keyword
MENU ▼
Read by QxMD icon Read
search

complement inhibitor

keyword
https://www.readbyqxmd.com/read/28102344/predicting-drug-combination-index-and-simulating-the-network-regulation-dynamics-by-mathematical-modeling-of-drug-targeted-egfr-erk-signaling-pathway
#1
Lu Huang, Yuyang Jiang, Yuzong Chen
Synergistic drug combinations enable enhanced therapeutics. Their discovery typically involves the measurement and assessment of drug combination index (CI), which can be facilitated by the development and applications of in-silico CI predictive tools. In this work, we developed and tested the ability of a mathematical model of drug-targeted EGFR-ERK pathway in predicting CIs and in analyzing multiple synergistic drug combinations against observations. Our mathematical model was validated against the literature reported signaling, drug response dynamics, and EGFR-MEK drug combination effect...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097887/pseudokinases-update-on-their-functions-and-evaluation-as-new-drug-targets
#2
Dominic P Byrne, Daniel M Foulkes, Patrick A Eyers
The pseudokinase complement of the human kinase superfamily consists of approximately 60 signaling proteins, which lacks one or more of the amino acids typically required to correctly align ATP and metal ions, and phosphorylate protein substrates. Recent studies in the pseudokinase field have begun to expose the biological relevance of pseudokinases, which are now thought to perform a diverse range of physiological roles and are connected to a multitude of human diseases, including cancer. In this review, we discuss how and why members of the 'pseudokinome' represent important new targets for drug discovery, and describe how knowledge of protein structure and function provides informative clues to help guide the rational chemical design or repurposing of inhibitors to target pseudokinases...
January 18, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28096160/determinants-of-antibacterial-spectrum-and-resistance-potential-of-the-elongation-factor-g-inhibitor-argyrin-b-in-key-gram-negative-pathogens
#3
Adriana K Jones, Angela L Woods, Kenneth T Takeoka, Xiaoyu Shen, Jun-Rong Wei, Ruth E Caughlan, Charles R Dean
Argyrins are natural products with antibacterial activity against Gram-negative pathogens such as P. aeruginosa, B. multivorans and S. maltophilia We previously showed that argyrin B targets elongation factor G (FusA). Here we show that Argyrin B activity against P. aeruginosa PAO1 (MIC = 8 μg/mL) was not affected by deletion of the MexAB-OprM, MexXY-OprM, MexCD-OprJ or MexEF-OprN efflux pumps. However, argyrin B induced expression of MexXY causing a slight but reproducible antagonism with the MexXY substrate antibiotic ciprofloxacin...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28094391/advantages-of-an-optical-nanosensor-system-for-the-mechanistic-analysis-of-a-novel-topoisomerase-i-targeting-drug-a-case-study
#4
Marie B Andersen, Cinzia Tesauro, María Gonzalez, Emil L Kristoffersen, Concepción Alonso, Gloria Rubiales, Andrea Coletta, Rikke Frøhlich, Magnus Stougaard, Yi-Ping Ho, Francisco Palacios, Birgitta R Knudsen
The continuous need for the development of new small molecule anti-cancer drugs calls for easily accessible sensor systems for measuring the effect of vast numbers of new drugs on their potential cellular targets. Here we demonstrate the use of an optical DNA biosensor to unravel the inhibitory mechanism of a member of a new family of small molecule human topoisomerase I inhibitors, the so-called indeno-1,5-naphthyridines. By analysing human topoisomerase I catalysis on the biosensor in the absence or presence of added drug complemented with a few traditional assays, we demonstrate that the investigated member of the indeno-1,5-naphthyridine family inhibited human topoisomerase I activity by blocking enzyme-DNA dissociation...
January 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28092989/therapeutic-complement-inhibition-a-promising-approach-for-treatment-of-neuroimmunological-diseases
#5
Kjara S Pilch, Peter Spaeth, Yuki Nobuhiro, Benjamin R Wakerley
Autoimmunity is an important cause of disease both in the central and peripheral nervous systems. Aetiologies and clinical manifestations are complex and heterogeneous. Inappropriate control of complement activation at inappropriate sites has been recognized as a major determinant in several neurological conditions, including Guillain-Barré syndrome and neuromyelitis optica. In each case pathogenesis is thought to be associated with generation of autoantibodies which upon binding guide activation of the complement system to self-tissue...
January 17, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28092392/the-in-silico-identification-of-human-bile-salt-export-pump-abcb11-inhibitors-associated-with-cholestatic-drug-induced-liver-injury
#6
Lili Xi, Jia Yao, Yuhui Wei, Xin'an Wu, Xiaojun Yao, Huanxiang Liu, Shuyan Li
Drug-induced liver injury (DILI) is one of the major causes of drug attrition and failure. Currently, there is increasing evidence that direct inhibition of the human bile salt export pump (BSEP/ABCB11) by drugs and/or metabolites is one of the most important mechanisms of cholestatic DILI. In the present study, we employ two in silico methods, random forest (RF) and the pharmacophore method, to recognize potential BSEP inhibitors that could cause cholestatic DILI, with the aim of mitigating the risk of cholestatic DILI to some extent...
January 16, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28076311/biomarkers-of-acute-kidney-injury-the-pathway-from-discovery-to-clinical-adoption
#7
Kianoush Kashani, Wisit Cheungpasitporn, Claudio Ronco
Acute kidney injury (AKI) is a common complication of critical illnesses and has a significant impact on outcomes, including mortality and morbidities. Unfortunately, apart from prophylactic measures, no effective treatment for this syndrome is known. Therefore, early recognition of AKI not only can provide better opportunities for preventive interventions, but also opens many gates for research and development of effective therapeutic options. Over the last few years, several new AKI biomarkers have been discovered and validated to improve early detection, differential diagnosis, and differentiation of patients into risk groups for progressive renal failure, need for renal replacement therapy (RRT), or death...
January 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28069958/properdin-binding-to-complement-activating-surfaces-depends-on-initial-c3b-deposition
#8
Morten Harboe, Christina Johnson, Stig Nymo, Karin Ekholt, Camilla Schjalm, Julie K Lindstad, Anne Pharo, Bernt Christian Hellerud, Kristina Nilsson Ekdahl, Tom Eirik Mollnes, Per H Nilsson
Two functions have been assigned to properdin; stabilization of the alternative convertase, C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversial. The presence of nonphysiological aggregates in purified properdin preparations and experimental models that do not allow discrimination between the initial binding of properdin and binding secondary to C3b deposition is a critical factor contributing to this controversy. In previous work, by inhibiting C3, we showed that properdin binding to zymosan and Escherichia coli is not a primary event, but rather is solely dependent on initial C3 deposition...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28063950/dietary-alpha-linolenic-acid-linoleic-acid-ratios-modulate-immune-response-physical-barrier-and-related-signaling-molecules-mrna-expression-in-the-gills-of-juvenile-grass-carp-ctenopharyngodon-idella
#9
Yun-Yun Zeng, Lin Feng, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study was conducted to explore the possible effects of dietary ALA/LNA ratios on the gill immunity, tight junction and antioxidant capacity, and the related signaling factor mRNA levels of juvenile grass carp (Ctenopharyngodon idella). Fish were fed diets with different ALA/LNA ratios (0.01, 0.34, 0.68, 1.03, 1.41, 1.76 and 2.15) for 60 days. The present results showed that ALA/LNA ratio of 1.03 significantly enhanced lysozyme and acid phosphatase activities, complement 3 contents, promoted mRNA levels of antimicrobial peptides (Hepcidin and liver expression antimicrobial peptide-2), anti-inflammatory cytokines (interleukin 10 and transforming growth factor β1) and inhibitor protein κBα, whereas suppressed pro-inflammatory cytokines (interleukin 1β, interleukin 8, tumor necrosis factor a and interferon γ2), and signal molecules (IκB kinase β, IκB kines γ and nuclear factor κB p65) mRNA levels in the gill, indicating that optimal dietary ALA/LNA ratio improve gill immunity of juvenile fish...
January 4, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28063198/functional-and-structural-studies-on-the-neisseria-gonorrhoeae-gmha-the-first-enzyme-in-the-glycero-manno-heptose-biosynthesis-pathways-demonstrate-a-critical-role-in-lipooligosaccharide-synthesis-and-gonococcal-viability
#10
Igor H Wierzbicki, Ryszard A Zielke, Konstantin V Korotkov, Aleksandra E Sikora
Sedoheptulose-7-phosphate isomerase, GmhA, is the first enzyme in the biosynthesis of nucleotide-activated-glycero-manno-heptoses and an attractive, yet underexploited, target for development of broad-spectrum antibiotics. We demonstrated that GmhA homologs in Neisseria gonorrhoeae and N. meningitidis (hereafter called GmhAGC and GmhANM , respectively) were interchangeable proteins essential for lipooligosaccharide (LOS) synthesis, and their depletion had adverse effects on neisserial viability. In contrast, the Escherichia coli ortholog failed to complement GmhAGC depletion...
January 7, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28061864/identification-of-brassinosteroid-genes-in-brachypodium-distachyon
#11
Claudia Corvalán, Sunghwa Choe
BACKGROUND: Brassinosteroids (BRs) are steroidal phytohormones that are involved in diverse physiological processes and affect many important traits, such as plant stature, stress tolerance, leaf angle, fertility, and grain filling. BR signaling and biosynthetic pathways have been studied in various plants, such as the model dicot Arabidopsis thaliana; however, relatively little is known about these pathways in monocots. RESULTS: To characterize BR-related processes in the model grass Brachypodium distachyon, we studied the response of these plants to the specific BR biosynthesis inhibitor, propiconazole (Pcz)...
January 6, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28058212/complement-related-kidney-diseases-recurrence-after-transplantation
#12
REVIEW
Maurizio Salvadori, Elisabetta Bertoni
The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss after kidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome (HUS), the membranoproliferative glomerulonephritis (MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital (genetic) or acquired (auto-antibodies) modifications of the alternative pathway of complement...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28057017/the-brain-penetrating-cxcr4-antagonist-prx177561-increases-the-antitumor-effects-of-bevacizumab-and-sunitinib-in-preclinical-models-of-human-glioblastoma
#13
Giovanni Luca Gravina, Andrea Mancini, Francesco Marampon, Alessandro Colapietro, Simona Delle Monache, Roberta Sferra, Flora Vitale, Peter J Richardson, Lee Patient, Stephen Burbidge, Claudio Festuccia
BACKGROUND: Glioblastoma recurrence after treatment with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is characterized by a highly infiltrative and malignant behavior that renders surgical excision and chemotherapy ineffective. It has been demonstrated that anti-VEGF/VEGFR therapies control the invasive phenotype and that relapse occurs through the increased activity of CXCR4. We therefore hypothesized that combining bevacizumab or sunitinib with the novel CXCR4 antagonist, PRX177561, would have superior antitumor activity...
January 5, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28056780/kinmap-a-web-based-tool-for-interactive-navigation-through-human-kinome-data
#14
Sameh Eid, Samo Turk, Andrea Volkamer, Friedrich Rippmann, Simone Fulle
BACKGROUND: Annotations of the phylogenetic tree of the human kinome is an intuitive way to visualize compound profiling data, structural features of kinases or functional relationships within this important class of proteins. The increasing volume and complexity of kinase-related data underlines the need for a tool that enables complex queries pertaining to kinase disease involvement and potential therapeutic uses of kinase inhibitors. RESULTS: Here, we present KinMap, a user-friendly online tool that facilitates the interactive navigation through kinase knowledge by linking biochemical, structural, and disease association data to the human kinome tree...
January 5, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28055124/interventions-for-the-management-of-oral-lichen-planus-a-review-of-the-conventional-and-novel-therapies
#15
REVIEW
Shikha Gupta, Sujoy Ghosh, Sunita Gupta
OBJECTIVE: This narrative review focuses on the rationale & role of conventional and newer therapies in the management of Oral lichen planus with emphasis on randomized controlled trials reported over 2 decades. MATERIALS AND METHODS: Literature search was conducted to identify randomized controlled trials for management of OLP from 1/1/1995 to 31/12/2015; Medline, and Cochrane databases complemented with manual search was used. Primary outcome as resolution of pain was evaluated with analysis of clinical resolution of erythema and ulceration as secondary outcome...
January 5, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28054006/western-blot-data-using-two-distinct-anti-o-glcnac-monoclonal-antibodies-showing-unique-glycosylation-status-on-cellular-proteins-under-2-deoxy-d-glucose-treatment
#16
Tetsuya Okuda
Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation) is one of the post transcriptional modifications occurring on cellular proteins. This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG)-treated human teratocarcinoma NCCIT cells in support of the research article entitled "A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis" (Okuda et al...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/28045905/human-leukocytes-kill-brugia-malayi-microfilariae-independently-of-dna-based-extracellular-trap-release
#17
Ciaran J McCoy, Barbara J Reaves, Steeve Giguère, Ruby Coates, Balázs Rada, Adrian J Wolstenholme
BACKGROUND: Wuchereria bancrofti, Brugia malayi and Brugia timori infect over 100 million people worldwide and are the causative agents of lymphatic filariasis. Some parasite carriers are amicrofilaremic whilst others facilitate mosquito-based disease transmission through blood-circulating microfilariae (Mf). Recent findings, obtained largely from animal model systems, suggest that polymorphonuclear leukocytes (PMNs) contribute to parasitic nematode-directed type 2 immune responses. When exposed to certain pathogens PMNs release extracellular traps (NETs) in the form of chromatin loaded with various antimicrobial molecules and proteases...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28045880/targeted-complement-inhibition-protects-vascularized-composite-allografts-from-acute-graft-injury-and-prolongs-graft-survival-when-combined-with-subtherapeutic-cyclosporine-a-therapy
#18
Peng Zhu, Stefanie R Bailey, Biao Lei, Chrystal M Paulos, Carl Atkinson, Stephen Tomlinson
BACKGROUND: Recipients of vascularized composite allografts require aggressive and life-long immunosuppression, and since the surgery is usually performed in nonlife threatening situations, the development of strategies to minimize immunosuppression is especially pertinent for this procedure. We investigated how complement affects acute graft injury, alloimmunity, and immunosuppressive therapy. METHODS: Vascularized composite allografts were transplanted from Balb/C to C57BL/6 mice that were complement deficient (C3 or double C3a Receptor (R)/C5aR), or treated with a targeted complement inhibitor (CR2-Crry)...
December 30, 2016: Transplantation
https://www.readbyqxmd.com/read/28036258/epstein-barr-virus-ebna2-directs-doxorubicin-resistance-of-b-cell-lymphoma-through-ccl3-and-ccl4-mediated-activation-of-nf-%C3%AE%C2%BAb-and-btk
#19
Joo Hyun Kim, Won Seog Kim, Jung Yong Hong, Kung Ju Ryu, Seok Jin Kim, Chaehwa Park
Epstein-Barr virus (EBV)-encoded nuclear antigen, EBNA2, expressed in EBV-infected B lymphocytes is critical for lymphoblastoid cell growth. Microarray profiling and cytokine array screening revealed that EBNA2 is associated with upregulation of the chemokines CCL3 and CCL4 in lymphoma cells. Depletion or inactivation of CCL3 or CCL4 sensitized DLBCL cells to doxorubicin. Our results indicate that EBV influences cell survival via an autocrine mechanism whereby EBNA2 increases CCL3 and CCL4, which in turn activate the Btk and NF-κB pathways, contributing to doxorubicin resistance of B lymphoma cells...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031371/screening-for-novel-small-molecule-inhibitors-targeting-the-assembling-of-influenza-virus-polymerase-complex-by-a-bilc-based-reporter-system
#20
Chunfeng Li, Zining Wang, Yang Cao, Lulan Wang, Jingyun Ji, Zhigao Chen, Tao Deng, Taijiao Jiang, Genhong Cheng, F Xiao-Feng Qin
: Influenza virus RNA-dependent RNA polymerase consists of three viral protein subunits: PA, PB1 and PB2. Protein-protein interactions (PPIs) of these subunits play pivotal roles in assembling the functional polymerase complex, which is essential for the replication and transcription of influenza virus RNA. Here we developed a highly specific and robust bimolecular luminescence complementation (BiLC) reporter system to facilitate the investigation for influenza virus polymerase complex formation...
December 28, 2016: Journal of Virology
keyword
keyword
39808
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"