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https://www.readbyqxmd.com/read/29145615/iptmnet-an-integrated-resource-for-protein-post-translational-modification-network-discovery
#1
Hongzhan Huang, Cecilia N Arighi, Karen E Ross, Jia Ren, Gang Li, Sheng-Chih Chen, Qinghua Wang, Julie Cowart, K Vijay-Shanker, Cathy H Wu
Protein post-translational modifications (PTMs) play a pivotal role in numerous biological processes by modulating regulation of protein function. We have developed iPTMnet (http://proteininformationresource.org/iPTMnet) for PTM knowledge discovery, employing an integrative bioinformatics approach-combining text mining, data mining, and ontological representation to capture rich PTM information, including PTM enzyme-substrate-site relationships, PTM-specific protein-protein interactions (PPIs) and PTM conservation across species...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29142256/quantitative-analysis-of-protein-protein-interactions-and-post-translational-modifications-in-rare-immune-populations
#2
Ayelet Avin, Maayan Levy, Ziv Porat, Jakub Abramson
In spite of recent advances in proteomics, quantitative analyses of protein-protein interactions (PPIs) or post-translational modifications (PTMs) in rare cell populations remain challenging. This is in particular true for analyses of rare immune and/or stem cell populations that are directly isolated from humans or animal models, and which are often characterized by multiple surface markers. To overcome these limitations, here we have developed proximity ligation imaging cytometry (PLIC), a protocol for proteomic analysis of rare cells...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29141584/sprint-ultrafast-protein-protein-interaction-prediction-of-the-entire-human-interactome
#3
Yiwei Li, Lucian Ilie
BACKGROUND: Proteins perform their functions usually by interacting with other proteins. Predicting which proteins interact is a fundamental problem. Experimental methods are slow, expensive, and have a high rate of error. Many computational methods have been proposed among which sequence-based ones are very promising. However, so far no such method is able to predict effectively the entire human interactome: they require too much time or memory. RESULTS: We present SPRINT (Scoring PRotein INTeractions), a new sequence-based algorithm and tool for predicting protein-protein interactions...
November 15, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29140691/on-the-importance-of-rigidity-in-designing-small-molecule-drugs-to-tackle-protein-protein-interactions-ppis-through-stabilisation-of-desired-confomers
#4
Alastair D G Lawson, Malcolm MacCoss, Jag P Heer
Tackling PPIs, particularly by stabilising clinically favoured conformations of target proteins, with orally available, bona fide small molecules remains a significant, but immensely worthwhile, challenge for the pharmaceutical industry. Success may be more likely through the application of nature's learnings to build intrinsic rigidity into the design of clinical candidates.
November 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29136547/natural-products-used-as-a-chemical-library-for-protein-protein-interaction-targeted-drug-discovery
#5
Xuemei Jin, Kyungro Lee, Nam Hee Kim, Hyun Sil Kim, Jong In Yook, Jiwon Choi, Kyoung Tai No
Protein-protein interactions (PPIs), which are essential for cellular processes, have been recognized as attractive therapeutic targets. Therefore, the construction of a PPI-focused chemical library is an inevitable necessity for future drug discovery. Natural products have been used as traditional medicines to treat human diseases for millennia; in addition, their molecular scaffolds have been used in diverse approved drugs and drug candidates. The recent discovery of the ability of natural products to inhibit PPIs led us to use natural products as a chemical library for PPI-targeted drug discovery...
October 27, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29134635/ribociclib-bioavailability-is-not-affected-by-gastric-ph-changes-or-food-intake-in-silico-and-clinical-evaluations
#6
Tanay S Samant, Shyeilla Dhuria, Yasong Lu, Marc Laisney, Shu Yang, Arnaud Grandeury, Martin Mueller-Zsigmondy, Kenichi Umehara, Felix Huth, Michelle Miller, Caroline Germa, Mohamed Elmeliegy
Ribociclib (KISQALI®), a cyclin-dependent kinase 4/6 inhibitor approved for the first-line treatment of HR+/HER2- advanced breast cancer with an aromatase inhibitor, is administered with no restrictions on concomitant gastric pH-elevating agents or food intake. The influence of proton pump inhibitors (PPIs) on ribociclib bioavailability was assessed using (1) biorelevant media solubility, (2) physiologically based pharmacokinetic (PBPK) modeling, (3) non-compartmental analysis (NCA) of clinical trial data, and (4) population PK (PopPK) analysis...
November 14, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29132520/gastroesophageal-reflux-disease
#7
REVIEW
Rick Kellerman, Thomas Kintanar
Gastroesophageal reflux disease (GERD) is a gastrointestinal motility disorder that results from the reflux of stomach contents into the esophagus or oral cavity resulting in symptoms or complications. The typical symptoms of GERD are heartburn and regurgitation of gastric contents into the oropharynx. GERD affects quality of life and may cause erosive esophagitis, esophageal strictures, and Barrett esophagus, a precursor to esophageal adenocarcinoma. GERD is a clinical diagnosis and is most effectively treated with proton-pump inhibitors (PPIs)...
December 2017: Primary Care
https://www.readbyqxmd.com/read/29132218/infant-reflux-in-the-primary-care-setting-a-brief-educational-intervention-and-management-changes
#8
Brendan Ryan Harris, William E Bennett
There has been a significant increase in prescription of acid suppression therapy to infants despite limited support for efficacy and safety. Prior studies have shown that educational interventions can improve clinician practices. Our aim is to implement an educational module with high-yield evidence to decrease the rate of prescribing these medications. Chart review of infants seen by residents after completing module was performed. Twelve clinic sessions before and after intervention were examined. 28 residents completed the intervention and required clinics...
November 1, 2017: Clinical Pediatrics
https://www.readbyqxmd.com/read/29128115/chronic-use-of-proton-pump-inhibitors-adverse-events-and-potential-biological-mechanisms-a-translational-analysis
#9
Farid Kheloufi, Diane Frankel, Elise Kaspi, Marion Lepelley, Michel Mallaret, Quentin Boucherie, Patrice Roll, Joelle Micallef
Proton pump inhibitors (PPIs) are among the most frequently prescribed drugs. Even if PPI are usually considered as safe, there is a growing concern for a range of adverse effects of chronic PPI therapy often in the absence of appropriate indications. We propose, after a summary of renal, cardiovascular and neurological complications (dementia, chronic kidney disease, myocardial infarction and stroke), an integrative overview of the potential biological mechanisms involved. Eleven positive pharmacoepidemiological studies, mainly based on health insurance database linkage to hospital database, reported an increased risk of complications associated to PPI use and often a graded association suggesting also a possible dose-response relationship...
October 14, 2017: Thérapie
https://www.readbyqxmd.com/read/29124117/proton-pump-inhibitors-and-the-risk-of-severe-cognitive-impairment-the%C3%A2-role-of-posttraumatic-stress-disorder
#10
Sean A P Clouston, Oren Shapira, Roman Kotov, Lan Lei, Monika Waszczuk, Evelyn J Bromet, Benjamin J Luft
Introduction: Proton pump inhibitors (PPIs), a common treatment for gastroesophageal reflux disease (GERD), were recently associated with increased risk of dementia. However, severe or chronic stress including, for example, posttraumatic stress disorder (PTSD) was not accounted for. This study examined whether PPI use was associated with severe cognitive impairment (SCI) and whether PTSD explained this association in a cohort of World Trade Center (WTC) responders. Method: A prospective cohort study of 3779 WTC responders attending a university-based monitoring and treatment program...
November 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29122616/practice-patterns-of-medications-for-patients-with-malignant-bowel-obstruction-using-a-nationwide-claims-database-and-the-association-between-treatment-outcomes-and-concomitant-use-of-h2-blockers-proton-pump-inhibitors-and-corticosteroids-with-octreotide
#11
Takaaki Minoura, Masato Takeuchi, Tatsuya Morita, Koji Kawakami
CONTEXT: Malignant bowel obstruction (MBO) impairs the quality of life in patients with advanced cancer. Octreotide, acid-suppressing medications such as H<sub>(2)</sub>-receptor antagonists (H<sub>(2)</sub> blockers) and proton pump inhibitors (PPIs), and corticosteroids are often used in combination for symptom control. OBJECTIVES: We evaluated the practice patterns of medications for patients hospitalized with MBO using a large claims database in Japan...
November 6, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/29122546/no-increase-in-risk-of-acute-myocardial-infarction-in-privately-insured-adults-prescribed-proton-pump-inhibitors-vs-histamine-2-receptor-antagonists-2002-2014
#12
Suzanne N Landi, Robert S Sandler, Virginia Pate, Jennifer L Lund
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly used medications. Recent studies reported an increased risk of acute myocardial infarction (MI) in PPI users vs non-users. We evaluated MI risk associated with PPIs compared with histamine-2 receptor antagonists (H2RAs) in privately insured adults in the United States. METHODS: Using administrative claims from commercial and Medicare Supplemental plans (2001-2014), we compared risk of MI in patients who started a new prescription for PPIs vs H2RAs...
November 6, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29121928/a-yeast-two-hybrid-system-for-the-screening-and-characterization-of-small-molecule-inhibitors-of-protein-protein-interactions-identifies-a-novel-putative-mdm2-binding-site-in-p53
#13
Jin Huei Wong, Mohammad Alfatah, Mei Fang Sin, Hong May Sim, Chandra S Verma, David P Lane, Prakash Arumugam
BACKGROUND: Protein-protein interactions (PPIs) are fundamental to the growth and survival of cells and serve as excellent targets to develop inhibitors of biological processes such as host-pathogen interactions and cancer cell proliferation. However, isolation of PPI inhibitors is extremely challenging. While several in vitro assays to screen for PPI inhibitors are available, they are often expensive, cumbersome, and require large amounts of purified protein. In contrast, limited in vivo assays are available to screen for small-molecule inhibitors of PPI...
November 9, 2017: BMC Biology
https://www.readbyqxmd.com/read/29118869/proton-pump-inhibitor-use-is-associated-with-an-increased-frequency-of-hospitalization-in-patients-with-cystic-fibrosis
#14
Fares Ayoub, Jorge Lascano, Giuseppe Morelli
Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications in clinical practice. PPI use has been associated with the development of community-acquired pneumonia. With a reported prevalence of gastroesophageal reflux disease (GERD) and PPI use that is higher than the general population, patients with cystic fibrosis (CF) are particularly vulnerable to PPI adverse effects. We sought to explore whether PPI use was associated with a higher number of hospitalizations for CF pulmonary exacerbation...
October 2017: Gastroenterology Research
https://www.readbyqxmd.com/read/29118552/drugs-for-improving-esophageal-mucosa-defense-where-are-we-now-and-where-are-we-going
#15
REVIEW
Edoardo Savarino, Patrizia Zentilin, Elisa Marabotto, Gaia Pellegatta, Claudia Coppo, Matteo Brunacci, Pietro Dulbecco, Vincenzo Savarino
In the past, the attention of physiologists and doctors has been mainly focused on the key role of acid in the pathogenesis of gastroesophageal reflux disease (GERD), but increasing evidence that 20-40% of reflux patients respond not at all or only partially to proton pump inhibitors (PPIs) has underlined the concept that factors other than acid are implicated in its development and the elicitation of symptoms. Among these, impaired mucosal integrity, particularly in most patients with non-erosive reflux disease, has recently been reincluded and the reinforcement of defensive mechanisms and/or its protection has been reappointed as a renewed therapeutic target for the management of GERD patients...
2017: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/29117139/protein-protein-interactions-prediction-using-a-novel-local-conjoint-triad-descriptor-of-amino-acid-sequences
#16
Jun Wang, Long Zhang, Lianyin Jia, Yazhou Ren, Guoxian Yu
Protein-protein interactions (PPIs) play crucial roles in almost all cellular processes. Although a large amount of PPIs have been verified by high-throughput techniques in the past decades, currently known PPIs pairs are still far from complete. Furthermore, the wet-lab experiments based techniques for detecting PPIs are time-consuming and expensive. Hence, it is urgent and essential to develop automatic computational methods to efficiently and accurately predict PPIs. In this paper, a sequence-based approach called DNN-LCTD is developed by combining deep neural networks (DNNs) and a novel local conjoint triad description (LCTD) feature representation...
November 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29116619/evaluation-of-efficiency-of-modified-polypropylenimine-ppi-with-alkyl-chains-as-non-viral-vectors-used-in-co-delivery-of-doxorubicin-and-trail-plasmid
#17
Mahboubeh Ebrahimian, Sahar Taghavi, Maryam Ghoreishi, Shahrzad Sedghi, Sara Amel Farzad, Mohammad Ramezani, Maryam Hashemi
In this study, co-delivery system was achieved via plasmid encoding TNF related apoptosis inducing ligand (pTRAIL) and doxorubicin (DOX) using carrier based on polypropylenimine (PPI) modified with 10-bromodecanoic acid. Incorporation of alkylcarboxylate chain to PPIs (G4 and G5) could improve transfection efficiency via overcoming the plasma membrane barrier of the cells and decrease cytotoxicity of PPI. Characterization of fabricated NPs revealed that PPI G5 in which 30% of primary amines were substituted by alkyl carboxylate chain (PPI G5-Alkyl 30%) has higher drug loading as compared to the other formulations...
November 7, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29116264/dynamic-sandwich-type-electrochemical-assay-for-protein-quantification-and-protein-protein-interaction
#18
Chao Li, Yaqin Tao, Yi Yang, Chang Feng, Yang Xiang, Genxi Li
The study of protein-protein interactions (PPIs) plays an important role in the understanding of biological systems; however, the established methods for PPI analysis often involve cumbersome sample preparation, multiple detecting steps, and costly instruments. Here we report a versatile and sensitive electrochemical method based on PPI-induced distinctive migration behavior of DNA deoxyribozyme (DNAzyme) on an electrode surface. In this method, the cleavage activity of DNAzyme toward the substrate DNA modified on the electrode surface is inversely correlated with the hydrodynamic diameter of the macromolecule attached to it...
November 8, 2017: Analyst
https://www.readbyqxmd.com/read/29112936/designing-anti-zika-virus-peptides-derived-from-predicted-human-zika-virus-protein-protein-interactions
#19
Tom Kazmirchuk, Kevin Dick, Daniel J Burnside, Brad Barnes, Houman Moteshareie, Maryam Hajikarimlou, Katayoun Omidi, Duale Ahmed, Andrew Low, Clara Lettl, Mohsen Hooshyar, Andrew Schoenrock, Sylvain Pitre, Mohan Babu, Edana Cassol, Bahram Samanfar, Alex Wong, Frank Dehne, James R Green, Ashkan Golshani
The production of anti-Zika virus (ZIKV) therapeutics has become increasingly important as the propagation of the devastating virus continues largely unchecked. Notably, a causal relationship between ZIKV infection and neurodevelopmental abnormalities has been widely reported, yet a specific mechanism underlying impaired neurological development has not been identified. Here, we report on the design of several synthetic competitive inhibitory peptides against key pathogenic ZIKV proteins through the prediction of protein-protein interactions (PPIs)...
November 2, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29112911/interactome-evolution-insights-from-genome-wide-analyses-of-protein-protein-interactions
#20
REVIEW
Mohamed A Ghadie, Jasmin Coulombe-Huntington, Yu Xia
We highlight new evolutionary insights enabled by recent genome-wide studies on protein-protein interaction (PPI) networks ('interactomes'). While most PPIs are mediated by a single sequence region promoting or inhibiting interactions, many PPIs are mediated by multiple sequence regions acting cooperatively. Most PPIs perform important functions maintained by negative selection: we estimate that less than ∼10% of the human interactome is effectively neutral upon perturbation (i.e. 'junk' PPIs), and the rest are deleterious upon perturbation; interfacial sites evolve more slowly than other sites; many conserved PPIs show signatures of co-evolution at the interface; PPIs evolve more slowly than protein sequence...
November 4, 2017: Current Opinion in Structural Biology
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