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https://www.readbyqxmd.com/read/28928828/screening-of-candidate-key-genes-associated-with-human-osteosarcoma-using-bioinformatics-analysis
#1
Kefeng Zhang, Jianwen Gao, Yong Ni
The aim of the present study was to identify the key genes associated with osteosarcoma (OS) using a bioinformatics approach. Microarray data (GSE36004) was downloaded from the Gene Expression Omnibus database, including 19 OS cell lines and 6 normal controls. Differentially expressed genes (DEGs) in the OS cell lines were identified using the Limma package, and differentially methylated regions were screened with methyAnalysis in R. Copy number analysis was performed and genes with copy number gains/losses were further screened using DNAcopy and cghMCR packages...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927677/std-nmr-experiments-identify-a-structural-motif-with-novel-second-site-activity-against-west-nile-virus-ns2b-ns3-protease
#2
Tobias Schöne, Lena Lisbeth Grimm, Naoki Sakai, Linlin Zhang, Rolf Hilgenfeld, Thomas Peters
West Nile virus (WNV) belongs to the genus Flavivirus of the family Flaviviridae. This mosquito-borne virus that is highly pathogenic to humans has been evolving into a global threat during the past two decades. Despite many efforts, neither antiviral drugs nor vaccines are available. The viral protease NS2B-NS3(pro) is essential for viral replication, and therefore it is considered a prime drug target. However, success in the development of specific NS2B-NS3(pro) inhibitors had been moderate so far. In the search for new structural motifs with binding affinity for NS2B-NS3(pro), we have screened a fragment library, the Maybridge Ro5 library, employing saturation transfer difference (STD) NMR experiments as readout...
September 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28927082/identification-of-target-gene-of-venous-thromboembolism-in-patients-with-lymphoma-via-microarray-analysis
#3
Pengfei Liu, Wenhua Jiang, Huilai Zhang
Patients with lymphoma are at high risk of developing venous thromboembolism (VTE). The purpose of the present study was to identify the target gene associated with VTE for patients with lymphoma. Microarray data was downloaded from the gene expression omnibus database (GSE17078), which comprised the control group, 27 normal blood outgrowth endothelial cell (BOEC) samples, and the case group, 3 BOEC samples of venous thrombosis with protein C deficiency. Differentially expressed genes (DEGs) were identified by the Limma package of R...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926253/understanding-the-role-of-dna-topology-in-target-search-dynamics-of-proteins
#4
Anupam Mondal, Arnab Bhattacherjee
A wide range of cellular processes initiates upon recognising and binding of proteins to specific DNA sites. Typically, the recognition process is incredibly fast owing to a complex mechanism that combines different 3D and 1D modes of translocation of the protein. While few studies performed on selected DNA topologies suggested that the DNA topology might alter the balance between these two modes and therefore the target search kinetics, its detail role in target search mechanism remains unclear. Here, we present a discrete-state stochastic approach that allows us to incorporate the topological information of DNA molecule explicitly and predict its role during the process when proteins search for their specific binding sites on DNA...
September 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28922916/a-discrete-state-kinetics-model-for-nmr-based-analysis-of-protein-translocation-on-dna-at-equilibrium
#5
Debashish Sahu, Junji Iwahara
In the target DNA search process, sequence-specific DNA-binding proteins first nonspecifically bind to DNA and stochastically move from one site to another before reaching their targets. To rigorously assess how the translocation process influences NMR signals from proteins interacting with nonspecific DNA, we incorporated a discrete-state kinetic model for protein translocation on DNA into the McConnell equation. Using this equation, we simulated line shapes of NMR signals from proteins undergoing translocations on DNA through sliding, dissociation / reassociation, and intersegment transfer...
September 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28921842/anchorquery-rapid-online-virtual-screening-for-small-molecule-protein-protein-interaction-inhibitors
#6
David R Koes, Alexander Dömling, Carlos J Camacho
AnchorQuery ( http://anchorquery.csb.pitt.edu) is a web application for rational structure-based design of protein-protein interaction (PPI) inhibitors. A specialized variant of pharmacophore search is used to rapidly screen libraries consisting of more than 31 million synthesizable compounds biased by design to preferentially target PPIs. Every library compound is accessible through one-step multi-component reaction (MCR) chemistry and contains an anchor motif that is bioisosteric to an amino acid residue...
September 16, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28921458/pharmacogenetics-and-pharmacogenomics-in-moderate-to-severe-psoriasis
#7
REVIEW
María C Ovejero-Benito, Ester Muñoz-Aceituno, Alejandra Reolid, Miriam Saiz-Rodríguez, Francisco Abad-Santos, Esteban Daudén
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis...
September 18, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#8
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28920498/an-update-on-biomarker-discovery-and-use-in-axial-spondyloarthritis
#9
Walter P Maksymowych
Evaluation of diagnosis, disease activity, and risk for joint damage all represent important unmet clinical needs in the management of axial spondyloarthritis that have been explored using biomarkers. Areas Covered: This review used the search terms biomarkers, ankylosing spondylitis, spondyloarthritis, spondyloarthropathy, pathogenesis, genetics, diagnostic tools, prognosis, to explore advances in biomarker development relevant to unmet clinical needs. Expert Commentary: Despite major advances in the identification of genetic risk markers, HLA-B*27 remains the only marker with clinical utility for diagnostic purposes...
September 16, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28917147/combined-in-silico-approaches-for-the-identification-of-novel-inhibitors-of-human-islet-amyloid-polypeptide-hiapp-fibrillation
#10
Palak Patel, Krupali Parmar, Vivek K Vyas, Dhaval Patel, Mili Das
Human islet amyloid polypeptide (hIAPP) is a natively unfolded polypeptide hormone of glucose metabolism, which is co-secreted with insulin by the β-cells of the pancreas. In patients with type 2 diabetes, IAPP forms amyloid fibrils because of diabetes-associated β-cells dysfunction and increasing fibrillation, in turn, lead to failure of secretory function of β-cells. This provides a target for the discovery of small organic molecules against protein aggregation diseases. However, the binding mechanism of these molecules with monomers, oligomers and fibrils to inhibit fibrillation is still an open question...
September 6, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28915673/prognositic-value-of-cd73-adenosinergic-pathway-in-solid-tumor-a-meta-analysis-and-systematic-review
#11
Rong Wang, Yingying Zhang, Xia Lin, Yalin Gao, Ying Zhu
CD73 is a glycosylphosphatidylinositol (GPI) anchored cell surface protein that is encoded by NT5E gene, plays multiple roles in tumor processes. Previous studies have presented a potential value of CD73 served as a detectable biomarker for prognosis of several solid tumors, but the results were more controversially. A comprehensive meta-analysis was conducted to precisely evaluate the prognostic role of CD73 in solid tumors. The included studies were searched in PubMed, Web of Science and EBSCO from Jan 1990 to Jan 2016...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915270/the-single-cyclic-nucleotide-specific-phosphodiesterase-of-the-intestinal-parasite-giardia-lamblia-represents-a-potential-drug-target
#12
Stefan Kunz, Vreni Balmer, Geert Jan Sterk, Michael P Pollastri, Rob Leurs, Norbert Müller, Andrew Hemphill, Cornelia Spycher
BACKGROUND: Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality, and treatment options are limited. According to the Center for Disease Control and Prevention, Giardia infections afflict nearly 33% of people in developing countries, and 2% of the adult population in the developed world. This study describes the single cyclic nucleotide-specific phosphodiesterase (PDE) of G. lamblia and assesses PDE inhibitors as a new generation of anti-giardial drugs...
September 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28914970/microrna-410-is-involved-in-mitophagy-after-cardiac-ischemia-reperfusion-injury-by-targeting-high-mobility-group-box-1-protein
#13
Fan Yang, Tong Li, Zhihuan Dong, Rui Mi
Mitochondrial dysfunction has emerged as a critical pathophysiological factor of myocardial ischemia/reperfusion (I/R) injury. A thorough understanding of mitochondrial dysfunction during I/R at the molecular level is urgently needed. One prominent microRNA, miR-410, was previously reported to be dynamically regulated in diverse cardiomyopathies, but its mechanism is unclear. In the present study, in a cardiac I/R injury mice model, the expression of miR-410 was significantly upregulated, accompanied with decreased mitochondrial function and mitophagy deficit...
September 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28911247/metabolic-pathways-and-pharmacokinetics-of-natural-medicines-with-low-permeability
#14
Mei Zeng, Lan Yang, Dan He, Yao Li, Mingxin Shi, Jingqing Zhang
Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine...
September 14, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28910747/transcriptome-analysis-of-rana-chensinensis-liver-under-trichlorfon-stress
#15
Yu Ma, Bo Li, Yang Ke, Yongan Zhang, Yuhui Zhang
Trichlorfon is a selective organophosphate insecticide that is widely applied in aquaculture and agriculture for control of various parasites. However, repeated and excess applications of trichlorfon often lead to water pollution and threaten non-targeted species. Our previous studies showed that trichlorfon could cause oxidative stress, lipid peroxidation and hepatic lesions in the liver of Rana chensinensis, but the related molecular mechanisms remain unclear. To explore the interference of trichlorfon in gene transcription, the differentially expressed genes in the liver of R...
September 11, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28905467/modeling-of-protein-complexes-in-capri-round-37-using-template-based-approach-combined-with-model-selection
#16
Justas Dapkūnas, Kliment Olechnovič, Česlovas Venclovas
We participated in CAPRI Round 37, held jointly with CASP12, having two major objectives. First, we intended to test the utility of our PPI3D web server in finding and selecting templates for comparative modeling of structures of protein complexes. Our second aim was to evaluate the ability of our model accuracy estimation method VoroMQA to score and rank structural models for protein-protein interactions. Using sequence search in PPI3D and HHpred servers we identified multimeric templates for 7 of 11 CAPRI targets, and models of at least acceptable quality were constructed for 6 of them...
September 14, 2017: Proteins
https://www.readbyqxmd.com/read/28905331/antibiotic-distribution-into-cerebrospinal-fluid-can-dosing-safely-account-for-drug-and-disease-factors-in-the-treatment-of-ventriculostomy-associated-infections
#17
Nilesh Kumta, Jason A Roberts, Jeffrey Lipman, Menino Osbert Cotta
Ventriculostomy-associated infections, or ventriculitis, in critically ill patients are associated with considerable morbidity. Efficacious antibiotic dosing for the treatment of these infections may be complicated by altered antibiotic concentrations in the cerebrospinal fluid due to variable meningeal inflammation and antibiotic properties. Therefore, doses used to treat infections with a higher degree of meningeal inflammation (such as meningitis) may often fail to achieve equivalent exposures in patients with ventriculostomy-associated infections such as ventriculitis...
September 13, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28903437/meta-analysis-of-micrornas-expression-in-head-and-neck-cancer-uncovering-association-with-outcome-and-mechanisms
#18
Joshua Lubov, Mariana Maschietto, Iman Ibrahim, Alex Mlynarek, Michael Hier, Luiz Paulo Kowalski, Moulay A Alaoui-Jamali, Sabrina Daniela da Silva
Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at advanced stages, incurring significant high mortality and morbidity. This review explored the risk stratification of miRNAs, and investigated the impact of miRNA networking in HNSCC prognostication. We performed a meta-analysis and a systematic literature search on online databases for papers published prior to December 1, 2016. The list of miRNAs was uploaded to MetacoreTM to construct a protein-protein interaction network, which was used to identify targets of the miRNAs and potential drugs...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903352/analysis-of-bos-taurus-and-sus-scrofa-x-and-y-chromosome-transcriptome-highlights-reproductive-driver-genes
#19
Faheem Ahmed Khan, Hui Liu, Hao Zhou, Kai Wang, Muhammad Tahir Ul Qamar, Nuruliarizki Shinta Pandupuspitasari, Zhang Shujun
The biology of sperm, its capability of fertilizing an egg and its role in sex ratio are the major biological questions in reproductive biology. To answer these question we integrated X and Y chromosome transcriptome across different species: Bos taurus and Sus scrofa and identified reproductive driver genes based on Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm. Our strategy resulted in 11007 and 10445 unique genes consisting of 9 and 11 reproductive modules in Bos taurus and Sus scrofa, respectively...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903337/targeting-the-apoptotic-mcl-1-puma-interface-with-a-dual-acting-compound
#20
Jiyuan Liu, Zhen Tian, Nan Zhou, Xueying Liu, Chenyi Liao, Beilei Lei, Jianing Li, Shengyong Zhang, Hui Chen
Despite intensive efforts in the search for small molecules with anti-cancer activity, it remains challenging to achieve both high effectiveness and safety, since many agents lack the selectivity to only act on cancer cells. The interface of two apoptotic proteins, myeloid cell leukemia-1 (Mcl-1) and p53 upregulated modulator of apoptosis (PUMA), has been recently affirmed as a target for treating cancers, as the disruption of Mcl-1-PUMA binding can reduce cancer cell survival and protect normal cells from apoptosis...
August 15, 2017: Oncotarget
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