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https://www.readbyqxmd.com/read/28340506/neuromedin-u-alters-bioenergetics-and-expands-the-cancer-stem-cell-phenotype-in-her2-positive-breast-cancer
#1
Vanesa G Martinez, John Crown, Richard K Porter, Lorraine O'Driscoll
Neuromedin U (NmU) is a neuropeptide belonging to the neuromedin family. Recently, we reported a significant association between NmU and breast cancer, particularly correlating with increased aggressiveness, resistance to HER2-targeted therapies and overall significantly poorer outcome for patients, although the mechanism through which it exerts this effect remained unexplained. Investigating this, here we found that ectopic over-expression of NmU in HER2-positive breast cancer cells induced aberrant metabolism, with increased glycolysis, likely due to enhanced pyruvate dehydrogenase kinase activity...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340497/p450-inhibitor-ketoconazole-increased-the-intratumor-drug-levels-and-antitumor-activity-of-fenretinide-in-human-neuroblastoma-xenograft-models
#2
Lluis Lopez-Barcons, Barry J Maurer, Min H Kang, C Patrick Reynolds
We previously reported that concurrent ketoconazole, an oral anti-fungal agent and P450 enzyme inhibitor, increased plasma levels of the cytotoxic retinoid, fenretinide (4-HPR) in mice. We have now determined the effects of concurrent ketoconazole on 4-HPR cytotoxic dose-response in four neuroblastoma (NB) cell lines in vitro and on 4-HPR activity against two cell line-derived, subcutaneous NB xenografts (CDX) and three patient-derived NB xenografts (PDX). Cytotoxicity in vitro was assessed by DIMSCAN assay...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28340481/metabolic-profiling-of-tyrosine-tryptophan-and-glutamate-in-human-urine-using-gas-chromatography-tandem-mass-spectrometry-combined-with-single-spe-cleanup
#3
Hyun Ju Shin, Na Hyun Park, Wonwoong Lee, Man Ho Choi, Bong Chul Chung, Jongki Hong
The tyrosine, tryptophan, and glutamate metabolic pathways play key roles on pathological state of neuronal functions and the change of their levels in biological systems reflects the progress degree of neuronal diseases. Comprehensive profiling of these metabolites is important to find new biomarkers for diagnosis or prognosis of various neuronal diseases. However, the overall profiling analysis of various neurochemicals in biological sample is confronted with several limitations due to their low concentration and physicochemical properties and the coexistence of matrices...
March 16, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28340474/studying-the-effects-of-natural-extracts-with-metabolomics-a-longitudinal-study-on-the-supplementation-of-healthy-rats-with-polygonum-cuspidatum-sieb-et-zucc
#4
Gregorio Peron, Jalal Uddin, Matteo Stocchero, Stefano Mammi, Elisabetta Schievano, Stefano Dall'Acqua
BACKGROUND: A longitudinal study was performed to evaluate the effects of Polygonum cuspidatum extract (standardized at 20% resveratrol) supplementation on healthy rats. The effects were explored by monitoring urinary metabolome changes using UPLC-HRMS and (1)H NMR-based approaches. The aim of the study was to explore the effects of P. cuspidatum supplementation on a healthy animal model using metabolomics, in order to determine possible modes of action and obtain information on bioactivity...
March 16, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28340451/the-role-of-drug-drug-interactions-in-prostate-cancer-treatment-focus-on-abiraterone-acetate-prednisone-and-enzalutamide
#5
REVIEW
Marzia Del Re, Stefano Fogli, Lisa Derosa, Francesco Massari, Paul De Souza, Stefania Crucitta, Sergio Bracarda, Daniele Santini, Romano Danesi
Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer drugs, is increased. Drug-drug interactions (DDIs) may occur in prostate cancer patients due to inhibition by abiraterone of liver cytochrome P450 (CYP)-dependent enzymes CYP2C8 and 2D6, which are involved in the metabolism of approximately 25% of all drugs, and induction by enzalutamide of CYP3A4, 2C9 and 2C19, which metabolize up to 50% of medications...
March 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28340434/potentially-direct-interspecies-electron-transfer-of-methanogenesis-for-syntrophic-metabolism-under-sulfate-reducing-conditions-with-stainless-steel
#6
Yue Li, Yaobin Zhang, Yafei Yang, Xie Quan, Zhiqiang Zhao
Direct interspecies electron transfer (DIET) is an alternative to syntrophic metabolism in natural carbon cycle as well as in anaerobic digesters, but its function in anaerobic treatment of sulfate-containing wastewater have not yet to be described. Here, conductive stainless steel was added into anaerobic digesters for treating sulfate-containing wastewater to investigate the potential role of DIET in the response to the sulfate impact. Results showed that adding the conductive stainless steel made the anaerobic digestion less affected by the sulfate reduction than adding insulative plastic material...
March 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28340400/pharmacoinformatics-exploration-of-polyphenol-oxidases-leading-to-novel-inhibitors-by-virtual-screening-and-molecular-dynamic-simulation-study
#7
Mubashir Hassan, Qamar Abbas, Zaman Ashraf, Ahmed A Moustafa, Sung-Yum Seo
Polyphenol oxidases (PPOs)/tyrosinases are metal-dependent enzymes and known as important targets for melanogenesis. Although considerable attempts have been conducted to control the melanin-associated diseases by using various inhibitors. However, the exploration of the best anti-melanin inhibitor without side effect still remains a challenge in drug discovery. In present study, protein structure prediction, ligand-based pharmacophore modeling, virtual screening, molecular docking and dynamic simulation study were used to screen the strong novel inhibitor to cure melanogenesis...
March 15, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28340398/proteomics-analysis-of-maize-zea-mays-l-grain-based-on-itraq-reveals-molecular-mechanisms-of-poor-grain-filling-in-inferior-grains
#8
Tao Yu, Geng Li, Peng Liu, Shuting Dong, Jiwang Zhang, Bin Zhao
In maize, inferior grains (IG) located on the upper part of the ear have poor grain filling process compared to superior grains (SG) located on the middle and lower parts of the ear. This difference limits satisfactory yield and quality; however, the underlying molecular mechanisms remain unknown. Here, using the isobaric tag for relative and absolute quantification (iTRAQ) technology, the proteomes of IG and SG during early and middle grain filling stages were investigated. In total, 4720 proteins were identified in maize grain and 305 differentially accumulated proteins (DiAPs) were detected between IG and SG...
March 11, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28340361/hdl-inhibits-saturated-fatty-acid-mediated-augmentation-of-innate-immune-responses-in-endothelial-cells-by-a-novel-pathway
#9
Wei-Yang Zhang, Daniel A Franco, Eric Schwartz, Karen D'Souza, Sheetal Karnick, Peter D Reaven
BACKGROUND AND AIMS: Peripheral insulin resistance is associated with several metabolic abnormalities, including elevated serum fatty acids that contribute to vascular injury and atherogenesis. Our goals were to examine whether saturated fatty acids can modify innate immune responses to subclinical concentrations of lipopolysaccharide (LPS) in endothelial cells, and to explore the underlying pathway and determine whether it is modified by high density lipoprotein (HDL) and other factors commonly altered in insulin resistance...
September 8, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28340340/selective-chemical-inhibition-of-pgc-1%C3%AE-gluconeogenic-activity-ameliorates-type-2-diabetes
#10
Kfir Sharabi, Hua Lin, Clint D J Tavares, John E Dominy, Joao Paulo Camporez, Rachel J Perry, Roger Schilling, Amy K Rines, Jaemin Lee, Marc Hickey, Melissa Bennion, Michelle Palmer, Partha P Nag, Joshua A Bittker, José Perez, Mark P Jedrychowski, Umut Ozcan, Steve P Gygi, Theodore M Kamenecka, Gerald I Shulman, Stuart L Schreiber, Patrick R Griffin, Pere Puigserver
Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340326/effects-of-coupling-a-uf-membrane-with-a-mesh-screen-and-elevating-temperature-in-the-methanogenic-digester-of-a-two-phased-anaerobic-system
#11
Min Ho Kim, Chul-Hwi Park, Gee-Bong Han
This study was conducted to investigate coupling of UF with a mesh screen under thermophilic temperatures and compare the effectiveness of membrane filtration and temperature change in the methanogenic digester. A two-phased anaerobic digester coupled with an ultrafiltration (UF) membrane system was used for anaerobic sludge digestion. The overall average chemical oxygen demand (COD) removal efficiency achieved in the two-phased anaerobic digester coupled with the UF membrane system was 97.9 ± 0.8%. In the methanogenic digester, 10...
March 24, 2017: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/28340292/combined-spiroergometry-and-31-p-mrs-of-human-calf-muscle-during-high-intensity-exercise
#12
K Moll, A Gussew, C Hein, N Stutzig, J R Reichenbach
Simultaneous measurements of pulmonary oxygen consumption (VO2 ), carbon dioxide exhalation (VCO2 ) and phosphorus magnetic resonance spectroscopy ((31) P-MRS) are valuable in physiological studies to evaluate muscle metabolism during specific loads. Therefore, the aim of this study was to adapt a commercially available spirometric device to enable measurements of VO2 and VCO2 whilst simultaneously performing (31) P-MRS at 3 T. Volunteers performed intense plantar flexion of their right calf muscle inside the MR scanner against a pneumatic MR-compatible pedal ergometer...
March 24, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28340243/finite-time-parametric-identification-for-the-model-representing-the-metabolic-and-genetic-regulatory-effects-of-sequential-aerobic-respiration-and-anaerobic-fermentation-processes-in-escherichia-coli
#13
Alfonso Sepúlveda-Gálvez, Jesús Agustín Badillo-Corona, Isaac Chairez
Mathematical modelling applied to biological systems allows for the inferring of changes in the dynamic behaviour of organisms associated with variations in the environment. Models based on ordinary differential equations are most commonly used because of their ability to describe the mechanisms of biological systems such as transcription. The disadvantage of using this approach is that there is a large number of parameters involved and that it is difficult to obtain them experimentally. This study presents an algorithm to obtain a finite-time parameter characterization of the model used to describe changes in the metabolic behaviour of Escherichia coli associated with environmental changes...
March 17, 2017: Mathematical Medicine and Biology: a Journal of the IMA
https://www.readbyqxmd.com/read/28340225/long-working-hours-and-metabolic-syndrome
#14
Tomoyuki Kawada
No abstract text is available yet for this article.
March 18, 2017: European Journal of Public Health
https://www.readbyqxmd.com/read/28340191/cardiac-health-and-fitness-of-colorado-male-female-firefighters
#15
K Li, T Lipsey, H J Leach, T L Nelson
Background: Cardiovascular disease (CVD) is documented as the leading cause of mortality in on-duty firefighters. Aims: To examine the prevalence of metabolic syndrome (MetS) components, cardiorespiratory fitness levels and the association between them in firefighters in Colorado, USA. Methods: This study included male and female Colorado firefighters. MetS was identified where three or more metabolic abnormalities were present, using Cholesterol Education Program/Adult Treatment Panel III guidelines...
March 16, 2017: Occupational Medicine
https://www.readbyqxmd.com/read/28340181/different-expression-patterns-of-sperm-motility-related-genes-in-testis-of-diploid-and-tetraploid-cyprinid-fish1
#16
Fangzhou Hu, Kang Xu, Yunfan Zhou, Chang Wu, Shi Wang, Jun Xiao, Min Wen, Rurong Zhao, Kaikun Luo, Min Tao, Wei Duan, Shaojun Liu
Sperm motility is an important standard to measure the fertility of male. In our previous study, we found that the diploid spermatozoa from allotetraploid hybrid (4nAT) had longer durations of rapid and slow progressive motility than haploid spermatozoa from common carp (COC). In this study, to explore sperm motility-related molecular mechanisms, we compared the testis tissues transcriptomes from two years old male COC and 4nAT. The RNA-seq data revealed that 2985 genes were differentially expressed between COC and 4nAT, including 2216 up-regulated and 769 down-regulated genes in 4nAT...
March 7, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28340138/a-life-without-worms
#17
Richard E Sanya, Gyaviira Nkurunungi, Irene Andia Biraro, Harriet Mpairwe, Alison M Elliott
Worms have co-evolved with humans over millions of years. To survive, they manipulate host systems by modulating immune responses so that they cause (in the majority of hosts) relatively subtle harm. Anthelminthic treatment has been promoted as a measure for averting worm specific pathology and to mitigate subtle morbidities which may include effects on anaemia, growth, cognitive function and economic activity. With our changing environment marked by rapid population growth, urbanisation, better hygiene practices and anthelminthic treatment, there has been a decline in worm infections and other infectious diseases and a rise in non-communicable diseases such as allergy, diabetes and cardiovascular disease...
March 18, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28340122/potential-role-of-patients-cyp3a-status-in-clozapine-pharmacokinetics
#18
Katalin Tóth, Gábor Csukly, Dávid Sirok, Ales Belic, Ádám Kiss, Edit Háfra, Máté Déri, Ádám Menus, István Bitter, Katalin Monostory
Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophrenia; however, the success or failure of clozapine therapy is substantially affected by the variables that impact the clozapine blood concentration. Thus, elucidating the inter-individual differences in clozapine pharmacokinetics can facilitate the personalized therapy. Methods: Since potential role in clozapine metabolism is assigned to CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes, the association between the patients' CYP-status (CYP genotypes, CYP expression) and clozapine clearance was evaluated in 92 psychiatric patients...
March 18, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28340039/infant-birth-outcomes-are-associated-with-dna-damage-biomarkers-as-measured-by-the-cytokinesis-block-micronucleus-cytome-assay-the-dadhi-study
#19
Mansi Dass Singh, Philip Thomas, Maryam Hor, Theodora Almond, Julie Owens, William Hague, Michael Fenech
Accumulation of DNA damage in the first 1000 days may increase risk of accelerated ageing and degenerative diseases in adult life such as cancers. The extent of DNA damage in infants and the correlation of maternal factors during pregnancy with neonate birth outcomes and DNA damage is not known in infants born in Australia. Therefore, we performed a prospective cohort study to collect data on DNA damage in lymphocytes of Australian infants (aged 0, 3 and 6 months), using the cytokinesis block micronucleus cytome (CBMN-Cyt) assay...
March 3, 2017: Mutagenesis
https://www.readbyqxmd.com/read/28339984/the-link-between-phenotype-and-fatty-acid-metabolism-in-advanced-chronic-kidney-disease
#20
Dan-Qian Chen, Hua Chen, Lin Chen, Nosratola D Vaziri, Ming Wang, Xiang-Ri Li, Ying-Yong Zhao
Background.: The kidney plays a central role in elimination of metabolic waste products and regulation of low-molecular weight metabolites via glomerular filtration, tubular secretion and reabsorption. Disruption of these processes results in profound changes in the biochemical milieu of the body fluids, which contribute to complications of chronic kidney disease (CKD) by inducing cytotoxicity and inflammation. Insight into the changes of the composition of metabolites and dysregulation of target genes and proteins enhances the understanding of the pathophysiology of CKD and its complications, and the development of novel therapeutic strategies...
March 1, 2017: Nephrology, Dialysis, Transplantation
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