The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunologi...The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunological adjuvant QS-21 still need to be improved.Based on poly(lactic-co-glycolic acid)(PLGA)delivery systems that are stable during the lyophilization and rehydration process and using a double-emulsion(w/o/w)solvent evaporation method,we designed a series of nanoparticles with varicella-zoster virus antigen glycoprotein E(VZV-g E)as an antigen and nucleic acids including polyinosinic-polycytidylic acid(Poly I:C)and phosphodiester Cp G oligodeoxynucleotide(Cp G ODN),encapsulated as immune stimulators.While cationic lipids(DOTAP)have more potential than neutral lipids(DOPC)for activating g E-specific cell-mediated immunity(CMI)in immunized mice,especially when g E is encapsulated in and presented on the surface of nanoparticles,PLGA particles without lipids have the greatest potential to induce not only the highest g Especific Ig G titers but also the strongest g E-specific CMI responses,including the highest proportions of interferon-c(IFNc)-and interleukin-2(IL-2)-producing CD4?/CD8?T cells according to a flow cytometry assay and the greatest numbers of IFN-c-and IL-2-producing splenocytes according to an enzyme-linked immunospot(ELISPOT)assay.These results showed that immune-stimulating nucleic acids together with the PLGA delivery system showed promise as a safe and economical varicella and zoster vaccine candidate.展开更多
E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a mo...E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.展开更多
AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS Thirty C57BL/6 mice were given either regular drinkin...AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 mu g/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-a (TNF-alpha), interleukin 17 (IL-17) and interferon-. (IFN-gamma). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-alpha, IL-17 and IFN-gamma. CONCLUSION Our study suggested that po展开更多
AIM: To study the role of luteolin(LUT) in the expression of toll-like receptors 3(TLR3) ligand poly I:C stimulated inflammatory factors in human corneal fibroblasts(HCFs).METHODS: HCFs cells were cultivated with or w...AIM: To study the role of luteolin(LUT) in the expression of toll-like receptors 3(TLR3) ligand poly I:C stimulated inflammatory factors in human corneal fibroblasts(HCFs).METHODS: HCFs cells were cultivated with or without LUT or poly I:C.The expression levels of interleukin(IL)-6, IL-8, monocyte chemotactic protein-1(MCP-1), vascular cell adhesion molecule(VCAM)-1, as well as intercellular adhesion molecule(ICAM)-1 were measured using enzymelinked immunosorbent assay(ELISA), immunoblotting or reverse transcription-quantitative polymerase chain reaction(PCR) analyses.Immunoblotting was used to assess toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-β(TRIF), TLR3, transforming growth factor-bactivated kinase 1(TAK1), tumor necrosis factor receptor-associated factor 6(TRAF6), the transcription factor AP-1, as well as transcription factor nuclear factor(NF-κB)–inhibitory protein IκB-α degradation and phosphorylation.Immunofluorescence assays were used to localize the cellular location of the p65 subunit of NF-κB.RESULTS: Corneal fibroblasts exposed to poly I:C demonstrated decreased VCAM-1, ICAM-1, MCP-1, IL-6, and IL-8 expression levels upon exposure to LUT in a time-dependent and concentration-dependent manner.LUT was observed to suppress poly I:C-triggered expression of TLR3, the translocation of NF-κB p65 into cell nuclei, as well as the phosphorylation of TAK, c-Jun, and IκB-α, while no impact on the expression levels of TRIF and TRAF6 were observed.CONCLUSION: LUT suppress the expression of proinflammatory adhesion molecules, chemokines, and cytokines in poly I:C exposed HCFs.These effects are likely mediated through TAK/NF-κB signal attenuation.Therefore, LUT is a candidate molecule that can prevent the TLR3-mediated inflammation response associated with corneal viral infection.展开更多
It has been revealed that poly I：C is a potent stimulator for NK cells, which can induce NK cell rapid activation and preferential accumulation into liver. However, the process mediating the influx of NK cells remain...It has been revealed that poly I：C is a potent stimulator for NK cells, which can induce NK cell rapid activation and preferential accumulation into liver. However, the process mediating the influx of NK cells remains obscure. In this study, we found that poly I：C administration increased the portion and absolute number of NK cells in liver, but largely decreased those in spleen. There were no obvious changes of these lymphocytes in other immune organs. The results from splenic adoptive transfer and splenectomy showed that the recruited spleen NK cells contributed to the accumulation of NK cells in liver, and this process was regulated by the production of chemokines and the presence of T cells. This investigation will help to understand the enhanced immune cell recruitment in liver upon viral infection. Cellular ＆ Molecular Immunology. 2005;2（6）：449-453.展开更多
基金financially supported by the CAMS Initiative for Innovative Medicine(Grant Number 2017-I2M3-022)Central basic scientific research in colleges and universities(Grant Number 3332019162)+1 种基金the National Natural Science Foundation of China(Grant Number 81503117)the Foundation for Studying Abroad from the China Scholarship Council(Grant Number 201808110121)
文摘The subunit herpes zoster vaccine Shingrix is superior to attenuated vaccine Zostavax in both safety and efficacy,yet its unlyophilizable liposome delivery system and the limited supply of naturally sourced immunological adjuvant QS-21 still need to be improved.Based on poly(lactic-co-glycolic acid)(PLGA)delivery systems that are stable during the lyophilization and rehydration process and using a double-emulsion(w/o/w)solvent evaporation method,we designed a series of nanoparticles with varicella-zoster virus antigen glycoprotein E(VZV-g E)as an antigen and nucleic acids including polyinosinic-polycytidylic acid(Poly I:C)and phosphodiester Cp G oligodeoxynucleotide(Cp G ODN),encapsulated as immune stimulators.While cationic lipids(DOTAP)have more potential than neutral lipids(DOPC)for activating g E-specific cell-mediated immunity(CMI)in immunized mice,especially when g E is encapsulated in and presented on the surface of nanoparticles,PLGA particles without lipids have the greatest potential to induce not only the highest g Especific Ig G titers but also the strongest g E-specific CMI responses,including the highest proportions of interferon-c(IFNc)-and interleukin-2(IL-2)-producing CD4?/CD8?T cells according to a flow cytometry assay and the greatest numbers of IFN-c-and IL-2-producing splenocytes according to an enzyme-linked immunospot(ELISPOT)assay.These results showed that immune-stimulating nucleic acids together with the PLGA delivery system showed promise as a safe and economical varicella and zoster vaccine candidate.
文摘E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.
基金the Scientific Research Foundation of HealthDepartment of Hebei Province,No.20160483
文摘AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 mu g/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-a (TNF-alpha), interleukin 17 (IL-17) and interferon-. (IFN-gamma). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-alpha, IL-17 and IFN-gamma. CONCLUSION Our study suggested that po
基金Supported by the National Natural Science Foundation of China (No.81770889)Administration of Traditional Chinese Medicine of Guangdong Province (No.20201070)。
文摘AIM: To study the role of luteolin(LUT) in the expression of toll-like receptors 3(TLR3) ligand poly I:C stimulated inflammatory factors in human corneal fibroblasts(HCFs).METHODS: HCFs cells were cultivated with or without LUT or poly I:C.The expression levels of interleukin(IL)-6, IL-8, monocyte chemotactic protein-1(MCP-1), vascular cell adhesion molecule(VCAM)-1, as well as intercellular adhesion molecule(ICAM)-1 were measured using enzymelinked immunosorbent assay(ELISA), immunoblotting or reverse transcription-quantitative polymerase chain reaction(PCR) analyses.Immunoblotting was used to assess toll-interleukin-1 receptor-domain-containing adapter-inducing interferon-β(TRIF), TLR3, transforming growth factor-bactivated kinase 1(TAK1), tumor necrosis factor receptor-associated factor 6(TRAF6), the transcription factor AP-1, as well as transcription factor nuclear factor(NF-κB)–inhibitory protein IκB-α degradation and phosphorylation.Immunofluorescence assays were used to localize the cellular location of the p65 subunit of NF-κB.RESULTS: Corneal fibroblasts exposed to poly I:C demonstrated decreased VCAM-1, ICAM-1, MCP-1, IL-6, and IL-8 expression levels upon exposure to LUT in a time-dependent and concentration-dependent manner.LUT was observed to suppress poly I:C-triggered expression of TLR3, the translocation of NF-κB p65 into cell nuclei, as well as the phosphorylation of TAK, c-Jun, and IκB-α, while no impact on the expression levels of TRIF and TRAF6 were observed.CONCLUSION: LUT suppress the expression of proinflammatory adhesion molecules, chemokines, and cytokines in poly I:C exposed HCFs.These effects are likely mediated through TAK/NF-κB signal attenuation.Therefore, LUT is a candidate molecule that can prevent the TLR3-mediated inflammation response associated with corneal viral infection.
文摘It has been revealed that poly I：C is a potent stimulator for NK cells, which can induce NK cell rapid activation and preferential accumulation into liver. However, the process mediating the influx of NK cells remains obscure. In this study, we found that poly I：C administration increased the portion and absolute number of NK cells in liver, but largely decreased those in spleen. There were no obvious changes of these lymphocytes in other immune organs. The results from splenic adoptive transfer and splenectomy showed that the recruited spleen NK cells contributed to the accumulation of NK cells in liver, and this process was regulated by the production of chemokines and the presence of T cells. This investigation will help to understand the enhanced immune cell recruitment in liver upon viral infection. Cellular ＆ Molecular Immunology. 2005;2（6）：449-453.
