehicle for topical agents to the skin surface and appendages. In the present study, an artificial sebum-loaded cell culture insert method for determining the sebum diffusion properties of topical agents was optimized for in vitro release testing (IVRT). This method was subsequently used to evaluate the transport kinetics of a model compound, kinetin, released from semi-solid coacervate formulations into sebum...
March 1, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28258794/brain-bioenergetics-and-redox-state-measured-by-31-p-magnetic-resonance-spectroscopy-in-unaffected-siblings-of-patients-with-psychotic-disorders
#7
Virginie-Anne Chouinard, Sang-Young Kim, Linda Valeri, Cagri Yuksel, Kyle P Ryan, Guy Chouinard, Bruce M Cohen, Fei Du, Dost Öngür
BACKGROUND: Brain bioenergetic anomalies and redox dysregulation have been implicated in the pathophysiology of psychotic disorders. The present study examined brain energy-related metabolites and the balance between nicotinamide adenine dinucleotide metabolites (oxidized NAD+ and reduced NADH) using (31)P-magnetic resonance spectroscopy ((31)P-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls. METHODS: 21 unaffected siblings, 32 FEP patients (including schizophrenia spectrum and affective psychoses), and 21 controls underwent (31)P-MRS in the frontal lobe (6×6×4cm(3)) on a 4T MR scanner, using custom-designed dual-tuned surface coil with outer volume suppression...
March 1, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28257891/combined-metabolic-and-transcriptional-profiling-identifies-pentose-phosphate-pathway-activation-by-hsp27-phosphorylation-during-cerebral-ischemia
#8
Taichiro Imahori, Kohkichi Hosoda, Tomoaki Nakai, Yusuke Yamamoto, Yasuhiro Irino, Masakazu Shinohara, Naoko Sato, Takashi Sasayama, Kazuhiro Tanaka, Hiroaki Nagashima, Masaaki Kohta, Eiji Kohmura
The metabolic pathophysiology underlying ischemic stroke remains poorly understood. To gain insight into these mechanisms, we performed a comparative metabolic and transcriptional analysis of the effects of cerebral ischemia on the metabolism of the cerebral cortex using middle cerebral artery occlusion (MCAO) rat model. Metabolic profiling by gas-chromatography/mass-spectrometry analysis showed clear separation between the ischemia and control group. The decreases of fructose 6-phosphate and ribulose 5-phosphate suggested enhancement of the pentose phosphate pathway (PPP) during cerebral ischemia (120-min MCAO) without reperfusion...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28254441/omega-3-polyunsaturated-fatty-acids-suppress-the-inflammatory-responses-of-lipopolysaccharide-stimulated-mouse-microglia-by-activating-sirt1-pathways
#9
Takayuki Inoue, Masashi Tanaka, Shinya Masuda, Ryuji Ohue-Kitano, Hajime Yamakage, Kazuya Muranaka, Hiromichi Wada, Toru Kusakabe, Akira Shimatsu, Koji Hasegawa, Noriko Satoh-Asahara
Obesity and diabetes are known risk factors for dementia, and it is speculated that chronic neuroinflammation contributes to this increased risk. Microglia are brain-resident immune cells modulating the neuroinflammatory state. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major ω-3 polyunsaturated fatty acids (PUFAs) of fish oil, exhibit various effects, which include shifting microglia to the anti-inflammatory phenotype. To identify the molecular mechanisms involved, we examined the impact of EPA, DHA, and EPA+DHA on the lipopolysaccharide (LPS)-induced cytokine profiles and the associated signaling pathways in the mouse microglial line MG6...
February 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28230641/peritransplant-energy-changes-and-their-correlation-to-outcome-after-human-liver-transplantation
#10
Bote G Bruinsma, James H Avruch, Gautham V Sridharan, Pepijn D Weeder, Marie Louise Jacobs, Kerry Crisalli, Beth Amundsen, Robert J Porte, James F Markmann, Korkut Uygun, Heidi Yeh
BACKGROUND: The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. METHODS: Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 min after portal venous (PVR) and hepatic arterial reperfusion (HAR) and analyzed by LC-MS for energetic cofactors (ATP/ADP/AMP, NADH/NAD, NADPH/NADP, FAD, GSSG/GSH)...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28230187/silencing-salusin-%C3%AE-attenuates-cardiovascular-remodeling-and-hypertension-in-spontaneously-hypertensive-rats
#11
Xing-Sheng Ren, Li Ling, Bing Zhou, Ying Han, Ye-Bo Zhou, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Salusin-β is a bioactive peptide involved in vascular smooth muscle cell proliferation, vascular fibrosis and hypertension. The present study was designed to determine the effects of silencing salusin-β on hypertension and cardiovascular remodeling in spontaneously hypertensive rats (SHR). Thirteen-week-old male SHR and normotensive Wistar-Kyoto rats (WKY) were subjected to intravenous injection of PBS, adenoviral vectors encoding salusin-β shRNA (Ad-Sal-shRNA) or a scramble shRNA. Salusin-β levels in plasma, myocardium and mesenteric artery were increased in SHR...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217084/nad-attenuates-bilirubin-induced-hyperexcitation-in-the-ventral-cochlear-nucleus-by-inhibiting-excitatory-neurotransmission-and-neuronal-excitability
#12
Min Liang, Xin-Lu Yin, Lu-Yang Wang, Wei-Hai Yin, Ning-Ying Song, Hai-Bo Shi, Chun-Yan Li, Shan-Kai Yin
Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little is known regarding the roles of NAD+ in neuronal excitation and excitotoxicity associated with many neurodegenerative disorders and diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons in the ventral cochlear nucleus (VCN), which is particularly vulnerable to bilirubin excitotoxicity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28203294/correlation-between-nad-p-h-quinone-oxidoreductase-1-c609t-polymorphism-and-increased-risk-of-esophageal-cancer-evidence-from-a-meta-analysis
#13
Jingfang Diao, Jie Bao, Jianxin Peng, Jiaqiang Mo, Qing Ye, Junming He
NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence the risk for esophageal cancer (EC) in many studies. However, the results remain controversial and ambiguous. We performed a meta-analysis, which included 13 independent studies with a total of 2357 subjects, to examine the association between NQO1 C609T polymorphism and EC. The association was assessed by five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of EC (odds ratio [OR] T versus C = 1...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28190822/phloridzin-inhibits-high-k-induced-contraction-via-the-inhibition-of-sodium-glucose-cotransporter-1-in-rat-ileum
#14
Hidenori Kanda, Takeharu Kaneda, Akira Kawaguchi, Noriyasu Sasaki, Tsuyoshi Tajima, Norimoto Urakawa, Kazumasa Shimizu, Hiroetsu Suzuki
Recent studies have shown that phloridzin, an inhibitor of sodium-glucose cotransporter (SGLT), strongly decreases high K(+)-induced contraction in phasic muscle, such as tenia coli, but slightly affects tonic muscle, such as trachea . In this study, we examined the inhibitory mechanism of phloridzin on high K(+)-induced muscle contraction in rat ileum, a phasic muscle. Phloridzin inhibited the high K(+)-induced contraction in the ileum and the aorta, and the relaxing effect of phloridzin at 1 mM in the ileum was approximately five-fold more potent than that in the aorta...
February 11, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28188924/daphnetin-mediated-nrf2-antioxidant-signaling-pathways-ameliorate-tert-butyl-hydroperoxide-t-bhp-induced-mitochondrial-dysfunction-and-cell-death
#15
Hongming Lv, Qinmei Liu, Junfeng Zhou, Guangyun Tan, Xuming Deng, Xinxin Ci
Daphnetin (Daph), a natural coumarin derivative isolated from plants of the Genus Daphne, possesses abundant biological activities, such as anti-inflammatory, antioxidant and anticancer properties. In the present study, we focused on investigating the protective effect of Daph against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage, mitochondrial dysfunction and the involvement of underlying molecular mechanisms. Our findings indicated that Daph effectively inhibited t-BHP-stimulated cytotoxicity, cell apoptosis, and mitochondrial dysfunction, which are associated with suppressed reactive oxygen species (ROS) generation, decreased malondialdehyde (MDA) formation, increased superoxide dismutase (SOD) levels and glutathione (GSH)/GSSG (oxidized GSH) ratio...
February 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28169456/evaluating-the-protective-effects-and-mechanisms-of-diallyl-disulfide-on-interlukin-1%C3%AE-induced-oxidative-stress-and-mitochondrial-apoptotic-signaling-pathways-in-cultured-chondrocytes
#16
Azam Hosseinzadeh, Davood Jafari, Tunku Kamarul, Abolfazll Bagheri, Ali M Sharifi
The protective effects and mechanisms of DADS on IL-1β-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. The effect of various concentrations of DADS (1, 5 10, 25, 50, and 100 μM) on C28I2 cell viability was evaluated in different times (2, 4, 8, 16, and 24 h) to obtain the non-cytotoxic concentrations of drug by MTT-assay. The protective effect of non-toxic concentrations of DADS on experimentally induced oxidative stress and apoptosis by IL-1β in C28I2 was evaluated...
February 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28152599/discovery-of-nicotinamide-adenine-dinucleotide-binding-proteins-in-the-escherichia-coli-proteome-using-a-combined-energetic-and-structural-bioinformatics-based-approach
#17
Lingfei Zeng, Woong-Hee Shin, Xiaolei Zhu, Sung Hoon Park, Chiwook Park, W Andy Tao, Daisuke Kihara
Protein-ligand interaction plays a critical role in regulating the biochemical functions of proteins. Discovering protein targets for ligands is vital to new drug development. Here, we present a strategy that combines experimental and computational approaches to identify ligand-binding proteins in a proteomic scale. For the experimental part, we coupled pulse proteolysis with filter-assisted sample preparation (FASP) and quantitative mass spectrometry. Under denaturing conditions, ligand binding affected protein stability, which resulted in altered protein abundance after pulse proteolysis...
February 3, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28149324/exploring-eukaryotic-formate-metabolisms-to-enhance-microbial-growth-and-lipid-accumulation
#18
Zhiguo Liu, Tolutola Oyetunde, Whitney D Hollinshead, Anna Hermanns, Yinjie J Tang, Wei Liao, Yan Liu
BACKGROUND: C1 substrates (such as formate and methanol) are promising feedstock for biochemical/biofuel production. Numerous studies have been focusing on engineering heterologous pathways to incorporate C1 substrates into biomass, while the engineered microbial hosts often demonstrate inferior fermentation performance due to substrate toxicity, metabolic burdens from engineered pathways, and poor enzyme activities. Alternatively, exploring native C1 pathways in non-model microbes could be a better solution to address these challenges...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28143522/aspirin-intervention-for-the-reduction-of-colorectal-cancer-risk-aspired-a-study-protocol-for-a-randomized-controlled-trial
#19
David A Drew, Samantha M Chin, Katherine K Gilpin, Melanie Parziale, Emily Pond, Madeline M Schuck, Kathleen Stewart, Meaghan Flagg, Crystal A Rawlings, Vadim Backman, Peter J Carolan, Daniel C Chung, Francis P Colizzo, Matthew Freedman, Manish Gala, John J Garber, Curtis Huttenhower, Dmitriy Kedrin, Hamed Khalili, Douglas S Kwon, Sanford D Markowitz, Ginger L Milne, Norman S Nishioka, James M Richter, Hemant K Roy, Kyle Staller, Molin Wang, Andrew T Chan
BACKGROUND: Although aspirin is recommended for the prevention of colorectal cancer, the specific individuals for whom the benefits outweigh the risks are not clearly defined. Moreover, the precise mechanisms by which aspirin reduces the risk of cancer are unclear. We recently launched the ASPirin Intervention for the REDuction of colorectal cancer risk (ASPIRED) trial to address these uncertainties. METHODS/DESIGN: ASPIRED is a prospective, double-blind, multidose, placebo-controlled, biomarker clinical trial of aspirin use in individuals previously diagnosed with colorectal adenoma...
February 1, 2017: Trials
https://www.readbyqxmd.com/read/28130305/modulation-of-the-acetone-butanol-ratio-during-fermentation-of-corn-stover-derived-hydrolysate-by-clostridium-beijerinckii-ncimb-8052
#20
Zi-Yong Liu, Xiu-Qing Yao, Quan Zhang, Zhen Liu, Ze-Jie Wang, Yong-Yu Zhang, Fu-Li Li
Producing biobutanol from lignocellulosic biomass has shown promise to ultimately reduce greenhouse gases and alleviate the global energy crisis. However, because of the recalcitrance of a lignocellulosic biomass, a pretreatment of the substrate is needed which in many cases releases soluble lignin compounds (SLCs), which inhibit growth of butanol-producing clostridia. In this study, we found that SLCs changed the acetone/butanol ratio (A/B ratio) during butanol fermentation. The typical A/B molar ratio during Clostridium beijerinckii NCIMB 8052 batch fermentation with glucose as the carbon source is about 0...
January 27, 2017: Applied and Environmental Microbiology
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