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1.
J Surg Res ; 186(1): 234-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24011916

ABSTRACT

BACKGROUND: The aim of the present study was to investigate the therapeutic effects of p75 tumor necrosis factor receptor monoclonal antibody D8F2 on a traumatic arthritis model in rats, and to explore the underlying mechanism. METHODS: Forty male Sprague Dawley rats were randomly divided into five groups: (A) sham operation control group, (B) traumatic arthritis model group, (C) low-dose D8F2 group (1 mg/kg), (D) medium-dose D8F2 group (3 mg/kg), and (E) high-dose D8F2 group (10 mg/kg). Joint fluid samples were collected at 72 h after surgery, and enzyme-linked immunosorbent assay was performed to measure the following inflammatory factors: tumor necrosis factor α (TNF-α) and interleukin 1ß. One week after the surgery, rats were killed, and immunohistochemical staining was applied to detect the matrix metalloproteinase (MMP1 and MMP3) expression in the synovium. In cultured synovial fibroblast experiments, the D8F2-induced ubiquitination of TNF receptor-associated factor 2 (TRAF2) was examined by immunoprecipitation, and nuclear translocation of p65 nuclear factor-κB (p65NF-κB) mediated by TNF-α and D8F2 was analyzed by western blotting. RESULTS: In the traumatic arthritis model group, the inflammatory factors and MMPs were significantly increased relative to the sham operation control group (P < 0.05), whereas D8F2 could downregulate these factors in a dose-dependent manner (P < 0.05). The results from in vitro studies indicated that D8F2 can induce TRAF2 ubiquitination and inhibit the nuclear translocation of p65NF-κB mediated by TNF-α. CONCLUSIONS: p75 Tumor necrosis factor receptor monoclonal antibody has a therapeutic effect on traumatic arthritis, which may occur via the downregulation of inflammatory factors and MMPs at the transcription level because of TRAF2 degradation and inhibited activation of NF-κB.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Arthritis/drug therapy , Joints/injuries , Receptors, Tumor Necrosis Factor, Type II/antagonists & inhibitors , Animals , Cytokines/analysis , Disease Models, Animal , Male , Matrix Metalloproteinase 1/analysis , NF-kappa B/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Receptors, Tumor Necrosis Factor, Type II/physiology , TNF Receptor-Associated Factor 2/metabolism
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 34(1): 57-60, 2013 Jan.
Article in Chinese | MEDLINE | ID: mdl-23648252

ABSTRACT

OBJECTIVE: To understand the biochemical characteristics, virulence genes and pathogenicity of Shigella flexneri Xv isolated in Beijing. METHODS: 61 strains of S. flexneri Xv isolated from diarrhea patients in Beijing were systematically determined through biochemical reactions and serological tests. Application of PCR technique in detection of virulence genes on ipaH, sen, virF, ial and pulsed-field gel electrophoresis (PFGE) was used to identify the related characteristics and on rat lung slices to determine its pathogenicity. RESULTS: All of the S. flexneri Xv could ferment glucose, mannitol, melibiose and arabinose. Using serum agglutination, we found that the antigen structure was (IV: 7, 8). IpaH, sen, virF and ial that carried rates of virulence genes appeared to be 100%, 81.97%, 75.41% and 80.30%, respectively. Among 61 strains of S. flexneri Xv, the PFGE typing of Shigella bacteria could be divided into 25 belt types while the results from rat lung slices showed inflammatory change of Xv. CONCLUSION: S. flexneri Xv was found that it carried high rate of Shigella virulence genes, exhibiting genetic polymorphism and highly invasive.


Subject(s)
Shigella flexneri/classification , Shigella flexneri/pathogenicity , Virulence/genetics , Animals , Humans , Microbial Sensitivity Tests , Rats , Shigella flexneri/isolation & purification
3.
J Surg Res ; 182(1): 127-33, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-22935315

ABSTRACT

OBJECTIVE: To investigate the effects of and mechanisms underlying the activation of the p75 tumor necrosis factor receptor (p75TNFR) signaling pathway in inflammatory responses in mice with traumatic brain injury. METHODS: We first generated hybridomas that produced antibodies specific for p75TNFR, by inoculating BALB/c mice with antigenic peptides derived from mouse p75TNFR, which is critical to the binding of tumor necrosis factor-alpha (TNF-α) and p75TNFR. The isotype, epitope, titer, specificity, and affinity constant of monoclonal antibodies (mAbs) were determined using commercial kits and enzyme-linked immunosorbent assay. We then screened the agonist antibody via L929 cytotoxicity assay. The levels of inflammatory factors were detected in C57BL/6 mice with traumatic brain injury and then the mice were injected with either saline (control) or p75TNFR agonist mAb. Furthermore, we investigated the effects of p75TNFR agonist mAb on p38MAPK and nuclear factor-κB signals. RESULTS: Seven mAbs against p75TNFR were generated. Among them, the mAb D8F2 could markedly enhance the cytotoxicity of TNF-α on L929 cells. In a traumatic brain injury model, D8F2 could inhibit the levels of inflammatory factors and downregulate RNA transcription of these factors by suppressing the activation of p38 mitogen-activated protein kinase and nuclear factor-κB. CONCLUSION: The mAb D8F2 could inhibit posttraumatic inflammatory responses effectively. In this study, we developed an agonist anti-mouse p75TNFR mAb, which may be used in the future to devise new strategies for the clinical treatment of inflammation after trauma.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Brain Injuries/complications , Encephalitis/etiology , Encephalitis/prevention & control , Receptors, Tumor Necrosis Factor, Type II/antagonists & inhibitors , Signal Transduction/physiology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Brain Injuries/metabolism , Disease Models, Animal , Encephalitis/metabolism , Female , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , NF-kappa B/metabolism , Receptors, Tumor Necrosis Factor, Type II/immunology , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
4.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 27(8): 832-4, 2011 Aug.
Article in Chinese | MEDLINE | ID: mdl-21806875

ABSTRACT

AIM: To study the interaction between MAVS and p21 regulates MAVS-mediated pathway. METHODS: Firstly, we cloned full-length p21 gene by PCR. And then the interaction between MAVS and p21 was further demonstrated by co-immunoprecipitation. The regulation of MAVS-mediated pathway by p21 was analyzed by luciferase reporter assays. RESULTS: There are interaction between p21 and MAVS in 293T cells. p21 downregulates activity of MAVS. CONCLUSION: It is shown that p21 inhibits MAVS-mediated activation of NF-κB and IFN-ß by Luciferase reporter assays. Overall, these results laid the foundation for further investigating the function of p21 in MAVS-mediated pathway.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Gene Expression Regulation , Cyclin-Dependent Kinase Inhibitor p21/genetics , Down-Regulation/genetics , HEK293 Cells , Humans , Protein Binding/physiology , Signal Transduction/genetics
5.
J Surg Res ; 161(1): 119-25, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-19482318

ABSTRACT

BACKGROUND: Organ dysfunction or multiple organ dysfunction syndrome caused by developing immunological dysfunction and subsequent sepsis or the systemic inflammatory response syndrome after trauma is the leading cause of death in trauma patient. It is believed that mitogen-activated protein kinase) (p38MAPK) is one of the most important kinases in inflammatory signaling. In this study, the change of p38 MAPK signaling pathway in trauma patient with different severity and its clinical significance in trauma inflammation were investigated. METHODS: One hundred fifty major trauma patients were included in the study and divided into three groups according to injury severity score (ISS). All data required to calculate ISS and determine organ function were registered on admission and during the ICU-stay. Peripheral blood samples were collected from trauma patients 6 h, 1 d, 3 d, 5 d, and 7 d after injury. RQ-PCR and Western blot was used to examine the changes in gene expression, protein expression, and activation level of leukocyte p38 MAPK. Plasma IL-6 and TNFalpha were assayed by ELISA. RESULTS: Organ dysfunction in 33 trauma patients developed and eight deaths occurred after 24 h in ICU. The causes of death included severe ARDS, MODS, and irreversible brain injury. Incidence of organ dysfunction was related to the increase of injury severity (P < 0.01). Compared with healthy control, the gene expression of p38 MAPK in trauma patients increased significantly 6 h after injury (P < 0.05), and reached a maximum in 1 d (P < 0.01). The expression maintained a high level for 7 d (P < 0.05). One day after injury, significant elevation was observed in protein expression and activation level of p38 MAPK (P < 0.05), as well as the plasma TNFalpha and IL-6 level (P < 0.01). Further investigation found that the gene expression, protein expression, and activation levels of p38 MAPK increased with higher ISS (P < 0.05), and the elevation of plasma TNFalpha and IL-6 level was associated with the increase of activated p38 MAPK and ISS (P < 0.05). CONCLUSION: p38 MAPK signal pathway was activated in trauma patients. The severity of trauma had highly positive correlation with the expression and activation of p38 MAPK, as well as the elevation of plasma TNFalpha and IL-6 expression. These findings indicate that p38 MAPK signaling pathway plays an important role in the pathological mechanism of trauma.


Subject(s)
Accidental Falls , Accidents, Traffic , MAP Kinase Signaling System , Wounds, Stab/enzymology , p38 Mitogen-Activated Protein Kinases/metabolism , Adolescent , Adult , Aged , Enzyme Activation , Female , Gene Expression , Humans , Interleukin-6/blood , Leukocytes/enzymology , Male , Middle Aged , Multiple Organ Failure/etiology , Severity of Illness Index , Tumor Necrosis Factor-alpha/blood , Young Adult
6.
Chin J Integr Med ; 12(1): 29-31, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16571280

ABSTRACT

OBJECTIVE: To explore the change of serious abdominal traumatic patients' cellular immunity and the effect of Astragalus Injection (AI) on it. METHODS: Sixty-three serious abdominal traumatic patients were randomly assigned into two groups, the conventional group and the treated group, patients in the conventional group were given conventional treatment, while others in the treated group were given conventional treatment as the basis, with AI 20 ml was added into 250 ml of 5% glucose solution given through intravenous dripping, and then on the first day and 14th day, their T cell activated antigens as well as that of 10 healthy subjects were monitored. RESULTS: On the first day, in the conventional group and treated group, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/homologous leucocytic antigen-DR (HLA-DR(+)) were apparently lower than those in the healthy group (P < 0.05), while the CD(8)(+) was significantly higher than that in the healthy group (P < 0.05), and there was no significant difference between the conventional group and the treated group (P > 0.05); on the 14th days, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/HLA-DR(+) of the treated group got closed to healthy subject value, and got even higher than those of conventional group (P < 0.05); CD(8)(+) got close to that of healthy subjects, while obviously lower than that of conventional group (P < 0.05). CONCLUSION: After serious abdominal trauma, cellular immunity lowered, auxiliary use of AI was beneficial to the restoration of cellular immunity.


Subject(s)
Abdominal Injuries/immunology , Adjuvants, Immunologic/therapeutic use , Astragalus propinquus , Drugs, Chinese Herbal/therapeutic use , Phytotherapy , Adult , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , Female , Humans , Immunity, Cellular , Lectins, C-Type , Lymphocyte Activation , Male , Middle Aged , Receptors, IgG/analysis , T-Lymphocyte Subsets
7.
Ai Zheng ; 23(9): 1065-8, 2004 Sep.
Article in Chinese | MEDLINE | ID: mdl-15363203

ABSTRACT

BACKGROUND & OBJECTIVE: Immunity, especially cellular immunity, of patients with tumor is related to tumorigenesis. The correlation of changes of T Lymphocyte phenotype to tumor stage and operative pattern of gastric cancer is unclear. This study was to evaluate the perioperative immune state in patients with gastric cancer (GC) of different stage and accepted different operative pattern. METHODS: Six kinds of T lymphocyte phenotype in 33 GC patients were measured by flow cytometry before and after operation, and compared with that of benign disease patients. RESULTS: With progress of cancer stage, CD3, CD4, CD4/CD8, CD16, and CD69 gradually decreased, while CD8 gradually increased (P< 0.05). There was no significant difference of activated T cell CD3+/HLA-DR+ among patients of stage I,II,III. After radical resection, CD8 decreased, while CD3, CD4, CD4/CD8, CD16, CD69, and CD3+/HLA-DR+ increased significantly (P< 0.01). CD3, and CD4 unchanged after palliative operation. CD16, and CD4/CD8 further decreased in patients with unresectable tumor (P< 0.05). CONCLUSIONS: The preoperative immune state of GC patients is negatively related to cancer stage. Tumor removal may improve the cellular immunity of patients.


Subject(s)
Antigens, CD/blood , Gastrectomy/methods , Stomach Neoplasms/immunology , T-Lymphocytes/pathology , Aged , Antigens, Differentiation, T-Lymphocyte/blood , CD3 Complex/blood , CD4-CD8 Ratio , Female , Humans , Immunity, Cellular , Intraoperative Period , Lectins, C-Type , Male , Middle Aged , Neoplasm Staging , Phenotype , Receptors, IgG/blood , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
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