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https://www.readbyqxmd.com/read/28819150/the-g%C3%AE-i-giv-binding-interface-is-a-druggable-protein-protein-interaction
#1
Vincent DiGiacomo, Alain Ibáñez de Opakua, Maria P Papakonstantinou, Lien T Nguyen, Nekane Merino, Juan B Blanco-Canosa, Francisco J Blanco, Mikel Garcia-Marcos
Heterotrimeric G proteins are usually activated by the guanine-nucleotide exchange factor (GEF) activity of GPCRs. However, some non-receptor proteins are also GEFs. GIV (a.k.a Girdin) was the first non-receptor protein for which the GEF activity was ascribed to a well-defined protein sequence that directly binds Gαi. GIV expression promotes metastasis and disruption of its binding to Gαi blunts the pro-metastatic behavior of cancer cells. Although this suggests that inhibition of the Gαi-GIV interaction is a promising therapeutic strategy, protein-protein interactions (PPIs) are considered poorly "druggable" targets requiring case-by-case validation...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814829/antibiotic-susceptibility-heteroresistance-and-updated-treatment-strategies-in-helicobacter-pylori-infection
#2
REVIEW
Maria Teresa Mascellino, Barbara Porowska, Massimiliano De Angelis, Alessandra Oliva
In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28812330/black-and-minority-ethnic-group-involvement-in-health-and-social-care-research-a-systematic-review
#3
REVIEW
Shoba Dawson, Stephen M Campbell, Sally J Giles, Rebecca L Morris, Sudeh Cheraghi-Sohi
BACKGROUND: Patient and public involvement (PPI) in research is growing internationally, but little is known about black and minority ethnic (BME) involvement and the factors influencing their involvement in health and social care research. OBJECTIVES: To characterize and critique the empirical literature on BME-PPI involvement in health and social care research. SEARCH STRATEGY: Systematic searches of six electronic bibliographic databases were undertaken, utilizing both MeSH and free-text terms to identify international empirical literature published between 1990 and 2016...
August 15, 2017: Health Expectations: An International Journal of Public Participation in Health Care and Health Policy
https://www.readbyqxmd.com/read/28811716/development-and-validation-of-a-simple-and-multifaceted-instrument-gerd-test-for-the-clinical-evaluation-of-gastroesophageal-reflux-and-dyspeptic-symptoms
#4
Koji Nakada, Nobuyuki Matsuhashi, Katsuhiko Iwakiri, Atsushi Oshio, Takashi Joh, Kazuhide Higuchi, Ken Haruma
AIM: To evaluate the psychometric properties of a newly developed questionnaire, known as the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test (GERD-TEST), in patients with GERD. METHODS: Japanese patients with predominant GERD symptoms recruited according to the Montreal definition were treated for 4 wk using a standard dose of proton pump inhibitor (PPI). The GERD-TEST and the Medical Outcome Study Short Form-8 Health Survey (SF-8) were administered at baseline and after 4 wk of treatment...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28811554/a-new-method-to-investigate-the-catalytic-mechanism-of-yhde-pyrophosphatase-by-using-a-pyrophosphate-fluorescence-probe
#5
Qingya Shen, Hongwei Tan, Guo-Wen Xing, Jimin Zheng, Zongchao Jia
YhdE is a Maf (multicopy associated filamentation) proteins from Escherichia coli which exhibits pyrophosphatase activity towards selected nucleotides, although its catalytic mechanism remains unclear. Herein we used a novel fluorescence probe (4-isoACBA-Zn(II) complex) to characterize the enzymatic properties of YhdE and its mutant, establishing a new method for assaying pyrophosphatase catalytic function. Our results reveal for the first time that the new fluorescence sensor confers high sensitivity and specificity and pyrophosphate (PPi) is the direct catalytic product of YhdE...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811466/time-lapse-crystallography-snapshots-of-a-double-strand-break-repair-polymerase-in-action
#6
Joonas A Jamsen, William A Beard, Lars C Pedersen, David D Shock, Andrea F Moon, Juno M Krahn, Katarzyna Bebenek, Thomas A Kunkel, Samuel H Wilson
DNA polymerase (pol) μ is a DNA-dependent polymerase that incorporates nucleotides during gap-filling synthesis in the non-homologous end-joining pathway of double-strand break repair. Here we report time-lapse X-ray crystallography snapshots of catalytic events during gap-filling DNA synthesis by pol μ. Unique catalytic intermediates and active site conformational changes that underlie catalysis are uncovered, and a transient third (product) metal ion is observed in the product state. The product manganese coordinates phosphate oxygens of the inserted nucleotide and PPi...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28811070/evaluation-of-sequence-variability-in-hiv-1-gp41-c-peptide-helix-grafted-proteins
#7
Rachel L Tennyson, Susanne N Walker, Terumasa Ikeda, Reuben S Harris, Brian R McNaughton
Many therapeutically-relevant protein-protein interactions (PPIs) have been reported that feature a helix and helix-binding cleft at the interface. Given this, different approaches to disrupting such PPIs have been developed. While short peptides (<15 amino acids) typically do not fold into a stable helix, researchers have reported chemical approaches to constraining helix structure. However, these approaches rely on laborious, and often expensive, chemical synthesis and purification. Our premise is that protein-based solutions that stabilize a therapeutically-relevant helix offer a number of advantages...
August 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28810559/identification-of-key-genes-and-pathways-associated-with-obesity-in-children
#8
Ling Li, Guangyu Wang, Ning Li, Haiyan Yu, Jianping Si, Jiwen Wang
The present study aimed to identify potential key genes and pathways in obese children in order to explore possible molecular mechanisms associated with child obesity. The array dataset GSE29718 was downloaded from the Gene Expression Omnibus database. Subcutaneous adipose tissue samples derived from 7 obese children and 8 lean children were selected for the analysis. Differentially expressed genes (DEGs) in samples from obese children compared with those from lean children were analyzed by the limma package...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810074/preliminary-data-on-the-role-of-emotional-intelligence-in-moderating-the-link-between-psychopathy-and-aggression-in-a-nonforensic-sample
#9
Tiziana Lanciano, Antonietta Curci, Francesca Guglielmi, Emanuela Soleti, Ignazio Grattagliano
This short report presents preliminary data on the role of emotional intelligence (EI) in moderating the relationship between psychopathy and aggression in a nonforensic sample. A sample of 109 volunteer men was administered the Psychopathic Personality Inventory-Revised (PPI-R), the Reactive-Proactive Aggression Questionnaire, and the Mayer-Salovey-Caruso emotional intelligence Test in individual sessions. Correlation and moderation analyzes showed that, at low levels of EI (in terms of strategic ability to understand and manage one's own and others' emotions), people scoring high on the total PPI-R and impulsivity dimension seemed to be both reactively and proactively aggressive...
August 15, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28807887/an-integrative-system-biology-approach-to-unravel-potential-drug-candidates-for-multiple-age-related-disorders
#10
Isha Srivastava, Pooja Khurana, Mohini Yadav, Yasha Hasija
Aging, though an inevitable part of life, is becoming a worldwide social and economic problem. Healthy aging is usually marked by low probability of age related disorders. Good therapeutic approaches are still in need to cure age related disorders. Occurrence of more than one ARD in an individual, expresses the need of discovery of such target proteins, which can affect multiple ARDs. Advanced scientific and medical research technologies throughout last three decades have arrived to the point where lots of key molecular determinants affect human disorders can be examined thoroughly...
August 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28806587/elucidation-of-host-pathogen-protein-protein-interactions-to-uncover-mechanisms-of-host-cell-rewiring
#11
REVIEW
Charlotte Nicod, Amir Banaei-Esfahani, Ben C Collins
Infectious diseases are the result of molecular cross-talks between hosts and their pathogens. These cross-talks are in part mediated by host-pathogen protein-protein interactions (HP-PPI). HP-PPI play crucial roles in infections, as they may tilt the balance either in favor of the pathogens' spread or their clearance. The identification of host proteins targeted by viral or bacterial pathogenic proteins necessary for the infection can provide insights into their underlying molecular mechanisms of pathogenicity, and potentially even single out pharmacological intervention targets...
August 11, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28805368/pyrophosphate-recognition-and-sensing-in-water-using-bis-zinc-ii-dipicolylamino-functionalized-peptides
#12
Katrina A Jolliffe
Phosphate oxoanions and phosphorylated biomolecules (such as nucleotides, lipids, and proteins) play key roles in a wide range of biological processes. The ability to selectively detect these ions in the presence of each other has numerous applications in biochemistry and biomedicine. However, receptors and sensors that can discriminate between polyphosphate species with high selectivity and in biologically relevant conditions are rare. In this Account, we show how peptides (both cyclic and linear) can be used to position two zinc(II)dipicolylamine [Zn(II)DPA] binding sites in an appropriate arrangement to provide selective binding of pyrophosphate (PPi) in the presence of other polyphosphate species, including ATP, and in complex media such as cell growth buffer...
August 14, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28802714/in-silico-structure-based-approaches-to-discover-protein-protein-interaction-targeting-drugs
#13
REVIEW
Woong-Hee Shin, Charles W Christoffer, Daisuke Kihara
A core concept behind modern drug discovery is finding a small molecule that modulates a function of a target protein. This concept has been successfully applied since the mid-1970s. However, the efficiency of drug discovery is decreasing because the druggable target space in the human proteome is limited. Recently, protein-protein interaction (PPI) has been identified as an emerging target space for drug discovery. PPI plays a pivotal role in biological pathways including diseases. Current human interactome research suggests that the number of PPIs ranges from 130,000 to 650,000, and only a small number of them have been targeted as drug targets...
August 9, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28801980/effects-of-proton-pump-inhibitors-and-famotidine-on-elimination-of-plasma-methotrexate-evaluation-of-drug-drug-interactions-mediated-by-organic-anion-transporter-3
#14
Katsuya Narumi, Yu Sato, Masaki Kobayashi, Ayako Furugen, Kumiko Kasashi, Takehiro Yamada, Takanori Teshima, Ken Iseki
Methotrexate (MTX) is an antifolate agent used in the treatment of numerous types of cancer, and eliminated by active tubular secretion via organic anion transporter 3 (OAT3). Gastric antisecretory drugs, such as proton pump inhibitors (PPIs) and histamine H2 receptor antagonists, are widely used among patients with cancer in clinical practice. The aim of the present study was to analyze the potential drug-drug interactions between MTX and gastric antisecretory drugs in high-dose MTX (HD-MTX) therapy. We retrospectively analyzed the impact of PPIs on the plasma MTX concentration on 73 cycles of HD-MTX therapy performed in 43 patients...
August 12, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28801194/medial-septum-modulates-hippocampal-gamma-activity-and-prepulse-inhibition-in-an-n-methyl-d-aspartate-receptor-antagonist-model-of-schizophrenia
#15
L Stan Leung, Jingyi Ma
We reviewed the participation of the septohippocampal system in an animal model of schizophrenia that was acutely induced by systemic injection of an N-methyl-d-aspartate (NMDA) receptor antagonist such as phencyclidine, MK-801 and ketamine. The NMDA receptor antagonist-induced model of schizophrenia is characterized by behavioral and electrophysiological disruptions, including a decrease in prepulse inhibition of the acoustic startle response (PPI), hyperlocomotion, decrease in gating of hippocampal auditory evoked potentials and robust increase in hippocampal gamma (30-100Hz) oscillations...
August 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28800317/identification-of-prostate-cancer-hub-genes-and-therapeutic-agents-using-bioinformatics-approach
#16
Enhao Fang, Xiuqing Zhang, Qi Wang, Daoming Wang
BACKGROUND: Prostate cancer (PCa) is the most common and the second leading cause of cancer-related death among men in America. As the molecular mechanism of PCa has not yet been completely discovered, identification of hub genes and potential drug of this disease is an important area of research that could provide new insights into exploring the mechanisms underlying PCa. OBJECTIVE: The aim of this study was to identify potential biomarkers and novel drug for prostate cancer treatment...
July 30, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28800146/the-relationship-between-open-versus-normal-contact-point-and-inter-proximal-papilla-dimensions-in-periodontally-healthy-young-adults-a-controlled-clinical-trial
#17
Ronaldo Barcellos de Santana, Jose Luis Carneiro de Miranda, Carolina Miller Mattos de Santana
AIM: The gingival architecture is determined by the spatial orientation of the gingival zenith (GZ) and the interdental papillae (IP). Among the factors commonly associated with the presence and morphology of the IP, the contact point (CP) and the interdental distance relationships have been considered the most important. The objective of the present controlled clinical trial was to evaluate the role of the CP in determining the clinical and morphometric parameters of the interdental papilla...
August 11, 2017: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/28799115/remnant-gastropathy-due-to-bile-reflux-after-roux-en-y-gastric-bypass-a-unique-cause-of-abdominal-pain-and-successful-treatment-with-ursodiol
#18
Nitin Kumar, Christopher C Thompson
BACKGROUND: Chronic abdominal pain can occur after Roux-en-Y gastric bypass (RYGB), and can remain unexplained despite extensive investigation. Bile can pool in the gastric remnant and create a bile reflux gastropathy. The aim of this study was to assess gastric remnant findings in patients with RYGB and chronic abdominal pain of unclear etiology, and to determine the effectiveness of ursodiol therapy for patients with confirmed remnant gastropathy. METHODS: All consecutive patients with RYGB and a diagnosis of chronic abdominal pain, and a negative diagnostic workup (including physical examination, routine laboratory work, cross-sectional imaging, and standard upper endoscopy), who underwent device-assisted enteroscopy for evaluation of the gastric remnant, were included...
August 10, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28798383/novel-giardicidal-compounds-bearing-proton-pump-inhibitor-scaffold-proceeding-through-triosephosphate-isomerase-inactivation
#19
B Hernández-Ochoa, G Navarrete-Vázquez, C Nava-Zuazo, A Castillo-Villanueva, S T Méndez, A Torres-Arroyo, S Gómez-Manzo, J Marcial-Quino, M Ponce-Macotela, Y Rufino-González, M Martínez-Gordillo, G Palencia-Hernández, N Esturau-Escofet, E Calderon-Jaimes, J Oria-Hernández, H Reyes-Vivas
Giardiasis is a worldwide parasitic disease that affects mainly children and immunosuppressed people. Side effects and the emergence of resistance over current used drugs make imperative looking for new antiparasitics through discovering of new biological targets and designing of novel drugs. Recently, it has determined that gastric proton-pump inhibitors (PPI) have anti-giardiasic activity. The glycolytic enzyme, triosephosphate isomerase (GlTIM), is one of its potential targets. Therefore, we employed the scaffold of PPI to design new compounds aimed to increase their antigiardial capacity by inactivating GlTIM...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797928/comparison-of-planar-pet-and-well-counter-measurements-of-total-tumor-radioactivity-in-a-mouse-xenograft-model
#20
Michael V Green, Jurgen Seidel, Mark R Williams, Karen J Wong, Anita Ton, Falguni Basuli, Peter L Choyke, Elaine M Jagoda
INTRODUCTION: Quantitative small animal radionuclide imaging studies are often carried out with the intention of estimating the total radioactivity content of various tissues such as the radioactivity content of mouse xenograft tumors exposed to putative diagnostic or therapeutic agents. We show that for at least one specific application, positron projection imaging (PPI) and PET yield comparable estimates of absolute total tumor activity and that both of these estimates are highly correlated with direct well-counting of these same tumors...
June 30, 2017: Nuclear Medicine and Biology
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