• The affected patients' genetic backgrounds revealed significant genetic heterogeneity in several genes involved in complement regulation, including the complement factor H, complement factor H-related proteins, complement factor I, complement factor B, complement component 3, and CD46 genes in the alternative complement pathway. (ekjt.org)
  • 10 This distinction is not absolute because genetic defects in complement proteins have been identified in secondary TMA. (jrheum.org)
  • The differentially expressed genes included those functioning in some important immune reaction and iron metabolism pathways, such as pattern recognition receptors, regulators of the JNK pathway, components of the phagosome pathway, regulators of the melanization response, activators of complement reactions, insulin signaling cascade members, oxidative stress and detoxification proteins. (biomedcentral.com)
  • The Microphthalmia-associated Transcription Factor (MiT) family proteins (MITF, TFEB, TFE3, TFEC) are considered master regulators of autophagy and lysosomal biogenesis and their activity is regulated in response to nutrient availability, therefore connecting cellular metabolism with ALP function. (eurac.edu)
  • An in vitro CRISPR knockout screen, complemented by genetic screens in C. elegans, will elucidate essential and conserved proteins in the MiT activation pathway. (eurac.edu)
  • At the site of infection, membrane receptors for complement proteins and immunoglobulins recognize and bind opsonized bacteria leading to the formation of pseudopodia, phagocytosis of the pathogen and destruction within the intracellular phagosome. (assignmentexpert.com)
  • In vivo, regulation of complement at the C3 and C5 activation steps is provided by both plasma and membrane proteins. (justia.com)
  • The plasma protein inhibitors are factor H and C4-binding protein, and the regulatory membrane proteins located on cell surfaces are complement receptors 1 (CR1), decay-accelerating factor (DAF), and membrane cofactor protein (MCP). (justia.com)
  • These proteins inhibit the C3 and C5 convertases (multi-subunit proteases), by promoting dissociation of the multisubunit complexes and/or by inactivating the complexes through proteolysis (catalyzed by factor I). Several pharmacological agents that regulate or modulate complement activity have been identified by in vitro assay, but most have been shown in vivo to be of low activity or toxic. (justia.com)
  • Western blot was carried out to detect the expression levels of autophagic-related proteins (Unc-51 like autophagy activating kinase 1, beclin 1, autophagy related 5, microtubule-associated protein 1A/1B-light chain 3, ubiquitin-binding protein p62), glycolysis-related proteins (hexokinase 2, phosphofructokinase, pyruvate kinase M2) and activated protein kinase signalling pathway proteins. (ijpsonline.com)
  • Autophagy is a process that relies on lysosomal pathways for the degradation of cytoplasmic proteins and organelles and plays an important role in the pathology of brain injury such as hypoxia ischemia[ 3 ]. (ijpsonline.com)
  • thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors. (medscape.com)
  • [ 9 ] All of these proteins interact with complement proteins, particularly C3b and C4b, dissociate the convertase complexes of the classic and alternative pathways, and halt the amplification of the activation process. (medscape.com)
  • The absence of these regulating proteins results in uncontrolled amplification of the complement system. (medscape.com)
  • The complement system is a tightly regulated, cascading protein network representing a key component linking the innate and humoral immune systems. (jrheum.org)
  • 7 - 9 A TMA is called "primary" when a genetic or acquired defect in a complement protein is identified (as in atypical hemolytic uremic syndrome [aHUS]) or "secondary" when occurring in the context of another disease process or factor such as infection, autoimmune disease, malignancy, or drugs. (jrheum.org)
  • The complement system is a tightly regulated, cascading protein network that performs multiple roles in homeostasis and disease prevention and is a key component of both the innate and the humoral immune systems. (jrheum.org)
  • Akt pathways have effects on apoptosis, protein synthesis, metabolism and cell cycle. (springer.com)
  • AMPK pathways inhibit biosynthetic pathways with energy consumption, such as protein, fatty acid and glycogen synthesis. (springer.com)
  • Compounds comprising peptides and peptidomimetics capable of binding the C3 protein and inhibiting complement activation are disclosed. (justia.com)
  • In particular, this invention provides peptides and peptidomimetics capable of binding the C3 protein and inhibiting complement activation. (justia.com)
  • The transcriptional repressor HBP1 is a target of the p38 mitogen-activated protein kinase pathway in cell cycle regulation. (nih.gov)
  • The DEPs were mainly enriched in gene ontology (GO) items associated with immunity, complement activation, and protein activation cascade regulation corresponding to 24 pathways, of which complement and coagulation cascades as well as platelet activation pathways were the most significant. (izon.com)
  • MIM 601231) are components of a protein complex that integrates nutrient- and growth factor-derived signals to regulate cell growth (Sarbassov et al. (nih.gov)
  • The mechanism may be related to the improvement of glycolysis dysfunction and alleviation of autophagy over activation of activated protein kinase. (ijpsonline.com)
  • Objective: To investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFβ/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium. (uea.ac.uk)
  • Repeated LPS injections induced an up-regulation of complement system protein c1q and distinct microglial phenotype with an enrichment of the complement-phagosome pathway. (imperial.ac.uk)
  • Receptor-interacting protein kinase 1 (RIPK1), a key molecule mediating necroptosis and regulated by transforming growth factor β-activated kinase 1 (TAK1), was reported to be associated with cognitive impairment in several neurodegenerative diseases. (imperial.ac.uk)
  • Blom, A. M. , Rytkönen, A., Vasquez, P., Dahlbäck, B. and Johnsson, A-B. (2001) A novel interaction between type IV pili of Neisseria gonorrhoeae and complement regulatory protein - C4b-binding protein. (lu.se)
  • Blom A. M. , Kask L. and B. Dahlbäck (2001) Structural requirements for the complement regulatory activities of C4b-binding protein. (lu.se)
  • Kask L., Hillarp A., Ramesh B., Dahlbäck B., and Blom A. M. (2002) Structural requirements for the intra-cellular subunit polymerization of the complement inhibitor C4b-binding protein. (lu.se)
  • Mark L., Lee W. H., Villoutreix B. O., Proctor D., Blackbourn, D., Spiller B. O. and Blom A. M. (2004) KSHV complement control protein mimics human molecular mechanisms for inhibition of the complement system. (lu.se)
  • Trouw L., Nilsson S., Goncalvez I., Landberg G. and Blom A. M. (2005) C4b-binding protein binds to necrotic cells and DNA, which limits DNA release and inhibits complement activation. (lu.se)
  • Sjöberg A., Trouw L., McGrath F., Hack E. C. and Blom A. M. (2006) Regulation of complement activation by C-reactive protein: targeting of the inhibitory activity of C4b-binding protein. (lu.se)
  • Factor H-Related Protein 1 Drives Disease Susceptibility and Prognosis in C3 Glomerulopathy. (cdc.gov)
  • The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. (assaygenie.com)
  • Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. (gliome.org)
  • The classical, lectin, and alternative pathways converge into a final common pathway when C3 convertase (C3 con) cleaves C3 into C3a and C3b. (msdmanuals.com)
  • A further complicating factor is the cross-talk between complement, neutrophils, and coagulation pathways in the pathophysiology of TMA. (jrheum.org)
  • Activation of the lectin pathway may also trigger the coagulation cascade via MASP-2 cleavage of prothrombin to thrombin. (biomedcentral.com)
  • Together, activation of complement and the coagulation cascade lead to a procoagulant state that may result in development of HSCT-TMA. (biomedcentral.com)
  • Atypical HUS (aHUS) represents 5-10% of HUS cases and is largely due to one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of the complement system, which is a group of immune signaling factors that promote inflammation, enhance the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the body, and directly attack the pathogen's cell membrane. (wikipedia.org)
  • The 3 types of HAE can be differentiated with complement testing and, in the case of HAE with normal C1 inhibitor levels, genetic testing. (medscape.com)
  • Many recent studies on atypical hemolytic uremic syndrome have described genetic abnormalities related to excessive activation of the alternative complement pathway. (ekjt.org)
  • Given the poor prognosis of posttransplant thrombotic microangiopathy, further research is necessary to improve the diagnosis and treatment protocols based on risk factors or genetic predisposition, and to develop new therapeutic agents. (ekjt.org)
  • Accumulating evidence suggests that a large percentage of the patients diagnosed with secondary TMA exhibit genetic abnormalities associated with complement dysregulation. (ekjt.org)
  • Recently, genetic factors linking immunological pathways to predisposition to preeclampsia have been identified. (frontiersin.org)
  • In this mini-review genetic variation in immunological factors are discussed in the context of preeclampsia. (frontiersin.org)
  • Mechanistic studies will determine how the MiT pathway links mitochondria-lysosomal dysfunctions in the disease cascade of PD in response to metabolic and genetic changes. (eurac.edu)
  • Using forward genetic screen as well as reverse genetics, we are interested in elucidating the genetic pathways that govern senescence. (umassmed.edu)
  • Recent research aimed mainly at a better understanding of the genetic risk factors and modifiers associated with the onset and phenotypic expression of the sporadic disease: Genome-Wide Association Studies (GWAS) of large sCJD cohorts confirmed the significant association with PRNP codon 129, the strongest genetic risk factor [ 10 ]. (biomedcentral.com)
  • It is characterized by normal C1 inhibitor and is sometimes due to genetic mutations that result in abnormal forms of factor XII, plasminogen , angiopoietin 1, or kininogen. (msdmanuals.com)
  • Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits. (cdc.gov)
  • In particular, the lectin pathway of complement is activated by damage-associated molecular patterns (DAMPs) on the surface of injured endothelial cells. (biomedcentral.com)
  • In this article, we review the role of the complement system in HSCT-TMA pathogenesis, with a focus on the lectin pathway. (biomedcentral.com)
  • Endothelial injury triggers activation of the complement system-significantly through the lectin pathway-via altered cell-surface patterns on injured endothelial cells, initiating an inflammatory response [ 7 ]. (biomedcentral.com)
  • Here we discuss evidence for the role of lectin pathway activation in endothelial injury-associated complications of HSCT and how targeting complement activity may provide therapeutic benefit for patients with HSCT-TMA. (biomedcentral.com)
  • The alternative complement pathway provides innate protection against microbial agents in the absence of specific antibody. (quidel.com)
  • The complement system is an integral part of the innate immune system but also augments adaptive immune responses. (wjgnet.com)
  • Complement is crucial part of innate immunity and thus protects host from infections and contributes to removal of dying cells. (lu.se)
  • Poor clinical outcome was correlated with elevated HIF-1α and podoplanin expression whilst expression of inflammatory and complement genes was predictive of extended survival. (elifesciences.org)
  • Upregulation of early and downregulation of terminal pathway complement genes in subcutaneous adipose tissue and adipocytes in acquired obesity. (nature.com)
  • Towards this goal, we have identified a number of genes that control senescence activation and will continue to search for additional senescence regulators. (umassmed.edu)
  • We are interested in understanding the underlying molecular mechanisms of senescence regulation by these genes. (umassmed.edu)
  • Continued studies focused on genes showing minimal changes in the TMA-induced model but with clear up-regulation in the ovalbumin model. (cdc.gov)
  • Two of these genes, arginase 1 and eotaxin 1 are the focus of continuing investigations in mouse models of asthma regarding differences in mechanistic pathways depending on the allergen. (cdc.gov)
  • Array studies provide candidate genes to identify common mechanistic pathways in the effector phase, as well as mechanistic pathways unique to individual allergens. (cdc.gov)
  • The pathways that lead to fibrosis are not fully understood, although chronic non-resolving inflammation in the kidney is likely to drive the fibrotic response that occurs. (wjgnet.com)
  • In this review we discuss current evidence that complement activation contributes to progression of CKD, how complement could cause renal inflammation and whether complement inhibition would slow progression of renal disease. (wjgnet.com)
  • Complement activation occurs in progressive chronic kidney disease and may contribute to the chronic inflammation that is characteristically found in the kidney. (wjgnet.com)
  • It is therefore possible that inhibiting complement activation would reduce inflammation, lead to reduced fibrosis and preservation of renal function. (wjgnet.com)
  • Mitochondrial DNA (mtDNA), released from dying cells, is a biomarker of inflammation, a mediator of immune activation and has been detected at elevated levels in the plasma of PLWH. (natap.org)
  • Neutrophils respond to multiple signals and respond by producing several cytokines and other inflammatory factors that influence and regulate inflammation and also the immune systemOnce neutrophils have left the circulation and passed through the endothelium, they migrate towards inflamed tissue along a chemotactic gradient. (assignmentexpert.com)
  • NF-κB pathways are associated with immunity, inflammation and cell survival. (springer.com)
  • The platelet-activating factor (PAF) is also an important secretory product of platelets mediating the platelet aggregation, inflammation and anaphylaxis[ 13 ] (Table 1 ). (biomedcentral.com)
  • Endothelial injury can trigger activation of the complement system, promoting inflammation and the development of endothelial injury syndromes, ultimately leading to organ damage and failure. (biomedcentral.com)
  • Sjöberg A., Önnerfjord, P., Mörgelin, M., Heinegård, D. and Blom A. M. (2005) Extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q. (lu.se)
  • describes the use of a phage-displayed combinatorial random peptide library to identify a 27-residue peptide that binds to C3 and inhibits complement activation. (justia.com)
  • 4 , 13 Complement plays a crucial role in host defense against foreign bodies by promoting phagocyte-mediated clearance of cell debris through activation of an inflammatory response, opsonization of pathogens, and lysis of susceptible bacteria and cells. (jrheum.org)
  • In this review, we studied on the effects and molecular mechanisms of Rhizoma coptidis on NF-κB/MAPK/PI3K-Akt/AMPK/ERS and oxidative stress pathways. (springer.com)
  • Evidence presented in this review implicated that Rhizoma coptidis exerted beneficial effects on various diseases by regulation of NF-κB/MAPK/PI3K-Akt/AMPK/ERS and oxidative stress pathways, which support the clinical application of Rhizoma coptidis and offer references for future researches. (springer.com)
  • Oxidative stress pathways are caused by the imbalance of oxidation and antioxidation in body. (springer.com)
  • Oxidative stress pathways regulate redox balance by Nrf2 and other ways. (springer.com)
  • In this review, we sorted out the relationship of Rhizoma coptidis among components, diseases and NF-κB/MAPK/PI3K/Akt/AMPK/ERS/oxidative stress pathways, systematically studying on how Rhizoma coptidis exerts beneficial effects to various diseases, which supported the clinical application of Rhizoma coptidis and provided references for the future researches. (springer.com)
  • Furthermore, senescence activated by aberrant oncogenic activation, DNA damage or oxidative stress provides a failsafe mechanism that prevents proliferation of cells at risk of neoplastic transformation. (umassmed.edu)
  • MAPK pathways refer to various cellular functions, including cell proliferation, differentiation and migration. (springer.com)
  • Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. (gliome.org)
  • These components are involved in antimicrobial activities, but also have the potential to regulate the maintenance and turn-over of adipocytes under normal and pathophysiological conditions through positive and negative regulation of the membrane attack complex. (nature.com)
  • Terminal stages of this pathway are related to the production of membrane attack complexes (MACs). (nature.com)
  • Fig. 1: Regulation of the membrane attack complex. (nature.com)
  • Cellular membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves C3b, an essential component of the complement system. (nature.com)
  • Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. (plos.org)
  • Its activation through the classical, alternative or lectin pathways leads to the generation of anaphylatoxic peptides C3a and C5a and formation of the C5b-9 membrane attack complex. (justia.com)
  • Activation of C3 by complement pathway C3 convertases and its subsequent attachment to target surface leads to assembly of the membrane attack complex and ultimately to damage or lysis of the target cells. (justia.com)
  • Complement-mediated tissue injuries are directly mediated by the membrane attack complex, and indirectly by the generation of C3a and C5a. (justia.com)
  • The term "nocturnal" refers to the belief that hemolysis is triggered by acidosis during sleep and activates complement to hemolyze an unprotected and abnormal RBC membrane. (medscape.com)
  • In autoimmune diseases, the alternative complement pathway may contribute directly to tissue damage. (quidel.com)
  • Complement Factor H has been implicated in the research of many autoimmune diseases. (quidel.com)
  • A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis. (assaygenie.com)
  • This review aims to provide an assessment of the nature and extent of complement involvement in TMA associated with autoimmune diseases such as systemic lupus erythematosus, antiphospholipid syndrome, and scleroderma renal crisis. (jrheum.org)
  • 10 This review aims to provide an assessment of the nature and extent of complement involvement in the underlying pathophysiology of TMA associated with autoimmune diseases that will help to stratify patients for targeted therapy. (jrheum.org)
  • Complement is implicated in several disease states, including various autoimmune diseases, and has been found to contribute to other clinical conditions such as adult respiratory syndrome, heart attack, rejection following xenotransplantation and burn injuries. (justia.com)
  • Studies have included using Factor H as a serum biomarker of multiple sclerosis disease state, as a therapy for renal diseases associated with Factor H abnormalities, and as a camouflage to tumor cells for protection against the host immune system. (quidel.com)
  • Fearon, D.T. and Austen, K.F. Current concepts in immunology: the alternative pathway of complement - a system for host resistance to microbial infection. (quidel.com)
  • Deficiencies in C1-INH allow unchecked activation of the classic complement pathway and other biochemical systems including the bradykinin system. (medscape.com)
  • The fetal tissues including the placenta must be protected from activation of the maternal immune system. (frontiersin.org)
  • Invading trophoblast cells will encounter maternal complement system (C) in the decidua and in the intervillous space. (frontiersin.org)
  • C4A: C4 plays a central role in the activation of the classical pathway of the complement system. (assaygenie.com)
  • Therefore, a clearer understanding of the role of the complement system in TMA associated with other conditions will help to identify patients who would benefit from these therapies. (jrheum.org)
  • 8 , 11 - 14 Numerous stimuli can drive the activation of the complement system, including apoptotic debris, pathogens, and antibody-antigen complexes, in addition to ischemia-reperfusion injuries associated with organ transplantation. (jrheum.org)
  • Activation of the complement system occurs through the classical (CP), lectin (LP), or alternative (AP) pathways. (jrheum.org)
  • Adipocytes have high levels of many components of the complement system. (nature.com)
  • Cellular lysis is counteracted by different cellular defence mechanisms that control this 'tug-of-war' behaviour of the complement system: it can be kept in check or let loose and activate a cell death pathway. (nature.com)
  • Up-regulation of the complement system in subcutaneous adipocytes from nonobese, hypertriglyceridemic subjects is associated with adipocyte insulin resistance. (nature.com)
  • The complement system is the first line of immunological defense against foreign pathogens. (justia.com)
  • C3 plays a central role in the activation of the complement system. (gliome.org)
  • Our work implicates that complement system may be a therapeutic target for developing therapies to prevent or treat cognitive disorders related to neuroinflammation or other disease conditions including neurodegenerative disease per se. (imperial.ac.uk)
  • Complement activation The complement system is an enzyme cascade that helps defend against infection. (msdmanuals.com)
  • C1 inhibitor deficiency or dysfunction not only affects complement activation but also results in increased levels of bradykinin because C1 inhibitor inhibits activated kallikrein (required for the generation of bradykinin) in the kinin system pathway. (msdmanuals.com)
  • Our research group is focused on studies of the regulation of the complement system in health and disease. (lu.se)
  • Peritoneal stomata constitute the principal pathways for the drainage of intraperitoneal contents from the PERITONEAL CAVITY to the LYMPHATIC SYSTEM. (bvsalud.org)
  • High-throughput screens will aim to discover novel regulators of the MiT pathway, possibly independent of the canonical mTOR pathway. (eurac.edu)
  • Results: Native human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFβ and BMP pathways. (uea.ac.uk)
  • Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFβ or BMP pathway activation. (uea.ac.uk)
  • Conclusions: Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. (uea.ac.uk)
  • This in turn results in an exponential production of multiple factors such as cytokines and growth factors leading to the clinical manifestations of PE [ 11 ]. (hindawi.com)
  • Preeclampsia is considered a two stage-disease in which poorly perfused placenta produces factor(s) leading to systemic vascular disease and the clinical manifestations of preeclampsia ( 5 ). (frontiersin.org)
  • To date, there are no inhibitors of complement activation used in the clinic, though certain candidates for clinical use exist, specifically, a recombinant form of complement receptor 1 known as soluble complement receptor 1 (sCR1) and a humanized monoclonal anti-C5 antibody (5G1.1-scFv). (justia.com)
  • Several complement inhibitors targeting various complement pathways are in clinical trials for the treatment of HSCT-TMA. (biomedcentral.com)
  • Exposure of neutrophils to chemoattractants such as N-formylmethionyl-leucyl-phenylalanine (fMLP) and complement component 5a (C5a) induces cellular polarization of chemoreceptors and formation of actin-rich pseudopodia at the leading edge of the cell. (assignmentexpert.com)
  • and regulation of complement activation, alternative pathway. (jax.org)
  • Factor H is involved in the regulation of the alternative pathway of complement. (quidel.com)
  • Factor H also regulates the spontaneous fluid-phase activation of the alternative complement pathway by C3b-like forms of C3 that continuously arise in plasma and serum. (quidel.com)
  • Pangburn, M.K. and Müller-Eberhard, H.J. The alternative pathway of complement. (quidel.com)
  • Ratnoff, W.E., Fearon, D.T., and Austen, K.F. The role of antibody in the activation of the alternative complement pathway. (quidel.com)
  • Schreiber, R.D. and Müller-Eberhard, H.J. New developments in the activation of the alternative pathway of complement. (quidel.com)
  • Gotze, O. and Müller-Eberhard, H.J. The alternative pathway of complement activation. (quidel.com)
  • Factor H (FH) is the primary negative regulator of the alternative pathway (AP) of complement. (ersjournals.com)
  • My research focuses on understanding the roles of factors involved in alternative complement pathway activation and regulation. (uiowa.edu)
  • Properdin is a serum glycoprotein that up-regulates the alternative pathway of complement by stabilizing the C3b-Bb complex. (embl.de)
  • Angiogenic factors and their receptors are important regulators of placental vascular development [ 13 ]. (hindawi.com)
  • The most widely studied serum markers for PE, to date, are vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). (hindawi.com)
  • Similarly, sEng is a truncated form of receptor for two subtypes of transforming growth factor beta (TGF β ) specifically, TGF β 1 and TGF β 2 which are highly expressed by vascular endothelial cells and syncytiotrophoblasts. (hindawi.com)
  • The role of complement dysregulation on vascular endothelial cells has been well established in atypical hemolytic uremic syndrome (aHUS), a thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and target organ injury. (jrheum.org)
  • Further, we study I detail some novel complement regulators such as CSMD1, SUSD4 and COMP which are all also involved in breast cancer. (lu.se)
  • Relative FH deficiency was associated with increased factor consumption as evidenced by lower FB and C3 levels and higher Ba:FB and C3a:C3 ratios. (ersjournals.com)
  • Conclusions Relative FH deficiency, higher Ba:FB and C3a:C3 ratios, and lower FB and C3 levels suggest a subset of ARDS with complement factor exhaustion, impaired AP function, and increased mortality that may be amenable to therapeutic targeting. (ersjournals.com)
  • Defects in C4A are the cause of complement component 4A deficiency (C4AD). (assaygenie.com)
  • This results in platelet activation, endothelial cell damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis (breakdown of red blood cells), damage to multiple organs, and ultimately death. (wikipedia.org)
  • Platelet activation means their aggregation, sludge formation, furthermore the release of the for-mentioned biologically very powerful factors, which can locally amplify and deepen the tissue specific cell reactions. (biomedcentral.com)
  • The plasticity and heterogeneity of fibroblasts in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has emerged as a key factor in determining tumor growth and therapeutic response. (elifesciences.org)
  • Activating or blocking the ferroptosis pathway to alleviate the progression of the disease, which provides a promising therapeutic strategy for many diseases. (nature.com)
  • This project aims at shedding light on a potential mechanistic role of the MiT transcription factor pathway in relation to cellular and mitochondrial health in the etiology of PD and seeks to identify novel targets with the capacity to upregulate the MiT pathway and to increase degradation of aggregates and defective organelles, which may serve as therapeutic approach. (eurac.edu)
  • This study examines exciting new hallmarks for the strict involvement of autophagy and TGF-β signaling pathways in the pathogenesis of diabetes and the design of novel therapeutic strategies. (frontiersin.org)
  • Consequently, several therapeutic agents such as adiponectin, ezetimibe, GABA tea, geniposide, liraglutide, guava extract, and vitamin D were shown to inhibit diabetes and its complications through modulation of the autophagy pathway. (frontiersin.org)
  • In terms of gene expression, microarray and RNA sequencing have been applied to determine the most affected biological processes and molecular pathways at various disease stages. (biomedcentral.com)
  • Since route of allergen exposure can influence mechanistic pathways, mice were sensitized by identical routes with a high molecular weight occupational allergen ovalbumin and a low molecular weight occupational allergen trimellitic anhydride (TMA). (cdc.gov)
  • Both host factors (genetics) and low molecular weight allergens. (cdc.gov)
  • Examples of high molecular environmental factors are known to influence the development weight occupational allergens include proteases used in the and expression of asthma, and a vast array of triggers of asthma detergent industry, laboratory animal allergens, and ovalbumin have been identified. (cdc.gov)
  • Therefore, when concentrations of Factor H fall below normal levels, there is rapid fluid-phase activation and consumption of complement components both in vivo and in vitro . (quidel.com)
  • Like sFlt1, soluble endoglin (sEng) is an antiangiogenic factor capable of inhibiting capillary tube formation in vitro [ 17 ]. (hindawi.com)
  • How the immune response can activate the cascade process is still unknown but it is proposed to act in synergy with additional exacerbating factors such as predisposing maternal and ambient factors [ 12 ]. (hindawi.com)
  • C3 is unique in that it possesses a rich architecture that provides a multiplicity of diverse ligand binding sites that are important in immune surveillance and immune response pathways. (justia.com)
  • Both genetics and environmental factors influence the expression of asthma, and not all asthma is the result of a specific immune response to allergen. (cdc.gov)
  • Involved in negative regulation of lipid transport and negative regulation of reactive oxygen species biosynthetic process. (nih.gov)
  • The signal (PAF, or other tissue/cell specific factors) comes from the stimulated (by the e.g., hypophyseal hormones, bacteria, external factors, etc.) organs or cells, and activates platelets. (biomedcentral.com)
  • After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. (gliome.org)
  • This gene encodes the basic form of complement factor 4, part of the classical activation pathway. (assaygenie.com)
  • RICTOR Amplification Promotes NSCLC Cell Proliferation through Formation and Activation of mTORC2 at the Expense of mTORC1. (nih.gov)
  • The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined. (uea.ac.uk)
  • Here we describe the cellular pathways involved in the host response to experimental pneumococcal meningitis in specified disease states and brain regions. (biomedcentral.com)
  • Thus, GAGs/PGs may modulate downstream signaling of key cellular mediators including insulin growth factor receptor (IGFR), epidermal growth factor receptor (EGFR), estrogen receptors (ERs), or Wnt members. (hindawi.com)
  • Spiller B. O., Blackbourne, D., Mark L, Proctor D. and * Blom A. M. , (2003) Functional activity of the complement regulator encoded by Kaposi's sarcoma associated herpesvirus. (lu.se)
  • internal or external triggers and/or stimuli may complement and connect regulatory pathways aimed towards target tissues and/or cells. (biomedcentral.com)
  • Recently, we initiated projects focused on studies of intracellular complement such as role of complement inhibitor CD59 in insulin secretion and C3 in regulation of autophagy. (lu.se)
  • Yet, a great deal of complexity exists around the role of complement in TMA associated with other diseases. (jrheum.org)
  • Defining the role of complement in TMA in these conditions will help to guide timely diagnosis and management. (jrheum.org)
  • This defect can be complemented by a calcium ionophore, indicating that activation of the calcium path- way is impaired. (unisi.it)
  • Several lines of evidence implicate Fyn in the regulation of calcium mobilization, at least in part through the activation of phospholipase C. Here we have investigated the potential involvement of Fyn in the TCR -CPM signaling defect. (unisi.it)
  • Hence the signaling defect generated by the TCR -CPM mutation results at least in part from an impaired coupling of the TCRCD3 complex to Fyn activation. (unisi.it)
  • A Warburg-like metabolic program coordinates Wnt, AMPK, and mTOR signaling pathways in epileptogenesis. (nih.gov)
  • Early signs of systemic complement-mediated TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%) and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin (the oxygen-containing component of blood), and/or the presence of schistocytes. (wikipedia.org)
  • Other project pursued in our group related to involvement of complement in pathology of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. (lu.se)
  • It is well known, that platelets have an armament of soluble molecules, factors, mediators, chemokines, cytokines and neurotransmitters in their granules, and have multiple adhesion molecules and receptors on their surface. (biomedcentral.com)
  • AMPK pathways are energy regulation pathways. (springer.com)
  • It is widely accepted that members of the complement pathway are expressed at high levels in white adipose tissue (WAT). (nature.com)
  • Complement-mediated tissue injury has also been found to result from bioincompatibility situations such as those encountered in patients undergoing dialysis or cardiopulmonary bypass. (justia.com)
  • Through these pathways activated platelets are accumulated in the follicular vessels surrounding the follicle and due to its released soluble molecules (factors, mediators, chemokines, cytokines, neurotransmitters) locally increase oocyte maturation and hormone secretion. (biomedcentral.com)
  • The results highlight a different functional impairment, with VV2 associated with higher impairment of the pathways related to dopamine secretion, regulation of calcium release and GABA signaling, showing some similarities with Parkinson's disease both on a genomic and a transcriptomic level. (biomedcentral.com)
  • Known levels of Factor H aid in the diagnosis of several disease states such as atypical Hemolytic-Uremic Syndrome (aHUS), age-related macular degeneration, and dense deposit disease. (quidel.com)
  • Whereas in the acute phase of the disease immunoregulatory processes prevail in the hippocampus and the cortex, we observed a strong activation of neurogenic processes in the hippocampal dentate gyrus, both by gene expression and immunohistology starting as early as 3 days after infection. (biomedcentral.com)
  • Dysfunctions of mitochondria and the autophagy-lysosomal pathway (ALP) take part in the pathologic process of Parkinson's disease (PD) and are induced by most PD-associated mutations. (eurac.edu)
  • Hematopoietic stem cell transplantation and associated risk factors precipitate endothelial injury, leading to HSCT-TMA and other endothelial injury syndromes such as hepatic veno-occlusive disease/sinusoidal obstruction syndrome, idiopathic pneumonia syndrome, diffuse alveolar hemorrhage, capillary leak syndrome, and graft-versus-host disease. (biomedcentral.com)
  • When the liver is saturated with glycogen, any additional glucose taken up by hepatocytes is shunted into pathways leading to synthesis of fatty acids, which are exported from the liver as lipoproteins. (assignmentexpert.com)
  • ERS pathways are triggered by the unbalance of ER environment, including hypoxia, disturbance of Ca 2+ homeostasis and glucose starvation. (springer.com)
  • The prominent role of autophagy signaling pathway was supported by the alteration of autophagy markers in patients and animal models of T1DM, T2DM, and gestational diabetes. (frontiersin.org)
  • We hypothesized that mechanistic pathways leading to asthma symptoms in the effector phase of the disorder differ with the inciting allergen. (cdc.gov)
  • 1-5 The activation of this complement pathway can be triggered by a variety of substances including microbial polysaccharides or lipids, gram negative bacterial lipopolysaccharides, and surface determinants present on some viruses, parasites, virally infected mammalian cells, and cancer cells. (quidel.com)
  • Being able to specifically eliminate pro-cancer fibroblasts requires a better understanding of the factors that shape the role of these cells, and how to identify them. (elifesciences.org)
  • Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting in a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. (nature.com)
  • Pattern-recognition molecules such as mannose-binding lectin (MBL), collectins, and ficolins-collectively termed lectins-bind to DAMPs on injured host cells, forming activation complexes with MBL-associated serine proteases 1, 2, and 3 (MASP-1, MASP-2, and MASP-3). (biomedcentral.com)
  • The mouse models we have generated to modulate senescence response in vivo are also used in our studies of senescence regulation in aging, with an emphasis on adult stem cells. (umassmed.edu)
  • Fresh whole blood has long been thought of as the criterion standard for transfusion, but the advent of whole blood fractionation techniques subsequent to World War II provided a means of more efficient use of the various components (i.e., packed red blood cells [PRBCs], fresh frozen plasma [FFP], individual factor concentrates, platelet concentrates, cryoprecipitate). (medscape.com)
  • Advancements in the understanding of the etiopathogenesis of aHUS paved the way for the successful development of anticomplement therapies (complement C5 inhibitors), which have revolutionized the treatment of aHUS. (jrheum.org)
  • Background Effective regulation of complement activation may be crucial to preserving complement function during ARDS. (ersjournals.com)
  • Blom A. M. , Webb J., Villoutreix B. and *Dahlbäck B. (1999) A cluster of positively charged amino acids in the N-terminal modules of C4BP a-chain is crucial for the C4b binding and factor I cofactor function. (lu.se)