Cytotoxic necrotizing factor type 2 (CNF2) produced by Escherichia coli strains isolated from intestinal and extraintestinal infections is a dermonecrotic toxin of 110 kDa. We cloned the CNF2 gene from a large plasmid carried by an Escherichia coli strain isolated from a lamb with septicemia. Hydropathy analysis of the deduced amino acid sequence revealed a largely hydrophilic protein with two potential hydrophobic transmembrane domains. The N-terminal half of CNF2 showed striking homology (27% identity and 80% conserved residues) to the N-terminal portion of Pasteurella multocida toxin. Methylamine protection experiments and immunofluorescence studies suggested that CNF2 enters the cytosol of the target cell through an acidic compartment and induces the reorganization of actin into stress fibers. Since the formation of stress fibers in eukaryotic cells involves Rho proteins, we radiolabeled these small GTP-binding proteins from CNF2-treated and control cells with a Rho-specific ...
SWISS-MODEL Template Library (SMTL) entry for 1hq0.1. CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF E.COLI CYTOTOXIC NECROTIZING FACTOR TYPE 1
Atherton, J.C., Cao, P., Peek Jr., R.M., Tummuru, M.K., Blaser, M.J. and Cover, T.L. (1995) Mosaicism in Vacuolating Cytotoxin Alleles of Helicobacter pylori. Association of Specific vacA Types with Cytotoxin Production and Peptic Ulceration. The Journal of Biological Chemistry, 270, 17771-17777.
Results A potentially important polymorphism was identified within an imperfect inverted repeat where an A was commonly replaced by a T at position -54. Strains possessing T at this position expressed higher cagA mRNA levels than those with an A (p=0.016). To test whether this was a direct determinant of cagA transcription level, a mutation was engineered at position −54 (T to A) in high transcription strain 83. This resulted in a 30% reduction in cagA transcript level when compared to an isogenic control strain without the change (p=0.073). In the complementary experiment, we engineered an A to T mutation in low transcription strain 126 and this led to a 20% increase in the level of cagA mRNA compared to its isogenic control (p=0.002). ...
Bell, R B. and Ivor, K L., The effects of a macrophage-derived cytotoxin on the growth and metabolism of target cells. (1976). Subject Strain Bibliography 1976. 826 ...
Principal Investigator:SUGAI Motoyuki, Project Period (FY):1997 - 1998, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Bacteriology (including Mycology)
Aarhus University. Bacteria that cause infectious diseases produce a number of cytotoxins, and an international research team has now found the mechanism behind one of these toxins. The new results could make it possible in the future to develop new treatment methods to impair the cytotoxic activity and thereby reduce the severity of infectious diseases.. In spite of the fact that the first antibiotics were discovered almost a century ago, infectious diseases such as tuberculosis, encephalitis and meningitis are still serious diseases for humans in the twenty-first century. The World Health Organization (WHO) estimates that there are more than 8 million new cases of tuberculosis per year on a global scale, and that more than 300,000 of these are due to multidrug-resistant strains that are not only difficult to treat, but are also emerging rapidly in regions such as Eastern Europe.. Bacterial tolerance is not just due to resistance, but also to the formation of persistent cells that have gone ...
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Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and
Cholesterol-dependent cytolysins (CDCs), a class of gram-positive bacterial exotoxins, bind cholesterol in cell membranes and oligomerize to form pores. We observe that CDCs induce pores in dendritic cells (DC) as well as other cell types in a dose dependent manner, which allows the subsequent release of adenosine triphosphate (ATP). Extracellular ATP can exert stimulatory effects on cells through engagement of surface purinergic receptors, several of which are expressed on DC, including P2X7, which upon ATP binding forms a pore in the plasma membrane. We show here that a mutant DC line selected for resistance to lytic CDC doses loses expression of the P2X7 receptor and also becomes insensitive to ATP-induced pore formation compared to wild type cells. A model is suggested where CDCs form pores in DC membranes, allowing the release of ATP that signals through P2X7 on DC. Chronic ATP stimulation of DC results in skewed DC maturation that favors type 2 immune responses. Thus, CDC-induced ATP ...
Epilepsy, one of the most common conditions affecting the brain, is characterized by neuroplasticity and brain cell energy defects. In this work, we demonstrate the ability of the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1) to counteract epileptiform phenomena in inbred DBA/2J mice, an animal model displaying genetic background with an high susceptibility to induced- and spontaneous seizures. Via modulation of the Rho GTPases, CNF1 regulates actin dynamics with a consequent increase in spine density and length in pyramidal neurons of rat visual cortex, and influences the mitochondrial homeostasis with remarkable changes in the mitochondrial network architecture. In addition, CNF1 improves cognitive performances and increases ATP brain content in mouse models of Rett syndrome and Alzheimers disease. The results herein reported show that a single dose of CNF1 induces a remarkable amelioration of the seizure phenotype, with a significant augmentation in neuroplasticity markers and
symplocamide A: a potent cytotoxin and chymotrypsin inhibitor from the marine Cyanobacterium Symploca sp.; structure in first source
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Glioblastomas are largely unresponsive to all available treatments and there is therefore an urgent need for novel therapeutics. Here we have probed the antineoplastic effects of a bacterial protein toxin, the cytotoxic necrotizing factor 1 (CNF1), in the syngenic GL261 glioma cell model. CNF1 produces a long-lasting activation of Rho GTPases, with consequent blockade of cytodieresis in proliferating cells and promotion of neuron health and plasticity. We have tested the antiproliferative effects of CNF1 on GL261 cells and human glioma cells obtained from surgical specimens. For the in vivo experiments, we injected GL261 cells into the adult mouse visual cortex, and five days later we administered either a single intracerebral dose of CNF1 or vehicle. To compare CNF1 with a canonical antitumoral drug, we infused temozolomide (TMZ) via minipumps for 1 week in an additional animal group. In culture, CNF1 was very effective in blocking proliferation of GL261 cells, leading them to multinucleation,
This application proposes studies to identify the mechanism by which the Helicobacter pylori vacuolating cytotoxin (VacA) is trafficked to mitochondria in host...
TY - JOUR. T1 - Cloning and nucleotide sequence of frpC, a second gene from Neisseria meningitidis encoding a protein similar to RTX cytotoxins. AU - Thompson, Stuart A.. AU - Wang, Lisa L.. AU - Sparling, P. Frederick. PY - 1993/7. Y1 - 1993/7. N2 - Neisseria meningitidis FAM20 has recently been shown to produce two Fe‐regulated proteins (FrpA and FrpC) related to the RTX family of cytotoxins. Here we report the cloning and DNA sequence of the locus containing the gene encoding the larger meningococcal RTX protein FrpC. FrpC was highly similar to FrpA throughout much of the predicted protein, with two main differences. Whereas the FrpA protein had 13 copies of the nine‐amino‐acid repeat units typical of RTX proteins, FrpC had 43 copies. The additional copies in FrpC apparently arose from a threefold tandem amplification of a 600bp DNA fragment encoding the repeats. In addition, the frpC gene lacked good promoter consensus sequences. An open reading frame (0RF1) of unknown function was ...
The vacuolating cytotoxin is encoded by a 3864 bp ORF in thevacA gene.22 The 137 kDa vacAgene product consists of three regions: a 33 amino acid amino-terminal signal peptide, a mature cytotoxin domain of approximately 87 kDa, and a carboxy-terminal 50 kDa segment which is cleaved from the molecule during transmembrane export.22 27 The recombinant protein described in this study predominantly covers the 87 kDa domain.. Previous studies indicated that the vacuolating cytotoxin, which induces cellular vacuolation in a number of epithelial cell lines in vitro, is produced only by a subset of H pyloriisolates.11 13 Furthermore, several studies suggested that infection by cytotoxin positive strains was correlated with the development of gastroduodenal diseases.12 29 Figuraet al 29 reported that 67% of H pylori strains isolated from 24 patients with peptic ulcers produced cytotoxin, whereas only 30% of strains from 53 patients with chronic gastritis produced cytotoxin. Fox et al 12 reported that the ...
Objective: To study the effect of Aloe Extract C ( AE - C) in inducing cytotoxic factors in mice. Methods: Mice were injected with AE - C through abdominal cavity for 5 days, blood was taken for separating serum on the sixth day. Y99 , L929 and A549 tumor cell lines were used as target cells to assay cytotoxic factors activity of the serum. The lasting time of the activity, its sensitivity to temperature and the cytotoxic activity of different concentration of the serum were observed. Results: AE - C could induce the production of cytotoxic factors in BALB/C mice, compared with the control, there was a significant differences ( P 0. 01 ) . Cytotoxic activity reached the peak 24 hours after last injection of AE - C and began to drop 4 days later. The cytotoxic activity disappeared 5 days later. The cytotoxic acitivity was still obvious with 200 times dilution of the serum. Conclusions: AE - C can induce the production of cytotoxic factors in BALB/C mice.
Campylobater jejuni, a major foodborne diarrhoeal pathogen is reported to produce a number of cytotoxins of which only a cytolethal distending toxin (CDT) has been characterised so far. One or more additional cytotoxins other than CDT, including a Chinese hamster ovary (CHO) cell active, Vero cell inactive cytotoxin, may mediate inflammatory diarrhoea. Our objective was to develop a method to enrich and thus partially characterise this cytotoxin, as a pathway to the eventual identification and characterisation of the toxin. A number of biochemical methods including cation- and anion-exchange chromatography were evaluated to enrich the cytotoxin from a cell lysate of a known cytotoxin-producing C. jejuni, C31. The cytotoxin in crude lysate was initially prepared by size-exclusion desalting and then subjected to high pressure liquid chromatography (HPLC) ion-exchange fractionation. One pooled fraction (pool B) was cytotoxic for CHO cells equivalent to crude toxin (tissue culture infectivity dose 50
1.C.14 The Cytohemolysin (CHL) Family The CHL family consists of hemolytic cytotoxins from various species of Vibrio, Aeromonas and Listonella. The proteins act on a variety of target animal cells such as enterocytes and immune cells. During secretion of the V. cholerae cytolysin, the N-terminal 25 residue leader peptide is cleaved off yielding an extracellular 79 kDa procytolysin which must be proteolytically activated. Removal of an N-terminal 14 kDa fragment of the procytolysin followed by further proteolytic cleavage in the C-terminal region yields an active 50 kDa species which oligomerizes in the presence of cholesterol-sphingolipid-containing membranes to generate a transmembrane water-filled pore of about 1.5 nm diameter. The complex is probably a homoheptamer (Olson & Gonaux, 2005). This family is distantly related to the αHL family (#1.C.3) of heptameric toxins from Gram-positive bacteria. Vibrio cholerae cytolysin (VCC; 1.C.14.1.1) is an oligomerizing pore-forming toxin that is ...
A low-molecular-mass cytotoxin produced by Klebsiella oxytoca isolated previously from patients with antibiotic-associated haemorrhagic enterocolitis was purified, and its biological and chemical properties were elucidated. The toxin inhibited the syntheses of DNA and RNA by HEp-2 cells dose-dependently, whereas protein synthesis was only slightly inhibited, as measured by the incorporation of radioactive precursors. When synchronously cultured HEp-2 cells were examined in the presence of cytotoxin, inhibition of DNA synthesis occurred promptly within 5 h, but cell-rounding, the earliest visible morphological change, was not observed until 6 h after exposure. The intracellular levels of ATP decreased with an approximately similar time course. These results suggest that cytotoxicity toward HEp-2 cells is primarily due to the inhibitory effect of the cytotoxin on nucleic acid synthesis, possibly on DNA synthesis. Cell rounding and cell death were induced even in the absence of the cytotoxin after
Cytotoxic necrotizing factors from E. coli (CNF1, CNF2) and Yersinia (CNFy) share N-terminal sequence similarity with Pasteurella multocida toxin (PMT). This common N-terminal region harbors the receptor-binding and translocation domains that mediate uptake and delivery of the C-terminal catalytic cargo domains into the host cytosol. Subtle variations in the N-terminal ~500 amino acids of CNFs and PMT could allow for selective recognition of cellular receptors and thus, selective target cell specificity. Through studies with cellular inhibitors, we have identified an additional novel function for this region in modulating responses of these toxin proteins to changes in pH during intoxication and delivery of the catalytic cargo domain into the cytosol.
Dinner was interesting, and I dare say promising: in our very first trial run, we managed to make it seem normal that someone could sit at dinner, eat less than four bites of food, and repeatedly hold a barf bucket to her face while we conversed about school and the weather.. *. There will be trace amounts of cytotoxins in Sadies urine, feces, and vomit. We need to be sure to wash carefully using soap and flush twice after shes used the toilet. Soiled bed linens and clothes should be rinsed separately first, then washed normally with the rest of the laundry. We should avoid touching her etoposide capsules.. *. Unless Sadie is seriously ill (as opposed to just feeling like shit and throwing up at random times), we are clear to go on vacation. If youre going to FLSATUART no matter what, seems like doing so in a balmy beach breeze beats doing it at home in bed.. ...
Death metalowcy z Cytotoxin opublikowali w całości do odsłuchu nowy krążek Gammageddon. Album ukazał się pod skrzydłami wytwórni Unique Leader Records.
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Cytokinetics is up $1.15 or 10% to $12.90 in a poor market environment. The only news is that the Company will be added to the S&P 600 small cap index. There is
Description. The project will be conducted in a highly stimulating, interdisciplinary and international environment in the department of Bacteriology of the Institut Pasteur, Paris. The successful candidate will start in 2018 the study of the interplay of bacterial toxins with the cellular ubiquitin and proteasome systems and consequences in infection. Funding for an additional 1 year will be dependent on the CV of the applicant and advancement of the project.. Post-translational modifications of proteins by ubiquitination are central reactions in the maintenance of cellular homeostasis, quality control of the proteome and innate immune signaling in reaction to the attacks by pathogens, which frequently have acquired the ability to divert ubiquitin-mediated reactions to their advantage. It is therefore essential to define the interplay between bacterial virulence factors and ubiquitin-mediated cellular regulations. The study of the cytotoxic necrotizing factor-1 (CNF1) from pathogenic ...
We purified a new cytolysin (HMgIII) from the sea anemone, Heteractis magnifica. HMgIII, which has a molecular mass of ~19 kDa, functions as both a cytolysin and a hemolysin. The full-length HMg III cDNA was obtained by reverse transcriptase-polymerase chain reaction, using primers designed from its N-terminal amino acid sequence and an internal conserved region of two other sea anemone cytolysins: equinatoxin II (EqT II) and cytolysin III. The cDNA contained an open reading frame of 633 bp, which encodes a protein of 211 amino acids. The nascent HMg III protein contained a prepropeptide of 34 amino acids, which includes a signal peptide of 19 amino acids. The mature HMg III has a predicted molecular mass of 19 kDa and a pI of 9.1, and shares 91%, 89%, 65% and 63% amino acid sequence similarity with cytolysin III, cytolysin ST I, tenebrosin-C and equinatoxin (EqT II), respectively. The predicted secondary structure of the mature HMg III comprises 16% α-helix, 23% extended strand and 60% random ...
Mechanical and Aerospace Engineering, ICMAE2011: Nanocomputational Observation of Interaction of Two Cytotoxins and Nanobio Membrane: Molecular Dynamics Simulation Study
Cytolysin refers to the substance secreted by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly. For instance, the cytolysins responsible for the destruction of red blood cells, thereby liberating hemoglobins, are named hemolysins, and so on. Cytolysins may be involved in immunity as well as in venoms. Hemolysin is also used by certain bacteria, such as Listeria monocytogenes, to disrupt the phagosome membrane of macrophages and escape into the cytoplasm of the cell. The term Cytolysin or Cytolytic toxin was first introduced by Alan Bernheimer to describe membrane damaging toxins (MDTs) that have cytolytic effects to cells. The first kind of cytolytic toxin discovered have hemolytic effects on erythrocytes of certain sensitive species, such as Human. For this reason Hemolysin was first used to describe any MDTs. In the 1960s ...
Activation of Rho, Rac and Cdc42 controls actin polymerization during phagocytosis. Left, a general model for phagocytic signalling. Phagocytosis generally involves the receptor-mediated, GEF-dependent activation of one or more Rho GTP-binding proteins, which will activate-through downstream effectors-the Arp2/3 complex and actin polymerisation. Several bacterial pathogens have the capacity to produce toxins or bacterial effectors (shown in double-lined boxes) that activate or inhibit the function or one or more Rho proteins, thereby modulating actin polymerization and phagocytosis. Right, the main signalling pathways activated during phagocytosis in mammalian cells. Type I phagocytosis is characterized by the independent activation of Rac and Cdc42, whereas only Rho activity is required during type II phagocytosis. GEF, guanine nucleotide exchange factor; CNF1, cytotoxic necrotizing factor 1 Tir, translocated intimin receptor; Yop, Yersinia outer protein; FcγR, Fcγ receptor; AC, apoptotic cell; CR3,
Oral administration of VacA in mice caused several aspects of the histological lesions in epithelium of gastric mucosa, namely loss of gastric gland architecture including epithelial vacuolization, edema, erosion, necrosis, and exfoliation 24 h after inoculation (Fig. 1⇓B). The marked infiltrations of mast cells and mononuclear cells and a few eosinophils were observed 24 h after inoculation (Fig. 1⇓, D and F). The mast cells located in the mucosal layer had spindle shape and less granules (Fig. 1⇓, G and H). In contrast, the epithelium of gastric mucosa in control mice 24 h after inoculation of saline did not show any lesion, with rare mucosal mast cells (MMC) and no inflammatory cells (Fig. 1⇓, A, C, and E). Administration of BSA as a high protein control did not show any epithelial lesions nor histological changes, as were seen in VacA-treated mice (data not shown). These pathological changes were not observed 72 h after inoculation of VacA with no mononuclear cell and less mast cell ...
Aberrant protein folding and self-assembly underlie over 30 human diseases called amyloidoses, for which currently there is no cure. The diseases range from tissue-specific to systemic and from geneti
We identify cytochrome P450 1A1 (CYP1A1) as a target for tumor-selective drug development in bladder cancer and describe the characterization of ICT2700, designed to be metabolized from a prodrug to a potent cytotoxin selectively by CYP1A1. Elevated CYP1A1 expression was demonstrated in human bladder cancer relative to normal human tissues. RT112 bladder cancer cells, endogenously expressing CYP1A1, were selectively chemosensitive to ICT2700, whereas EJ138 bladder cells which do not express CYP1A1 were significantly less responsive. Introduction of CYP1A1 into EJ138 cells resulted in 75-fold increased chemosensitivity to ICT2700 relative to wild-type EJ138. Negligible chemosensitivity was observed to ICT2700 in EJ138 cells expressing CYP1A2, or with exposure of EJ138 cells to CYP1B1 or CYP3A4 generated metabolites of ICT2700. Chemosensitivity to ICT2700 was also negated in EJ138-CYP1A1 cells by the CYP1 inhibitor α-naphthoflavone. Furthermore, ICT2700 did not induce expression of the ...
Although protein-based drugs have shown success, they have been limited mostly to cytokines, growth factors, enzymes and monoclonal antibodies, all of which function primarily extracellularly.
Researchers at Harvard have programmed stem cells embedded in a tumor to deliver a toxic dose of cytotoxins, killing the cancer cells from the inside.
As a result of pre-natal or early post-natal exposure to a variety of agents (viruses, irradiation and cytotoxins) humans may develop microencephaly, characterized by reduction of brain size (Crome &...
Runkel, S (2014) Endogenous production and detoxification of a potent cytotoxin, nitric oxide, in Salmonella enterica serovar Typhimurium and Escherichia coli. Doctoral thesis, University of East Anglia. ...
β-PFT sind in ihrer Proteinstruktur aus β-Faltblättern aufgebaut. α-Hämolysin[7] und Leukozidin S[8] sind strukturell verwandt, ebenso Aerolysin[9] und Clostridium ε-Toxin.[10] β-PFT sind Proteine, die als lösliche Monomere oder porenbildende Proteinkomplexe vorliegen. Der Kopf des heptameren α-Hämolysins ragt aus der Membran heraus, während der Stamm in der Lipiddoppelschicht der Membran liegt. Der Stamm besteht aus einem vierzehnsträngigen β-barrel, mit zwei Strängen aus jedem Monomer. Das Vibrio cholerae Cytolysin ist ebenfalls heptamer.[11] Das Staphylococcus aureus γ-Hämolysin bildet eine oktamere Pore aus sechzehn Strängen.[12] Das Panton-Valentine-Leukozidin S besitzt als Monomer eine ähnliche Form.[13] Die Bindung der Monomere aneinander und die Einfügung in die Membran erfolgt ähnlich wie bei den Zytolysinen durch Zusammenlagerung peripher an der Membran, gefolgt von einer Änderung der Proteinfaltung und der Einfügung des Stamms in die Membran anhand hydrophober ...
The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX (repeats in toxin) refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon. RTX proteins range from 40 to over 600 kDa in size and all contain C-terminally located glycine and aspartate-rich repeat sequences of nine amino acids. The repeats contain the common sequence structure [GGXGXDX[L/I/V/W/Y/F]X], (where X represents any amino acid), but the number of repeats varies within RTX protein family members. These consensus regions function as sites for Ca2+ binding, which facilitate folding of the RTX protein following export via an ATP-mediated type 1 ...
PG Colon Course - Rocco Ricciardi C. diff-27 sec https://www.ncbi.nlm.nih.gov/pubmed/15238490 https://www.ncbi.nlm.nih.gov/pubmed/?term=17638799 trend changes-2:24 https://www.ncbi.nlm.nih.gov/pubmed/?term=15116 Keyword(s): antibody response, bowel prep, C. diff colitis, CD, CDC, clinical severity score, CMS, community-acquired, cytotoxins, diarrhea, disease severity, donor stool, end ileostomy, enema, epidemic, Flagyl, fulminant pseudomembranous colitis, gastric acid-suppressive agents, hospital-acquired, IBD, immunoglobulins, lactate, laparoscopy, Malecot, Medicare reimbursement, mucous […] ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The idea is that in response to vaccination, the body generates antibodies only against those proteins - those will bind to the surface of the bacteria when someone coughs at you and prevent the bacteria from sticking to your respiratory tract. Everything that is not circled in red is NOT in the vaccine. There is no chance that some surface bits injected into your arm or leg cause an illness that requires loads of bacteria sticking to those tiny cilia in your respiratory tract. Furthermore, the vaccine also does not contain the tracheal cytotoxin, which the bacteria release and which paralyses those cilia and prevent them from clearing your airways, which is what causes the characteristic cough (,- click on that link - this is what pertussis sounds like ...
Fig. S1. The apoptotic effect of caffeic acid phenethyl ester (CAPE) on human CD4+ T cells. CD4+ T cells (106 cells/ml) were cultured for 48 h in the indicated concentrations of CAPE (0-100 μM). The percentage of annexin-V+ and 7-amino actinomycin D (7-AAD)+ cells were measured by flow cytometry.. Fig. S2. The apoptotic effect of caffeic acid phenethyl ester (CAPE) on stimulated human CD4+ T cells. CD4+ T cells (106 cells/ml) were cultured for 48 h in the absence or presence of CAPE (10 μM) with soluble anti-CD3 and anti-CD28 monoclonal antibodies (2 μg/ml) stimulation. The percentage of annexin-V+ and 7-amino actinomycin D (7-AAD)+ cells from four asthmatic patients were measured by flow cytometry.. Fig. S3. Caffeic acid phenethyl ester (CAPE) inhibits interferon (IFN)-γ and interleukin (IL)-5 production by polarized T helper type 1 (Th1) and Th2 cells. Polarized helper T cells (106 cells/ml) were cultured for 48 h in the absence or presence of CAPE (10 μM) with soluble anti-CD3 and ...
In vivo and in vitro antıneoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives.. Akyol S1, Ozturk G, Ginis Z, Armutcu F, Yigitoglu MR, Akyol O.. Author information. Abstract. Cancer prevention and treatment strategies have attracted increasing interest. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, specifically inhibits NF-κB at μM concentrations and shows ability to stop 5-lipoxygenase-catalyzed oxygenation of linoleic acid and arachidonic acid. Previous studies have demonstrated that CAPE exhibits antioxidant, antiinflammatory, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and, most improtantly, antineoplastic properties. The primary goal of the present review is to summarize and critically evaluate the current knowledge regarding the anticancer effect of CAPE in different cancer types.. PMID: 23659443 [PubMed - indexed for MEDLINE]. ...
TY - JOUR. T1 - Caffeic acid phenethyl ester inhibits nuclear factor-κB and protein kinase B signalling pathways and induces caspase-3 expression in primary human CD4+ T cells. AU - Wang, L. C.. AU - Chu, K. H.. AU - Liang, Y. C.. AU - Lin, Y. L.. AU - Chiang, B. L.. PY - 2010/5. Y1 - 2010/5. N2 - Summary Caffeic acid phenethyl ester (CAPE), an active component in propolis, is known to have anti-tumour, anti-inflammatory and anti-oxidant properties. In this study, the effects of CAPE on the functions of primary human CD4+ T cells were evaluated in vitro. CAPE significantly suppressed interferon (IFN)-γ and interleukin (IL)-5 production and proliferation of CD4+ T cells stimulated by soluble anti-CD3 and anti-CD28 monoclonal antibodies in both healthy subjects and asthmatic patients. CAPE inhibited nuclear factor (NF)-κB activation and protein kinase B (Akt) phosphorylation, but not p38 mitogen-activated protein kinase (MAPK) phosphorylation in T cells. CAPE also induced active caspase-3 ...
We found that micromolar concentrations of caffeic acid phenethyl ester blocked voltage-gated sodium channel activity in several invasive cell lines from different cancers, including breast (MDA-MB-231 and MDA-MB-468), colon (SW620) and non-small cell lung cancer (H460). In the MDA-MB-231 cell line, which was adopted as a model, long-term (48h) treatment with 18μM caffeic acid phenethyl ester reduced the peak current density by 91% and shifted steady-state inactivation to more hyperpolarized potentials and slowed recovery from inactivation. The effects of long-term treatment were also dose-dependent, 1μM caffeic acid phenethyl ester reducing current density by only 65%. The effects of caffeic acid phenethyl ester on metastatic cell behaviours were tested on the MDA-MB-231 cell line at a working concentration (1μM) that did not affect proliferative activity. Lateral motility and Matrigel invasion were reduced by up to 14% and 51%, respectively. Co-treatment of caffeic acid phenethyl ester ...
CAPE (caffeic acid phenethyl ester) is one of the most valuable and investigated component of propolis which is composed by honeybees. In the current study, we aimed at examining apoptotic effects of CAPE on CCRF-CEM leukemic cells and at determining the roles of mitochondrial membrane potential (MMP) in cell death. ...
Objective(s): Pulmonary fibrosis (PF) is the most common outcome of a collection of diverse lung disorders known as interstitial lung diseases. It is proposed that alterations in the levels of fibrogenic mediators and the profibrotic/antifibrotic imbalance play a substantial role in the progression of PF in animal models and possibly in humans. Caffeic acid phenethyl ester (CAPE), an active component of propolis, has numerous biological effects. In the present study, the main objective was to investigate the effects of CAPE on some key mediators including TGF-β1, TNF-α and prostaglandin E2 (PGE2 ) involved in profibrotic/antifibrotic balance and pathogenesis of idiopathic pulmonary fibrosis (IPF). Materials and Methods: In this study, forty male Sprague-Dawley rats were divided into 5 groups (n=8). (1)
Background: To investigate the effects of propofol and caffeic acid phenethyl ester (CAPE) on prevention of lung injury as a remote organ after performing hindlimb ischaemia-reperfusion (IR) in a rat model. ...
Caffeic acid phenethyl ester is Inhibits ornithine decarboxylase, protein tyrosine kinase and lipoxygenase activities. Cited in 17 publications
The optimal production of P. haemolytica leukotoxin in the culture supernatant of a fluid medium is dependent on a number of factors. The leukotoxin has to be produced by using a strain that is known for its ability to produce high quantities of leukotoxin, inoculated into the most suitable type of medium at the correct culture density containing the necessary supplements and harvested after a certain growth period. The volume in which it is produced may also have an influence. Two different procedures are described to produce the leukotoxin in 5 to 15-ℓ quantities in RPMI 1640 medium. The first method used to produce leukotoxin is one that has been repeatedly described since the presence of the leukotoxin was first established in 1978. Using this method seven batches of leukotoxin were produced in litre quantities with leukotoxin activity ranging from 23-67 u/mℓ. The seed culture inoculum is prepared in brain heart infusion broth, which is centrifuged before the organisms are inoculated ...
Definition of clostridial toxin in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is clostridial toxin? Meaning of clostridial toxin as a finance term. What does clostridial toxin mean in finance?
In 1999, an infectious disease prevention law was enacted in Japan that affected the nationwide infectious surveillance system. A total of 19,304 laboratory-confirmed verocytotoxin-producing Escherichia coli cases were reported through 2004. The annual incidence was 2.74/100,000 population; its fluctuation over time and space was associated with climate, socioeconomic, and population factors.
Abstract Streptococcus pneumoniae (pneumococcal) meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium
Title:Synthesis of Icaritin and β-anhydroicaritin Mannich Base Derivatives and Their Cytotoxic Activities on Three Human Cancer Cell Lines. VOLUME: 17 ISSUE: 1. Author(s):Van-Son Nguyen, Ling Shi, Sheng-Chun Wang and Qiu-An Wang. Affiliation:Technology Faculty of Thanh Hoa Campus, Industrial University of Ho Chi Minh City, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082. Keywords:Icaritin, β-anhydroicaritin, Mannich base derivatives, synthesis, cytotoxic activity.. Abstract:Background: Prenyl flavonoid icaritin (1) and β-anhydroicaritin (2) are two natural products with important biological and pharmacological effects. such as antiosteoporosis, estrogen regulation and antitumor properties. Objective: The present study investigates the synthesis and cytotoxic activities on three Human cancer cell ...
Vibrio cholerae produces a cytolytic toxin named El Tor cytolysin/hemolysin which is encoded by the hlyA gene. This cytolysin is produced as a 79-kDa precursor form (pro-HlyA) into the culture supernatant after cleavage of the signal peptide of the hlyA product (prepro-HlyA). The pro-HlyA is then processed to a 65-kDa mature cytolysin (mature HlyA) after cleavage of the 15-kDa N-terminal peptide (pro region) of the 79-kDa precursor, usually at the bond between Ala-157 and Asn-158. We investigated whether proteases could process the recombinant 79-kDa pro-HlyA to the 65-kDa mature HlyA. We observed that the soluble hemagglutinin/ protease (HA/protease; a major protease of V. cholerae), trypsin, alpha-chymotrypsin, subtilisin BPN, papain, and thermolysin all processed the pro-HlyA to the 65-kDa mature form of the protein. Along with this, the protease-processed HlyA showed drastically increased hemolytic activity. The N-terminal amino acid of the mature form of cytolysin generated by HA/protease ...
While LPS changes may possibly help the biofilm bacteria escape host immune system in vivo, more direct evidence of increases in virulence of the pathogen comes from investigation of its secreted proteases and cytotoxins (leucocidin). Virulence-specific azocasein and micro-culture tetrazolium (MTT) assays against both monospecies and binary biofilms of Pseudomonas aeruginosa indicate significant increases in virulence potential of proteases and cytotoxins, respectively. These results were further substantiated in phase contrast microscopy images showing advanced stages of oncosis in tissue cultured mouse spleen myeloma (Sp2) cells treated with leucocidin isolated from Ps. aeruginosa treated with sub-MIC ...
As usual, an episode synopsis can be found over at Scotts Polite Dissent. Im Mentioning Cytotoxins Just for the Search Engine Hits Epidermal blistering and tissue necrosis do indeed match the symptoms from cytotoxins, and so this section is designed solely to increase my search engine hits for this Deconstruction review of Fringe. While Im…
article{279c7ca3-4c9b-4e92-95e9-36ca7d4d1564, abstract = {In the 20 years since the discovery of Helicobacter pylori the number of formally described Helicobacter spp. has increased dramatically. The majority of species in the genus have been associated with some form of pathology. Similar to other Gram-negative bacteria, all helicobacters have lipopolysaccharides or endotoxins in the outer leaflet of their outer membrane which is an important modulator of the immune system. H. pylori endotoxin has a number of roles in the pathogenesis of the bacterium. Its relatively low biological and immunological activity and molecular mimicry may contribute to the chronic nature of infection through avoidance of host defence mechanisms and adhesion. In addition to endotoxins, various helicobacters also secrete distinct exotoxins capable of host cell damage. H. pylori has been shown to possess a cytotoxin capable of inducing vacuoles in epithelial cells termed vacuolating cytotoxin or VacA. Although VacA has ...
General Information: This genus consists of organisms that colonize the mucosal layer of the gastrointestinal tract or are found enterohepatically (in the liver). It was only recently discovered (1983) by two Australians (Warren and Marshall) that this organism was associated with peptic ulcers. It is one of the most common chronic infectious organisms, and is found in half the worlds population. This organism attacks the gastric epithilial surface, resulting in chronic gastritis, and can cause more severe diseases including those that lead to gastric carcinomas and lymphomas, peptic ulcers, and severe diarrhea. It is an extracellular pathogen that persists in the gastric environment, which has a very low pH, by production of the urease enzyme, which converts urea to ammonia and carbon dioxide, a process which can counteract the acidic environment by production of a base. The toxins include cytolethal distending toxin, vacuolating cytotoxin (VacA) that induces host epithelial cell apopoptosis ...
General Information: This genus consists of organisms that colonize the mucosal layer of the gastrointestinal tract or are found enterohepatically (in the liver). It was only recently discovered (1983) by two Australians (Warren and Marshall) that this organism was associated with peptic ulcers. It is one of the most common chronic infectious organisms, and is found in half the worlds population. This organism attacks the gastric epithilial surface, resulting in chronic gastritis, and can cause more severe diseases including those that lead to gastric carcinomas and lymphomas, peptic ulcers, and severe diarrhea. It is an extracellular pathogen that persists in the gastric environment, which has a very low pH, by production of the urease enzyme, which converts urea to ammonia and carbon dioxide, a process which can counteract the acidic environment by production of a base. The toxins include cytolethal distending toxin, vacuolating cytotoxin (VacA) that induces host epithelial cell apopoptosis ...
epithelial cells by means of a complex terminal organelle at the tip of one end of the organism. Cytoadherence is mediated by interactive adhesins and accessory proteins clustered on this organelle. After extracellular attachment, M. pneumoniae causes injury to host respiratory tissue. The mechanism of injury is thought to be mediated by the production of hydrogen peroxide and of a recently identified ADP-ribosylating and vacuolating cytotoxin of M. pneumoniae that has many similarities to pertussis toxin. Because mycoplasmas lack a cell wall, they also lack cell wall-derived stimulators of the innate immune system, such as lipopolysaccharide, lipoteichoic acid, and murein (peptidoglycan) fragments. However, lipoproteins from the mycoplasmal cell membrane appear to have inflammatory properties, probably acting through Toll-like receptors (primarily TLR2) on macrophages and other cells. Lung ...
ABSTRACTCytotoxic Necrotizing Factor 1 (CNF1) is a protein toxin from Escherichia coli that constitutively activates the Rho, Rac and Cdc42 GTPases. These regulatory proteins oscillate between a cytosolic GDP-bound inactive form and a membrane-linked GTP-bound active form, orchestrating the actin cy
1O72: Crystal and Electron Microscopy Structures of Sticholysin II Actinoporin Reveal Insights Into the Mechanism of Membrane Pore Formation
1GWY: Crystal and Electron Microscopy Structures of Sticholysin II Actinoporin Reveal Insights Into the Mechanism of Membrane Pore Formation
Epingaione (4-Methyl-1-(5-methyl-2,3,4,5-tetrahydro-[2,3]bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24% and 50.83% anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 μg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. ...
Michelet, Nathalie ; Granum, Per Einar ; Mahillon, Jacques. Bacillus cereus enterotoxins, bi- and tri- component cytolysins and other haemolysins. In: Author : J, Alouf ; Editor(s) : Alouf and Popoff, The Comprehensive Sourcebook of Bacterial Protein Toxins, Elsevier 2005, p. 779- ...
Herein, we report the pathogenic and phylogenetic characteristics of seven Shiga toxin (Stx)-producing Escherichia coli (STEC) isolates from 434 retail meats in Korea during 2006-2012. The experimental analyses revealed that all the isolates (i) were identified as non-O157 STEC, including O91:H14 (3 isolates), O121:H10 (2), O91:H21 (1), and O18:H20 (1), (ii) carried diverse Stx subtype genes (stx1, stx2c, stx2e, or stx1+stx2b) whose expression levels were varied strain by strain, and (iii) lacked the locus of enterocyte effacement (LEE) pathogenicity island, a major virulence factor of STEC, but possessed one or more alternative virulence genes encoding cytotoxins (Cdt and SubAB) and/or adhesins (Saa, Iha, and EcpA ...
Highly virulent enterococcal strains have a pathogenicity island within their genome that encodes, among other traits, a cytolytic toxin that uses a quorum-sensing mechanism to affect autoinduction. Coburn et al. (see the Perspective by Garsin) show that the bacterium actively secretes two components, an autoinducer and an anti-autoinducer. In the absence of target cells, these two interact and prevent the autoinducer from feeding back to induce high-level expression of the cytolysin. In the presence of the target cell, however, the anti-autoinducer binds to the target cell and allows the autoinducer to accumulate to the threshold level required for quorum induction of the cytolysin operon. The anti-autoinducer is itself a toxin component and effectively tags the target for destruction. P. S. Coburn, C. M. Pillar, B. D. Jett, W. Haas, M. S. Gilmore, Enterococcus faecalis senses target cells and in response expresses cytolysin. Science 306, 2270-2272 (2004). [Abstract] [Full Text]. D. A. Garsin, ...
Pathogenesis of Gardenerella vaginalis A. Adherence of G. vaginalis to Host Epithelium: Initial Steps in Invasion The initial steps of establishing infection include adherence to host receptor sites, production of cytotoxic substances specific for host cells, and biofilm formation. vaginais produces vaginolysin, a cholesterol-dependent cytolysin, for human cells and encodes a pore-forming toxin that binds … Read more Pathogenesis and Clinical manifestation of Gardenerella vaginalis. ...
Derived from Maytansinoid,a group of cytotoxins structurally similar to rifamycin, geldanamycin, and ansatrienin. The eponymous natural cytotoxic agent maytansine is a 19-member lactam (ansa macrolide) structure originally isolated from the Ethiopian shrub Maytenus ovatus. Maytansinoids can bind to tubulin at or near the vinblastine-binding site, which interfere the formation of microtubules and depolymerize already formed microtubules, inducing mitotic arrest in the intoxicated cells ...
STRO-001 was developed with Sutros proprietary cell-free protein synthesis and site-specific conjugation platforms, which facilitate multiple rounds of antibody and ADC optimization, said Dr. Arturo Molina, a medical oncologist and Sutros chief medical officer.. Sutros Xpress CF+™ platform enables it to produce novel ADCs that directly target cancer cells and avoid a toxic bystander effect on adjacent healthy cells, he added.. Unlike conventional cell-based expression systems, Sutros technology isolates a cells protein production machinery into a cell-free extract, Xtract CF™, which includes all the necessary biochemical components for energy production, transcription and translation. The Xpress CF+™ platform further supports incorporation of non-natural amino acids in specific positions in the protein of interest, allowing for site-specific conjugation of cytotoxins and the creation of homogeneous ADCs. This process is capable of producing single proteins at large scale within ...
Cytotoxic Shock Prostration of bodily functions caused by high levels of cytotoxins. It can be treated with inaprovaline.. Darnays Disease A deadly ailment that attacks the brain and nervous system of its victim.. Dermal Dysplasia Skin disorder caused by an overexposure of the skin to dangerous levels of thermal and ultraviolet radiation.. Forrester-Trent Syndrome Degenerative neurological disorder that is very rare and, if left untreated, can cause paralysis and even death.. Hesperan Thumping Cough A flu-like affliction.. Holodiction A psychological condition where an individual gets so caught up in holographic simulations that the real world becomes unimportant. Also known as Holodeck Addiction.. HTDS Holo-Transference Dementia Syndrome. A medical condition in which someone becomes so disoriented within a holographic simulation that they lose their sense of identity and start to think that they are part of the program.. Irumodic Syndrome Degenerative disorder that causes progressive ...
Introduction This report is an update on my thinking on Cytokinetics. It should be read in conjunction with earlier reports, especially my initiation report of March 15, Cytokinetics: Critical Phase IIB Data is Upcoming in 2013 for Omecamtiv Mecarbil and Tirasemtiv (CYTK, $6.30). In that report, I first recommended
LAA047Hu81, FITC-Linked Polyclonal Antibody to Hepatocyte Growth Factor (HGF), 肝细胞生长因子(HGF)多克隆抗体(异硫氰酸荧光素标记), HGF; F-TCF; HGFB; HPTA; SF; Scatter Factor; Hepapoietin A; Fibroblast-Derived Tumor Cytotoxic Factor; Lung Fibroblast-Derived Mitogen | 仅供体外研究使用,不用于临床诊断!请索取进口关税税单及报关单!
The MTT assay is based on the conversion of MTT into formazan crystals by living cells, that determines number of viable cells. The treatment of K562 cells with different concentrations of metylthiosemicarbazon complex with Zn2+ (30, 50, 80, 100, 130, 150 and 200µM) at 24, 48 and 72 h. As showen Fig, metylthiosemicarbazon complex with Zn2+ has cytotoxic activity on the K562 cell line and was able to inhibit the proliferation of the K562 cell line. The IC50 is a measure of the effectiveness of metylthiosemicarbazon complex with Zn2+ in inhibiting of proliferation of K562 cells. The IC50 value of this compound is 100µM in 72 h.. Figure 1: Effect of metylthiosemicarbazon complex with Zn2+ on K562 cells. The K562 cells were treated with various concentrations (30-150µM) of metylthiosemicarbazon complex with Zn2+ for 24, 48, 72 h and then were investigated by MTT assay. Data are shown as mean ± SD.. 3.2 Morphological study of K562 ...
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This Histri was built automatically but not manually verified. As a consequence, the Histri can be incomplete or can contain errors ...
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