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https://www.readbyqxmd.com/read/28938598/proton-pump-inhibitors-increase-the-chemosensitivity-of-patients-with-advanced-colorectal-cancer
#1
Xiaoyu Wang, Chun Liu, Jiaqi Wang, Yue Fan, Zhenghua Wang, Yuanyuan Wang
Changes in pH can alter the uptake of chemotherapy drugs. Proton pump inhibitors (PPIs) may therefore increase the chemosensitivity of cancer cells and cytotoxicity of chemotherapeutic drugs by increasing their uptake. We investigated the chemosensitizing potential of PPIs in colorectal cancer (CRC). Our in vitro data show that the PPI pantoprazole increases the chemosensitivity of CRC HT29 and RKO cells to fluorouracil (5-FU). Our in vivo data demonstrate that pantoprazole also increases the ability of 5-FU to inhibit CRC tumor growth in mice...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28933779/genetically-encoded-releasable-photo-cross-linking-strategies-for-studying-protein-protein-interactions-in-living-cells
#2
Yi Yang, Haiping Song, Dan He, Shuai Zhang, Shizhong Dai, Xiao Xie, Shixian Lin, Ziyang Hao, Huangtao Zheng, Peng R Chen
Although protein-protein interactions (PPIs) have crucial roles in virtually all cellular processes, the identification of more transient interactions in their biological context remains challenging. Conventional photo-cross-linking strategies can be used to identify transient interactions, but these approaches often suffer from high background due to the cross-linked bait proteins. To solve the problem, we have developed membrane-permeable releasable photo-cross-linkers that allow for prey-bait separation after protein complex isolation and can be installed in proteins of interest (POIs) as unnatural amino acids...
October 2017: Nature Protocols
https://www.readbyqxmd.com/read/28932087/modified-helicobacter-test-using-a-new-test-meal-and-a-13-c-urea-breath-test-in-helicobacter-pylori-positive-and-negative-dyspepsia-patients-on-proton-pump-inhibitors
#3
Bojan Tepeš, Peter Malfertheiner, Joachim Labenz, Sitke Aygen
AIM: To determine the sensitivity and specificity of the (13)C-urea breath test (UBT) in patients taking proton pump inhibitors (PPIs), using a new test meal Refex. METHODS: One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori (H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the (13)C-UBT with the new test meal was performed the next morning...
August 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28930292/proton-pump-inhibitors-understanding-the-complications-and-risks
#4
REVIEW
Peter Malfertheiner, Arne Kandulski, Marino Venerito
Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection...
September 20, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28924374/no-association-of-proton-pump-inhibitor-use-with-fasting-or-postload-glycaemia-in-patients-with-cardiovascular-disease-a-cross-sectional-retrospective-study
#5
Olga Kruszelnicka, Marcin Kuźma, Iwona Z Pena, Ian B Perera, Bernadeta Chyrchel, Ewa Wieczorek-Surdacka, Andrzej Surdacki
Background: Proton pump inhibitor (PPI) use was reportedly associated with an excess of adverse cardiovascular (CV) events, thus making their systemic effects relevant to public health. PPIs reduce gastric acid secretion, causing increased gastrin release. Gastrin stimulates β-cell neogenesis and enhances insulin release, exerting an incretin-like effect. Our aim was to assess, if PPI usage is associated with altered glycaemia in patients with CV disease. Methods: We retrospectively analyzed medical records of 102 subjects (80 with ischemic heart disease) who underwent a routine oral glucose tolerance test while hospitalized in a cardiology department...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28924108/proton-pump-inhibitor-induction-of-gastric-cobblestone-like-lesions-in-the-stomach
#6
Kosuke Takahari, Ken Haruma, Hiroshi Ohtani, Sho Kiyoto, Akifumi Watanabe, Tomoari Kamada, Noriaki Manabe, Yu Hatano
Objective The long-term use of proton pump inhibitors (PPIs) may induce adverse events in many organs, including the stomach. The chronic use of PPIs has been associated with the growth of fundic gland polyps (FGPs) and of gastric black spots. This study assessed the incidence of gastric lesions with cobblestone-like appearance in PPI users. Methods The clinical characteristics and endoscopic findings of patients who underwent upper gastrointestinal endoscopy after using PPIs for at least six months were analyzed...
September 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28922596/privileged-substructures-to-modulate-protein-protein-interactions
#7
Nicolas Bosc, Mélaine A Kuenemann, Jérome Bécot, Marek Vavrusa, Adrien H Cerdan, Olivier Sperandio
Given the difficulties to identify chemical probes that can modulate protein-protein interactions (PPIs), actors in the field start to agree on the necessity to use PPI-tailored screening chemical collections. However, which type of scaffolds may promote the binding of compounds to PPI targets remains unclear. In this big data analysis, we have identified a list of privileged chemical substructures that are most often observed within inhibitors of PPIs. Using molecular frameworks as a way to perceive chemical substructures with the combination of an experimental and a machine-learning based predicted dataset of iPPI compounds, we propose a list of privileged substructures in the form of scaffolds and chemical moieties that can be substantially chemically functionalized and do not present any toxicophore nor Pan-assay interference (PAINS) alerts...
September 18, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28921842/anchorquery-rapid-online-virtual-screening-for-small-molecule-protein-protein-interaction-inhibitors
#8
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/28918174/14-3-3-adaptor-protein-protein-interactions-as-therapeutic-targets-for-cns-diseases
#9
REVIEW
Andrew Kaplan, Christian Ottmann, Alyson E Fournier
14-3-3sare a family of ubiquitously expressed adaptor proteins that regulate hundreds of functionally diverse 'client proteins.' In humans, there are seven isoforms with conserved structure and function. 14-3-3s typically bind to client proteins at phosphorylated serine/threonine motifs via a linear binding groove. Binding can have a variety of effects on the stability, activity and/or localization of the client protein. 14-3-3s are generating significant interest as potential drug targets for their involvement in cellular homeostasis and disease...
September 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28914863/-chronic-gastritis-instructions-for-use-of-medications
#10
V I Simanenkov, S S Vyalov
The paper highlights the features of drug use in the legal aspect. It analyzes instructions for medical use of proton pump inhibitors (PPIs) and gastric protective agents. Taking into account the characteristics of indications registered in the instruction, the authors discuss the possibility of using various PPIs. The instruction for medical application is an official document approved by the Ministry of Health, the basis of which is the data of trials carried out by a manufacturer, and it should be a key or fundamental source for a physician in choosing a medication...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28912807/a-meta-analysis-and-systematic-review-of-the-efficacy-of-twice-daily-ppis-versus-once-daily-for-treatment-of-gastroesophageal-reflux-disease
#11
REVIEW
Hongying Zhang, Zhiping Yang, Zhen Ni, Yongquan Shi
BACKGROUND: To investigate whether PPIs BID is superior to QD for treatment of GERD in a short time. METHODS: We searched PubMed, Cochrane Library, Scopus, EMBASE, Ovid, EBSCO, and Web of Science databases (from 1998 to May 2016) to select RCTs, which compared the efficacy of PPIs BID versus QD for GERD. The primary outcomes were symptom relief or esophageal mucosal healing at weeks 4 and 8. The M-H method with fixed-effect or random-effect model was used to calculate RR and 95% CIs...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28912038/proton-pump-inhibitor-use-is-associated-with-a-reduced-risk-of-infection-with-intestinal-protozoa
#12
Johnathan M Sheele
OBJECTIVE: Proton pump inhibitors (PPIs) can kill some human protozoan parasites in cell culture better than the drug metronidazole. Clinical data showing an antiprotozoal effect for PPIs are lacking. The objective of the study is to determine if PPI use is associated with a reduced risk of having intestinal parasites. METHODS: We obtained electronic medical record data for all persons who received a stool ova and parasite (O & P) examination at our tertiary care academic medical center in Cleveland, Ohio, between January 2000 and September 2014...
September 11, 2017: Wilderness & Environmental Medicine
https://www.readbyqxmd.com/read/28911949/postprandial-high-resolution-impedance-manometry-identifies-mechanisms-of-non-response-to-proton-pump-inhibitors
#13
Rena Yadlapati, Michael Tye, Sabine Roman, Peter J Kahrilas, Katherine Ritter, John E Pandolfino
BACKGROUND & AIMS: Recognition of rumination and supragastric belching is often delayed as symptoms may be mistakenly attributed to gastroesophageal reflux disease (GERD). However, distinct from GERD, rumination and supragastric belching are more responsive to behavioral interventions than to acid-suppressive and anti-reflux therapies. Postprandial high-resolution impedance manometry (PP-HRIM) is an efficient method to identify rumination and belches. We investigated the distribution of postprandial profiles determined by PP-HRIM, and identified patient features associated with postprandial profiles among patients with non-response to proton pump inhibitors (PPIs)...
September 11, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28911847/analysis-of-structural-features-contributing-to-weak-affinities-of-ubiquitin-protein-interactions
#14
REVIEW
Ariel Cohen, Eran Rosenthal, Julia M Shifman
Ubiquitin is a small protein that enables one of the most common post-translational modifications, where the whole ubiquitin molecule is attached to various target proteins, forming mono- or polyubiquitin conjugations. As a prototypical multispecific protein, ubiquitin interacts non-covalently with a variety of proteins in the cell, including ubiquitin modifying enzymes and ubiquitin receptors that recognize signals from ubiquitin-conjugated substrates. To enable recognition of multiple targets and to support fast dissociation from the ubiquitin modifying enzymes, ubiquitin/protein interactions are characterized with low affinities, frequently in the higher μM and lower mM range...
September 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28910750/analysis-of-methylation-profiling-data-of-hyperplasia-and-primary-and-metastatic-endometrial-cancers
#15
Xihai Wu, Jilan Miao, Jingyan Jiang, Fangmei Liu
OBJECTIVE: Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. STUDY DESIGN: Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases...
September 1, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28910296/the-impact-of-the-protein-interactome-on-the-syntenic-structure-of-mammalian-genomes
#16
Isa Kristina Kirk, Nils Weinhold, Søren Brunak, Kirstine Belling
Conserved synteny denotes evolutionary preserved gene order across species. It is not well understood to which degree functional relationships between genes are preserved in syntenic blocks. Here we investigate whether protein-coding genes conserved in mammalian syntenic blocks encode gene products that serve the common functional purpose of interacting at protein level, i.e. connectivity. High connectivity among protein-protein interactions (PPIs) was only moderately associated with conserved synteny on a genome-wide scale...
2017: PloS One
https://www.readbyqxmd.com/read/28905803/diagnosis-and-treatment-of-gastroesophageal-reflux-disease-complicated-by-barrett-s-esophagus
#17
Andriy Stasyshyn
The aim of the study was to evaluate the effectiveness of a diagnostic and therapeutic algorithm for gastroesophageal reflux disease complicated by Barrett's esophagus in 46 patients. MATERIALS AND METHODS: A diagnostic and therapeutic algorithm for complicated GERD was developed. To describe the changes in the esophagus with reflux esophagitis, the Los Angeles classification was used. Intestinal metaplasia of the epithelium in the lower third of the esophagus was assessed using videoendoscopy, chromoscopy, and biopsy...
August 31, 2017: Polski Przeglad Chirurgiczny
https://www.readbyqxmd.com/read/28905435/isatin-induced-increase-in-the-affinity-of-human-ferrochelatase-and-adrenodoxin-reductase-interaction
#18
Pavel Ershov, Yuri Mezentsev, Andrey Gilep, Sergey Usanov, Olga Buneeva, Alexei Medvedev, Alexis Ivanov
Isatin (indol-2,3-dione) is an endogenous non-peptide regulator exhibiting a wide range of biological and pharmacological activities, which are poorly characterized in terms of their molecular mechanisms. Identification of many isatin-binding proteins in the mammalian brain and liver suggests that isatin may influence their functions. We have hypothesized that besides direct action on particular protein targets, isatin can act as a regulator of protein-protein interactions (PPIs). In this SPR-based biosensor study we have found that physiologically relevant concentrations of isatin (25-100 μM) increase affinity of interactions between human recombinant ferrochelatase (FECH) and NADPH-dependent adrenodoxin reductase (ADR)...
September 14, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28904190/exploring-the-human-nipah-virus-protein-protein-interactions
#19
Luis Martinez-Gil, Natalia M Vera-Velasco, Ismael Mingarro
Nipah virus is an emerging, highly pathogenic, zoonotic virus of the paramyxoviridiae family. Human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. Currently, we lack therapeutic or prophylactic treatments for Nipah virus. To develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. This aim led us to perform the present work, in which we identified (101) human-Nipah virus protein-protein interactions (PPIs), most of which (88) are novel...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28902459/exome-sequences-of-multiplex-multigenerational-families-reveal-schizophrenia-risk-loci-with-potential-implications-for-neurocognitive-performance
#20
Mark Z Kos, Melanie A Carless, Juan Peralta, Joanne E Curran, Ellen E Quillen, Marcio Almeida, August Blackburn, Lucy Blondell, David R Roalf, Michael F Pogue-Geile, Ruben C Gur, Harald H H Göring, Vishwajit L Nimgaonkar, Raquel E Gur, Laura Almasy
Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder...
September 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
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