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https://www.readbyqxmd.com/read/28088772/thrombospondin-immune-regulation-and-the-kidney
#1
Claudio Ponticelli, Hans-Joachim Anders
Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088556/regulation-of-docetaxel-sensitivity-in-prostate-cancer-cells-by-hsa-mir-125a-3p-via-modulation-of-mta1-signaling
#2
Jian-Zhou Liu, Feng-Yan Yin, Chang-You Yan, Hui Wang, Xiao-Hui Luo
OBJECTIVE: To identify the potential down-stream targets of hsa-miR-125a-3p, a mature form of miR-125a, during the pathogenesis of chemoresistance in prostate cancer (PCa). METHODS: Expression levels of hsa-miR-125a-3p was assessed in chemoresistant PCa tissues and experimentally-established chemoresistant cells using quantitative RT-PCR (qRT-PCR). The effect of hsa-miR-125a-3p knockdown or hsa-miR-125a-3p overexpression on the Dox-induced cell death was evaluated using apoptosis ELISA in chemosensitive PC-3 cells or in chemoresistant PC-3 cells (PC-3R)...
January 11, 2017: Urology
https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#3
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28088504/novel-insights-into-the-transport-mechanism-of-the-human-amino-acid-transporter-lat1-slc7a5-probing-critical-residues-for-substrate-translocation
#4
Lara Napolitano, Michele Galluccio, Mariafrancesca Scalise, Chiara Parravicini, Luca Palazzolo, Ivano Eberini, Cesare Indiveri
BACKGROUND: LAT1 (SLC7A5) is the transport competent unit of the heterodimer formed with the glycoprotein CD98 (SLC3A2). It catalyzes antiport of His and some neutral amino acids such as Ile, Leu, Val, Cys, Met, Gln and Phe thus being involved in amino acid metabolism. Interestingly, LAT1 is over-expressed in many human cancers that are characterized by increased demand of amino acids. Therefore LAT1 was recently acknowledged as a novel target for cancer therapy. However, knowledge on molecular mechanism of LAT1 transport is still scarce...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088493/apoptosis-induced-by-the-methanol-extract-of-salvia-miltiorrhiza-bunge-in-non-small-cell-lung-cancer-through-pten-mediated-inhibition-of-pi3k-akt-pathway
#5
Yin-Tao Ye, Wei Zhong, Pei Sun, Dong Wang, Chen Wang, Li-Min Hu, Jun-Qiang Qian
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies have reported that the active component tanshinones displayed a variety of biological activities: antithrombous, antiplatelet aggregation, antioxidant and antitumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28088449/the-role-of-sumoylation-in-ageing-and-senescent-decline
#6
REVIEW
Andrea Princz, Nektarios Tavernarakis
Posttranslational protein modifications are playing crucial roles in essential cellular mechanisms. SUMOylation is a reversible posttranslational modification of specific target proteins by the attachment of a small ubiquitin-like protein. Although the mechanism of conjugation of SUMO to proteins is analogous to ubiquitination, it requires its own, specific set of enzymes. The consequences of SUMOylation are widely variable, depending on the physiological state of the cell and the attached SUMO isoform. Accumulating recent findings have revealed a prominent role of SUMOylation in molecular pathways that govern senescence and ageing...
January 11, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28088445/synthesis-and-exploration-of-novel-radiolabeled-bombesin-peptides-for-targeting-receptor-positive-tumor
#7
Kakali De, Indranil Banerjee, Samarendu Sinha, Shantanu Ganguly
Increasing evidence of peptide receptor overexpression in various cancer cells, warrant the development of receptor specific radiolabeled peptides for molecular imaging and therapy in nuclear medicine. Gastrin-releasing-peptide (GRP) receptor, are overexpressed in a variety of human cancer cells. The present study report the synthesis and biological evaluation of new bombesin (BBN) analogs, HYNIC-Asp-[Phe(13)]BBN(7-13)-NH-CH2-CH2-CH3:BA1, HYNIC-Pro-[Tyr(13)Met(14)]BBN(7-14)NH2:BA2 as prospective tumor imaging agent with compare to BBN(7-14)NH2:BS as standard...
January 11, 2017: Peptides
https://www.readbyqxmd.com/read/28088330/genomic-insights-in-gynecologic-cancer
#8
Erika Roddy, Jocelyn Chapman
Recent technological advances in DNA sequencing have enabled a remarkably detailed understanding of the molecular changes that define gynecologic and other cancers. Several groups have carried out large-scale genomic analyses of ovarian, uterine, and most recently, cervical cancer. These analyses have led to new insights into the molecular changes characterizing these cancers, which provide insight into clinical outcomes. These molecular characterizations have similarly led to new genomic-based classification schemas, which may better stratify clinical outcomes, help prognosticate and guide treatments...
November 11, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28088161/efficient-free-energy-calculations-by-combining-two-complementary-tempering-sampling-methods
#9
Liangxu Xie, Lin Shen, Zhe-Ning Chen, Mingjun Yang
Although energy barriers can be efficiently crossed in the reaction coordinate (RC) guided sampling, this type of method suffers from identification of the correct RCs or requirements of high dimensionality of the defined RCs for a given system. If only the approximate RCs with significant barriers are used in the simulations, hidden energy barriers with small to medium height would exist in other degrees of freedom (DOFs) relevant to the target process and consequently cause the problem of insufficient sampling...
January 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28088086/design-and-synthesis-of-new-raf-kinase-inhibiting-antiproliferative-quinoline-derivatives-part-2-diarylurea-derivatives
#10
Mohammed I El-Gamal, Mohammad Ashrafuddin Khan, Hamadeh Tarazi, Mohammed S Abdel-Maksoud, Mahmoud M Gamal El-Din, Kyung Ho Yoo, Chang-Hyun Oh
This article describes the design, synthesis, and biological screening of a new series of diarylurea derivatives possessing quinoline nucleus. Nine target compounds were selected by the National Cancer Institute (NCI, Bethesda, Maryland, USA) for in vitro antiproliferative screening against a panel of 58 cancer cell lines of nine cancer types. Following one-dose initial screening, compounds 1d-g and 2b were selected for 5-dose screening in order to calculate their IC50 and total growth inhibition (TGI) values against the cell lines...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#11
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28087697/development-of-high-affinity-and-high-specificity-inhibitors-of-metalloproteinase-14-through-computational-design-and-directed-evolution
#12
Valeria Arkadash, Gal Yosef, Jason Shirian, Itay Cohen, Yuval Horev, Moran Grossman, Irit Sagi, Evette S Radisky, Julia M Shifman, Niv Papo
Degradation of the extracellular matrices in the human body is controlled by matrix metalloproteinases (MMPs), a family of more than 20 homologous enzymes. Imbalance in MMP activity can result in many diseases, such as arthritis, cardiovascular diseases, neurological disorders, fibrosis, and cancers. Thus, MMPs present attractive targets for drug design and have been a focus for inhibitor design for as long as three decades. Yet, to date, all MMP inhibitors have failed in clinical trials because of their broad activity against numerous MMP family members and the serious side effects of the proposed treatment...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087659/plant-parasitic-nematodes-towards-understanding-molecular-players-in-stress-responses
#13
REVIEW
François-Xavier Gillet, Caroline Bournaud, Jose Dijair Antonino de Souza Júnior, Maria Fatima Grossi-de-Sa
BACKGROUND: Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence...
January 13, 2017: Annals of Botany
https://www.readbyqxmd.com/read/28087641/molecular-pathways-targeting-protein-tyrosine-phosphatases-in-cancer
#14
Lakshmi Reddy Bollu, Abhijit Mazumdar, Michelle I Savage, Powel H Brown
The aberrant activation of oncogenic signaling pathways is a universal phenomenon in cancer and drives tumorigenesis and malignant transformation. This abnormal activation of signaling pathways in cancer is due to the altered expression of protein kinases and phosphatases. In response to extra cellular signals, protein kinases activate downstream signaling pathways through a series of protein phosphorylation events, ultimately producing a signal response. Protein tyrosine phosphatases (PTPs) are a family of enzymes that hydrolytically remove phosphate groups from proteins...
January 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28087598/bayesian-network-inference-modeling-identifies-trib1-as-a-novel-regulator-of-cell-cycle-progression-and-survival-in-cancer-cells
#15
Rina Gendelman, Heming Xing, Olga K Mirzoeva, Preeti Sarde, Christina Curtis, Heidi Feiler, Paul McDonagh, Joe W Gray, Iya Khalil, W Michael Korn
Molecular networks governing cellular responses to targeted therapies are complex dynamic systems with non-intuitive behaviors. Here we applied a novel computational strategy to infer probabilistic causal relationships between network components based on gene expression. We constructed a model comprised of an ensemble of networks using multidimensional data from cell line models of cell cycle arrest caused by inhibition of MEK1/2. Through simulation of reverse-engineered Bayesian network modeling, we generated predictions of G1-S transition...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28087532/establishment-and-validation-of-rna-based-predictive-models-for-understanding-survival-of-vibrio-parahaemolyticus-in-oysters-stored-at-low-temperatures
#16
Chao Liao, Yong Zhao, Luxin Wang
: This study developed RNA-based predictive models describing the survival of Vibrio parahaemolyticus in Eastern oysters (Crassostrea virginica) during storage at 0, 4, and 10°C. Post-harvested oysters were inoculated with a cocktail of five V. parahaemolyticus strains and were then stored at 0, 4, and 10°C for 21 or 11 days. A real-time RT-PCR assay targeting expression of tlh gene was used to evaluate the number of surviving V. parahaemolyticus, which was then used to establish primary molecular models (MMs)...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28087462/impact-of-disease-linked-mutations-targeting-the-oligomerization-interfaces-of-aldehyde-dehydrogenase-7a1
#17
David A Korasick, John J Tanner, Michael T Henzl
Aldehyde dehydrogenase 7A1 (ALDH7A1) is involved in lysine catabolism, catalyzing the oxidation of α-aminoadipate semialdehyde to α-aminoadipate. Certain mutations in the ALDH7A1 gene, which are presumed to reduce catalytic activity, cause an autosomal recessive seizure disorder known as pyridoxine-dependent epilepsy (PDE). Although the genetic association between ALDH7A1 and PDE is well established, little is known about the impact of PDE-mutations on the structure and catalytic function of the enzyme. Herein we report the first study of the molecular consequences of PDE mutations using purified ALDH7A1 variants...
January 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#18
REVIEW
Miguel Vidal, Katharzina Starowicz
Hematopoiesis, the process by which blood cells are continuously produced, is one of the best studied differentiation pathways. Hematological diseases are associated to reiterated mutations in genes encoding important gene expression regulators, including chromatin regulators. Among them, the Polycomb group (PcG) of proteins is an essential system of gene silencing involved in the maintenance of cell identities during differentiation. PcG proteins assemble into two major types of Polycomb repressive complexes (PRC) endowed with distinct histone tail modifying activities...
January 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28087344/up-regulation-of-the-active-form-of-small-gtpase-rab13-promotes-macroautophagy-in-vascular-endothelial-cells
#19
Lu Zhang, Fang Dai, LiuQing Cui, Bo Zhou, YuQi Guo
The importance of macroautophagy (hereafter referred to as autophagy) in vascular endothelial cell (VEC) biology and dysfunction is increasingly recognized, but the molecular mechanisms of autophagy in VECs in the presence of serum are still poorly understood. Previously, we identified pterostilbene as a potent autophagy inducer of VECs in the presence of serum. In this study, we used pterostilbene as a tool to induce VEC autophagy and identified the differentially expressed genes using high-throughput DAN microarray...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087315/assessing-light-independent-effects-of-hypericin-on-cell-viability-ultrastructure-and-metabolism-in-human-glioma-and-endothelial-cells
#20
Veronika Huntosova, Marta Novotova, Zuzana Nichtova, Lucia Balogova, Maria Maslanakova, Dana Petrovajova, Katarina Stroffekova
Cell exposure to light-independent effects of photosensitizers (PS) used in PDT is clinically relevant when PS affect the pro-apoptotic cascade.In many malignant cells, Hypericin (Hyp) has PS displayed light-dependent anti-proliferative and cytotoxic effects with no cytotoxicity in the dark. Recent studies have shown that Hyp also exhibited light-independent cytotoxic effects in a wide range of concentrations. The molecular mechanisms underlying Hyp light-independent (dark) toxicity may be due to its interaction with different molecules at the Hyp accumulation sites including mitochondria, and these mechanisms are not understood in detail...
January 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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