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https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#1
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538700/stability-profiles-and-therapeutic-effect-of-cu-zn-superoxide-dismutase-chemically-coupled-to-o-quaternary-chitosan-derivatives-against-dextran-sodium-sulfate-induced-colitis
#2
Nan Zhao, Zhaolong Feng, Meng Shao, Jichao Cao, Fengshan Wang, Chunhui Liu
Superoxide dismutase (SOD) has attracted considerable attention on treatment of reactive oxygen species (ROS)-related disorders. We previously conjugated Cu/Zn SOD to O-quaternary chitosan derivatives (O-HTCC) to yield a polymer-enzyme conjugate O-HTCC-SOD that demonstrated superior therapeutic effect to native SOD. The present study demonstrated that O-HTCC-SOD had wider pH activity range, better thermal stability, excellent long-term stability for storage, as well as unique reinstatement of activity exposure to proteolytic degradation that was helpful for longer half-life in vivo...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538675/secondary-sulfonamides-as-effective-lactoperoxidase-inhibitors
#3
Zeynep Köksal, Ramazan Kalin, Yasemin Camadan, Hande Usanmaz, Züleyha Almaz, İlhami Gülçin, Taner Gokcen, Ahmet Ceyhan Gören, Hasan Ozdemir
Secondary sulfonamides (4a-8h) incorporating acetoxybenzamide, triacetoxybenzamide, hydroxybenzamide, and trihydroxybenzamide and possessing thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups were synthesized. Lactoperoxidase (LPO, E.C.1.11.1.7), as a natural antibacterial agent, is a peroxidase enzyme secreted from salivary, mammary, and other mucosal glands. In the present study, the in vitro inhibitory effects of some secondary sulfonamide derivatives (4a-8h) were examined against LPO. The obtained results reveal that secondary sulfonamide derivatives (4a-8h) are effective LPO inhibitors...
May 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28538665/molecular-basis-of-alcohol-related-gastric-and-colon-cancer
#4
REVIEW
Hye-Kyung Na, Ja Young Lee
Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538659/the-effects-of-dithiothreitol-on-dna
#5
Søren Fjelstrup, Marie Bech Andersen, Jonas Thomsen, Jing Wang, Magnus Stougaard, Finn Skou Pedersen, Yi-Ping Ho, Marianne Smedegaard Hede, Birgitta Ruth Knudsen
With the novel possibilities for detecting molecules of interest with extreme sensitivity also comes the risk of encountering hitherto negligible sources of error. In life science, such sources of error might be the broad variety of additives such as dithiothreitol (DTT) used to preserve enzyme stability during in vitro reactions. Using two different assays that can sense strand interruptions in double stranded DNA, we here show that DTT is able to introduce nicks in the DNA backbone. DTT was furthermore shown to facilitate the immobilization of fluorescent DNA on an NHS-ester functionalized glass surface...
May 24, 2017: Sensors
https://www.readbyqxmd.com/read/28538417/clinical-and-electrocardiographic-characteristics-of-infarctional-ventricular-ectopic-beats-an-observational-study
#6
Yuechun Li, Shi Zhe-Wei, Zheng Cheng, Chen Guang-Yi, Zhou De-Pu, Li Xiao-Wei, Guan Xueqiang, Lin Jiafeng, Chen Peng
The purpose of this study was to explore the clinical and electrocardiographic characteristics of infarctional ventricular ectopic beats (IVEBs).Thirty-eight acute myocardial infarction (AMI) patients with IVEB and 109 AMI patients without IVEB were analyzed. The morphological changes of QRS complex, ST segment, and T wave were compared to IVEB with sinus rhythm from the same period and fully evolved phase.An IVEB QRS complex often revealed the right bundle branch block morphology, in addition to Q wave AMI; no-Q wave AMI also had IVEB...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538406/dexmedetomidine-based-intravenous-anesthesia-of-a-pediatric-patient-with-glucose-6-phosphate-dehydrogenase-g6pd-deficiency-a-case-report
#7
Nanae Takahashi, Takashi Ogawa, Zen'ichiro Wajima, Akibumi Omi
RATIONALE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, resulting in deficits in nicotinamide adenine dinucleotide phosphate production, an important intracellular antioxidant enzyme. G6PD-deficient subjects present with a susceptibility of erythrocytes to oxidative stress and hemolysis, and should avoid drugs or stressors that have oxidative actions. Dexmedetomidine is an anesthetic agent with antioxidant actions. PATIENT CONCERNS AND DIAGNOSES: A 5-year-old boy with G6PD deficiency...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538210/correlation-of-hamp-gene-polymorphisms-and-expression-with-the-susceptibility-and-length-of-hospital-stays-in-taiwanese-children-with-kawasaki-disease
#8
Ying-Hsien Huang, Kuender D Yang, Yu-Wen Hsu, Hsing-Fang Lu, Henry Sung-Ching Wong, Hong-Ren Yu, Hsing-Chun Kuo, Fu-Chen Huang, Mao-Hung Lo, Kai-Sheng Hsieh, Su-Fen Chen, Wei-Chiao Chang, Ho-Chang Kuo
Kawasaki disease (KD) is a form of systemic vasculitis. Regarding its pathogenesis, HAMP gene encoding hepcidin, which is significant for iron metabolism, has a vital function. In this study, we recruited a total of 381 KD patients for genotyping. Data from 997 subjects (500 subjects from cohort 1; 497 subjects from cohort 2) were used for analysis. Using TaqMan allelic discrimination, we determined five tag SNPs (rs916145, rs10421768, rs3817623, rs7251432, and rs2293689). Treatment outcome data related to such clinical phenotypes as coronary artery lesions (CAL), coronary artery aneurysms (CAA), and intravenous immunoglobulin (IVIG) effects were also collected...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28538202/development-of-nanobiocatalysts-through-the-immobilization-of-pseudomonas-fluorescens-lipase-for-applications-in-efficient-kinetic-resolution-of-racemic-compounds
#9
Bharat P Dwivedee, Jayeeta Bhaumik, Shushil K Rai, Joydev K Laha, Uttam C Banerjee
The present work reports covalent immobilization of Pseudomonas fluorescens lipase (PFL) on functionalized multiwalled carbon nanotubes (MWCNTs) as a nanobiocatalyst (NBC). This nanobiocatalyst facilitates efficient kinetic resolution of (RS)-1-phenylethanol into (S)-1-phenylethanol [C=49.7%, eep=99.5%, ees=98.1% and E value=191.4]. The immobilized preparation (MWCNTs-PFL) showed ten-fold increase in activity, thermal stability upto 80 °C and recyclability (8 cycles). MWCNTs-PFL nanobioconjugate demonstrated better stability and enhanced activity compared to covalently immobilized PFL on other matrices (silver nanoparticles, gold nanoparticles and chitosan beads) used for the study...
May 11, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28538163/metabolic-signatures-of-t-cells-and-macrophages-in-rheumatoid-arthritis
#10
REVIEW
Cornelia M Weyand, Markus Zeisbrich, Jörg J Goronzy
In most autoimmune diseases, a decade-long defect in self-tolerance eventually leads to clinically relevant, tissue-destructive inflammatory disease. The pathogenic potential of chronic persistent immune responses during the pre-clinical and clinical phase is ultimately linked to the bioenergetic fitness of innate and adaptive immune cells. Chronic immune cell stimulation, high cellular turn-over, structural damage to the host tissue and maladaptive wound healing, all require a reliable supply of nutrients, oxygen, and biosynthetic precursors...
May 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28538158/glnk-facilitates-the-dynamic-regulation-of-bacterial-nitrogen-assimilation
#11
Adam Gosztolai, Jörg Schumacher, Volker Behrends, Jacob G Bundy, Franziska Heydenreich, Mark H Bennett, Martin Buck, Mauricio Barahona
Ammonium assimilation in Escherichia coli is regulated by two paralogous proteins (GlnB and GlnK), which orchestrate interactions with regulators of gene expression, transport proteins, and metabolic pathways. Yet how they conjointly modulate the activity of glutamine synthetase, the key enzyme for nitrogen assimilation, is poorly understood. We combine experiments and theory to study the dynamic roles of GlnB and GlnK during nitrogen starvation and upshift. We measure time-resolved in vivo concentrations of metabolites, total and posttranslationally modified proteins, and develop a concise biochemical model of GlnB and GlnK that incorporates competition for active and allosteric sites, as well as functional sequestration of GlnK...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538147/structural-and-functional-investigations-of-the-n-terminal-ubiquitin-binding-region-of-usp25
#12
Yuanyuan Yang, Li Shi, Yiluan Ding, Yanhong Shi, Hong-Yu Hu, Yi Wen, Naixia Zhang
Ubiquitin-specific protease 25 (Usp25) is a deubiquitinase that is involved in multiple biological processes. The N-terminal ubiquitin-binding region (UBR) of Usp25 contains one ubiquitin-associated domain, one small ubiquitin-like modifier (SUMO)-interacting motif and two ubiquitin-interacting motifs. Previous studies suggest that the covalent sumoylation in the UBR of Usp25 impairs its enzymatic activity. Here, we raise the hypothesis that non-covalent binding of SUMO, a prerequisite for efficient sumoylation, will impair Usp25's catalytic activity as well...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538105/linezolid-induced-lactic-acidosis-the-thin-line-between-bacterial-and-mitochondrial-ribosomes
#13
Alessandro Santini, Dario Ronchi, Manuela Garbellini, Daniela Piga, Alessandro Protti
Introduction - Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered - The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion - Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes...
May 24, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28538100/enzymatic-hydrolysis-of-polyester-thin-films-at-the-nanoscale-effects-of-polyester-structure-and-enzyme-active-site-accessibility
#14
Michael Thomas Zumstein, Daniela Rechsteiner, Nicolas Roduner, Veronika Perz, Doris Ribitsch, Georg M Guebitz, Hans-Peter E Kohler, Kristopher McNeill, Michael Sander
Biodegradable polyesters have a large potential to replace persistent polymers in numerous applications and to thereby reduce the accumulation of plastics in the environment. Ester hydrolysis by extracellular carboxylesterases is considered the rate-limiting step in polyester biodegradation. In this work, we systematically investigated the effects of polyester and carboxylesterase structure on the hydrolysis of nanometer-thin polyester films using a quartz-crystal microbalance with dissipation monitoring. Hydrolyzability increased with increasing polyester-chain flexibility as evidenced from differences in the hydrolysis rates and extents of aliphatic polyesters varying in the length of their dicarboxylic acid unit and of poly(butylene adipate co-terephthalate) (PBAT) polyesters varying in their terephthalate-to-adipate ratio by Rhizopus oryzae lipase and Fusarium solani cutinase...
May 24, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28538098/two-dimensional-metal-organic-framework-nanosheets-as-an-enzyme-inhibitor-modulation-of-the-%C3%AE-chymotrypsin-activity
#15
Ming Xu, Shuai Yuan, Xin-Yu Chen, Yu-Jie Chang, Gregory Steven Day, Zhi-Yuan Gu, Hong-Cai Zhou
Two-dimensional metal-organic framework (MOF) nanosheets are utilized as effective enzyme inhibitors, providing an in-spiring means to enhance the control of cellular processes as well as improve our understanding of the surface chemistry between MOFs and enzymes. In this paper, we demonstrated that the activity of α-Chymotrypsin (ChT) can be effectively inhibited with 96.9% inhibition by the 2-D Cu(bpy)2(OTf)2 nanosheets, while the other Zn2(bim)4 nanosheets show no significant inhibition effect towards ChT...
May 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28538097/biochemical-characterization-of-the-functional-roles-of-residues-in-the-active-site-of-the-%C3%AE-galactosidase-from-bacillus-circulans-atcc-31382
#16
Huifang Yin, Tjaard Pijning, Xiangfeng Meng, Lubbert Dijkhuizen, Sander Sebastiaan van Leeuwen
The β-galactosidase enzyme from Bacillus circulans ATCC 31382 BgaD is widely used in the food industry to produce prebiotic galactooligosaccharides (GOS). Recently, the crystal structure of a C-terminally truncated version of the enzyme (BgaD-D) has been elucidated. The roles of active site amino acid residues in β-galactosidase enzyme reaction and product specificity have remained unknown. Based on a structural alignment of the β-galactosidase enzymes BgaD-D from Bacillus circulans and BgaA from Streptococcus pneumoniae, and the complex of BgaA with LacNAc, we identified 8 active site amino acid residues (Arg185, Asp481, Lys487, Tyr511, Trp570, Trp593, Glu601, and Phe616) in BgaD-D...
May 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28537988/prevention-of-trastuzumab-and-anthracycline-induced-cardiotoxicity-using-angiotensin-converting-enzyme-inhibitors-or-%C3%AE-blockers-in-older-adults-with-breast-cancer
#17
Saranrat Wittayanukorn, Jingjing Qian, Salisa C Westrick, Nedret Billor, Brandon Johnson, Richard A Hansen
PURPOSE: Although clinical trials have provided some data on the benefit of angiotensin-converting enzyme inhibitors (ACEIs) or β-blockers (BBs) in patients with chemotherapy-induced cardiotoxicity, evidence of ACEIs/BBs on prevention of trastuzumab and/or anthracycline-induced cardiotoxicity outside trials is limited. MATERIALS AND METHODS: A cohort study of 142,990 women (66 y and above) newly diagnosed with breast cancer from 2001 to 2009 was conducted using the Surveillance, Epidemiology, and End Results-Medicare-linked database...
May 23, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28537967/nortriptyline-enhances-morphine-conditioned-place-preference-in-neuropathic-rats-role-of-the-central-noradrenergic-system
#18
Wenli Mi, Shuxing Wang, Zerong You, Grewo Lim, Michael F McCabe, Hyangin Kim, Lucy Chen, Jianren Mao
BACKGROUND: Combination drug therapy is commonly used to treat chronic pain conditions such as neuropathic pain, and antidepressant is often used together with opioid analgesics. While rewarding is an intrinsic property of opioid analgesics, it is unknown whether the use of an antidepressant would influence opioid reward, which may contribute to opioid addiction. In this study, we examined whether nortriptyline (a tricyclic antidepressant and a first-line medication for neuropathic pain) would enhance the morphine rewarding property in both naive and chronic constriction sciatic nerve injury (CCI) rats...
May 19, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28537930/3-decylcatechol-induces-autophagy-mediated-cell-death-through-the-ire1%C3%AE-jnk-p62-in-hepatocellular-carcinoma-cells
#19
Da-Hye Go, Yu Geon Lee, Da-Hye Lee, Jin-A Kim, In-Hwa Jo, Yeon Soo Han, Yong Hun Jo, Kwang-Youn Kim, Young-Kyo Seo, Jae-Hak Moon, Chang Hwa Jung, Tae-Il Jeon
The natural, phenolic lipid urushiol exhibits both antioxidant and anticancer activities; however, its biological activity on hepatocellular carcinoma (HCC) has not been previously investigated. Here, we demonstrate that an urushiol derivative, 3-decylcatechol (DC), induces human HCC Huh7 cell death by induction of autophagy. DC initiates the autophagic process by activation of the mammalian target of rapamycin signaling pathway via Unc-51-like autophagy activating kinase 1, leading to autophagosome formation...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537929/orphan-nuclear-receptor-nur77-inhibits-poly-i-c-triggered-acute-liver-inflammation-by-inducing-the-ubiquitin-editing-enzyme-a20
#20
Xiu-Ming Li, Tian-Yu Yang, Xiao-Shun He, Jing-Ru Wang, Wen-Juan Gan, Shen Zhang, Jian-Ming Li, Hua Wu
Inflammation is a key contributor to various types of acute and chronic liver disease. We recently reported that lack of Nur77, an orphan nuclear receptor, contributes to the pathogenesis of inflammatory diseases including inflammatory bowel disease and sepsis. However, whether Nur77 plays a critical role in liver inflammation remains to be fully understood. Employing in vivo acute liver inflammation model in wild-type (Nur77+/+) and Nur77-/- mice, we here found that Nur77 deficiency dramatically increased the production of pro-inflammatory cytokines and accelerated liver injury induced by Poly (I:C)/D-GalN in Nur77-/- mice...
May 9, 2017: Oncotarget
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