Ionizing radiations are tools in diagnosis and treatment of diseases. Leukopenia from exposure to ionizing radiation has been reported. Due to their radiosensitivity, leukocytes are a biological model to analyze cell ...Ionizing radiations are tools in diagnosis and treatment of diseases. Leukopenia from exposure to ionizing radiation has been reported. Due to their radiosensitivity, leukocytes are a biological model to analyze cell damage. Therefore, cell viability, DNA damage, and Hsp70 and p53 expression in human leukocytes exposed to low-dose gamma radiation fields from a <sup>137</sup>Cs source were evaluated. A decrease in cell viability, DNA damage and an increase in the expression of Hsp70 and p53 proportional to the radiation dose received was found, which was 0.2, 0.4, 0.6, 0.8 and 1.0 mGy.展开更多
Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in l...Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in liver diseases is less clear.In the past two decades,accumulating evidence revealed thatγδT cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans.More recent studies demonstrated that the functional effect ofγδT cells on liver disease progression depends on the subsets involved,which can be identified by the expression of distinct T cell receptor chains and of specific cytokines.Fascinatingly,γδT cells may have protective as well as pathogenic functions in liver diseases.Interferonγ-producingγδT cells,for example,induce apoptosis in hepatocytes but also in hepatic tumor cells;while interleukin-17-expressingγδT cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells.However,the results obtained in human liver disease as well as murine models are not fully conclusive at present,and the effects ofγδT cells on the outcome of liver disease might vary dependent on etiology and stage of disease.Further definitions of theγδT cell subsets in-volved in acute and chronic liver inflammation,as well as their effector cytokines might uncover whether interference withγδT cells could be a useful target for the treatment of liver disease.展开更多
BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepa...BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10 -3 -10 -1 mg/100 μL), andinterferon gamma (10 -2 -10 -1 μg/100 μL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10 -1 μg/100 μL, P<0.05, 10 -2 -10 -3 μg/100 μL, P>0.05) and a time-dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.展开更多
Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very uncommon and extremely aggressive tumor, and is described in the newly re-vised World health organization for research and treatment of cancer classif...Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very uncommon and extremely aggressive tumor, and is described in the newly re-vised World health organization for research and treatment of cancer classification of cutaneous lymphomas. A 43-year-old male patient presented with a 4 months history of cutaneous lesion over upper lip, without plaque and any constitutional symptom. Histopathological examination of skin biopsy revealed infiltration of atypical lymphocytes with hyperchromatic irregular nuclei. Immunophenotyping pattern of skin biopsy was compatible with PCGD-TLC. It is a highly aggressive tumor resistant to chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by a worse prognosis with a median survival of 15 months. Early diagnosis is essential and aggressive therapy is necessary.展开更多
Objective: To develop a gold nanoparticles complex conjugated with interferon-gamma(IFN-g) and methionine along with application of hyperthermia using near-infrared laser beams for the treatment of cancer cells.Method...Objective: To develop a gold nanoparticles complex conjugated with interferon-gamma(IFN-g) and methionine along with application of hyperthermia using near-infrared laser beams for the treatment of cancer cells.Methods: Gold nanorods(10 nm) were conjugated with IFN-g and methionine using carbodiimide family and characterized after purification by dialysis bags. Breast cancer cells were cultured and incubated with gold nanorods at different concentrations followed by irradiation with near-infrared laser beam. Samples were then evaluated for their viability in order to determine the effect of treatment and variables by MTT assy.Results: Zetasizer results confirmed the conjugation of gold nanorods with methionine and IFN-g. The median percentage of cell viability in 0.30 mg/m L concentration of gold nanorods was 82%. The cell viability reached to 85% at the same concentration of gold nanorods, which existed in the assayed complex. The results of MTT assay showed that the 0.60 mg/m L concentration of gold nanoparticles complex was toxic on tumor cells(P < 0.05). After exposure to hyperthermia, the viability of cells at 6 min decreased to77% in 0.30 mg/m L concentration of gold nanorods complex.Conclusions: The size and concentration of gold nanorods was not cytotoxic. However,their presence during irradiation near-infrared laser increased the number of dead cells during the treatment of cells.展开更多
Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bact...Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bacterial infections,and cancer.Compromised endothelial sealing leads to leaking blood vessels,followed by vasogenic edema.Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death.Brain microvascular endothelial cells,together with astrocytes,pericytes,microglia,and neurons form a selective barrier,the so-called blood-brain barrier,which regulates the movement of molecules inside and outside of the brain.Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood.Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years.One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3.In this review,we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.展开更多
BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activa...BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activated receptor gamma(PPAR-γ) on rat hepatic fibrosis. METHODS:Hepatic fibrosis in rats was induced by CCl4 for 2 weeks(early fibrosis)and 8 weeks(sustained fibrosis).The rats were randomly divided into four groups:normal control, fibrosis,blank vector,and PPAR-γ.They were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene by portal vein injection.The liver of the rats was examined histologically and hydroxyproline was assessed.In vitro primary hepatic stellate cells(HSCs)were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene.The status of HSC proliferation was measured by the MTT assay.The protein levels of PPAR-γ,α-smooth muscle actin(α-SMA)and type I collagen expression were evaluated by the Western blotting method. RESULTS:In vitro studies revealed that expression of PPAR-γ inhibited expression ofα-SMA and type I collagen in activated HSCs(P<0.01)as well as HSC proliferation(P<0.01).In vivo experiments indicated that in the early hepatic fibrosis group,the hydroxyproline content and the level of collagen I protein in the liver in the PPAR-γtransfected group were not significantly different compared to the hepatic fibrosis group and the blank vector group;whereas the expressions of PPAR-γ andα-SMA were different compared to the hepatic fibrosis group(P<0.01).In the sustained hepatic fibrosis group,there were significant differences in the hydroxyproline content and the expression of PPAR-γ,α-SMA,and type I collagen between each group.CONCLUSION:PPAR-γcan inhibit HSC proliferation and hepatic fibrosis,and suppressα-SMA and type I collagen expression.展开更多
文摘Ionizing radiations are tools in diagnosis and treatment of diseases. Leukopenia from exposure to ionizing radiation has been reported. Due to their radiosensitivity, leukocytes are a biological model to analyze cell damage. Therefore, cell viability, DNA damage, and Hsp70 and p53 expression in human leukocytes exposed to low-dose gamma radiation fields from a <sup>137</sup>Cs source were evaluated. A decrease in cell viability, DNA damage and an increase in the expression of Hsp70 and p53 proportional to the radiation dose received was found, which was 0.2, 0.4, 0.6, 0.8 and 1.0 mGy.
基金Supported by The German Research FoundationNo.DFG Ta434/2-1 and SFB/TRR57the Interdisciplinary Center for Clinical Research(IZKF) Aachen
文摘Conventional adaptive T cell responses contribute to liver inflammation and fibrogenesis,especially in chronic viral infections and autoimmune hepatitis.However,the role of unconventional gamma-delta(γδ)T cells in liver diseases is less clear.In the past two decades,accumulating evidence revealed thatγδT cell numbers remarkably increase in the liver upon various inflammatory conditions in mice and humans.More recent studies demonstrated that the functional effect ofγδT cells on liver disease progression depends on the subsets involved,which can be identified by the expression of distinct T cell receptor chains and of specific cytokines.Fascinatingly,γδT cells may have protective as well as pathogenic functions in liver diseases.Interferonγ-producingγδT cells,for example,induce apoptosis in hepatocytes but also in hepatic tumor cells;while interleukin-17-expressingγδT cells can downregulate pathogenic effector functions of other immune cells and can promote apoptosis of fibrogenic stellate cells.However,the results obtained in human liver disease as well as murine models are not fully conclusive at present,and the effects ofγδT cells on the outcome of liver disease might vary dependent on etiology and stage of disease.Further definitions of theγδT cell subsets in-volved in acute and chronic liver inflammation,as well as their effector cytokines might uncover whether interference withγδT cells could be a useful target for the treatment of liver disease.
文摘BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10 -3 -10 -1 mg/100 μL), andinterferon gamma (10 -2 -10 -1 μg/100 μL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10 -1 μg/100 μL, P<0.05, 10 -2 -10 -3 μg/100 μL, P>0.05) and a time-dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.
文摘Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very uncommon and extremely aggressive tumor, and is described in the newly re-vised World health organization for research and treatment of cancer classification of cutaneous lymphomas. A 43-year-old male patient presented with a 4 months history of cutaneous lesion over upper lip, without plaque and any constitutional symptom. Histopathological examination of skin biopsy revealed infiltration of atypical lymphocytes with hyperchromatic irregular nuclei. Immunophenotyping pattern of skin biopsy was compatible with PCGD-TLC. It is a highly aggressive tumor resistant to chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by a worse prognosis with a median survival of 15 months. Early diagnosis is essential and aggressive therapy is necessary.
基金Supported by a grant from Iran National Science Foundation under the grant number 91002993
文摘Objective: To develop a gold nanoparticles complex conjugated with interferon-gamma(IFN-g) and methionine along with application of hyperthermia using near-infrared laser beams for the treatment of cancer cells.Methods: Gold nanorods(10 nm) were conjugated with IFN-g and methionine using carbodiimide family and characterized after purification by dialysis bags. Breast cancer cells were cultured and incubated with gold nanorods at different concentrations followed by irradiation with near-infrared laser beam. Samples were then evaluated for their viability in order to determine the effect of treatment and variables by MTT assy.Results: Zetasizer results confirmed the conjugation of gold nanorods with methionine and IFN-g. The median percentage of cell viability in 0.30 mg/m L concentration of gold nanorods was 82%. The cell viability reached to 85% at the same concentration of gold nanorods, which existed in the assayed complex. The results of MTT assay showed that the 0.60 mg/m L concentration of gold nanoparticles complex was toxic on tumor cells(P < 0.05). After exposure to hyperthermia, the viability of cells at 6 min decreased to77% in 0.30 mg/m L concentration of gold nanorods complex.Conclusions: The size and concentration of gold nanorods was not cytotoxic. However,their presence during irradiation near-infrared laser increased the number of dead cells during the treatment of cells.
文摘Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bacterial infections,and cancer.Compromised endothelial sealing leads to leaking blood vessels,followed by vasogenic edema.Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death.Brain microvascular endothelial cells,together with astrocytes,pericytes,microglia,and neurons form a selective barrier,the so-called blood-brain barrier,which regulates the movement of molecules inside and outside of the brain.Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood.Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years.One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3.In this review,we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.
基金supported by a grant from the Science and Technology Commission of Shanghai Municipality(No.07JC14036)
文摘BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activated receptor gamma(PPAR-γ) on rat hepatic fibrosis. METHODS:Hepatic fibrosis in rats was induced by CCl4 for 2 weeks(early fibrosis)and 8 weeks(sustained fibrosis).The rats were randomly divided into four groups:normal control, fibrosis,blank vector,and PPAR-γ.They were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene by portal vein injection.The liver of the rats was examined histologically and hydroxyproline was assessed.In vitro primary hepatic stellate cells(HSCs)were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene.The status of HSC proliferation was measured by the MTT assay.The protein levels of PPAR-γ,α-smooth muscle actin(α-SMA)and type I collagen expression were evaluated by the Western blotting method. RESULTS:In vitro studies revealed that expression of PPAR-γ inhibited expression ofα-SMA and type I collagen in activated HSCs(P<0.01)as well as HSC proliferation(P<0.01).In vivo experiments indicated that in the early hepatic fibrosis group,the hydroxyproline content and the level of collagen I protein in the liver in the PPAR-γtransfected group were not significantly different compared to the hepatic fibrosis group and the blank vector group;whereas the expressions of PPAR-γ andα-SMA were different compared to the hepatic fibrosis group(P<0.01).In the sustained hepatic fibrosis group,there were significant differences in the hydroxyproline content and the expression of PPAR-γ,α-SMA,and type I collagen between each group.CONCLUSION:PPAR-γcan inhibit HSC proliferation and hepatic fibrosis,and suppressα-SMA and type I collagen expression.
