1.Therapeutic effect of 4-1BBmAb on immune-mediated hepatitis induced by ConA and its influ-ences on CD4+CD25+T lymphocytes
Guangtao XIA ; Yuanchao ZHANG ; Sensen WU ; Xiaoyan LIN
Chinese Journal of Rheumatology 2008;12(11):751-753,插1
Objective To investigate the therapeutic effect of 4-1BB monoclone antibodies on mice hepatitis induced by Coneanavalin A (ConA) and its influenes on CD4+CD25+T lymphoeytes during the course. Methods The miee model of hepatic injury was indueed by ConA and monitored by hepatic function tests and hepatic pathology. The expressions of 4-1BB were examined by flow eytometry. 4-1BB monoelone antibodies were intravenously injected to the mice. The therapeutic efficacy was then examined by hepatic function tests and hepatic pathology. The expressions of CD4+CD25+T lymphoeytes were also examined by flow eytometry. Results The group of immune hepatic injury induced by ConA showed damage and marked increase of ALT and AST which were (139±22) U/L and (130±16) U/L respectively. The expression level of 4-1BB was 8.1±2.6. Compared with the eontrol group, the difference was significant (P<0.05). The overall eondition of the miee was improved after being treated with 4-1BB monoelone antibodies. ALT and AST were lowed down to (98±14) U/L and (89±11) U/L respectively and the differenee was signifieant (P<0.01). The expression of 4-1BB of the control group was 3.0±0.8 and that of the treatment group was 8.3±3.0. The difference was significant (P<0.01). Conclusion 4-1BB eontributes to the immune-mediated hepatic injury induced by Con-A.
2.Therapeutic effect of 4-1BB monoclonal antibodies and glucocorticosteroid on immune hepatitis induced by ConA
Guangtao XIA ; Yuanchao ZHANG ; Min FU ; Sensen WU
Chinese Journal of Rheumatology 2013;(3):186-190,封3
Objective To investigate the therapeutic effect of 4-1BB monoclonal antibodies (4-1BBmAb) and glucocorticosteroid and the affect of the expression of CD4+CD25+T lymphocytes on the mouse hepatitis induced by ConA.Methods Mouse model of hepatic injury was induced by the application of ConA and checked by hepatic function tests and hepatic pathology.Mter the animal models were constructed,the mice in the group of therapeutic alliance were treated with glucocorticosteroid and 4-1BBmAb.In contrast,mice in the control group were treated with 4-1BBmAb or glucocorticosteroid alone.The groups were then compared.After blood was collected respectively from the control group,the model group and the therapy group,flow cytometry was used to examine CD4+CD25+T lymphocytes.Chi-square test and t-test were used for statistical analysis.Results Compared with the control group,the conditions of the mice were improved after being disposed with 4-1BBmAb.The conditions became even better when 4-1BBmAb were used combined with glucocorticosteroid.ALT and AST of the control group were (140±22) U/L and (131±16) U/L respectively,that of 4-1BBmAb group were (98±14) U/L and (89±11) U/L respectively.The ALT and AST of the glucocorticosteroid treatment group were (76±11) U/L and (71±10) U/L respectively,ALT was (61±8) U/L and AST was (55±7) U/L in the combination treatment group.Differences among groups was statistically significant (P<0.01).The expression of CD4+CD25+T lymphocytes was (3.0±0.8)% in the control group,(8.5±2.9)% in the gluco-corticosteroid treatment group,(8.4±3.5)% in the 4-1BBmAb treatment group and was (11.2±3.5)% in the combination treatment group.The difference was significant among the groups (P<0.05).Conclusion 4-1BB-mAb have therapeutic effect for hepatic injury.The effectiveness will become even more evident when 4-1BB monoclonal antibodies are used together with glucocorticosteroid.During the course of treatment,4-1BBmAb and glucocorticosteroid can impact the expressions of CD4+CD25+T lymphocytes and this is the mechanism for the effectiveness in treating immune-mediated hepatic injury.
3.Research on apoptosis mechanism of HT-29 colon cancer cell induced by NDGA
Guangtao XIA ; Yuanchao ZHANG ; Sensen WU ; Lixia YIN
Chinese Journal of Current Advances in General Surgery 1999;0(04):-
Objective:To find out the apoptosis mechanism of HT-29 colon cancer cell induced by NDGA,the lipoxygenase inhibitor in vitro.Methods:We applied respectively:RT-PCR to detect colon cancer cell’s expression of 5-LOX messenger ribonucleic acid(5-LOXmRNA) and that of messenger ribonucleic acid about human telomerase reverse transcriptase(hTERTmRNA)respectively,confocal laser scanning electron microscope to examine intracellular free calcium.Results:Colon cancer cell lines HT-29 showed positive expression of 5-LOXmRNA.This expression became weaker following the rise of cell’s apoptosis and so were hTERTmRNA.Intracellular Free calcium increased following the rise of cell’s apoptosis.Conclusion:The apoptosis of tumor cell is caused by a combination of factors,with 5-LOX,telomerase and free calcium all active in the course.
4.The Inhibitory Effect of NDGA on the Growth of Colon Cancer Cell Line HT-29 and Its Impact on the Expression of Telomerase
Guangtoo XIA ; Yuanchao ZHANG ; Sensen WU ; Shangzhong ZHANG
Chinese Journal of Cancer Biotherapy 1996;0(04):-
Objective; To investigate the effect of NDGA, the lipoxygenase inhibitor, on colon cancer cell line HT-29 in vitro from the aspects of cell growth inhibition, cell apoptosis and its impact on the expression of telomerase. Methods: We applied respectively i) MTT to draw the growth curve. ii) inverted phase contrast microscope to observe morphologic change of cells, iii) scanning electron microscope to observe changes of cell's ultra-microstructure and apoptotic body. iv) RT-PCR to detect the changes of the expression of human telomerase reverse transeriptase (hTERT). Results: Different concentrations of NDGA were used to dispose cancer cells separately, with the rise of the drugis concentration, the form of cells became round, the volume waned, cells abscised from the inner surface of the bottle. and growth inhibition became increasing abvious. Also through scaming electron microscope, apoptic bodies could be found colon cancer cell line HT-29 showed positive expression of hTERTmRNA, which became weaker following the rising of the drugs concentration. Conclusions: NDGA which, displays the relying effect of doses, can inhibit the growth of colon cancer cell line HT-29 and induce its apoptosis, telomerase plays an active role in this course.
5.Detection of vaginal discharge by ultra-high power microscope and conventional microscope.
Fei WU ; Lei WANG ; Sensen ZHANG ; Tinghong SUN
Chinese Journal of Medical Instrumentation 2010;34(4):291-292
OBJECTTo study the significance of the ultra-high power microscope in the examination of vaginal discharge.
METHODSBy the ACT-2000 ultra-high power microscope system and Olympus CX21 microscope, the vaginal discharge of 1,100 gynaecology out-patients was examined respectively.
RESULTSThe positive rate of mould in the patients was 11.55% by CX21 and was 20.27% by ACT-2000, respectively. The positive rate of trichomonas vaginalis was 2.55% by CX21 and 3.0% by ACT-2000, respectively. The clue cell was detected in 11.27% of the patients by ACT-2000, but no such cell reported by CX21. Totally, positive results were obtained in 14.09% of the patients by CX21 and 32.55% by ACT-2000.
CONCLUSIONBy using the ultra-high power microscope, the positive result can be increased obviously in the examination of vaginal discharge. It is very important in clinical practices.
Adult ; Female ; Humans ; Microscopy ; methods ; Microscopy, Electron ; methods ; Middle Aged ; Vaginal Discharge ; pathology ; Young Adult
6. Treatment of central nervous system leukemia with CD19-chimeric antigen receptor T-cell immunotherapy: two cases report and literature review
Mengying JIN ; Yue HAN ; Yuejun LIU ; Bin GU ; Jia CHEN ; Sensen SHI ; Mingzhu XU ; Chengsen CAI ; Yaqiong TANG ; Depei WU
Chinese Journal of Hematology 2018;39(8):650-653
Objective:
To explore the efficacy and safety of chimeric antigen receptor T (CAR-T) cells in the treatment of central nervous system leukemia (CNSL).
Methods:
Two leukemia patients with CNSL were treated with CD19-CAR-T cells. The process and results of the entire treatment is reported and related literature review is conducted.
Results:
The patients were diagnosed as acute myeloid leukemia (AML)-M2 with B lymphoid antigen expression and B cell acute lymphoblastic leukemia(B-ALL) by morphology and immunophenotype assay. The immunophenotype was consistent with the abnormal manifestations of AML-M2 and B-ALL. Their clinical manifestations and laboratory tests met the diagnostic criteria of CNSL. The diagnosis was clear and the two patients were treated with CD19-CAR-T cell immunotherapy. Central nervous system symptoms were relieved. The imaging abnormalities of patient one has disappeared but cytokines release syndrome (CRS) occurred during the treatment. Cerebrospinal fluid of patient two was negative and no obvious CRS reaction was found.
Conclusions
CAR-T cell immunotherapy is likely to induce the remission of CNSL and improve the prognosis.
7.Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen α.
Xinyue ZHANG ; Meng WU ; Wei ZHUO ; Jinke GU ; Sensen ZHANG ; Jingpeng GE ; Maojun YANG
Protein & Cell 2015;6(10):757-766
Bone sialoprotein-binding protein (Bbp), a MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family protein expressed on the surface of Staphylococcus aureus (S. aureus), mediates adherence to fibrinogen α (Fg α), a component in the extracellular matrix of the host cell and is important for infection and pathogenesis. In this study, we solved the crystal structures of apo-Bbp(273-598) and Bbp(273-598)-Fg α(561-575) complex at a resolution of 2.03 Å and 1.45 Å, respectively. Apo-Bbp(273-598) contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional D1 strand in N2 domain and D1' and D2' strands in N3 domain. The peptide mapped to the Fg α(561-575) bond to Bbp(273-598) on the open groove between the N2 and N3 domains. Strikingly, the disordered C-terminus in the apo-form reorganized into a highly-ordered loop and a β-strand G'' covering the ligand upon ligand binding. Bbp(Ala298-Gly301) in the N2 domain of the Bbp(273-598)-Fg α(561-575) complex, which is a loop in the apo-form, formed a short α-helix to interact tightly with the peptide. In addition, Bbp(Ser547-Gln561) in the N3 domain moved toward the binding groove to make contact directly with the peptide, while Bbp(Asp338-Gly355) and Bbp(Thr365-Tyr387) in N2 domain shifted their configurations to stabilize the reorganized C-terminus mainly through strong hydrogen bonds. Altogether, our results revealed the molecular basis for Bbp-ligand interaction and advanced our understanding of S. aureus infection process.
Bacterial Proteins
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chemistry
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genetics
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metabolism
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Carrier Proteins
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chemistry
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genetics
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metabolism
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Crystallography, X-Ray
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Fibrinogen
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metabolism
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Ligands
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Models, Molecular
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Mutation
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Peptide Fragments
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chemistry
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metabolism
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Protein Binding
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Protein Structure, Tertiary
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Staphylococcus aureus