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Natural Killer (NK) cells have been implicated in the response to poxviruses, but the interaction between NK and infected cells is not well characterized. We show that downregulation of class I major histocompatibility complex (MH...
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Natural Killer (NK) cells have been implicated in the response to poxviruses, but the interaction between NK and infected cells is not well characterized. We show that downregulation of class I major histocompatibility complex (MHC-1) molecules in human cells by vaccinia virus (VV) sensitizes the cells to lysis by NK cells. We provide evidence suggesting that NK cells are infected as a consequence Of co-culture with infected target cells. We also show that infection of NK cells leads to a marked depression of cytotoxicity. Moreover, the effect on NK cytotoxicity occurs within hours of infection and is prevented by UV inactivation of the virus but is only partially prevented by blocking late gene expression. VV infection also renders the NK cells more sensitive to inhibitory signals. Together Our observations Suggest that VV infection of NK cells call modulate their signaling ill a manner that prevents them from acting on infected target cells. (C) 2005 Elsevier Inc. All rights reserved.
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In this research, a phenol extract of high hydroxytyrosol (OLPE) content was obtained from olive leaves (Olea europaea L.), and subsequently tested under different contexts. The method used to obtain the OLPE basically involved tw...
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In this research, a phenol extract of high hydroxytyrosol (OLPE) content was obtained from olive leaves (Olea europaea L.), and subsequently tested under different contexts. The method used to obtain the OLPE basically involved two steps: the use of strongly-acid aqueous steam, generated from 10% HCl (v/v) at 100pC, to directly hydrolyse the native complex phenols from integral olive leaves, and OLPE recovery by liquid-liquid extraction with ethyl acetate. Hydrolysis time was 1 h. Finally, the dried extract was dissolved in distilled water. The OLPE total phenols were determined by Folin-Ciocalteu's method and by HPLC analysis. Hydroxytyrosol was about 92% of the total phenols present in OLPE, and the yield was about 0.2% on fresh leaves. OLPE showed antioxidant effects on different food lipids and did not inhibit lactic acid bacteria growth; however, it showed cytotoxicity on NIH/3T3 fibroblasts and human umbilical vein endothelial cells at concentrations higher than 0.32 mM (as hydroxytyrosol).
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Xenotransplantation of pig organs into humans is a potential solution for the shortage of donor organs for transplantation. However, multiple immune barriers preclude its clinical application. In particular, the initial type of re...
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Xenotransplantation of pig organs into humans is a potential solution for the shortage of donor organs for transplantation. However, multiple immune barriers preclude its clinical application. In particular, the initial type of rejection in xenotransplantation is an acute cellular rejection by host CD8(+) cytotoxic T lymphocyte (CTL) cells that react to donor major histocompatibility complex (MHC) class 1. The human cytomegalovirus (HCMV) glycoprotein Unique Short (US) 2 specifically targets MHC class I heavy chains to relocate them from the endoplasmic reticulum (ER) membrane to the cytosol, where they are degraded by the proteasome. In this study we transfected the US2 gene into minipig fetal fibroblasts and established four US2 clonal cell lines. The integration of US2 into transgenic fetal cells was confirmed using PCR and Southern blot assay. The reduction of Swine Leukocyte Antigen (SLA)-I by US2 was also detected using Flow cytometry assay (FACS). The FACS analysis of the US2 clonal cell lines demonstrated a substantial reduction in SLA-I surface expression. The level (44% to 76%) of SLA-I expression in US2 clonal cell lines was decreased relative to the control. In cytotoxicity assay the rate of CD8+ T cell-mediated cytotoxicity was significantly reduced to 23.8 +/- 15.1% compared to the control (59.8 +/- 8.4%, p<0.05). In conclusion, US2 can directly protect against CD8(+)-mediated cell lysis. These results indicate that the expression of US2 in pig cells may provide a new approach to overcome the CTL-mediated immune rejection in xenotransplantation.
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The risk of nanoparticles (NPs) to organisms and the environment has become more noticeable alongside their rapid applications in many fields. The release of Cd2+ from CdTe-based NPs (CdTe-NPs), an important class of engineered na...
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The risk of nanoparticles (NPs) to organisms and the environment has become more noticeable alongside their rapid applications in many fields. The release of Cd2+ from CdTe-based NPs (CdTe-NPs), an important class of engineered nanomaterials, is one of the possible factors responsible for the cytotoxicity of these NPs. Based on the same CdTe core, CdTe/CdS, CdTe/ZnS and CdTe/SiO2 NPs were synthesized and their Cd2+ release rates were carefully studied based on dialysis using inductively coupled plasma mass spectrometry (ICPMS). Results obtained indicated that the Cd2+ release rates of the CdTe-NPs decreased in the order CdTe (8.78 ng mL(-1) mg(-1) h(-1)) > CdTe/CdS (2.63) > CdTe/SiO2 (0.89) > CdTe/ZnS (0.72). Phaeodactylum tricornutum was used as a model diatom for evaluating the cytotoxicity of the CdTe-NPs. Results obtained from the CdTe-NPs exposure experiments together with ICPMS and fluorescence microscopy studies suggested that the cytotoxicity of the CdTe-NPs increased along with the increase in their Cd2+ release rates. Effective coating materials such as ZnS and SiO2 for the CdTe core significantly reduced the cytotoxicity of CdTe.
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Background: Apoptosis has recently emerged as a key component of acute and chronic liver diseases and it could be related to alcoholic liver disease. In the present study, we attempted to analyze the cytotoxic profile of circulati...
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Background: Apoptosis has recently emerged as a key component of acute and chronic liver diseases and it could be related to alcoholic liver disease. In the present study, we attempted to analyze the cytotoxic profile of circulating lymphocytes in chronic alcoholic patients grouped according to ethanol intake status and presence of liver disease.
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We previously reported the discovery of a simple conjugated cyano pharmacophore which had led to the development of (Z)-2-(3,4-dichlorophenyl)-3- (4-nitrophenyl)acrylonitrile (1), as a selective inhibitor of oestrogen receptor pos...
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We previously reported the discovery of a simple conjugated cyano pharmacophore which had led to the development of (Z)-2-(3,4-dichlorophenyl)-3- (4-nitrophenyl)acrylonitrile (1), as a selective inhibitor of oestrogen receptor positive (ER+ve) human breast cancer cell line, MCF-7. Further exploration though modification of the acrylonitrile and aromatic substituents has highlighted key structural components necessary for broad spectrum cytotoxicity. The acrylic acid derivates (Z)-2-(3,4-dichlorophenyl)-3-(4-nitrophenyl)acrylic acid (8) and (Z)-2-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)acrylic acid (9) were inactive; confirming the importance of the cyanide moiety. The most potent 2-phenylacrylonitriles synthesized were (Z)-2-(3,4-dichlorophenyl)-3-(1H-indol- 3-yl)acrylonitrile (3) and (Z)-2-(3,4-dichlorophenyl)-3-(1H-indol-5-yl) acrylonitrile (20) with an average GI50 values of 1.4 and 0.53 μM respectively. Five additional (Z)-2-(3,4-dichlorophenyl)-3-(indolyl) acrylonitriles also displayed average GI50 values of ≤8.4 μM. In the case of indole 20, this represents a 32-fold increase in broad spectrum cytotoxicity relative to the lead (1).
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The cytochrome P450s are an essential group of enzymes involved in metabolism of drugs, foreign chemicals, arachidonic acid, cholesterol, steroids and other important lipids. The cytochrome P450 enzyme system is responsible for mu...
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The cytochrome P450s are an essential group of enzymes involved in metabolism of drugs, foreign chemicals, arachidonic acid, cholesterol, steroids and other important lipids. The cytochrome P450 enzyme system is responsible for much of the phase I metabolism of chemotherapeutic agents. At the simplest level the detoxification properties of the cytochrome P450s are used to help clear a cytotoxic before it results in serious irreversible toxicity to the patient while at other levels the cytochrome P450s are involved to varying extents in drug bioactivation. This metabolism primarily occurs in organs and tissues of the body known to express cytochrome P450 ubiquitously (i.e. liver and gastrointestinal tract), but there is also evidence to suggest that it occurs within the tumor microenvironment due to localized, tumor specific expression of certain P450 isoforms. Several of today's currently prescribed cytotoxics (e.g. cyclophosphamide and tamoxifen) undergo systematic bioactivation by cytochrome P450, which often results in toxicity to the patient. The realization that many tumors have differential cytochrome P450 expression when compared to the corresponding normal tissue has allowed the rational design of the next generation of cytotoxic around cytochrome P450 enzymology. Several new agents now entering clinical trials (e.g. Phortress and AQ4N) are specifically designed to exploit tumor cytochrome P450, resulting in local bioactivation of the cytotoxic at the tumor site. Specific activation of pro-drugs by isoforms whose expression or particular catalytic activity is limited to cancer cells offers the possibility of truly targeted chemotherapy with minimized systemic toxicity.
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Although functional only as secondary metabolites in citrus, a class of compounds called limonoids is a family of molecules that have powerful cancer prevention and possibly cancer therapeutic application in human medicine. Postul...
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Although functional only as secondary metabolites in citrus, a class of compounds called limonoids is a family of molecules that have powerful cancer prevention and possibly cancer therapeutic application in human medicine. Postulated to protect plants and fruits from marauding insects and other herbivores, limonoids have the capacity to arrest growth and induce apoptosis in several cancer cell lines in culture. This devastating action is not seen in non-cancerous mammalian epithelial cells. Unbeknown at this time is the mechanism of their fatal action on cancer cells. In this paper, we will review the evidence for limonoid's selective anticancer properties and speculate on the structural features in the molecule that give it this unique action.
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SummaryWe have previously shown an expansion of cytotoxic antigen-experienced CD4+T cells (CTLs) that express perforin (PF) in the peripheral blood of patients with B cell chronic lymphocytic leukaemia (B-CLL). Increased frequenci...
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SummaryWe have previously shown an expansion of cytotoxic antigen-experienced CD4+T cells (CTLs) that express perforin (PF) in the peripheral blood of patients with B cell chronic lymphocytic leukaemia (B-CLL). Increased frequencies of CD4+CTLs have since been attributed to chronic viral infections, particularly, human cytomegalovirus (HCMV). The present study examined the involvement of CD4+CTLs in responses to HCMV in B-CLL, and characterized their differentiation. We studied 36 HCMV seropositive (SP) and seronegative B-CLL patients and 20 healthy age-matched individuals. The HCMV reactivity of CD4+PF+ and CD4+PF− cells was determined by interferon-gamma expression, and expression of CD45RA and CCR7 was assessed by flow cytometry. Fluorescence in-situ hybridization was used to measure relative telomere lengths. CD4+PF+T cell expansion in B-CLL patients and controls was strongly associated with HCMV seropositivity. CD4+PF+ compared to CD4+PF− cells from SP B-CLL patients elicited major histocompatibility complex (MHC) class II-restricted responses to HCMV. CD4+PF+T cells from patients and controls were enriched with highly differentiated T-effector/memory (CCR7−) and revertant (CCR7−CD45RA+) phenotype. CD4+PF+T cells from B-CLL patients had shorter telomeres than CD4+PF−T cells, indicating an extensive replicative history. We conclude that persistent exposure to HCMV antigens in SP B-CLL patients leads to an expansion of the circulating MHC class II-restricted CD4+PF+T cell population with effector/memory phenotype.
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Abstract 6-nitrobenzofuran-2-carbohydrazide Schiff base derivatives have been synthesized and their structure has been confirmed via H 1 NMR, Mass spectrometry and elemental (CHN/S) analysis. These synthesized analogs showed signi...
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Abstract 6-nitrobenzofuran-2-carbohydrazide Schiff base derivatives have been synthesized and their structure has been confirmed via H 1 NMR, Mass spectrometry and elemental (CHN/S) analysis. These synthesized analogs showed significant cytotoxic and antioxidant activity. Doxorubicin (IC 50 = 0.94 ± 0.20μM) and n -propyl gallate (IC 50 = 30.30 ± 0.40μM) were used as standard in cytotoxic and antioxidant activities, respectively. Compound 1 (IC 50 = 3.30 ± 0.90μM), 2 (IC 50 = 2.70 ± 0.25μM), 3 (IC 50 = 2.70 ± 0.25μM), 10 (IC 50 = 2.70 ± 1.10μM), 11 (IC 50 = 1.00 ± 1.20μM), and 17 (IC 50 = 3.75 ± 0.90μM) showed excellent while 21 (IC 50 = 7.50 ± 0.60μM) and 28 (IC 50 = 7.50 ± 0.66μM) showed moderate anti cancer activity. Furthermore, compound 10 (IC 50 = 17.50 ± 0.85μM), 11 ( IC 50 = 24.20 ± 0.55μM), 12 (IC 50 = 21.10 ± 1.58μM), 13 (IC 50 = 14.60 ± 0.32μM), 14 (IC 50 = 29.20 ± 0.75μM) and 15 (IC 50 = 9.26 ± 0.15μM) showed better antioxidant activity than the standard n -propyl gallate. This study will be useful to develop potential lead molecules with cytotoxic and antioxidant potential. Highlights ? Enhanced the knowledge to develop anticancer drug. ? Provided new lead molecules for further study. ? The research is aligned with the government policy to develop safe and effective drug for cancer.
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