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https://www.readbyqxmd.com/read/28445176/novel-lipid-modifying-drugs-to-lower-ldl-cholesterol
#1
Arjen J Cupido, Laurens F Reeskamp, John J P Kastelein
PURPOSE OF REVIEW: Statins have long been the cornerstone for the prevention of cardiovascular disease (CVD). However, because of perceived adverse effects and insufficient efficacy in certain groups of patients, considerable interest exists in the search for alternatives to lower LDL-cholesterol (LDL-C), and the recent approvals of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors underlines the success of this quest. Here, we give an updated overview on the most recent developments in the area of LDL-C lowering agents...
April 25, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28441666/a-microrna-124-polymorphism-is-associated-with-fracture-healing-via-modulating-bmp6-expression
#2
Lin Zou, Guichun Zhang, Lifeng Liu, Chen Chen, Xuecheng Cao, Jinfang Cai
BACKGROUND: miR-124-3p has been reported to be involved in the pathogenesis of many diseases by modulating a variety of signaling pathways. In this study, we aimed to understand the impact of miR-124-3p expression level on the fracture healing in the patients of metaphyseal fracture of distal tibia, who received minimal invasive percutaneous plate osteosynthesis. METHODS: We firstly collected 195 patients of metaphyseal fracture of distal tibia, and the genotype of rs531564 was determined: GG (n=124) and GC+CC (n=71)...
April 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28431407/prognositic-value-of-cd73-adenosinergic-pathway-in-solid-tumor-a-meta-analysis-and-systematic-review
#3
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...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430673/antimicrobial-resistant-streptococcus-pneumoniae-prevalence-mechanisms-and-clinical-implications
#4
Regine Cherazard, Marcia Epstein, Thien-Ly Doan, Tanzila Salim, Sheena Bharti, Miriam A Smith
BACKGROUND: Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics. STUDY DESIGN: Systematic literature review of prevalence, mechanisms, and clinical implications in S. pneumoniae resistance. AREAS OF UNCERTAINTY: Since S. pneumoniae resistance to penicillin was first reported with subsequent development of resistance to other classes of drugs, selection of appropriate antibiotic treatment is challenging...
April 19, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28428947/update-on-programmed-death-1-and-programmed-death-ligand-1-inhibition-in-the-treatment-of-advanced-or-metastatic-non-small-cell-lung-cancer
#5
REVIEW
Marco A J Iafolla, Rosalyn A Juergens
PURPOSE: Non-small-cell lung cancer (NSCLC) has a large worldwide prevalence with a high mortality rate. Chemotherapy has offered modest improvements in survival over the past two decades. Immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has shown the promise of changing the future landscape of cancer therapy. This update reviews recent advances in the treatment of NSCLC with immune checkpoint modulation. METHODS: Publications and proceedings were identified from searching PubMed and proceedings from the annual meetings of the American Society of Clinical Oncology, European Society for Medical Oncology, and European Lung Cancer Conference...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28426805/evidence-of-horizontal-gene-transfer-by-transposase-gene-analyses-in-fervidobacterium-species
#6
Alba Cuecas, Wirojne Kanoksilapatham, Juan M Gonzalez
Horizontal Gene Transfer (HGT) plays an important role in the physiology and evolution of microorganisms above all thermophilic prokaryotes. Some members of the Phylum Thermotogae (i.e., Thermotoga spp.) have been reported to present genomes constituted by a mosaic of genes from a variety of origins. This study presents a novel approach to search on the potential plasticity of Fervidobacterium genomes using putative transposase-encoding genes as the target of analysis. Transposases are key proteins involved in genomic DNA rearrangements...
2017: PloS One
https://www.readbyqxmd.com/read/28423550/quantitative-proteomic-analysis-of-gastric-cancer-tissue-reveals-novel-proteins-in-platelet-derived-growth-factor-b-signaling-pathway
#7
Fang Liu, Yuan Zhang, Tingting Men, Xingyue Jiang, Chunhua Yang, He Li, Xiaodan Wei, Dong Yan, Gangming Feng, Jianke Yang, Jonas Bergquist, Bin Wang, Wenguo Jiang, Jia Mi, Geng Tian
Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419258/eigenthreader-analogous-protein-fold-recognition-by-efficient-contact-map-threading
#8
Daniel Wa Buchan, David T Jones
Motivation: Protein fold recognition when appropriate, evolutionarily-related, structural templates can be identified is often trivial and may even be viewed as a solved problem. However in cases where no homologous structural templates can be detected, fold recognition is a notoriously difficult problem (Moult, Fidelis et al. 2014). Here we present EigenTHREADER, a novel fold recognition method capable of identifying folds where no homologous structures can be identified. EigenTHREADER takes a query amino acid sequence, generates a map of intra-residue contacts, and then searches a library of contact maps of known structures...
April 13, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28416764/a-recombinant-fungal-compound-induces-anti-proliferative-and-pro-apoptotic-effects-on-colon-cancer-cells
#9
Lili Nimri, Orly Spivak, Dana Tal, Dominik Schälling, Irena Peri, Lutz Graeve, Tomer M Salame, Oded Yarden, Yitzhak Hadar, Betty Schwartz
Finding intracellular pathways and molecules that can prevent the proliferation of colon cancer cells can provide significant bases for developing treatments for this disease. Ostreolysin (Oly) is a protein found in the mushroom Pleurotus ostreatus, and we have produced a recombinant version of this protein (rOly).We measured the viability of several colon cancer cells treated with rOly. Xenografts and syngeneic colon cancer cells were injected into in vivo mouse models, which were then treated with this recombinant protein...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415132/genetic-alterations-in-mesiodens-as-revealed-by-targeted-ngs-and-gene-co-occurrence-network-analysis
#10
Young Youn Kim, Jihye Hwang, Hye-Sung Kim, Hee Jun Kwon, Sanguk Kim, Ji Hyun Lee, Jae Hoon Lee
OBJECTIVE: Mesiodens is the most common type of supernumerary tooth which includes a population prevalence of 0.15-1.9%. Alongside evidence that the condition is heritable, mutations in single genes have been reported in few human supernumerary tooth cases. Gene sequencing methods in tradition way are time-consuming and labor-intensive, whereas next generation sequencing and bioinformatics are cost-effective for large samples and target sizes. MATERIALS AND METHODS: We describe the application of a targeted next generation sequencing (NGS) and bioinformatics approach to samples from 17 mesiodens patients...
April 17, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28412930/large-scale-analysis-of-post-translational-modifications-in-e-coli-under-glucose-limiting-conditions
#11
Colin W Brown, Viswanadham Sridhara, Daniel R Boutz, Maria D Person, Edward M Marcotte, Jeffrey E Barrick, Claus O Wilke
BACKGROUND: Post-translational modification (PTM) of proteins is central to many cellular processes across all domains of life, but despite decades of study and a wealth of genomic and proteomic data the biological function of many PTMs remains unknown. This is especially true for prokaryotic PTM systems, many of which have only recently been recognized and studied in depth. It is increasingly apparent that a deep sampling of abundance across a wide range of environmental stresses, growth conditions, and PTM types, rather than simply cataloging targets for a handful of modifications, is critical to understanding the complex pathways that govern PTM deposition and downstream effects...
April 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28409625/privileged-structural-motif-detection-and-analysis-using-generative-topographic-maps
#12
Shilva Kayastha, Dragos Horvath, Erik Gilberg, Michael Gütschow, Jürgen Bajorath, Alexandre Varnek
Identification of "privileged structural motifs" associated with specific target families is of particular importance for designing novel bioactive compounds. Here, we demonstrate that they can be extracted from a data distribution represented on a two-dimensional map obtained by Generative Topographic Mapping (GTM) . In GTM, structurally related molecules are grouped together on the map. Zones of the map preferentially populated by target-specific compounds were delineated, which helped to capture common substructures on the basis of which these compounds were grouped together by the GTM...
April 14, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28409380/bacterial-thiol-oxidoreductases-from-basic-research-to-new-antibacterial-strategies
#13
REVIEW
Katarzyna M Bocian-Ostrzycka, Magdalena J Grzeszczuk, Anna M Banaś, Elżbieta Katarzyna Jagusztyn-Krynicka
The recent, rapid increase in bacterial antimicrobial resistance has become a major public health concern. One approach to generate new classes of antibacterials is targeting virulence rather than the viability of bacteria. Proteins of the Dsb system, which play a key role in the virulence of many pathogenic microorganisms, represent potential new drug targets. The first part of the article presents current knowledge of how the Dsb system impacts function of various protein secretion systems that influence the virulence of many pathogenic bacteria...
May 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28406185/knockdown-of-stem-cell-regulator-oct4a-in-ovarian-cancer-reveals-cellular-reprogramming-associated-with-key-regulators-of-cytoskeleton-extracellular-matrix-remodelling
#14
Chantel Samardzija, David W Greening, Ruth Escalona, Maoshan Chen, Maree Bilandzic, Rodney Luwor, George Kannourakis, Jock K Findlay, Nuzhat Ahmed
Oct4A is a master regulator of self-renewal and pluripotency in embryonic stem cells. It is a well-established marker for cancer stem cell (CSC) in malignancies. Recently, using a loss of function studies, we have demonstrated key roles for Oct4A in tumor cell survival, metastasis and chemoresistance in in vitro and in vivo models of ovarian cancer. In an effort to understand the regulatory role of Oct4A in tumor biology, we employed the use of an ovarian cancer shRNA Oct4A knockdown cell line (HEY Oct4A KD) and a global mass spectrometry (MS)-based proteomic analysis to investigate novel biological targets of Oct4A in HEY samples (cell lysates, secretomes and mouse tumor xenografts)...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28403668/neat-flex-predicting-the-conformational-flexibility-of-amino-acids-using-neuroevolution-of-augmenting-topologies
#15
Bruno Grisci, Márcio Dorn
The development of computational methods to accurately model three-dimensional protein structures from sequences of amino acid residues is becoming increasingly important to the structural biology field. This paper addresses the challenge of predicting the tertiary structure of a given amino acid sequence, which has been reported to belong to the NP-Complete class of problems. We present a new method, namely NEAT-FLEX, based on NeuroEvolution of Augmenting Topologies (NEAT) to extract structural features from (ABS) proteins that are determined experimentally...
March 16, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/28402951/characterization-of-a-secreted-macrophage-migration-inhibitory-factor-homologue-of-the-parasitic-nematode-haemonchus-contortus-acting-at-the-parasite-host-cell-interface
#16
Yujian Wang, MingMin Lu, Shuai Wang, Muhammad Ehsan, RuoFeng Yan, XiaoKai Song, LiXin Xu, XiangRui Li
Modulation and suppression of the immune response of the host by nematode parasites have been reported extensively and the migration inhibitory factor (MIF) is identified as one of the major immunomodulator. In the present study, we cloned and produced recombinant MIF protein from the small ruminant's nematode parasite Haemonchus contortus (rHCMIF-1), and investigated its immunomodulatory effects on goat monocyte. Enzymatic assays indicated that rHCMIF-1 possessed tautomerase activity. Immunohistochemical test demonstrated that the native HCMIF-1 protein was predominantly localized at the body surface and internal surface of the worm's gut...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402259/the-design-of-novel-inhibitors-for-treating-cancer-by-targeting-cdc25b-through-disruption-of-cdc25b-cdk2-cyclin-a-interaction-using-computational-approaches
#17
Hong-Lian Li, Ying Ma, Ying Ma, Yu Li, Xiu-Bo Chen, Wei-Li Dong, Run-Ling Wang
Cell division cycle 25B is a key cell cycle regulator and widely considered as potent clinical drug target for cancers. This research focused on identifying potential compounds in theory which are able to disrupt transient interactions between CDC25B and its CDK2/Cyclin A substrate.By using the method of ZDOCK and RDOCK, the most optimized 3D structure of CDK2/Cyclin A in complex with CDC25B was constructed and validated using two methods: 1) the superimposition of proteins; 2) analysis of the hydrogen bond distances of Arg 488(N1)-Asp 206(OD1), Arg 492(NE)-Asp 206(OD1), Arg 492(N1)-Asp 206(OD2) and Tyr 497(NE)-Asp 210(OD1)...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400782/genomic-and-phenomic-screens-for-flower-related-ring-type-ubiquitin-e3-ligases-in-arabidopsis
#18
Mirko Pavicic, Katriina Mouhu, Feng Wang, Marcelina Bilicka, Erik Chovanček, Kristiina Himanen
Flowering time control integrates endogenous as well as environmental signals to promote flower development. The pathways and molecular networks involved are complex and integrate many modes of signal transduction. In plants ubiquitin mediated protein degradation pathway has been proposed to be as important mode of signaling as phosphorylation and transcription. To systematically study the role of ubiquitin signaling in the molecular regulation of flowering we have taken a genomic approach to identify flower related Ubiquitin Proteasome System components...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28394263/elevating-expression-of-mecp2-t158m-rescues-dna-binding-and-rett-syndrome-like-phenotypes
#19
Janine M Lamonica, Deborah Y Kwon, Darren Goffin, Polina Fenik, Brian S Johnson, Yue Cui, Hengyi Guo, Sigrid Veasey, Zhaolan Zhou
Mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome (RTT), a neurological disorder affecting cognitive development, respiration, and motor function. Genetic restoration of MeCP2 expression reverses RTT-like phenotypes in mice, highlighting the need to search for therapeutic approaches. Here, we have developed knockin mice recapitulating the most common RTT-associated missense mutation, MeCP2 T158M. We found that the T158M mutation impaired MECP2 binding to methylated DNA and destabilized MeCP2 protein in an age-dependent manner, leading to the development of RTT-like phenotypes in these mice...
April 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28393690/hepatic-amp-kinase-as-a-potential-target-for-treating-nonalcoholic-fatty-liver-disease-evidence-from-studies-of-natural-products
#20
Gang Xu, Kaixun Huang, Jun Zhou
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is the leading cause of cryptogenic cirrhosis and has consistently been implicated in related metabolic disorders, such as dyslipidemia and type 2 diabetes (T2D). However, the pathogenesis of NAFLD remains to be elucidated, and no established therapeutic regimens for treating NAFLD exist. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main cellular energy sensor, has been implicated as a key regulator of hepatic lipid and glucose metabolism...
April 4, 2017: Current Medicinal Chemistry
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