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https://www.readbyqxmd.com/read/28107631/overcoming-the-heat-endurance-of-tumor-cells-by-interfering-the-anaerobic-glycolysis-metabolism-for-improved-photothermal-therapy
#1
Wei-Hai Chen, Guo-Feng Luo, Qi Lei, Sheng Hong, Wen-Xiu Qiu, Li-Han Liu, Si-Xue Cheng, Xian-Zheng Zhang
In this study, we developed a general method to decorate plasmonic gold nanorods (GNRs) with a CD44-targeting functional polymer, containing hyaluronic acid (HA) targeting moiety and a small molecule Glut1 inhibitor of diclofenac (DC), to obtain GNR/HA-DC. This nanosystem exhibited the superiority of selectively sensitizing tumor cells for photothermal therapy (PTT) by inhibiting the unique anaerobic glycolysis. Upon specifically targeting CD44, sequentially time-dependent DC release could be achieved by the trigger of hyaluronidase (HAase), which abundantly existed in tumor tissue...
January 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28107516/liver-amp-activated-protein-kinase-is-unnecessary-for-gluconeogenesis-but-protects-energy-state-during-nutrient-deprivation
#2
Clinton M Hasenour, D Emerson Ridley, Freyja D James, Curtis C Hughey, E Patrick Donahue, Benoit Viollet, Marc Foretz, Jamey D Young, David H Wasserman
AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes...
2017: PloS One
https://www.readbyqxmd.com/read/28107461/inhibition-of-fatty-acid-synthase-reduces-blastocyst-hatching-through-regulation-of-the-akt-pathway-in-pigs
#3
Jing Guo, Nam-Hyung Kim, Xiang-Shun Cui
Fatty acid synthase (FASN) is an enzyme responsible for the de novo synthesis of long-chain fatty acids. During oncogenesis, FASN plays a role in growth and survival rather than acting within the energy storage pathways. Here, the function of FASN during early embryonic development was studied using its specific inhibitor, C75. We found that the presence of the inhibitor reduced blastocyst hatching. FASN inhibition decreased Cpt1 expression, leading to a reduction in mitochondria numbers and ATP content. This inhibition of FASN resulted in the down-regulation of the AKT pathway, thereby triggering apoptosis through the activation of the p53 pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28106753/naphthalimides-selectively-inhibit-the-activity-of-bacterial-replicative-dna-ligases-and-display-bactericidal-effects-against-tubercle-bacilli
#4
Malgorzata Korycka-Machala, Marcin Nowosielski, Aneta Kuron, Sebastian Rykowski, Agnieszka Olejniczak, Marcin Hoffmann, Jaroslaw Dziadek
The DNA ligases, enzymes that seal breaks in the backbones of DNA, are essential for all organisms, however bacterial ligases essential for DNA replication use β-nicotinamide adenine dinucleotide as their co-factor, whereas those that are essential in eukaryotes and viruses use adenosine-5'-triphosphate. This fact leads to the conclusion that NAD⁺-dependent DNA ligases in bacteria could be targeted by their co-factor specific inhibitors. The development of novel alternative medical strategies, including new drugs, are a top priority focus areas for tuberculosis research due to an increase in the number of multi-drug resistant as well as totally drug resistant tubercle bacilli strains...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106559/abca1-deficiency-affects-basal-cognitive-deficits-and-dendritic-density-in-mice
#5
Nicholas F Fitz, Alexis Y Carter, Victor Tapias, Emilie L Castranio, Ravindra Kodali, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer's disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106547/phenotype-dependent-interactions-between-n-acetyl-l-aspartate-and-acetyl-coa-in-septal-sn56-cholinergic-cells-exposed-to-an-excess-of-zinc
#6
Marlena Zyśk, Hanna Bielarczyk, Sylwia Gul-Hinc, Aleksandra Dyś, Beata Gapys, Anna Ronowska, Monika Sakowicz-Burkiewicz, Andrzej Szutowicz
Pyruvate dehydrogenase reaction utilizing glucose-derived pyruvate is an almost exclusive source of acetyl-CoA in different cell mitochondrial compartments of the brain. In neuronal mitochondria, the largest fraction of acetyl-CoA is utilized for energy production and the much smaller one for N-acetyl-L-aspartate (NAA) synthesis. Cholinergic neurons, unlike others, require additional amounts of acetyl-CoA for acetylcholine synthesis. Therefore, several neurotoxic signals, which inhibit pyruvate dehydrogenase, generate deeper shortages of acetyl-CoA and greater mortality of cholinergic neurons than noncholinergic ones...
January 20, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28106284/oxidative-stress-promotes-doxorubicin-induced-pgp-and-bcrp-expression-in-colon-cancer-cells-under-hypoxic-conditions
#7
Martha L Pinzón-Daza, Yenith Cuellar-Saenz, Francisco Nualart, Alejandro Ondo-Mendez, Lilia Del Riesgo, Fabio Castillo-Rivera, Ruth Garzón
P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) are ATP binding cassette (ABC) transporters that are overexpressed in different drug-resistant cancer cell lines. In this study, we investigated whether doxorubicin promotes Pgp and/or BCRP expression to induce drug resistance in colon cancer cells under hypoxic conditions. We analyzed HIF-1α activity via ELISA, Pgp and BCRP expression by qRT-PCR and the relationship between doxorubicin uptake and ABC transporter expression via confocal microscopy in HT-29WT and HT-29 doxorubicin-resistant colon cancer cells (HT-29DxR)...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106122/comparative-genomics-and-transcriptome-analysis-of-aspergillus-niger-and-metabolic-engineering-for-citrate-production
#8
Xian Yin, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Long Liu, Jian Chen
Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains-namely, A. niger H915-1 (citrate titer: 157 g L(-1)), A1 (117 g L(-1)), and L2 (76 g L(-1))-to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106073/high-resolution-cryo-em-structure-of-the-proteasome-in-complex-with-adp-alfx
#9
Zhanyu Ding, Zhenglin Fu, Cong Xu, Yifan Wang, Yanxing Wang, Junrui Li, Liangliang Kong, Jinhuan Chen, Na Li, Rongguang Zhang, Yao Cong
The 26S proteasome is an ATP-dependent dynamic 2.5 MDa protease that regulates numerous essential cellular functions through degradation of ubiquitinated substrates. Here we present a near-atomic-resolution cryo-EM map of the S. cerevisiae 26S proteasome in complex with ADP-AlFx. Our biochemical and structural data reveal that the proteasome-ADP-AlFx is in an activated state, displaying a distinct conformational configuration especially in the AAA-ATPase motor region. Noteworthy, this map demonstrates an asymmetric nucleotide binding pattern with four consecutive AAA-ATPase subunits bound with nucleotide...
January 20, 2017: Cell Research
https://www.readbyqxmd.com/read/28105941/the-loss-of-photosynthetic-pathways-in-the-plastid-and-nuclear-genomes-of-the-non-photosynthetic-mycoheterotrophic-eudicot-monotropa-hypopitys
#10
Nikolai V Ravin, Eugeny V Gruzdev, Alexey V Beletsky, Alexander M Mazur, Egor B Prokhortchouk, Mikhail A Filyushin, Elena Z Kochieva, Vitaly V Kadnikov, Andrey V Mardanov, Konstantin G Skryabin
BACKGROUND: Chloroplasts of most plants are responsible for photosynthesis and contain a conserved set of about 110 genes that encode components of housekeeping gene expression machinery and photosynthesis-related functions. Heterotrophic plants obtaining nutrients from other organisms and their plastid genomes represent model systems in which to study the effects of relaxed selective pressure on photosynthetic function. The most evident is a reduction in the size and gene content of the plastome, which correlates with the loss of genes encoding photosynthetic machinery which become unnecessary...
November 16, 2016: BMC Plant Biology
https://www.readbyqxmd.com/read/28105870/association-of-serum-uric-acid-with-high-sensitivity-c-reactive-protein-in-postmenopausal-women
#11
A Raeisi, A Ostovar, K Vahdat, P Rezaei, H Darabi, D Moshtaghi, I Nabipour
OBJECTIVES: To explore the independent correlation between serum uric acid and low-grade inflammation (measured by high-sensitivity C-reactive protein, hs-CRP) in postmenopausal women. METHODS: A total of 378 healthy Iranian postmenopausal women were randomly selected in a population-based study. Circulating hs-CRP levels were measured by highly specific enzyme-linked immunosorbent assay method and an enzymatic calorimetric method was used to measure serum levels of uric acid...
February 2017: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/28105835/silver-nanoclusters-beacon-as-stimuli-responsive-versatile-platform-for-multiplex-dnas-detection-and-aptamer-substrate-complexes-sensing
#12
Guoliang Liu, Jingjing Li, Da-Qian Feng, Jun-Jie Zhu, Wei Wang
An activatable silver nanoclusters beacon (ASNCB) was synthesized through a facile one-pot approach and applied for multiplex DNAs, small molecule, and protein sensing. Multifunctional single-stranded DNA sequences are rationally designed and used for ASNCB in situ synthesis. Via target-responsive structure transformation of ASNCB, target recognition induced ASNCB conformational transition and lit up the fluorescent signal of silver nanoclusters. By further implementing two different color ASNCBs (520 and 600 nm), the parallel multiplexed analysis of two target genes (Influenza A virus genes H1N1 and H5N1) is achieved...
January 3, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28105746/mitochondrial-energetics-and-calcium-coupling-in-the-heart
#13
Michael Kohlhaas, Alexander G Nickel, Christoph Maack
Contraction and relaxation of the heart consume large amounts of energy that need to be replenished by oxidative phosphorylation in mitochondria, and matching energy supply to demand involves the complimentary control of respiration through ADP and Ca(2+) . In heart failure, an imbalance between ADP and Ca(2+) oxidizes mitochondrial pyridine nucleotides, where NADH oxidation may limit ATP production and contractile function, while NADPH oxidation can induce oxidative stress with consecutive maladaptive remodeling...
January 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28104983/hydrogen-sulfide-attenuates-gastric-mucosal-injury-induced-by-restraint-water-immersion-stress-via-activation-of-katp-channel-and-nf-%C3%AE%C2%BAb-dependent-pathway
#14
Hong-Zhao Sun, Shan Zheng, Kai Lu, Feng-Tian Hou, Jie-Xue Bi, Xue-Lian Liu, Shan-Shan Wang
AIM: To explore the effect of hydrogen sulfide (H2S) on restraint water-immersion stress (RWIS)-induced gastric lesions in rats and the influence of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway on such an effect. METHODS: Male Wistar rats were randomly divided into a control group, a physiological saline (PS) group, a sodium hydrosulfide (NaHS) group, a glibenclamide (Gl) group, Gl plus NaHS group, a pyrrolidine dithiocarbamate (PDTC) group, and a PDTC plus NaHS group...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28104982/mirna-133a-ucp2-pathway-regulates-inflammatory-bowel-disease-progress-by-influencing-inflammation-oxidative-stress-and-energy-metabolism
#15
Xi Jin, Dong Chen, Ruo-Heng Zheng, Hong Zhang, Yi-Peng Chen, Zun Xiang
AIM: To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. METHODS: C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28104912/paclitaxel-resistant-cancer-cell-derived-secretomes-elicit-abcb1-associated-docetaxel-cross-resistance-and-escape-from-apoptosis-through-foxo3a-driven-glycolytic-regulation
#16
Mark Borris D Aldonza, Ji-Young Hong, Sang Kook Lee
Chemotherapy-induced cancer cell secretomes promote resistance due, in part, to a predominant glycolytic energy metabolism, which drives aggressive cancer cell proliferation. However, the characterization of these secretomes and the molecular events that associate them with acquired drug resistance remain poorly understood. In this study, we show that secretomes of cancer cells with high-level paclitaxel resistance stimulated cell proliferation and suppressed drug-induced apoptosis of drug-sensitive cells. We also found that drug (docetaxel)-stimulated induction of interferon-α (IFN-α), IFN-λ and tumor necrosis factor-α (TNF-α) release in drug-sensitive cells was lowered by these secretomes...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104838/distortion-of-histone-octamer-core-promotes-nucleosome-mobilization-by-a-chromatin-remodeler
#17
Kalyan K Sinha, John D Gross, Geeta J Narlikar
Adenosine 5'-triphosphate (ATP)-dependent chromatin remodeling enzymes play essential biological roles by mobilizing nucleosomal DNA. Yet, how DNA is mobilized despite the steric constraints placed by the histone octamer remains unknown. Using methyl transverse relaxation-optimized nuclear magnetic resonance spectroscopy on a 450-kilodalton complex, we show that the chromatin remodeler, SNF2h, distorts the histone octamer. Binding of SNF2h in an activated ATP state changes the dynamics of buried histone residues...
January 20, 2017: Science
https://www.readbyqxmd.com/read/28104397/pink1-alleviates-myocardial-hypoxia-reoxygenation-injury-by-ameliorating-mitochondrial-dysfunction
#18
Yang Li, Liangxian Qiu, Xiping Liu, Zhiwen Hou, Bo Yu
PTEN inducible kinase-1 (PINK1) mutant induces mitochondrial dysfunction of cells, resulting in an inherited form of Parkinson's disease. However its exact role in the cardiomyocytes is unclear. The present study examined the function of PINK1 in hypoxia-reoxygenation (H/R) induced H9c2 cell damage and its potential mechanism. The H/R model in H9c2 cells was established by 6 h of hypoxia and 12 h of reoxygenation. The CCK8 and LDH assay indicated that the cell viability was obviously reduced after H/R. The expression of PINK1 was decreased in H/R-induced H9c2 cells compared with control group...
January 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28104365/mitochondrial-dysfunction-and-mitochondrial-dynamics-the-cancer-connection
#19
REVIEW
Satish Srinivasan, Manti Guha, Anna Kashina, Narayan G Avadhani
Mitochondrial dysfunction is a hallmark of many diseases. The retrograde signaling initiated by dysfunctional mitochondria can bring about global changes in gene expression that alters cell morphology and function. Typically, this is attributed to disruption of important mitochondrial functions, such as ATP production, integration of metabolism, calcium homeostasis and regulation of apoptosis. Recent studies showed that in addition to these factors, mitochondrial dynamics might play an important role in stress signaling...
January 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28104364/mechanism-of-action-of-abc-importers-conservation-divergence-and-physiological-adaptations
#20
REVIEW
Oded Lewinson, Nurit Livnat-Levanon
The past decade has seen a remarkable surge in structural characterization of ATP Binding Cassette (ABC) transporters, which have spurred more focused functional analysis of these elaborate molecular machines. As a result, it has become increasingly apparent that there is a substantial degree of mechanistic variation between ABC transporters that function as importers, which correlates with their physiological roles. Here, we summarize recent advances in ABC importers structure-function studies and provide an explanation as to the origin of the different mechanisms of action...
January 16, 2017: Journal of Molecular Biology
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