This report characterizes the J6-1 cell line derived from a Chinese acute myelomonocytic leukemia patient and previously reported to be associated with EBV. These studies showed that J6-1 cells were also infected with...This report characterizes the J6-1 cell line derived from a Chinese acute myelomonocytic leukemia patient and previously reported to be associated with EBV. These studies showed that J6-1 cells were also infected with HHV-6 as demonstrate at the DNA level by PCR and Southern blot hybridization and by expression of HHV-6 early membrane antigen on the J6-1 cell surface. Further characterization showed J6-1 was co-infected with EBV type 2. Generally, cells infected with EBV type 2 do not grow well in vitro. However, J6-1 , although difficult to maintain in vitro, has been grown for 15 years. Possibly, co-infection with HHV6 confers this property. In this regard, J6-1 cells exhibited density dependent growth which could be inhibited with an anti-HHV-6-MA monoclonal antibody(MAb). In contrast, anti-HHV-6-VCA MAb stimulated the J6-1 cell proliferation. Electron microscopic analysis showed that, morphologically, there were two types of J6-1 cell, one with lymphoblastoid features and one with a monocytoid appearance. Accordingly, the flow profile of the J6-1 cell line showed heterogeneity. with two populations comprised of CD15-, CD19+ cells with low light scatter(small cells) and a population with greater light scatter(larger cells) which was CD15+ , CD19+. The population was negative for progenitor cell markers(CD33, 34 ), and T cell markers. Southern analysis showed no T cell receptor rearrangement, however there was a clonal JH and kappa light chain expressing population. Glycocytochemical analysis showed several endogenous lectin receptors on the J6-1 cell surface: BSA-Xylose, BSA-Rhamnose, BSAGal. BSA-Lac. This cell line shares many characteristics with other monocytic/ lymphoblastoid cell lines isolated elsewhere and provides circumstantial evidence linking Herpes viruses, as least as co- factors,to leukemia cell growth.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
To investigate the inhibitory effects of Ginsenoside Rbl （GRbl） on apoptosis caused by Herpes Simplex Virus-1 （HSV-1） in Human Glioma Cells （U251）, U251 cells were infected by HSV-1 at a multiplicity of infectio...To investigate the inhibitory effects of Ginsenoside Rbl （GRbl） on apoptosis caused by Herpes Simplex Virus-1 （HSV-1） in Human Glioma Cells （U251）, U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRbl, GRbl＋HSV-1, HSV-1 and control groups. MTT and cell apoptosis assays were used to detect the inhibitory effects of GRbl on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay. We found that in the 400 μg/mL GRb 1 and 400 μg/mL GRbl＋HSV-1 groups, MTT values were higher than control group at all times （P〈0.05）. Moreover, the apoptosis rate in the 400 μg/mL GRbl＋HSV-1 group was lower than the HSV-1 group （P〈0. 05）. These results confirmed that, at appropriate concentrations, GRbl could inhibit nerve cell apoptosis in HSV-1 infections.展开更多
BACKGROUND Kaposi’s sarcoma(KS)is a malignancy that usually affects the skin of the lower extremities,and may involve internal organs.It originates from the vascular endothelium.It is well known that the development ...BACKGROUND Kaposi’s sarcoma(KS)is a malignancy that usually affects the skin of the lower extremities,and may involve internal organs.It originates from the vascular endothelium.It is well known that the development of KS is associated with human herpes virus 8(i.e.HHV8)infections.Sporadic KS cases have mainly been found in Africa.Isolated splenic KS in Asia has rarely been reported.We present here a case of KS primarily involving the spleen in a human immunodeficiency virus(HIV)-negative Chinese patient.CASE SUMMARY A 50-year-old male patient was admitted to hospital due to abdominal distension and discomfort,reduced food intake and weight loss.Medical examination revealed that the patient had moderate anemia,a low platelet count,slight fatty liver and a huge mass in the spleen.Spleen lymphoma was considered.An anti-HIV test was negative.The whole spleen was surgically excised.The final pathological diagnosis was nodular stage spleen KS,and the patient underwent total splenectomy.He recovered well and was discharged from hospital 12 d after surgery.Two weeks later,the patient developed liver metastasis and died within 1 mo after surgery.CONCLUSION KS is difficult to diagnose and pathological examination is necessary.KS has a poor prognosis and should be diagnosed and treated early to improve survival.展开更多
Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention a...Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.展开更多
AIM:To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome(AIDS)-related Kaposi’s sarcoma(KS).METHODS:Patients with histologically proven non-AIDS-related KS...AIM:To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome(AIDS)-related Kaposi’s sarcoma(KS).METHODS:Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis.In some cases,the human herpes virus 8 status was assessed by immunohistochemistry.The patients were staged according to the Mediterranean KS staging system.A multivariable model was constructed using a forward stepwise selection procedure.A P value<0.05 was considered statistically significant,and all tests were two-sided.RESULTS:Thirty-two cases were included in this analysis.The average age at diagnosis was 70 years,with a male/female ratio of approximately 2:1.Eighty-four percent of the cases had classic KS.All patients received systemic chemotherapy containing one of the following agents:vinca alkaloid,taxane,and pegylated liposomal doxorubicin.Ten patients(31.5%)experienced a partial response,and a complete response was achieved in four patients(12.4%)and stable disease in sixteen cases(50%).Two patients(6.2%)were refractory to the systemic treatment.The median progression-free survival(PFS)was 11.7 mo,whereas the median overall survival was 28.5 mo.At multivariate analysis,the presence of nodular lesions(vs macular lesions only)was significantly related to a lower PFS(hazard ratio:3.09;95%CI:1.18-8.13,P=0.0133).CONCLUSION:Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies.Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.展开更多
Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(l...Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(+)CD8^(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI(r=-0.578,P=0.015).Notably,in the first month of AHI,few CD3^(+)CD8^(low) T cells,but comparable amounts of CD3^(+)CD8^(high) T cells,responded to Gag peptides.Then,weaker HIV-1-specific T-cell responses were induced in CD3^(+)CD8^(low) T cells than CD3^(+)CD8^(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3^(+)CD8^(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response.Subsequently,CD3^(+)CD8^(low) T-cell number decreased gradually as infection persisted,and their anti-HIV functions were inferior to those of CD3^(+)CD8^(high) T cells.展开更多
文摘This report characterizes the J6-1 cell line derived from a Chinese acute myelomonocytic leukemia patient and previously reported to be associated with EBV. These studies showed that J6-1 cells were also infected with HHV-6 as demonstrate at the DNA level by PCR and Southern blot hybridization and by expression of HHV-6 early membrane antigen on the J6-1 cell surface. Further characterization showed J6-1 was co-infected with EBV type 2. Generally, cells infected with EBV type 2 do not grow well in vitro. However, J6-1 , although difficult to maintain in vitro, has been grown for 15 years. Possibly, co-infection with HHV6 confers this property. In this regard, J6-1 cells exhibited density dependent growth which could be inhibited with an anti-HHV-6-MA monoclonal antibody(MAb). In contrast, anti-HHV-6-VCA MAb stimulated the J6-1 cell proliferation. Electron microscopic analysis showed that, morphologically, there were two types of J6-1 cell, one with lymphoblastoid features and one with a monocytoid appearance. Accordingly, the flow profile of the J6-1 cell line showed heterogeneity. with two populations comprised of CD15-, CD19+ cells with low light scatter(small cells) and a population with greater light scatter(larger cells) which was CD15+ , CD19+. The population was negative for progenitor cell markers(CD33, 34 ), and T cell markers. Southern analysis showed no T cell receptor rearrangement, however there was a clonal JH and kappa light chain expressing population. Glycocytochemical analysis showed several endogenous lectin receptors on the J6-1 cell surface: BSA-Xylose, BSA-Rhamnose, BSAGal. BSA-Lac. This cell line shares many characteristics with other monocytic/ lymphoblastoid cell lines isolated elsewhere and provides circumstantial evidence linking Herpes viruses, as least as co- factors,to leukemia cell growth.
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.
基金Supported by National Natural Science Foundation of China(Grant No.81070501 and 30770105)Shandong Provincial Outstanding Medical Academic Professional Program
文摘To investigate the inhibitory effects of Ginsenoside Rbl （GRbl） on apoptosis caused by Herpes Simplex Virus-1 （HSV-1） in Human Glioma Cells （U251）, U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRbl, GRbl＋HSV-1, HSV-1 and control groups. MTT and cell apoptosis assays were used to detect the inhibitory effects of GRbl on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay. We found that in the 400 μg/mL GRb 1 and 400 μg/mL GRbl＋HSV-1 groups, MTT values were higher than control group at all times （P〈0.05）. Moreover, the apoptosis rate in the 400 μg/mL GRbl＋HSV-1 group was lower than the HSV-1 group （P〈0. 05）. These results confirmed that, at appropriate concentrations, GRbl could inhibit nerve cell apoptosis in HSV-1 infections.
文摘BACKGROUND Kaposi’s sarcoma(KS)is a malignancy that usually affects the skin of the lower extremities,and may involve internal organs.It originates from the vascular endothelium.It is well known that the development of KS is associated with human herpes virus 8(i.e.HHV8)infections.Sporadic KS cases have mainly been found in Africa.Isolated splenic KS in Asia has rarely been reported.We present here a case of KS primarily involving the spleen in a human immunodeficiency virus(HIV)-negative Chinese patient.CASE SUMMARY A 50-year-old male patient was admitted to hospital due to abdominal distension and discomfort,reduced food intake and weight loss.Medical examination revealed that the patient had moderate anemia,a low platelet count,slight fatty liver and a huge mass in the spleen.Spleen lymphoma was considered.An anti-HIV test was negative.The whole spleen was surgically excised.The final pathological diagnosis was nodular stage spleen KS,and the patient underwent total splenectomy.He recovered well and was discharged from hospital 12 d after surgery.Two weeks later,the patient developed liver metastasis and died within 1 mo after surgery.CONCLUSION KS is difficult to diagnose and pathological examination is necessary.KS has a poor prognosis and should be diagnosed and treated early to improve survival.
文摘Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.
文摘AIM:To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome(AIDS)-related Kaposi’s sarcoma(KS).METHODS:Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis.In some cases,the human herpes virus 8 status was assessed by immunohistochemistry.The patients were staged according to the Mediterranean KS staging system.A multivariable model was constructed using a forward stepwise selection procedure.A P value<0.05 was considered statistically significant,and all tests were two-sided.RESULTS:Thirty-two cases were included in this analysis.The average age at diagnosis was 70 years,with a male/female ratio of approximately 2:1.Eighty-four percent of the cases had classic KS.All patients received systemic chemotherapy containing one of the following agents:vinca alkaloid,taxane,and pegylated liposomal doxorubicin.Ten patients(31.5%)experienced a partial response,and a complete response was achieved in four patients(12.4%)and stable disease in sixteen cases(50%).Two patients(6.2%)were refractory to the systemic treatment.The median progression-free survival(PFS)was 11.7 mo,whereas the median overall survival was 28.5 mo.At multivariate analysis,the presence of nodular lesions(vs macular lesions only)was significantly related to a lower PFS(hazard ratio:3.09;95%CI:1.18-8.13,P=0.0133).CONCLUSION:Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies.Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.
基金supported by grants from the National Natural Science Foundation of China(NSFC,81974303)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018)+7 种基金the Ministry of Science and Technology of China(CPL-1233)the“Climbing the peak(Dengfeng)”Talent Training Program of Beijing Hospitals Authority(DFL20191701 and DFL20181701)the Beijing Health Technologies Promotion Program(BHTPP2020)Beijing Key Laboratory for HIV/AIDS Research(BZ0089 and BZ0373)Beijing Natural Science Foundation(7191004)Beijing Municipal Science and Technology Project(Z211100002521024)the Natural Science Foundation of Capital Medical University(PYZ21126)and the Scientific Research Project of Beijing Youan Hospital(CCMU-2020-BJYAYY-2020YC-01 and CCMU-2021-YNKTXF2021001).
文摘Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(+)CD8^(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI(r=-0.578,P=0.015).Notably,in the first month of AHI,few CD3^(+)CD8^(low) T cells,but comparable amounts of CD3^(+)CD8^(high) T cells,responded to Gag peptides.Then,weaker HIV-1-specific T-cell responses were induced in CD3^(+)CD8^(low) T cells than CD3^(+)CD8^(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3^(+)CD8^(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response.Subsequently,CD3^(+)CD8^(low) T-cell number decreased gradually as infection persisted,and their anti-HIV functions were inferior to those of CD3^(+)CD8^(high) T cells.
