AIM To investigate the interaction of Zot withmicrotubule.METHODS Zot affinity column was applied topurify Zot-binding protein(s)from crudeintestinal cell lysates.After incubation at roomtemperature,the column was w...AIM To investigate the interaction of Zot withmicrotubule.METHODS Zot affinity column was applied topurify Zot-binding protein(s)from crudeintestinal cell lysates.After incubation at roomtemperature,the column was washed and theproteins bound to the Zot affinity column wereeluted by step gradient with NaCl(0.3 mol·L<sup>-1</sup>-0.5mol·L<sup>-1</sup>).The fractions were subjected to6.0%-15.0%(w/v)gradient SDS-PAGE andthen transferred to PVDF membrane for N-terminal sequencing.Purified Zot and tauprotein were blotted by using anti-Zot or anti-tauantibodies.Finally,purified Zot was tested in anin vitro tubulin binding assay.RESULTS Fractions from Zot affinity columnyielded two protein bands with a Mr of 60 kU and45kU respectively.The N-terminal sequence ofthe 60 kU band resulted identical to β-tubulin.Zot also cross-reacts with anti-tau antibodies.Inthe in vitro tubulin binding assay,Zot co-precipitate with Mt,further suggesting that Zotpossesses tubulin-binding properties.CONCLUSION Taken together,these resultssuggest that Zot regulates the permeability ofintestinal tight junctions by binding tointracellular Mt,with the subsequent activationof the intracellular signaling leading to thepermeabilization of intercellular tight junctions.展开更多
兔肠致病性大肠杆菌(rEPEC)菌株RDEC-1的基因组中lifA基因与LEE (Locus for enterocyte effacement)致病岛相毗邻。本试验通过DNA序列分析、基因打靶技术、细胞因子检测以及动物试验,分析lifA基因完整核苷酸序列及其生物学功能。结果表...兔肠致病性大肠杆菌(rEPEC)菌株RDEC-1的基因组中lifA基因与LEE (Locus for enterocyte effacement)致病岛相毗邻。本试验通过DNA序列分析、基因打靶技术、细胞因子检测以及动物试验,分析lifA基因完整核苷酸序列及其生物学功能。结果表明,RDEC-1的lifA基因的核苷酸序列与人肠致病性大肠杆菌的完全相同;lifA基因具有降低家兔外周血单核细胞IL-2表达的作用。与野生型菌株RDEC-1相比,被定点敲除lifA基因的RDEC-1突变株(RDEC-1ΔlifA)口服接种家兔后,排菌量明显降低。利用野生型RDEC-1和RDEC-1ΔlifA基因缺失菌株同时口服接种家兔,从粪便中分离细菌,结果显示野生型RDEC-1是优势菌,而RDEC-1ΔlifA基因缺失菌数量极少。RDEC-1ΔlifA基因缺失菌株和野生型RDEC-1都能引起特征性家兔肠道上皮的黏附与细胞脱落病变(A/Elesion)。表明rEPEC的lifA基因在免疫调节和细菌的肠道定居中起重要作用,这为研究lifA基因的生物学功能提供了直接证据。展开更多
Liver is a site of viral replication and liver dysfunction is a characteristic of severe dengue infection. To understand these mechanisms, we analyzed the response of a hepatic cell linage, HepG2 to infection with den...Liver is a site of viral replication and liver dysfunction is a characteristic of severe dengue infection. To understand these mechanisms, we analyzed the response of a hepatic cell linage, HepG2 to infection with dengue 3 virus (strain 16562). Steady state levels of mRNA accumulation were assessed for 14 genes involved in modulation of the host immune responses, at 6, 24 and 48 hpi, by quantitative reverse transcription real-time PCR (qRT-PCR). Fourteen genes showed altered expression upon infection with D3V including;cytokines/chemokines (IL-1β, IL-6, IL-8, RANTES, MCP-2, IL-2Rα and TGF-βIIIR), type I interferon (IFN-α and IFN-β), and pattern-recognition receptors (TLR3, TLR8, RIG-1, MDA5 and MyD88). Although these genes are associated with mechanism of innate immune response and anti-viral activity, their altered expression does not inhibit D3V (strain 16562) growth kinetics and virus yield in HepG2 cells. Gene expression in liver may explain pathological changes associated with dengue virus infection.展开更多
Before the founding of the People's Republic of China 70 years ago,both extreme poverty and parasitic infections and other neglected tropical diseases were highly prevalent.Owing to social development,particularly...Before the founding of the People's Republic of China 70 years ago,both extreme poverty and parasitic infections and other neglected tropical diseases were highly prevalent.Owing to social development,particularly economic reforms since the 1980s,poverty has since been dramatically reduced,and China became increasingly urbanized and industrialized.In parallel,China's economic transformation translated into similar and remarkable reductions in neglected tropical diseases.Qian and colleagues report in their review published in Infectious Diseases of Poverty,the elimination or near elimination as a public health problem of lymphatic filariasis,trachoma,soil-transmitted helminth infections,schistosomiasis and other neglected tropical diseases.Of note,neglected tropical disease control and poverty reduction each appear to reinforce the other.China's formula for success in parasitic and neglected tropical disease control might translate to other parts of the world,such as in sub-Saharan Africa through China's new Belt and Road Initiative.展开更多
The control of inflammation is an essential process for maintaining immunehomeostasis, but the regulatory mechanisms which govern this event remain poorly understood. Endotoxin tolerance is a convenient experimental m...The control of inflammation is an essential process for maintaining immunehomeostasis, but the regulatory mechanisms which govern this event remain poorly understood. Endotoxin tolerance is a convenient experimental model which can be used to elucidate potentially relevant mechanisms that control the host's inflammatory response. Endotoxin tolerance is marked by a transitory period of hyporesponsiveness to lipopolysaccharide (LPS, also known as endotoxin) stimulation following an initial exposure to LPS. Although the alteration of intracellular signaling has been well described, there are likely multiple mechanisms and pathways which contribute to the phenomenon called endotoxin tolerance.展开更多
More than 100 million people are facing a return to extreme poverty because of coronavirus disease 2019(COVID-19),while new estimates suggest that three nations—India,Nigeria,and the Democratic Republic of the Congo-...More than 100 million people are facing a return to extreme poverty because of coronavirus disease 2019(COVID-19),while new estimates suggest that three nations—India,Nigeria,and the Democratic Republic of the Congo-may suffer the greatest economic contractions.Such findings will have profound consequences in terms of our ability to control or eliminate the most widely prevalent neglected tropical diseases.展开更多
文摘AIM To investigate the interaction of Zot withmicrotubule.METHODS Zot affinity column was applied topurify Zot-binding protein(s)from crudeintestinal cell lysates.After incubation at roomtemperature,the column was washed and theproteins bound to the Zot affinity column wereeluted by step gradient with NaCl(0.3 mol·L<sup>-1</sup>-0.5mol·L<sup>-1</sup>).The fractions were subjected to6.0%-15.0%(w/v)gradient SDS-PAGE andthen transferred to PVDF membrane for N-terminal sequencing.Purified Zot and tauprotein were blotted by using anti-Zot or anti-tauantibodies.Finally,purified Zot was tested in anin vitro tubulin binding assay.RESULTS Fractions from Zot affinity columnyielded two protein bands with a Mr of 60 kU and45kU respectively.The N-terminal sequence ofthe 60 kU band resulted identical to β-tubulin.Zot also cross-reacts with anti-tau antibodies.Inthe in vitro tubulin binding assay,Zot co-precipitate with Mt,further suggesting that Zotpossesses tubulin-binding properties.CONCLUSION Taken together,these resultssuggest that Zot regulates the permeability ofintestinal tight junctions by binding tointracellular Mt,with the subsequent activationof the intracellular signaling leading to thepermeabilization of intercellular tight junctions.
基金NIDDK 1RO1DK51507 (ECB)VA/DOD Merit Review Award
文摘兔肠致病性大肠杆菌(rEPEC)菌株RDEC-1的基因组中lifA基因与LEE (Locus for enterocyte effacement)致病岛相毗邻。本试验通过DNA序列分析、基因打靶技术、细胞因子检测以及动物试验,分析lifA基因完整核苷酸序列及其生物学功能。结果表明,RDEC-1的lifA基因的核苷酸序列与人肠致病性大肠杆菌的完全相同;lifA基因具有降低家兔外周血单核细胞IL-2表达的作用。与野生型菌株RDEC-1相比,被定点敲除lifA基因的RDEC-1突变株(RDEC-1ΔlifA)口服接种家兔后,排菌量明显降低。利用野生型RDEC-1和RDEC-1ΔlifA基因缺失菌株同时口服接种家兔,从粪便中分离细菌,结果显示野生型RDEC-1是优势菌,而RDEC-1ΔlifA基因缺失菌数量极少。RDEC-1ΔlifA基因缺失菌株和野生型RDEC-1都能引起特征性家兔肠道上皮的黏附与细胞脱落病变(A/Elesion)。表明rEPEC的lifA基因在免疫调节和细菌的肠道定居中起重要作用,这为研究lifA基因的生物学功能提供了直接证据。
文摘Liver is a site of viral replication and liver dysfunction is a characteristic of severe dengue infection. To understand these mechanisms, we analyzed the response of a hepatic cell linage, HepG2 to infection with dengue 3 virus (strain 16562). Steady state levels of mRNA accumulation were assessed for 14 genes involved in modulation of the host immune responses, at 6, 24 and 48 hpi, by quantitative reverse transcription real-time PCR (qRT-PCR). Fourteen genes showed altered expression upon infection with D3V including;cytokines/chemokines (IL-1β, IL-6, IL-8, RANTES, MCP-2, IL-2Rα and TGF-βIIIR), type I interferon (IFN-α and IFN-β), and pattern-recognition receptors (TLR3, TLR8, RIG-1, MDA5 and MyD88). Although these genes are associated with mechanism of innate immune response and anti-viral activity, their altered expression does not inhibit D3V (strain 16562) growth kinetics and virus yield in HepG2 cells. Gene expression in liver may explain pathological changes associated with dengue virus infection.
文摘Before the founding of the People's Republic of China 70 years ago,both extreme poverty and parasitic infections and other neglected tropical diseases were highly prevalent.Owing to social development,particularly economic reforms since the 1980s,poverty has since been dramatically reduced,and China became increasingly urbanized and industrialized.In parallel,China's economic transformation translated into similar and remarkable reductions in neglected tropical diseases.Qian and colleagues report in their review published in Infectious Diseases of Poverty,the elimination or near elimination as a public health problem of lymphatic filariasis,trachoma,soil-transmitted helminth infections,schistosomiasis and other neglected tropical diseases.Of note,neglected tropical disease control and poverty reduction each appear to reinforce the other.China's formula for success in parasitic and neglected tropical disease control might translate to other parts of the world,such as in sub-Saharan Africa through China's new Belt and Road Initiative.
文摘The control of inflammation is an essential process for maintaining immunehomeostasis, but the regulatory mechanisms which govern this event remain poorly understood. Endotoxin tolerance is a convenient experimental model which can be used to elucidate potentially relevant mechanisms that control the host's inflammatory response. Endotoxin tolerance is marked by a transitory period of hyporesponsiveness to lipopolysaccharide (LPS, also known as endotoxin) stimulation following an initial exposure to LPS. Although the alteration of intracellular signaling has been well described, there are likely multiple mechanisms and pathways which contribute to the phenomenon called endotoxin tolerance.
文摘More than 100 million people are facing a return to extreme poverty because of coronavirus disease 2019(COVID-19),while new estimates suggest that three nations—India,Nigeria,and the Democratic Republic of the Congo-may suffer the greatest economic contractions.Such findings will have profound consequences in terms of our ability to control or eliminate the most widely prevalent neglected tropical diseases.