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https://www.readbyqxmd.com/read/28930695/metabolomics-assessment-of-the-effects-of-diclofenac-exposure-on-mytilus-galloprovincialis-potential-effects-on-osmoregulation-and-reproduction
#1
Bénilde Bonnefille, Elena Gomez, Mellis Alali, David Rosain, Hélène Fenet, Frédérique Courant
The presence of pharmaceutically active compounds in aquatic environments has become a major concern over the past 20years. Elucidation of their mode of action and effects in non-target organisms is thus now a major ecotoxicological challenge. Diclofenac (DCF) is among the pharmaceutical compounds of interest based on its inclusion in the European Union Water Framework Directive Watch List. In this study, our goal was to investigate the potential of a metabolomic approach to acquire information without any a priori hypothesis about diclofenac effects on marine mussels...
September 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28930683/differential-mechanisms-for-shp2-binding-and-activation-are-exploited-by-geographically-distinct-helicobacter-pylori-caga-oncoproteins
#2
Takeru Hayashi, Miki Senda, Nobuhiro Suzuki, Hiroko Nishikawa, Chi Ben, Chao Tang, Lisa Nagase, Kaori Inoue, Toshiya Senda, Masanori Hatakeyama
Helicobacter pylori East Asian CagA is more closely associated with gastric cancer than Western CagA. Here we show that, upon tyrosine phosphorylation, the East Asian CagA-specific EPIYA-D segment binds to the N-SH2 domain of pro-oncogenic SHP2 phosphatase two orders of magnitude greater than Western CagA-specific EPIYA-C. This high-affinity binding is achieved via cryptic interaction between Phe at the +5 position from phosphotyrosine in EPIYA-D and a hollow on the N-SH2 phosphopeptide-binding floor. Also, duplication of EPIYA-C in Western CagA, which increases gastric cancer risk, enables divalent high-affinity binding with SHP2 via N-SH2 and C-SH2...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930674/a-protein-scaffold-coordinates-src-mediated-jnk-activation-in-response-to-metabolic-stress
#3
Shashi Kant, Claire L Standen, Caroline Morel, Dae Young Jung, Jason K Kim, Wojciech Swat, Richard A Flavell, Roger J Davis
Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH2-terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930482/diagnostic-and-prognostic-cytogenetics-of-chronic-myeloid-leukaemia-an-update
#4
Matteo Molica, Fulvio Massaro, Massimo Breccia
Despite the advent of molecular assessment, banding cytogenetics and fluorescence in situ hybridization (FISH) still have a significant role in diagnostic and prognostic approaches to chronic myeloid leukaemia (CML). Area covered. At diagnosis and duringtreatment with tyrosine kinase inhibitors (TKIs), cytogenetics is used to detect the Philadelphia chromosome, with its typical translocation t(9;22)(q34;q11.2), and any additional or other chromosomal aberrations (ACAs and OCAs) that may arise in 5-10% of cases, the latter associated to transformation of the disease in blast phases...
September 20, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28930282/esophageal-cancer-genomic-and-molecular-characterization-stem-cell-compartment-and-clonal-evolution
#5
REVIEW
Ugo Testa, Germana Castelli, Elvira Pelosi
Esophageal cancer (EC) is the eighth most common cancer and is the sixth leading cause of death worldwide. The incidence of histologic subtypes of EC, esophageal adenocarcinoma (EAC) and esophageal squamous carcinoma (ESCC), display considerable geographic variation. EAC arises from metaplastic Barrett's esophagus (BE) in the context of chronic inflammation secondary to exposure to acid and bile. The main risk factors for developing ESCC are cigarette smoking and alcohol consumption. The main somatic genetic abnormalities showed a different genetic landscape in EAC compared to ESCC...
September 14, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28929822/genetic-and-ethnic-modulation-of-cardiovascular-toxicity-of-vascular-endothelial-growth-factor-inhibitors
#6
Yen-Chou Chen, Cheng-Chih Chung, Yung-Kuo Lin, Yi-Jen Chen
Vascular endothelial growth factor (VEGF) inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors (TKIs), are important as anticancer treatments through curbing tumor angiogenesis and growth. VEGF inhibitors have significant cardiovascular effects. By blocking VEGF receptors, ligands, or signal pathways, VEGF inhibitors disturb the balance between vasodilation and vasoconstriction, undermine endothelial cell integrity, and activate cardiomyocyte apoptosis. VEGF inhibitors increase risks of hypertension, heart failure, thromboembolism, and arrhythmia...
September 20, 2017: Annals of Medicine
https://www.readbyqxmd.com/read/28929752/speciation-and-sources-of-brown-carbon-in-precipitation-at-seoul-korea-insights-from-excitation-emission-matrix-spectroscopy-and-carbon-isotopic-analysis
#7
Ge Yan, Guebuem Kim
Brown carbon (BrC) plays a significant role in the Earth's radiative balance, yet its sources and chemical composition remain poorly understood. In this work, we investigated BrC in the atmospheric environment of Seoul by characterizing dissolved organic matter in precipitation using excitation-emission matrix (EEM) fluorescence spectroscopy coupled with parallel factor analysis (PARAFAC). The two independent fluorescent components identified by PARAFAC were attributed to humic-like substance (HULIS) and biologically-derived material based on their significant correlations with measured HULIS isolated using solid-phase extraction and total hydrolyzable tyrosine...
September 20, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28929598/levels-of-serum-circulating-angiogenic-factors-within-1-week-prior-to-delivery-are-closely-related-to-conditions-of-pregnant-women-with-pre-eclampsia-gestational-hypertension-and-or-fetal-growth-restriction
#8
Sakiko Nanjo, Sawako Minami, Mika Mizoguchi, Madoka Yamamoto, Tamaki Yahata, Saori Toujima, Michihisa Shiro, Aya Kobayashi, Yasuteru Muragaki, Kazuhiko Ino
AIM: We aimed to investigate maternal serum angiogenic marker profiles within 1 week prior to delivery in cases of gestational hypertension (GH), pre-eclampsia (PE), and/or fetal growth restriction (FGR) with different clinical conditions. METHODS: We enrolled 165 women with singleton pregnancy. The participants were classified based on three characteristics: (i) proteinuria (GH and PE); (ii) FGR (PE with FGR [PE + FGR], PE alone, and FGR alone); and (iii) onset (early onset PE [EO PE] and late-onset PE [LO PE])...
September 20, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28929190/mining-the-complex-family-of-protein-tyrosine-phosphatases-for-checkpoint-regulators-in-immunity
#9
Claudia Penafuerte, Luis Alberto Perez-Quintero, Valerie Vinette, Teri Hatzihristidis, Michel L Tremblay
The family of protein tyrosine phosphatases (PTPs) includes 107 genes in humans that are diverse in their structures and expression profiles. The majority are present in immune cells and play various roles in either inhibiting or promoting the duration and amplitude of signaling cascades. Several PTPs, including TC-PTP (PTPN2) and SHP-1 (PTPN6), have been recognized as being crucial for maintaining proper immune response and self-tolerance, and have gained recognition as true immune system checkpoint modulators...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28928660/-1-h-nmr-based-metabolomics-study-of-the-toxicological-effects-in-rats-induced-by-renqing-mangjue-pill-a-traditional-tibetan-medicine
#10
Can Xu, Caidan Rezeng, Jian Li, Lan Zhang, Yujing Yan, Jian Gao, Yingfeng Wang, Zhongfeng Li, Jianxin Chen
"RenqingMangjue" pill (RMP), as an effective prescription of Traditional Tibetan Medicine (TTM), has been widely used in treating digestive diseases and ulcerative colitis for over a thousand years. In certain classical Tibetan Medicine, heavy metal may add as an active ingredient, but it may cause contamination unintentionally in some cases. Therefore, the toxicity and adverse effects of TTM became to draw public attention. In this study, 48 male Wistar rats were orally administrated with different dosages of RMP once a day for 15 consecutive days, then half of the rats were euthanized on the 15th day and the remaining were euthanized on the 30th day...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28928525/structural-changes-evaluation-with-raman-spectroscopy-in-meat-batters-prepared-by-different-processes
#11
Zhuang-Li Kang, Xiang Li, Hong-Ju He, Han-Jun Ma, Zhao-Jun Song
A comprehensive study was conducted to evaluate the structural changes of meat and protein of pork batters produced by chopping or beating process through the phase-contrast micrograph, laser light scattering analyzer, scanning electronic microscopy and Raman spectrometer. The results showed that the shattered myofibrilla fragments were shorter and particle-sizes were smaller in the raw batter produced by beating process than those in the chopping process. Compared with the raw and cooked batters produced by chopping process, modifications in amide I and amide III bands revealed a significant decrease of α-helix content and an increase of β-sheet, β-turn and random coils content in the beating process...
August 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28928277/jnk-activation-of-bim-promotes-hepatic-oxidative-stress-steatosis-and-insulin-resistance-in-obesity
#12
Sara A Litwak, Lokman Pang, Sandra Galic, Mariana Igoillo-Esteve, William J Stanley, Jean-Valery Turatsinze, Kim Loh, Helen E Thomas, Arpeeta Sharma, Eric Trepo, Christophe Moreno, Daniel J Gough, Decio L Eizirik, Judy B de Haan, Esteban N Gurzov
The BCL-2 family are crucial regulators of the mitochondrial pathway of apoptosis in normal physiology and disease. Besides their role in cell death, BCL-2 proteins have been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism. It remains unclear, however, whether these proteins have a physiological role in glucose homeostasis and metabolism in vivo Here we report that fat accumulation in the liver increases JNK-dependent BIM expression in hepatocytes. To determine the consequences of hepatic BIM deficiency in diet-induced obesity, we generated liver-specific BIM knockout (BLKO) mice...
September 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28928221/upregulation-of-autophagy-related-gene-5-protects-dopaminergic-neurons-in-a-zebrafish-model-of-parkinson-s-disease
#13
Zhan-Ying Hu, Bo Chen, Jing-Pu Zhang, Yuan-Yuan Ma
Parkinson's disease (PD) is one of the most epidemic neurodegenerative diseases, and is characterized by movement disorders arising from loss of midbrain dopaminergic (DA) neurons. Recently, the relationship between PD and autophagy has received considerable attention, but information about the mechanisms involved is lacking. Here, we report that autophagy-related gene 5 (ATG5) is potentially important in protecting dopaminergic neurons in a 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928163/high-bcr-abl-gusis-levels-at-diagnosis-of-chronic-phase-cml-are-associated-with-unfavorable-responses-to-standard-dose-imatinib
#14
Paolo Vigneri, Fabio Stagno, Stefania Stella, Alessandra Cupri, Stefano Forte, Michele Massimino, Agostino Antolino, Sergio Siragusa, Donato Mannina, Stefana S Impera, Caterina Musolino, Alessandra Malato, Giuseppe Mineo, Carmela Tomaselli, Pamela Murgano, Maurizio Musso, Fortunato Morabito, Stefano Molica, Bruno Martino, Livia Manzella, Martin C Müller, Andreas Hochhaus, Francesco Di Raimondo
PURPOSE: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate Imatinib responses. EXPERIMENTAL DESIGN: We correlated BCR-ABL/GUSIS and BCR-ABL/ABLIS transcripts at diagnosis with the outcome - defined by the 2013 European LeukemiaNet recommendations - of 272 newly diagnosed CML patients receiving Imatinib 400 mg/daily...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928160/quantitative-and-mechanistic-understanding-of-azd1775-penetration-across-human-blood-brain-barrier-in-glioblastoma-patients-using-an-ivive-pbpk-modeling-approach
#15
Jing Li, Jianmei Wu, Xun Bao, Norissa Honea, Youming Xie, Seongho Kim, Alex Sparreboom, Nader Sanai
PURPOSE: AZD1775, a first-in-class, small molecule inhibitor of the Wee1 tyrosine kinase, is under evaluation as a potential chemo- and radio-sensitizer for treating glioblastoma. This study was to prospectively, quantitatively, and mechanistically investigate the penetration of AZD1775 across human blood-brain barrier (BBB). EXPERIMENTAL DESIGN: AZD1775 plasma and tumor pharmacokinetics were evaluated in 20 glioblastoma patients. The drug metabolism, transcellular passive permeability, and interactions with efflux and uptake transporters were determined using human derived in vitro systems...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28927814/first-and-second-trimester-serum-sflt-1-plgf-ratio-and-subsequent-preeclampsia-a-systematic-review
#16
REVIEW
Arif M Yusuf, Alyssa Kahane, Joel G Ray
OBJECTIVE: Angiogenic biomarkers may be predictive of preeclampsia before clinical symptoms. The objective of this review was to determine the relationship between first and second trimester soluble fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) ratio and preeclampsia. METHODS: A search algorithm using appropriate medical subject headings was developed. PubMed, EMBASE, and Cochrane were searched for publications from inception to July 4, 2017...
September 15, 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28927784/safety-and-efficacy-of-blinatumomab-in-combination-with-a-tyrosine-kinase-inhibitor-for-the-treatment-of-relapsed-philadelphia-chromosome-positive-leukemia
#17
Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
OBJECTIVE: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy...
August 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28927112/non-small-cell-lung-cancer-pc-9-cells-exhibit-increased-sensitivity-to-gemcitabine-and-vinorelbine-upon-acquiring-resistance-to-egfr-tyrosine-kinase-inhibitors
#18
Junko Hamamoto, Hiroyuki Yasuda, Kaito Aizawa, Makoto Nishino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR-activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR-TKIs. The majority of patients whose lung cancer acquires resistance to EGFR-TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR-TKIs also develop altered sensitivity to cytotoxic agents...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927099/interleukin-6-identified-as-an-important-factor-in-hypoxia-and-aldehyde-dehydrogenase-based-gefitinib-adaptive-resistance-in-non-small-cell-lung-cancer-cells
#19
Shi-Min An, Hui-Min Lei, Xu-Ping Ding, Fan Sun, Chun Zhang, Ya-Bin Tang, Hong-Zhuan Chen, Ying Shen, Liang Zhu
Gefitinib resistance and relapse of the disease were the greatest challenges facing clinical therapy of non-small-cell lung cancer (NSCLC). Of note, regarding the hypoxia condition in solid tumor tissues in vivo, roles of hypoxia in gefitinib adaptive resistance and its association with lung cancer stem cells (LCSCs) have not been fully elucidated. In the present study, the role of hypoxia in gefitinib adaptive resistance and its association with aldehyde dehydrogenase (ALDH)-based LCSC gefitinib resistance were comparatively studied using RNA-sequencing (RNA-seq) technology...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927044/isolation-and-characterization-of-adult-mammary-stem-cells-from-breast-cancer-adjacent-tissues
#20
Ai-Ping Shi, Zhi-Min Fan, Ke-Wei Ma, Yan-Fang Jiang, Lei Wang, Ke-Wei Zhang, Shi-Bo Fu, Ning Xu, Zhi-Ru Zhang
Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo...
September 2017: Oncology Letters
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