Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic chang...Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.展开更多
AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of...AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.展开更多
The papers in this special topic of Sino-India Monitor on NDCs,authored by a select group of researchers from both China and India,provide a perspective on areas of common interest for societies in both countries as w...The papers in this special topic of Sino-India Monitor on NDCs,authored by a select group of researchers from both China and India,provide a perspective on areas of common interest for societies in both countries as well as a focus on common objectives defining global action.Climate展开更多
Immune cell accumulation and white matter anomaly are common features of HIV(human immunodeficiency virus)-infected patients in combination antiretroviral therapy(cART) era.Neuroimaging tests on cART treated patients ...Immune cell accumulation and white matter anomaly are common features of HIV(human immunodeficiency virus)-infected patients in combination antiretroviral therapy(cART) era.Neuroimaging tests on cART treated patients displayed prominent diffuse white matter lesions.Notably,immune cell nodular lesion(NL) was a conspicuous type of pathological change in HIV/SIV(simian immunodeficiency virus) infected brain before cART.Therefore,we used SIV infected brain to investigate the distribution of those NLs in gray and white matters.We found a significant higher number of NLs in white matter than that in gray matter.However,virus infection correlated with macrophage NLs but not with microglia NLs,especially in white matter.In addition,NLs interrupted white matter integrity more severely,since even tiny nodules could disconnect nerve fibers in white matter tracts.In the gray matter with dense myelinated axons,NLs obviously encroached those fibers;in the area of few myelinated axons,small nodules well co-localized with extracellular matrix between neurons.展开更多
Plasma viral RNA load is widely accepted as the most relevant parameter to assess the status and progression of Simian immunodeficiency virus (SIV) infections. To accurately measure RNA levels of the virus, a one-step...Plasma viral RNA load is widely accepted as the most relevant parameter to assess the status and progression of Simian immunodeficiency virus (SIV) infections. To accurately measure RNA levels of the virus, a one-step fluorescent quantitative assay was established based on the SYBR green Real-time reverse transcription-polymerase chain reaction (RT-PCR). The lower detection limit of the assay was 10 copies per reaction for the virus. This method was successfully applied to quantify SIVmac251 and SIVmac239 viruses produced in CEM×174 cells. Additionally, the performance of the SYBR green RT-PCR was assessed in a SIVmac251 infected rhesus macaque. The result demonstrated that the method could detect as little as 215 copies per milliliter of plasma and the dynamic pattern of viral load was highly consistent with previous results. With regard to convenience, sensitivity and accuracy our assay represents a realistic alternative to both branched-chain DNA (b-DNA) assays or real-time PCR assays based on TaqMan probes.展开更多
To purify and identify the simian parvovirus (SPV) protein Vp2 expressed in E.coli, fusion protein of SPV Vp2 was expressed in E.coli DH5α competent cells transformed with vector pThioHis A-Vp2, and the new bacterial...To purify and identify the simian parvovirus (SPV) protein Vp2 expressed in E.coli, fusion protein of SPV Vp2 was expressed in E.coli DH5α competent cells transformed with vector pThioHis A-Vp2, and the new bacterial protein extraction reagent was used to extract the protein. Detergents with different characteristics were used to solubilize the fusion protein, and metal chelating resin (ProBond) with a continuous elusion polyacrylamide gel electrophoresis procedure was employed to purify the fusion protein. SDS-PAGE gel stained with coomassie blue and Western-blotting probed with anti-thio and anti-SPV Vp2 antibodies were used to identify the specificity of the expressed and purified fusion proteins. It was found that the SPV Vp2 protein expressed in E.coli was highly insoluble, and could not be solublized by the commonly used detergent. However, 6 M urea could solubilize the fusion proteins and was then employed for the further purification procedure, but metal chelating resin could not be used for this procedure, because of the loss of the tertiary structure of HP-thiaoredoxin and the metal-binding domain. The technique with continuous elusion polyacrylamide gel electrophoresis yielded a homogenous protein with a single band on the gel stained with coomassie blue and retained reactivity with anti-thio or anti-SPV Vp2 antibodies. It is evident that this technique with successful purification of SPV Vp2 protein has practical significance for the further investigation on the simian parvovirus infection.展开更多
OBJECTIVE:To investigate the traditional Chinese Medicine(TCM) etiology and pathogenesis of acquired immune deficiency syndrome(AIDS) by 18-month observation of Chinese rhesus macaques infected with simian immunodefic...OBJECTIVE:To investigate the traditional Chinese Medicine(TCM) etiology and pathogenesis of acquired immune deficiency syndrome(AIDS) by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus(SIV) mac 239.METHODS:Thirty-five healthy Chinese rhesus macaques were divided into a model group(n=30) and a control group(n=5).The model was established by inoculating monkeys intravenously with SIVmac 239.Changes in TCM symptoms after SIV infection within 18 months were then observed and recorded.Routine blood tests,SIV viral load,T-lymphocyte subsets,plasma triiodothyronine(T3),tetraiodothyronine(T4),adrenocorticotropic hormone(ACTH) and cortisol(Cor) were tested periodically during the experiment.RESULTS:During the acute infection period of SIV,model monkeys temporarily showed clinical symptoms such as diarrhea,dysphoria and slight weight loss.Decrease percentages of CD4+ T-lymphocytes were observed but levels of T3,T4,Cor,and ACTH were relatively unchanged.Monkeys in the model group during the early and middle periods of infection showed no obvious symptoms,except few monkeys exhibited transient diarrhea and reduced food intake.All variables at this stage showed normal fluctuations.In the middle period model group monkeys showed chronic and persistent diarrhea,weight loss,reduced food intake and low levels of T3 and Cor.In the late period,symptoms including emaciation,weight loss,listlessness,crouching in corners and low levels of T3 appeared.CONCLUSION:The results suggest that the rhesus monkey SIV/SAIDS model can be applied to research on TCM etiology and pathogenesis of AIDS.According to this model,the etiology of disease is the SIV virus.The pathogenesis manifests as the invasion of SIV virus,incubation of the virus,balance between virus and healthy "Qi",damage to spleen and kidney as the disease progressed,exhaustion of vitality and finally the failure of five zang and six fu organs.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271963(to HJL),81771806(to HJL),61936013(to HJL),82001914(to ZCT),81871511(to HZ)National Key R&D Program of China,No.2021YFA1301603(to ZCT)the Natural Science Foundation of Beijing,No.7212051(to HJL).
文摘Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.
基金Supported by National Natural Science Foundation of China(No.81273212,81100651)Project of Science and Technology of Shandong Province(No.2014GSF118044)
文摘AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
文摘The papers in this special topic of Sino-India Monitor on NDCs,authored by a select group of researchers from both China and India,provide a perspective on areas of common interest for societies in both countries as well as a focus on common objectives defining global action.Climate
基金supported by R01 NS063878,R01 NS077873 and P30 MH062261(to H.X.and H.S.F.)。
文摘Immune cell accumulation and white matter anomaly are common features of HIV(human immunodeficiency virus)-infected patients in combination antiretroviral therapy(cART) era.Neuroimaging tests on cART treated patients displayed prominent diffuse white matter lesions.Notably,immune cell nodular lesion(NL) was a conspicuous type of pathological change in HIV/SIV(simian immunodeficiency virus) infected brain before cART.Therefore,we used SIV infected brain to investigate the distribution of those NLs in gray and white matters.We found a significant higher number of NLs in white matter than that in gray matter.However,virus infection correlated with macrophage NLs but not with microglia NLs,especially in white matter.In addition,NLs interrupted white matter integrity more severely,since even tiny nodules could disconnect nerve fibers in white matter tracts.In the gray matter with dense myelinated axons,NLs obviously encroached those fibers;in the area of few myelinated axons,small nodules well co-localized with extracellular matrix between neurons.
基金National 973 Program(2006CB504208)Natural Science Foundation of Guangdong Province(07118293)The Grant of Science and Technology Plans ofGuangdong Province(2006B36005002)
文摘Plasma viral RNA load is widely accepted as the most relevant parameter to assess the status and progression of Simian immunodeficiency virus (SIV) infections. To accurately measure RNA levels of the virus, a one-step fluorescent quantitative assay was established based on the SYBR green Real-time reverse transcription-polymerase chain reaction (RT-PCR). The lower detection limit of the assay was 10 copies per reaction for the virus. This method was successfully applied to quantify SIVmac251 and SIVmac239 viruses produced in CEM×174 cells. Additionally, the performance of the SYBR green RT-PCR was assessed in a SIVmac251 infected rhesus macaque. The result demonstrated that the method could detect as little as 215 copies per milliliter of plasma and the dynamic pattern of viral load was highly consistent with previous results. With regard to convenience, sensitivity and accuracy our assay represents a realistic alternative to both branched-chain DNA (b-DNA) assays or real-time PCR assays based on TaqMan probes.
文摘To purify and identify the simian parvovirus (SPV) protein Vp2 expressed in E.coli, fusion protein of SPV Vp2 was expressed in E.coli DH5α competent cells transformed with vector pThioHis A-Vp2, and the new bacterial protein extraction reagent was used to extract the protein. Detergents with different characteristics were used to solubilize the fusion protein, and metal chelating resin (ProBond) with a continuous elusion polyacrylamide gel electrophoresis procedure was employed to purify the fusion protein. SDS-PAGE gel stained with coomassie blue and Western-blotting probed with anti-thio and anti-SPV Vp2 antibodies were used to identify the specificity of the expressed and purified fusion proteins. It was found that the SPV Vp2 protein expressed in E.coli was highly insoluble, and could not be solublized by the commonly used detergent. However, 6 M urea could solubilize the fusion proteins and was then employed for the further purification procedure, but metal chelating resin could not be used for this procedure, because of the loss of the tertiary structure of HP-thiaoredoxin and the metal-binding domain. The technique with continuous elusion polyacrylamide gel electrophoresis yielded a homogenous protein with a single band on the gel stained with coomassie blue and retained reactivity with anti-thio or anti-SPV Vp2 antibodies. It is evident that this technique with successful purification of SPV Vp2 protein has practical significance for the further investigation on the simian parvovirus infection.
基金Supported by the National Science and Technology Major Project "Optimization for prescription of anti-HIV Chinese medicine and the study on animal model for AIDS with TCM symptoms(No.2008ZX10005-005)National Key Discipline Construction funding for clinical basic of TCM in Guangzhou university of Chinese Medicine
文摘OBJECTIVE:To investigate the traditional Chinese Medicine(TCM) etiology and pathogenesis of acquired immune deficiency syndrome(AIDS) by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus(SIV) mac 239.METHODS:Thirty-five healthy Chinese rhesus macaques were divided into a model group(n=30) and a control group(n=5).The model was established by inoculating monkeys intravenously with SIVmac 239.Changes in TCM symptoms after SIV infection within 18 months were then observed and recorded.Routine blood tests,SIV viral load,T-lymphocyte subsets,plasma triiodothyronine(T3),tetraiodothyronine(T4),adrenocorticotropic hormone(ACTH) and cortisol(Cor) were tested periodically during the experiment.RESULTS:During the acute infection period of SIV,model monkeys temporarily showed clinical symptoms such as diarrhea,dysphoria and slight weight loss.Decrease percentages of CD4+ T-lymphocytes were observed but levels of T3,T4,Cor,and ACTH were relatively unchanged.Monkeys in the model group during the early and middle periods of infection showed no obvious symptoms,except few monkeys exhibited transient diarrhea and reduced food intake.All variables at this stage showed normal fluctuations.In the middle period model group monkeys showed chronic and persistent diarrhea,weight loss,reduced food intake and low levels of T3 and Cor.In the late period,symptoms including emaciation,weight loss,listlessness,crouching in corners and low levels of T3 appeared.CONCLUSION:The results suggest that the rhesus monkey SIV/SAIDS model can be applied to research on TCM etiology and pathogenesis of AIDS.According to this model,the etiology of disease is the SIV virus.The pathogenesis manifests as the invasion of SIV virus,incubation of the virus,balance between virus and healthy "Qi",damage to spleen and kidney as the disease progressed,exhaustion of vitality and finally the failure of five zang and six fu organs.
基金Supported by the National Natural Science Foundation of China（No.21375153）, the Fundamental Research Funds for the Central Universities of China（No. 131gzd05） and the Open Project of Beijing National Laboratory for Molecular Sciences, China.
