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https://www.readbyqxmd.com/read/29784864/group-iia-secreted-phospholipase-a-2-in-human-serum-kills-commensal-but-not-clinical-enterococcus-faecium-isolates
#1
Fernanda L Paganelli, Helen L Leavis, Samantha He, Nina M van Sorge, Christine Payré, Gérard Lambeau, Rob J L Willems, Suzan H M Rooijakkers
Human innate immunity employs cellular and humoral mechanisms to facilitate rapid killing of invading bacteria. The direct killing of bacteria by human serum is mainly attributed to the activity of the complement system that forms pores in Gram-negative bacteria. Although Gram-positive bacteria are considered resistant to serum killing, we here uncover that normal human serum effectively kills Enterococcus faecium. Comparison of a well-characterized collection of commensal and clinical E. faecium isolates revealed that human serum specifically kills commensal E...
May 21, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29784858/production-of-staphylococcal-complement-inhibitor-scin-and-other-immune-modulators-during-the-early-stages-of-staphylococcus-aureus-biofilm-formation-in-a-mammalian-cell-culture-medium
#2
Andi R Sultan, Jasper W Swierstra, Nicole A Lemmens-den Toom, Susan V Snijders, Silvie Hansenová Maňásková, Annelies Verbon, Willem J B van Wamel
Immune modulators are known to be produced by matured biofilms and during different stages of planktonic growth of Staphylococcus aureus. Little is known about immune modulator production during the early stages of biofilm formation, thus raising the question: how does S. aureus protect itself from the innate immune responses at these stages? Therefore, we determined the production of the following immune modulators: chemotaxis inhibitory protein of staphylococci (CHIPS), staphylococcal complement inhibitor (SCIN), formyl peptide receptor-like 1 inhibitor, gamma-hemolysin component B, leukocidin D, E, and S, staphylococcal superantigen-like protein 1, 3, 5 and 9, and staphylococcal enterotoxin A...
May 21, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29780635/liquid-biopsy-for-lung-cancer-early-detection
#3
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Alessandro D'Aveni, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Chiara Lazzari, Giuseppe Altavilla, Rafael Rosell
Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients...
April 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29775936/from-hit-to-lead-structure-based-discovery-of-naphthalene-1-sulfonamide-derivatives-as-potent-and-selective-inhibitors-of-fatty-acid-binding-protein-4
#4
Ding-Ding Gao, Hui-Xia Dou, Hai-Xia Su, Ming-Ming Zhang, Ting Wang, Qiu-Feng Liu, Hai-Yan Cai, Hai-Peng Ding, Zhuo Yang, Wei-Liang Zhu, Ye-Chun Xu, He-Yao Wang, Ying-Xia Li
Fatty acid binding protein 4 (FABP4) plays a critical role in metabolism and inflammatory processes and therefore is a potential therapeutic target for immunometabolic diseases such as diabetes and atherosclerosis. Herein, we reported the identification of naphthalene-1-sulfonamide derivatives as novel, potent and selective FABP4 inhibitors by applying a structure-based design strategy. The binding affinities of compounds 16dk, 16do and 16du to FABP4, at the molecular level, are equivalent to or even better than that of BMS309403...
May 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29769288/targeted-complement-inhibition-salvages-stressed-neurons-and-inhibits-neuroinflammation-after-stroke-in-mice
#5
Ali Alawieh, E Farris Langley, Stephen Tomlinson
Ischemic stroke results from the interruption of blood flow to the brain resulting in long-term motor and cognitive neurological deficits, and it is a leading cause of death and disability. Current interventions focus on the restoration of blood flow to limit neuronal death, but these treatments have a therapeutic window of only a few hours and do not address post-stroke cerebral inflammation. The complement system, a component of the innate immune system, is activated by natural immunoglobulin M (IgM) antibodies that recognize neoepitopes expressed in the brain after ischemic stroke...
May 16, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29768958/bevacizumab-induced-atypical-hemolytic-uremic-syndrome-and-treatment-with-eculizumab
#6
Anusha Vakiti, Daulath Singh, Ravi Pilla, Muhamad A Moustafa, Kelly W Fitzpatrick
Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody used for the management of various solid malignancies including colorectal, lung, brain, renal, and ovarian cancers as well as age-related macular degeneration of the eye. It is a vascular endothelial growth factor inhibitor which exhibits its action by blocking the growth of blood vessels in cancerous tissue. Common side effects include hypertension, fatigue, headaches, and increased risk of infections. Atypical hemolytic uremic syndrome is a serious side effect associated with bevacizumab due to its anti-angiogenic effect...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29768491/plasmodium-falciparum-dipeptidyl-aminopeptidase-3-activity-is-important-for-efficient-erythrocyte-invasion-by-the-malaria-parasite
#7
Christine Lehmann, Michele Ser Ying Tan, Laura E de Vries, Ilaria Russo, Mateo Isidrio Sanchez, Daniel E Goldberg, Edgar Deu
Parasite egress from infected erythrocytes and invasion of new red blood cells are essential processes for the exponential asexual replication of the malaria parasite. These two tightly coordinated events take place in less than a minute and are in part regulated and mediated by proteases. Dipeptidyl aminopeptidases (DPAPs) are papain-fold cysteine proteases that cleave dipeptides from the N-terminus of protein substrates. DPAP3 was previously suggested to play an essential role in parasite egress. However, little is known about its enzymatic activity, intracellular localization, or biological function...
May 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29767896/-high-grade-serous-ovarian-cancer-2018-advances-and-controversies
#8
Nuria Mederos, Anita Wolfer, Patrice Mathevet, Maged Zaher, Apostolos Sarivalasis
The primary treatment of ovarian cancer consists in a complete surgical debulking followed by adjuvant chemotherapy combining platinum with taxanes. Despite this treatment, patient survival has remained stable over the last 20 years. Recently, advances in the sequence, regimens, and route of administration of treatment have enhanced effectiveness and reduced toxicity. Targeted anti-angiogenic therapy and recently PARP inhibitors are now complementing standard treatment and have improved patient progression-free survival...
May 16, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29765257/spotlight-on-certolizumab-pegol-in-the-treatment-of-axial-spondyloarthritis-efficacy-safety-and-place-in-therapy
#9
REVIEW
Josefina Marin, María Laura Acosta Felquer, Enrique R Soriano
Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of ankylosing spondylitis (AS) in the USA and for AS and non-radiographic axial spondyloarthritis (nr-axSpA) in Europe and in some Latin American countries. CZP lacks Fc region, preventing complement fixation and cytotoxicity mediated by antibody; CZP does not actively cross the placenta, unlike other TNFi. RAPID-axSpA study is a Phase III trial conducted in patients with AS and nr-axSpA as double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204...
2018: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/29762495/role-of-sdia-on-biofilm-formation-by-atypical-enteropathogenic-escherichia-coli
#10
Hebert F Culler, Samuel C F Couto, Juliana S Higa, Renato M Ruiz, Min J Yang, Vanessa Bueris, Marcia R Franzolin, Marcelo P Sircili
Atypical enteropathogenic Escherichia coli are capable to form biofilm on biotic and abiotic surfaces, regardless of the adherence pattern displayed. Several E. coli mechanisms are regulated by Quorum sensing (QS), including virulence factors and biofilm formation. Quorum sensing is a signaling system that confers bacteria with the ability to respond to chemical molecules known as autoinducers. Suppressor of division inhibitor (SdiA) is a QS receptor present in atypical enteropathogenic E. coli (aEPEC) that detects acyl homoserine lactone (AHL) type autoinducers...
May 15, 2018: Genes
https://www.readbyqxmd.com/read/29755649/evaluation-of-the-primitive-fraction-by-functional-in-vitro-assays-at-the-rna-and-dna-level-represents-a-novel-tool-for-complementing-molecular-monitoring-in-chronic-myeloid-leukemia
#11
María Sol Ruiz, María Belén Sanchez, Leandro Gutiérrez, Daniel Koile, Patricio Yankilevich, Celeste Mosqueira, Santiago Cranco, María Del Rosario Custidiano, Josefina Freitas, Cecilia Foncuberta, Beatriz Moiraghi, Carolina Pavlovsky, Mariel Ana Pérez, Verónica Ventriglia, Julio Sanchez Ávalos, José Mordoh, Irene Larripa, Michele Bianchini
Quantification of BCR-ABL1 mRNA levels in peripheral blood of chronic myeloid leukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI) treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a "functional leukemic burden" (FLB)...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29751512/screening-of-natural-product-derivatives-identifies-two-structurally-related-flavonoids-as-potent-quorum-sensing-inhibitors-against-gram-negative-bacteria
#12
Suvi Manner, Adyary Fallarero
Owing to the failure of conventional antibiotics in biofilm control, alternative approaches are urgently needed. Inhibition of quorum sensing (QS) represents an attractive target since it is involved in several processes essential for biofilm formation. In this study, a compound library of natural product derivatives ( n = 3040) was screened for anti-quorum sensing activity using Chromobacterium violaceum as reporter bacteria. Screening assays, based on QS-mediated violacein production and viability, were performed in parallel to identify non-bactericidal QS inhibitors (QSIs)...
May 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29748881/anti-inflammatory-effects-of-ivy-leaves-dry-extract-influence-on-transcriptional-activity-of-nf%C3%AE%C2%BAb
#13
Janka Schulte-Michels, Christina Keksel, Hanns Häberlein, Sebastian Franken
EA 575® is an ivy leaves dry extract (DER 5-7.5:1, 30% ethanol) used against diseases of the lower respiratory tract associated with productive cough. EA 575® improves symptoms associated with chronic inflammatory bronchial conditions. Compared to its bronchospasmolytic and secretolytic properties, the anti-inflammatory effects of EA 575® are mostly untried. Therefore, we addressed the question of whether the anti-inflammatory effect of EA 575® is due to an impact on the NFκB pathway. NFκB nuclear translocation was visualized by immunofluorescence in J774...
May 11, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29744595/synthesis-and-biocompatibility-of-an-argatroban-modified-polysulfone-membrane-that-directly-inhibits-thrombosis
#14
Xiao Fu, Jian-Ping Ning
Anticoagulation therapy plays a vital role in the prevention of blood clot formation during hemodialysis and hemofiltration, especially for critical care patients. Here, we synthesized a novel argatroban (Arg)-modified polysulfone (PSf) membrane for anticoagulation. Arg was grafted onto the PSF membrane via chemical modification to increase membrane hydrophilicity. Protein adsorption, coagulation, as well as activation of platelets and complement systems were greatly reduced on the Arg-modified PSf membrane...
May 9, 2018: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/29739922/bordetella-pertussis-isolates-vary-in-their-interactions-with-human-complement-components
#15
Charlotte Brookes, Irene Freire-Martin, Breeze Cavell, Frances Alexander, Stephen Taylor, Ruby Persaud, Norman Fry, Andrew Preston, Dimitri Diavatopoulos, Andrew Gorringe
Whooping cough is a re-emerging respiratory tract infection. It has become clear that there is a need for better understanding of protective immune responses and variation between Bordetella pertussis strains to aid the development of improved vaccines. In order to survive in the host, B. pertussis has evolved mechanisms to evade complement-mediated killing, including the ability to bind complement-regulatory proteins. Here we evaluate the variation in interactions with the complement system among recently isolated strains...
May 9, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29739594/comparative-proteomics-analysis-of-human-and-ruminant-milk-serum-reveals-variation-in-protection-and-nutrition
#16
Jing Lu, Shuwen Zhang, Lu Liu, Xiaoyang Pang, Changlu Ma, Shilong Jiang, Jiaping Lv
In present study, 198, 169, 213 and 128 proteins were identified and quantified in human, cow, goat and yak milk serum respectively by using proteomics techniques. Large variations were observed between human and ruminant milk proteins. Human milk contained higher concentration of mucosal immune response, complement proteins and regulators. The concentration of bactericidal proteins were relatively higher in ruminants milk. Human milk exclusively expressed proteins important for delivery or utilization of nutrients...
September 30, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29737533/a-randomized-first-in-human-healthy-volunteer-trial-of-bivv009-a-humanized-antibody-for-the-specific-inhibition-of-the-classical-complement-pathway
#17
Johann Bartko, Christian Schoergenhofer, Michael Schwameis, Christa Firbas, Martin Beliveau, Colin Chang, Jean-Francois Marier, Darrell Nix, James C Gilbert, Sandip Panicker, Bernd Jilma
Aberrant activation of the classical complement pathway is the common underlying pathophysiology of orphan diseases such as bullous pemphigoid, antibody-mediated rejection of organ transplants, cold agglutinin disease and warm autoimmune haemolytic anaemia. Therapeutic options for these complement-mediated disorders are limited and BIVV009, a humanized monoclonal antibody directed against complement factor C1s, may be potentially useful for inhibition of the classical complement pathway. A phase-1, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single and multiple doses of BIVV009 or placebo was conducted in 64 volunteers to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic profiles...
May 8, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29735903/pharmaceutical-machine-learning-virtual-high-throughput-screens-identifying-promising-and-economical-small-molecule-inhibitors-of-complement-factor-c1s
#18
Jonathan J Chen, Lyndsey N Schmucker, Donald P Visco
When excessively activated, C1 is insufficiently regulated, which results in tissue damage. Such tissue damage causes the complement system to become further activated to remove the resulting tissue damage, and a vicious cycle of activation/tissue damage occurs. Current Food and Drug Administration approved treatments include supplemental recombinant C1 inhibitor, but these are extremely costly and a more economical solution is desired. In our work, we have utilized an existing data set of 136 compounds that have been previously tested for activity against C1...
May 7, 2018: Biomolecules
https://www.readbyqxmd.com/read/29733904/c1qtnf1-attenuates-angiotensin-ii-induced-cardiac-hypertrophy-via-activation-of-the-ampka-pathway
#19
Leiming Wu, Lu Gao, Dianhong Zhang, Rui Yao, Zhen Huang, Binbin Du, Zheng Wang, Lili Xiao, Pengcheng Li, Yapeng Li, Cui Liang, Yanzhou Zhang
RATIONALE: Complement C1q tumor necrosis factor related proteins (C1QTNFs) have been reported to have diverse biological influence on the cardiovascular system. C1QTNF1 is a member of the CTRP superfamily. C1QTNF1 is expressed in the myocardium; however, its function in myocytes has not yet been investigated. OBJECTIVE: To systematically investigate the roles of C1QTNF1 in angiotensin II (Ang II)-induced cardiac hypertrophy. METHODS AND RESULTS: C1QTNF1 knock-out mice were used with the aim of determining the role of C1QTNF1 in cardiac hypertrophy in the adult heart...
May 4, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29732117/isoform-selective-activity-based-profiling-of-erk-signaling
#20
Myungsun Shin, Caroline E Franks, Ku-Lung Hsu
Extracellular signal-regulated kinases (ERKs) mediate downstream signaling of RAS-RAF-MEK as key regulators of the mitogen-activated protein kinase (MAPK) pathway. Activation of ERK signaling is a hallmark of cancer and upstream MAPK proteins have been extensively pursued as drug targets for cancer therapies. However, the rapid rise of resistance to clinical RAF and MEK inhibitors has prompted interest in targeting ERK (ERK1 and ERK2 isoforms) directly for cancer therapy. Current methods for evaluating activity of inhibitors against ERK isoforms are based primarily on analysis of recombinant proteins...
March 7, 2018: Chemical Science
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