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https://www.readbyqxmd.com/read/28941979/proteolytic-degradation-and-inflammation-play-critical-roles-in-polypoidal-choroidal-vasculopathy
#1
Sandeep Kumar, Hiroyuki Nakashizuka, Alex Jones, Alyssia Lambert, Xuchen Zhao, Megan Shen, Mackenzie Parker, Shixian Wang, Zachary Berriochoa, Amrita Fnu, Stephanie VanBeuge, Patricia Chévez-Barrios, Mark Tso, Jon Rainier, Yingbin Fu
Polypoidal choroidal vasculopathy (PCV) is a common subtype of wet age-related macular degeneration (AMD) in Asian populations while choroidal neovascularization (CNV) is the typical subtype in Western populations. The etiology of PCV is unknown. By comparing the phenotype of a PCV mouse model expressing protease HTRA1 in retinal pigment epithelium with transgenic mice expressing the inactive HTRA1(S328A), we showed that HTRA1 mediated degradation of elastin in choroidal vessels is critical for the development of PCV, which exhibited destructive extracellular matrix remodeling and vascular smooth muscle cell loss...
September 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28940570/encouraging-experience-using-multi-transgenic-xenografts-in-a-pig-to-baboon-cardiac-xenotransplantation-model
#2
Joshua L Chan, Avneesh K Singh, Philip C Corcoran, Marvin L Thomas, Billeta Gt Lewis, David L Ayares, Todd Vaught, Keith A Horvath, Muhammad M Mohiuddin
BACKGROUND: Innovations in transgenic technology have facilitated improved xenograft survival. Additional gene expression appears to be necessary to overcome the remaining immune and biologic incompatibilities. We report for the first time the novel use of six-gene modifications within a pig-to-baboon cardiac xenotransplantation model. METHODS: Baboons (8-15 kg) underwent heterotopic cardiac transplantation using xenografts obtained from genetically engineered pigs...
September 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28939396/novel-therapies-for-angiotensin-converting-enzyme-inhibitor-induced-angioedema-a-systematic-review-of-current-evidence
#3
Heidi M Riha, Bryant B Summers, Jessica V Rivera, Megan A Van Berkel
BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema can occur at any point during therapy and, when severe, can require mechanical ventilation. Standard agents for anaphylactic reactions have limited efficacy for bradykinin-mediated angioedema and, therefore, agents approved for hereditary angioedema are increasingly prescribed for these patients. OBJECTIVE OF THE REVIEW: This systematic review critically evaluates evidence describing the off-label use of fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), complement 1 esterase inhibitor (C1-INH), icatibant, and ecallantide for treatment of ACEI-induced angioedema...
September 19, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28939078/rationale-for-neoadjuvant-immunotherapy-in-head-and-neck-squamous-cell-carcinoma
#4
REVIEW
Glenn J Hanna, Douglas R Adkins, Paul Zolkind, Ravindra Uppaluri
The clinical benefit of immunotherapy in recurrent, metastatic head and neck squamous cell carcinoma has fueled interest in revisiting neoadjuvant approaches to complement definitive treatment. Neoadjuvant strategies incorporating immune checkpoint inhibitors and other novel immune-based therapies in head and neck cancer are reviewed here, with particular attention paid to the rationale for these approaches from both a clinical and biologic discovery standpoint. The potential benefits of neoadjuvant immunotherapy include reduction of extent of surgery and the intensity of adjuvant therapy by tumor downstaging, reduction of the risk of distant metastatic spread by early introduction of systemic therapy, conversion of unresectable to resectable disease, and early evaluation of biomarkers of tumor response...
October 2017: Oral Oncology
https://www.readbyqxmd.com/read/28938516/naturally-occurring-anthocyanin-cyanidin-3-rutinoside-possesses-inherent-vasorelaxant-actions-and-prevents-methylglyoxal-induced-vascular-dysfunction-in-rat-aorta-and-mesenteric-arterial-bed
#5
Thavaree Thilavech, Mahinda Y Abeywardena, Michael Adams, Julie Dallimore, Sirichai Adisakwattana
Cyanidin-3-rutinoside (C3R) possesses anti-oxidant, anti-inflammatory and anti-glycation properties. Methylglyoxal (MG), a highly reactive dicarbonyl aldehyde by-product of glycolysis, is a precursor of advanced glycation end products and contributes to vascular dysfunction, particularly during hyperglycemia. We investigated the possible inherent vasoactivity of C3R, and its effectiveness against MG-induced vascular abnormalities in isolated blood vessel preparations from male Wistar Kyoto rat. C3R induced vasorelaxation concentration-dependently in aortic rings (92% maximum relaxation; EC50: 2...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28933846/inhibition-of-calcium-dependent-protein-kinase-1-cdpk1-by-pyrazolopyrimidine-analogs-decreases-establishment-and-reoccurrence-of-central-nervous-system-disease-by-toxoplasma-gondii
#6
Florentine U Rutaganira, Jennifer Barks, Mary Savari Dhason, Qiuling Wang, Michael Steven Lopez, Shaojun Long, Joshua B Radke, Nathaniel G Jones, Amarendar R Maddirala, James W Janetka, Majida El Bakkouri, Raymond Hui, Kevan M Shokat, L David Sibley
Calcium dependent protein kinase 1 (CDPK1) is an essential enzyme in the opportunistic pathogen Toxoplasma gondii. CDPK1 controls multiple processes that are essential to the intracellular replicative cycle of T. gondii including secretion of adhesins, motility, invasion, and egress. Remarkably, CDPK1 contains a small glycine gatekeeper residue in the ATP binding pocket making it sensitive to ATP-competitive inhibitors with bulky substituents that complement this expanded binding pocket. Here we explored structure-activity relationships of a series of pyrazolopyrimidine inhibitors of CDPK1 with the goals of increasing selectivity over host enzymes, improving anti-parasite potency, and improving metabolic stability...
September 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28932227/targeted-delivery-of-neutralizing-anti-c5-antibody-to-renal-endothelium-prevents-complement-dependent-tissue-damage
#7
Paolo Durigutto, Daniele Sblattero, Stefania Biffi, Luca De Maso, Chiara Garrovo, Gabriele Baj, Federico Colombo, Fabio Fischetti, Antonio F Di Naro, Francesco Tedesco, Paolo Macor
Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28927688/effects-of-dietary-hawthorn-extract-on-growth-performance-immune-responses-growth-and-immune-related-genes-expression-of-juvenile-golden-pompano-trachinotus-ovatus-and-its-susceptibility-to-vibrio-harveyi-infection
#8
Xiaohong Tan, Zhenzhu Sun, Zhong Huang, Chuanpeng Zhou, Heizhao Lin, Lianjie Tan, Pengwei Xun, Qian Huang
The present study was conducted to investigate the effects of dietary hawthorn extract (HTE) supplementation on growth performance, immune responses, hepatic antioxidant abilities, growth- and immune-related and heat shock protein genes expression and resistance to the pathogen Vibrio harveyi in Trachinotus ovatus. A basal diet supplemented with HTE at 0 (Diet 1), 0.50 (Diet 2), 1.00 (Diet 3), 2.00 (Diet 4), 4.00 (Diet 5) and 10.00 (Diet 6) g kg(-1) were fed to golden pompano for 8 weeks. The highest final body weight, weight gain rate, specific growth rate, feed efficiency ratio and protein efficiency rate were observed in fish fed Diet 2 (P < 0...
September 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28927687/transcriptome-analysis-of-the-spleen-of-the-darkbarbel-catfish-pelteobagrus-vachellii-in-response-to-aeromonas-hydrophila-infection
#9
Chuanjie Qin, Quan Gong, Zhengyong Wen, Dengyue Yuan, Ting Shao, Jun Wang, Huatao Li
Intensive aquaculture has increased the susceptibility of fish to Aeromonas hydrophila, and this has led to severe economic damage. There has been little study of the host defense mechanism against A. hydrophila infection in scaleless fish. Therefore, in the present study, the transcriptome profiles of the spleen of Pelteobagrus vachellii were examined after infection with A. hydrophila. In total, 37,730 unigenes from 322 KEGG pathways were identified. Following A. hydrophila infection, 27,803 differentially expressed genes were identified, including 13,934 upregulated and 13,869 downregulated genes...
September 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28927101/effects-of-p38mapk-mediated-excision-repair-cross-complementation-1-expression-on-prognosis-of-patients-with-non-small-cell-lung-cancer
#10
Dan He, Xiaomei Ma, Zhenhua Wu, Yang Wang, Shuyuan Zhao, Feng Han, Wei Sun
The present study aimed to investigate the effects of excision repair cross-complementation 1 (ERCC1) expression on the prognosis of patients with non-small cell lung cancer (NSCLC). A total of 140 patients with NSCLC who underwent radical resection were included. Immunohistochemical staining was performed on the tissue specimens obtained from patients and correlation analysis was used to determine the association between ERCC1 expression and clinicopathological characteristics. Cell proliferation was assessed using an MTT assay...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923507/pentagalloylglucose-a-highly-bioavailable-polyphenolic-compound-present-in-cortex-moutan-efficiently-blocks-hepatitis-c-virus-entry
#11
Patrick Behrendt, Paula Perin, Nicolas Menzel, Dominic Banda, Stephanie Pfaender, Marco P Alves, Volker Thiel, Phillip Meulemann, Che C Colpitts, Luis M Schang, Florian W R Vondran, Anggakusuma, Michael P Manns, Eike Steinmann, Thomas Pietschmann
Approximately 142 million people worldwide are infected with hepatitis C virus (HCV). Although potent direct acting antivirals are available, high costs limit access to treatment. Chronic hepatitis C virus infection remains a major cause of orthotopic liver transplantation. Moreover, re-infection of the graft occurs regularly. Antivirals derived from natural sources might be an alternative and cost-effective option to complement therapy regimens for global control of hepatitis C virus infection. We tested the antiviral properties of a mixture of different Chinese herbs/roots named Zhi Bai Di Huang Wan (ZBDHW) and its individual components on HCV...
September 15, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28920587/complement-in-cancer-untangling-an-intricate-relationship
#12
REVIEW
Edimara S Reis, Dimitrios C Mastellos, Daniel Ricklin, Alberto Mantovani, John D Lambris
In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis...
September 18, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28920104/variable-phenotypic-penetrance-of-thrombosis-in-adult-mice-after-tissue-selective-and-temporally-controlled-thbd-gene-inactivation
#13
Thijs E van Mens, Hai-Po H Liang, Sreemanti Basu, Irene Hernandez, Mark Zogg, Jennifer May, Min Zhan, Qiuhui Yang, Jamie Foeckler, Shawn Kalloway, Rashmi Sood, Caren Sue Karlson, Hartmut Weiler
Thrombomodulin (Thbd) exerts pleiotropic effects on blood coagulation, fibrinolysis, and complement system activity by facilitating the thrombin-mediated activation of protein C and thrombin-activatable fibrinolysis inhibitor and may have additional thrombin- and protein C (pC)-independent functions. In mice, complete Thbd deficiency causes embryonic death due to defective placental development. In this study, we used tissue-selective and temporally controlled Thbd gene ablation to examine the function of Thbd in adult mice...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/28919885/trypanosoma-cruzi-evades-the-complement-system-as-an-efficient-strategy-to-survive-in-the-mammalian-host-the-specific-roles-of-host-parasite-molecules-and-trypanosoma-cruzi-calreticulin
#14
REVIEW
Galia Ramírez-Toloza, Arturo Ferreira
American Trypanosomiasis is an important neglected reemerging tropical parasitism, infecting about 8 million people worldwide. Its agent, Trypanosoma cruzi, exhibits multiple mechanisms to evade the host immune response and infect host cells. An important immune evasion strategy of T. cruzi infective stages is its capacity to inhibit the complement system activation on the parasite surface, avoiding opsonizing, immune stimulating and lytic effects. Epimastigotes, the non-infective form of the parasite, present in triatomine arthropod vectors, are highly susceptible to complement-mediated lysis while trypomastigotes, the infective form, present in host bloodstream, are resistant...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28918059/regulatory-role-of-the-microrna-29b-il-6-signaling-in-the-formation-of-vascular-mimicry
#15
Jian-Hong Fang, Zhi-Yuan Zheng, Jin-Yu Liu, Chen Xie, Zi-Jun Zhang, Shi-Mei Zhuang
Vascular mimicry (VM) is a critical complement for microcirculation and is implicated in tumor progression. We showed that IL-6 derived from tumor cells and stroma cells promoted tumor cells to form a VM structure, whereas blocking the IL-6 signaling by RNA interference, IL-6-neutralizing antibody, or STAT3 inhibitor suppressed the VM formation of tumor cells. Mechanism investigations revealed that IL-6 stimulated VM formation by activating STAT3, in turn upregulating VE-cadherin expression and MMP2 activity...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917247/the-optimism-surrounding-stereotactic-body-radiation-therapy-and-immunomodulation
#16
Hannah Tharmalingam, Peter J Hoskin
In recent years, rapidly evolving radiation techniques have enabled the precise delivery of very high doses of radiation to local targets with stereotactic ablative body radiotherapy (SABR). In addition to its direct cytotoxicity, radiation and in particular SABR has powerful immunomodulatory effects resulting in immunogenic cell death and potentiation of the anti-tumour immune response. However, due to the immunosuppressive nature of non-irradiated sites of metastases, radiotherapy alone is seldom sufficient to induce the systemic response required for distant tumour rejection...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28916198/treatment-outcome-and-quality-of-life-of-1239-patients-with-advanced-non-small-cell-lung-cancer-final-results-from-the-prospective-german-tlk-cohort-study
#17
Ulla von Verschuer, Roland Schnell, Hans Werner Tessen, Jochen Eggert, Adrian Binninger, Lisa Spring, Martina Jänicke, Norbert Marschner
OBJECTIVES: Real-life data on advanced non-small cell lung cancer (NSCLC) are centrally important to complement the results from clinical trials and to improve the standard of care. We present data on the choice of systemic first- and second-line treatment, number of treatment lines, survival and longitudinal data on health-related quality of life (HRQOL) of patients treated by medical oncologists in Germany. MATERIALS AND METHODS: 1239 patients with advanced NSCLC were recruited at start of first-line therapy into the prospective German clinical cohort study TLK (Tumour Registry Lung Cancer) by 107 sites between February 2010 and December 2013 and followed-up until January 2016...
August 22, 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28915952/iga-nephropathy-during-treatment-with-tnf-alpha-blockers-could-it-be-predicted
#18
Vito Di Lernia
Immunoglobulin A (IgA) nephropathy (IgAN) may sometimes be related to exposure to pharmacological agents, among which anti-Tumor Necrosis Factor (TNF)-alpha agents. The characteristic pathological feature is a deposition of IgA-containing immune complexes in vessel walls in the kidney mesangium. The link between TNF-alpha blockers and IgAN may be hypothesized examining diseases which share pathologic features. In this respect, idiopathic IgAN and Henoch Schonlein Purpura have been the object of studies revealing a pathogenetic role of aberrant glycosylation of IgA1 molecules...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28915270/the-single-cyclic-nucleotide-specific-phosphodiesterase-of-the-intestinal-parasite-giardia-lamblia-represents-a-potential-drug-target
#19
Stefan Kunz, Vreni Balmer, Geert Jan Sterk, Michael P Pollastri, Rob Leurs, Norbert Müller, Andrew Hemphill, Cornelia Spycher
BACKGROUND: Giardiasis is an intestinal infection correlated with poverty and poor drinking water quality, and treatment options are limited. According to the Center for Disease Control and Prevention, Giardia infections afflict nearly 33% of people in developing countries, and 2% of the adult population in the developed world. This study describes the single cyclic nucleotide-specific phosphodiesterase (PDE) of G. lamblia and assesses PDE inhibitors as a new generation of anti-giardial drugs...
September 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28912782/the-sand-fly-salivary-protein-lufaxin-inhibits-the-early-steps-of-the-alternative-pathway-of-complement-by-direct-binding-to-the-proconvertase-c3b-b
#20
Antonio F Mendes-Sousa, Vladimir Fazito do Vale, Naylene C S Silva, Anderson B Guimaraes-Costa, Marcos H Pereira, Mauricio R V Sant'Anna, Fabiano Oliveira, Shaden Kamhawi, José M C Ribeiro, John F Andersen, Jesus G Valenzuela, Ricardo N Araujo
Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B...
2017: Frontiers in Immunology
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