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Alternative complement pathway

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https://www.readbyqxmd.com/read/27918307/vegf-regulates-local-inhibitory-complement-proteins-in-the-eye-and-kidney
#1
Lindsay S Keir, Rachel Firth, Lyndsey Aponik, Daniel Feitelberg, Susumu Sakimoto, Edith Aguilar, Gavin I Welsh, Anna Richards, Yoshihiko Usui, Simon C Satchell, Valeryia Kuzmuk, Richard J Coward, Jonathan Goult, Katherine R Bull, Ruchi Sharma, Kapil Bharti, Peter D Westenskow, Iacovos P Michael, Moin A Saleem, Martin Friedlander
Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact...
December 5, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27917290/functional-analysis-of-alternative-splicing-of-the-flowering-locus-t-orthologous-gene-in-chrysanthemum-morifolium
#2
Yachao Mao, Jing Sun, Peipei Cao, Rong Zhang, Qike Fu, Sumei Chen, Fadi Chen, Jiafu Jiang
As the junction of floral development pathways, the FLOWERING LOCUS T (FT) protein called 'florigen' plays an important role in the process of plant flowering through signal integration. We isolated four transcripts encoding different isoforms of a FT orthologous gene CmFTL1, from Chrysanthemum morifolium cultivar 'Jimba'. Sequence alignments suggested that the four transcripts are related to the intron 1. Expression analysis showed that four alternative splicing (AS) forms of CmFTL1 varied depending on the developmental stage of the flower...
2016: Horticulture Research
https://www.readbyqxmd.com/read/27913483/atypical-hemolytic-uremic-syndrome
#3
Vahid Afshar-Kharghan
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) that affects multiple organs and the kidneys in particular. aHUS can be sporadic or familial and is most commonly caused by dysregulation of the alternative complement pathway. The initial attack of aHUS can occur at any age, and is associated with a high rate of progression to end stage renal disease. Many aHUS patients relapse in the native or transplanted kidneys, and require close monitoring and long-term management. Availability of anticomplement therapy has revolutionized the management of aHUS, and can change the natural course of aHUS by inducing hematologic remission, improving or stabilizing kidney functions, and preventing graft failure...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27904864/nephrotic-range-proteinuria-and-peripheral-edema-in-a-child-not-only-idiopathic-nephrotic-syndrome
#4
Valentina Dolcemascolo, Marina Vivarelli, Manuela Colucci, Francesca Diomedi-Camassei, Rossella Piras, Marta Alberti, Francesco Emma
Hemolytic uremic syndrome (HUS) is defined by the simultaneous occurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury due to thrombotic microangiopathy (TMA) mainly occurring in renal and cerebral microvessels. Although the most common cause of HUS in children is Shiga toxin-producing Escherichia coli, atypical forms in which Shiga toxin is not the trigger may occur. Research over the last few years has shown that complement dysregulation secondary to mutations of genes coding for proteins involved in the regulation of the alternative pathway of complement account for most forms of atypical HUS (aHUS)...
September 2016: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/27902465/gene-and-microrna-modulation-upon-trabectedin-treatment-in-a-human-intrahepatic-cholangiocarcinoma-paired-patient-derived-xenograft-and-cell-line
#5
Caterina Peraldo Neia, Giuliana Cavalloni, Giovanna Chiorino, Paola Ostano, Massimo Aglietta, Francesco Leone
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy with limited therapeutic options. Trabectedin has a high antitumor activity in preclinical models of biliary tract carcinoma (BTC), being a promising alternative treatment. Here, we studied the effect of trabectedin at transcriptomic level on an ICC patient derived xenograft (PDX) and on the derived cell line, MT-CHC01. Further, putative targets of trabectedin were explored in the in vitro model. In vitro, trabectedin inhibited genes involved in protein modification, neurogenesis, migration, and motility; it induced the expression of genes involved in keratinization, tissues development, and apoptotic processes...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900694/methods-for-the-isolation-of-genes-encoding-novel-pha-metabolism-enzymes-from-complex-microbial-communities
#6
Jiujun Cheng, Ricardo Nordeste, Maria A Trainer, Trevor C Charles
Development of different PHAs as alternatives to petrochemically derived plastics can be facilitated by mining metagenomic libraries for diverse PHA cycle genes that might be useful for synthesis of bio-plastics. The specific phenotypes associated with mutations of the PHA synthesis pathway genes in Sinorhizobium meliloti and Pseudomonas putida, allows the use of powerful selection and screening tools to identify complementing novel PHA synthesis genes. Identification of novel genes through their function rather than sequence facilitates the functional proteins that may otherwise have been excluded through sequence-only screening methodology...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27895415/factoring-the-intestinal-microbiome-into-the-pathogenesis-of-autoimmune-hepatitis
#7
EDITORIAL
Albert J Czaja
The intestinal microbiome is a reservoir of microbial antigens and activated immune cells. The aims of this review were to describe the role of the intestinal microbiome in generating innate and adaptive immune responses, indicate how these responses contribute to the development of systemic immune-mediated diseases, and encourage investigations that improve the understanding and management of autoimmune hepatitis. Alterations in the composition of the intestinal microflora (dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal bacteria...
November 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27889746/distinct-in-vitro-complement-activation-by-various-intravenous-iron-preparations
#8
Julia Cordelia Hempel, Felix Poppelaars, Mariana Gaya da Costa, Casper F M Franssen, Thomas P G de Vlaam, Mohamed R Daha, Stefan P Berger, Marc A J Seelen, Carlo A J M Gaillard
BACKGROUND: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). METHODS: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways...
November 26, 2016: American Journal of Nephrology
https://www.readbyqxmd.com/read/27878657/c3-glomerulopathy-and-current-dilemmas
#9
Naoko Ito, Ryuji Ohashi, Michio Nagata
C3 glomerulopathy (C3G) is a recently identified disease entity caused by dysregulation of the alternative complement pathway, and dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are its components. Because laboratory detection of complement dysregulation is still uncommon in practice, "dominant C3 deposition by two orders greater than that of immunoglobulins in the glomeruli by immunofluorescence", as stated in the consensus report, defines C3G. However, this morphological definition possibly includes the cases with glomerular diseases of different mechanisms such as post-infectious glomerulonephritis...
November 23, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27864172/the-ebpa-rpon-regulatory-pathway-of-the-pathogen-leptospira-interrogans-is-essential-for-survival-in-the-environment
#10
Wei-Lin Hu, Christopher J Pappas, Jun-Jie Zhang, You-Yun Yang, Jie Yan, Mathieu Picardeau, X Frank Yang
Leptospira interrogans is the agent of leptospirosis, a re-emerging zoonotic disease. Leptospirosis is transmitted to humans through environmental surface waters contaminated by the urine of mammals that are chronically infected by pathogenic strains that are able to survive in water for long periods. Little is known about the regulatory pathways underlying environmental sensing and host adaptation of L. interrogans during its enzootic cycle. This study identifies the EbpA-RpoN regulatory pathway in L. interrogans In this pathway, EbpA, a σ(54) activator and putative prokaryotic enhancer-binding protein (EBP), and the alternative sigma factor RpoN (σ(54)) control expression of at least three genes - encoding AmtB (an ammonium transport protein) and two proteins of unknown function...
November 18, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27864148/three-pentraxins-c-reactive-protein-serum-amyloid-p-component-and-pentraxin-3-mediate-complement-activation-using-collectin-cl-p1
#11
Nitai Roy, Katsuki Ohtani, Yoshihiko Hidaka, Yoshiro Amano, Yasuyuki Matsuda, Kenichiro Mori, Insu Hwang, Norimitsu Inoue, Nobutaka Wakamiya
BACKGROUND: Pentraxins (PTXs) are a superfamily of multifunctional conserved proteins involved in acute-phase responses. Recently, we have shown that collectin placenta 1 (CL-P1) and C-reactive protein (CRP) mediated complement activation and failed to form terminal complement complex (TCC) in normal serum conditions because of complement factor H inhibition. METHODS: We used CL-P1 expressing CHO/ldlA7 cells to study the interaction with PTXs. Soluble type CL-P1 was used in an ELISA assay for the binding, C3 and TCC deposition experiments...
November 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27863511/analysis-of-complement-biomarkers-in-systemic-sclerosis-indicates-a-distinct-pattern-in-scleroderma-renal-crisis
#12
Marcin Okrój, Martin Johansson, Tore Saxne, Anna M Blom, Roger Hesselstrand
BACKGROUND: The complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc. METHODS: The presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters...
November 18, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27857715/complementary-roles-of-the-classical-and-lectin-complement-pathways-in-the-defense-against-aspergillus-fumigatus
#13
Anne Rosbjerg, Ninette Genster, Katrine Pilely, Mikkel-Ole Skjoedt, Gregory L Stahl, Peter Garred
Aspergillus fumigatus infections are associated with a high mortality rate for immunocompromised patients. The complement system is considered to be important in protection against this fungus, yet the course of activation is unclear. The aim of this study was to unravel the role of the classical, lectin, and alternative pathways under both immunocompetent and immunocompromised conditions to provide a relevant dual-perspective on the response against A. fumigatus. Conidia (spores) from a clinical isolate of A...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27857140/immune-disorders-blocking-the-alternative-complement-pathway
#14
Sarah Crunkhorn
No abstract text is available yet for this article.
November 18, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27854228/toxicological-characterization-of-exon-skipping-phosphorodiamidate-morpholino-oligomers-pmos-in-non-human-primates
#15
Michael P Carver, Jay S Charleston, Courtney Shanks, Jianbo Zhang, Mark Mense, Alok K Sharma, Harjeet Kaur, Peter Sazani
BACKGROUND: Phosphorodiamidate morpholino oligomers (PMOs) are a class of exon skipping drugs including eteplirsen, which has shown considerable promise for treatment of the degenerative neuromuscular disease, Duchenne musculardystrophy (DMD). OBJECTIVE: Toxicity studies in non-human primates (NHPs) of 12 weeks duration with two new PMOs for DMD, SRP-4045 and SRP-4053, along with results from a chronic study in NHPs of 39 weeks duration for eteplirsen, are described here...
August 30, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27848226/atypical-hemolytic-uremic-syndrome-in-the-setting-of-complement-amplifying-conditions-case-reports-and-a-review-of-the-evidence-for-treatment-with-eculizumab
#16
REVIEW
Arif Asif, Ali Nayer, Christian S Haas
Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, progressive, life-threatening form of thrombotic microangiopathy (TMA) predominantly caused by dysregulation of the alternative pathway of the complement system. Complement-amplifying conditions (CACs), including pregnancy complications [preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome], malignant hypertension, autoimmune diseases, transplantation, and others, are associated with the onset of TMA in up to 69 % of cases of aHUS...
November 15, 2016: Journal of Nephrology
https://www.readbyqxmd.com/read/27846429/effects-of-bothrops-atrox-venom-and-two-isolated-toxins-on-the-human-complement-system-modulation-of-pathways-and-generation-of-anaphylatoxins
#17
Danilo L Menaldo, Carolina P Bernardes, Anna L Jacob-Ferreira, Cíntia G Nogueira-Santos, Tania M Casare-Ogasawara, Luciana S Pereira-Crott, Suely V Sampaio
The complement system plays important biological roles, including the activation of inflammatory processes in response to the generation of proteolytic fragments of its components. Here we evaluated the effects of Bothrops atrox venom and two of its toxins (the P-I metalloprotease Batroxase and the acidic phospholipase A2 BatroxPLA2) on the human complement system, evaluating their effects on the classical (CP), lectin (LP) and alternative (AP) pathways, as well as on different complement components associated to the generation of anaphylatoxins...
November 12, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27834928/anti-complementary-components-of-helicteres-angustifolia
#18
Xiang Yin, Yan Lu, Zhi-Hong Cheng, Dao-Feng Chen
A first phenalenon derivative with an acetyl side chain at C-8, 8-acetyl-9-hydroxy-3-methoxy-7-methyl-1-phenalenon (compound 1), and a pair of new sesquilignan epimers at C-7″ of hedyotol C and hedyotol D analogs, hedyotol C 7″-O-β-d-glucopyranoside (compound 2) and hedyotol D 7″-O-β-d-glucopyranoside (compound 3) were isolated from the aerial parts of Helicteres angustifolia together with nine known compounds (4-12). Their structures were elucidated on the basis of spectroscopic methods, including mass spectroscopy, and 1D and 2D nuclear magnetic resonance...
November 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27822748/suppression-of-ehrlich-carcinoma-growth-by-cobra-venom-factor
#19
T I Terpinskaya, V S Ulashchik, A V Osipov, V I Tsetlin, Yu N Utkin
Cobra venom factor (CVF) depletes the complement system of the blood by forming stable convertase C3/C5 of the alternative pathway. We found that CVF from the Thailand cobra venom slows down the growth of subcutaneous Ehrlich carcinoma (EC) in mice at a dose of 1.7 nmol/g. Previously, we described a similar effect for the nerve growth factor (NGF) from the venom of this cobra. However, these factors did not exhibit either synergy or additive effect. On the contrary, they neutralized the antitumor effect of each other when they were administered simultaneously...
September 2016: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/27818336/vegetable-oil-induced-inflammatory-response-by-altering-tlr-nf-%C3%AE%C2%BAb-signalling-macrophages-infiltration-and-polarization-in-adipose-tissue-of-large-yellow-croaker-larimichthys-crocea
#20
Peng Tan, Xiaojing Dong, Kangsen Mai, Wei Xu, Qinghui Ai
High level of vegetable oil (VO) in diets could induce strong inflammatory response, and thus decrease nonspecific immunity and disease resistance in most marine fish species. The present study was conducted to investigate whether dietary VO could exert these anti-immunological effects by altering TLR-NF-κB signalling, macrophages infiltration and polarization in adipose tissue of large yellow croaker (Larimichthys crocea). Three iso-nitrogenous and iso-lipid diets with 0% (FO, fish oil, the control), 50% (FV, fish oil and vegetable oil mixed) and 100% (VO, vegetable oil) vegetable oil were fed to fish with three replicates for ten weeks...
December 2016: Fish & Shellfish Immunology
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