Biomedical subjects

Jun Peng

Publications and source records attributed to Jun Peng.

At least 55 records · Page 3Linked to original sources

PubMed2004

The herbicide paraquat induces dopaminergic nigral apoptosis through sustained activation of the JNK pathway.

Environmental exposure to the oxidant-producing herbicide paraquat has been implicated as a risk factor in Parkinson's disease. Although intraperitoneal paraquat injections in mice cause a selective loss of dopaminergic neurons in the substantia nigra pars compacta, the exact mechanism involved is still poorly understood. Our data show that paraquat induces the sequential phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun and the activation of caspase-3 and sequential neuronal death both in vitro and in vivo. These effects are diminished by the specific JNK inhibitor SP600125 and the antioxidant manganese(III) tetrakis (4-benzoic acid) porphyrin in vitro. Furthermore, JNK pathway inhibitor CEP-11004 effectively blocks paraquat-induced dopaminergic neuronal death in vivo. These results suggest that the JNK signaling cascade is a direct activator of the paraquat-mediated nigral dopaminergic neuronal apoptotic machinery and provides a molecular linkage between oxidative stress and neuronal apoptosis.

Animals↗

PubMed2004

Delayed cardioprotection afforded by nitroglycerin is mediated by alpha-CGRP via activation of inducible nitric oxide synthase.

Previous investigations have demonstrated that delayed preconditioning induced by nitroglycerin is mediated by endogenous calcitonin gene-related peptide (CGRP). In the present study, we examined whether CGRP-mediated delayed preconditioning induced by nitroglycerin is involved in activation of inducible nitric oxide synthase (iNOS). Male Wistar rats were pretreated with nitroglycerin 24 h before the experiment, and then the left main coronary artery of rat heart was subjected to 60-min occlusion followed by 3 h reperfusion. Infarct size, the plasma level of cGMP and CGRP, and expression of CGRP isoforms (alpha-CGRP and beta-CGRP) mRNA in lumbar dorsal root ganglia were measured. Pretreatment with nitroglycerin (120 microg/kg, i.v.) markedly reduced infarct size. Nitroglycerin caused a significant increase in the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, concomitant with an increase in plasma concentrations of cGMP and CGRP. These effects of nitroglycerin were completely abolished by pretreatment with aminoguanidine (300 mg/kg, i.p.), a selective inhibitor of iNOS activity, or dexamethasone (5 mg/kg, i.p.), the iNOS expression inhibitor. The present results suggest that delayed cardioprotection afforded by nitroglycerin is mediated by the alpha-CGRP isoform via generation of NO derived from iNOS.

Analysis of Variance↗

PubMed2004

Protective effects of evodiamine on myocardial ischemia-reperfusion injury in rats.

Previous investigations have indicated that the pharmacological activities of evodiamine, a major alkaloidal component of the dried, unripe fruit of Evodia rutaecarpa Bentham (Rutaceae), are associated with the stimulation of calcitonin gene-related peptide (CGRP) release and that CGRP protects the myocardium against ischemia-reperfusion injury. In the present study, we have examined whether evodiamine protects against myocardial ischemia-reperfusion injury in rats and whether the protective effects of evodiamine are related to the activation of capsaicin-sensitive sensory nerves. Rats were pretreated with evodiamine 10 min before the experiment, and then the left main coronary artery of rat hearts was subjected to 60 min occlusion followed by 180 min reperfusion. Infarct size, the activity of serum creatine kinase, serum concentrations of TNF-alpha and plasma concentrations of CGRP were measured. Pretreatment with evodiamine (30 or 60 microg/kg, i.v.) markedly increased the content of CGRP in plasma concomitantly with a significant reduction in infarct size, the activity of serum creatine kinase, and TNF-alpha level, and the effects of evodiamine were completely abolished by capsazepine (5.0 mg/kg, s.c.), a competitive vanilloid receptor antagonist. These results suggest that evodiamine exerts a protection against myocardial ischemia-reperfusion injury in rats and that the protective effects of evodiamine are related to stimulation of CGRP release via activation of vanilloid receptors.

Animals↗

PubMed2004

[Study of the clonal characteristics of autoantibodies in chronic idiopathic thrombocytopenic purpura].

OBJECTIVE: To define the clonality characteristics of autoantibodies in chronic idiopathic thrombocytopenic purpura (ITP). METHODS: The heavy-chain and light-chain phenotype composition of the glycoprotein (GP)-specific IgG antibodies were analysed with a modified monoclonal antibody specific immobilization of platelet antigens (MAIPA) technique. The immunoglobulin heavy-chain gene rearrangement was analysed by PCR amplification. RESULTS: 16 out of the 43 patient sera reacted with least one of the following five GPs, namely GPIIb/IIIa, GPIb, GPIa, GPIV and GPV. Eight of 11 (73%) GP-specific antibodies displayed a restricted heavy-chain phenotypes. 80% (16/20) of the GP-specific antibodies showed a restricted kappa or lambda light-chain phenotype. Moreover, in 6 patients the GP-specific antibodies were found to be both light-chain and heavy-chain restricte. Using PCR amplification of immunoglobulin heavy-chain genes, 3 patients displayed heavy-chain genes rearrangement. CONCLUSION: The GP-specific autoantibodies are derived from a restricted number of B-cell clones in proportion of ITP patients.

Adolescent↗

PubMed2004

[Expression of three kinds of GPI-anchor proteins in paroxysmal nocturnal hemoglobinuria, aplastic anemia and myelodysplastic syndromes patients and their clinical implications].

OBJECTIVE: To investigate the expressions of three kinds of glycosyl-phosphatidylinositol anchor proteins (GPI-AP), the CD(55), CD(59) and CD(87) on the peripheral granulocytes and the soluble u-PAR (su-PAR) level in serum from patients with paroxysmal nocturnal hemoglobinuria (PNH), aplastic anemia (AA), and myelodysplastic syndromes (MDS), and to analyse their clinical implications. METHODS: Twenty-two PNH patients, including 4 complicated with thrombotic diseases and 5 with AA-PNH syndrome, 30 AA patients, including 9 being severe AA (SAA) and 11 chronic AA (CAA), 27 MDS-RA patients, and 20 healthy individuals were tested. The expressions of CD(55), CD(59) and CD(87) on peripheral granulocytes were analyzed with flow cytometry. Serum su-PAR was assayed by ELISA. RESULTS: The CD(55)(+), CD(59)(+) and CD(87)(+) granulocytes in peripheral blood of 20 normal controls were all more than 90%. The expressions of three kinds of GPI-APs in 22 PNH patients were significantly decreased as compared with that in normal controls, AA patients and MDS-RA patients. The serum level of su-PAR in PNH group was higher than that of the other three groups. The expression of CD(87) was significantly decreased in thrombotic PNH patients as compared with that in non-thrombotic PNH patients. The expression of CD(87) was significantly decreased in AA patients than in normal controls. The expressions of three kinds of GPI-APs in 5 AA-PNH syndrome patients were remarkably reduced as compared with AA patients, but no significant difference was found for these indexes between AA-PNH syndrome and PNH patients and between 27 MDS-RA patients and 20 normal controls. CONCLUSION: Measurement of CD(55), CD(59) and CD(87) expressions levels on the peripheral granulocytes and su-PAR in serum would be alternative approaches for diagnosis and differential diagnosis of PNH. Serum level of su-PAR may be helpful to monitor thrombosis in PNH patients.

Adult↗

PubMed2004

[Larynx cancer in France: descriptive epidemiology and incidence estimation].

The epidemiology of cancers is known in France through mortality data provided by Inserm and morbidity data obtained by French tumor registries. The purpose of this study was to compare the incidence of laryngeal cancers in 9 French departments and to give an estimate of this incidence for the whole of France, based on this data. Incidence and mortality data were collected over the period 1978-1997. The incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The estimated number of laryngeal cancers was 3,865 in males and 361 in females. There were pronounced contrasts in laryngeal cancer incidence between cancer registries. The incidence rate of laryngeal cancers were especially high in the Somme and Calvados department compared to those observed in Haut-Rhin and Tarn. The ratio incidence/mortality was 2.4 in Doubs and 1.3 in Somme. France is among the countries which have the highest rates of incidence and mortality for laryngeal cancer in Europe.

Adult↗

PubMed2004

Anti-proliferation effect of oridonin on HL-60 cells and its mechanism.

OBJECTIVE: To investigate the anti-proliferation effect of oridonin on leukemic HL-60 cells and its mechanism. METHODS: HL-60 cells in vitro in culture medium were given different concentrations of oridonin. The inhibitory rate of cells were measured by microculture tetrazolium (MTT) assay, cell apoptotic rate was detected by flow cytometry (FCM), morphology of cell apoptosis was observed by hoechst 33258 fluorescence staining, and the activity of telomerase was detected using telomere repeat amplification protocol (TRAP) PCR-ELISA before and after apoptosis occurred. RESULTS: Oridonin could decrease telomerase activity, inhibit growth of HL-60 cells, and cause apoptosis significantly. The suppression was both in time- and dose-dependent manner. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly by hoechst 33258 fluorescence staining especially after cells were treated 48-60 hours by oridonin. CONCLUSIONS: Oridonin has apparent anti-proliferation and apoptotic effects on HL-60 cells in vitro, decreasing telomerase activity of HL-60 cells may be one of its most important mechanisms. These results will provide strong laboratory evidence of oridonin for clinical treatment of acute leukemia.

Antineoplastic Agents, Phytogenic↗

PubMed2004

[Study on the clonal characteristics of idiopathic thrombocytopenic purpura-review].

The autoantigenic epitopes carried by the platelet glycoprotein in patients with idiopathic thrombocytopenic purpura (ITP) have been observed to localize on the specific regions of glycoprotein. There is a limited number of autoantigenic epitopes on the respective glycoproteins. The clonal B-cell and/or T cell expansion have been detected in some patients with ITP, and the autoantibodies is clonally derived. This research is of clinical importance since identification of clonally derived autoantibodies not only may help to discover the pathogenesis of ITP but also lead to less toxic and more specific therapies. In this review, the clonal limitation of autoantibody and clonal expansion of B-lymphocyte is ITP, clonal characteristics of T-lymphocyte in ITP, and significance of research on clones in ITP were discussed and summarized.

Autoantibodies↗

PubMed2004

[Progress of studies on molecular immunology of human platelets].

In autoimmune thrombocytopenic purpura (AITP) specific autoantibodies bind platelet GP via their Fab fragments. Both splenic CD5+ B and CD5- B cells produce platelet glycoprotein-specific antibodies. There is limited number of antigenic determinants, and the GP-specific autoantibodies are derived from a restricted number of B-cell clones in chronic AITP. Blocking co-stimulatory signals could induce platelet-specific T cell anergy. MMF could be used as a second line agent for the treatment of steroid-resistant AITP. Detection of plasma thrombopoietin levels play an important role in the differentiation of thrombocytopenic states caused by platelet destruction or due to bone marrow hypoplasia. Endogenous TPO level is also important on the differential diagnosis of ET and RT. Quinine- or heparin-dependent antibodies could induce thrombocytopenia. PCR-SSP is useful for the genotyping of the platelet-specific alloantigen HPA. Biotinylated platelets have an impaired response to agonists as evidenced by in vitro platelet aggregation tests.

Antigens, Human Platelet↗

PubMed2003

A novel three-dimensional network constructed from tetramolybdate clusters linked via two types of copper complex fragments: synthesis, characterization, and magnetic behavior of [[CuII(2,2'-bpy)][CuII(IN)2][Mo4O12(OH)2]].

A novel three-dimensional copper molybdate with mixed ligands, [[Cu(II)(2,2'-bpy)][Cu(II)(IN)(2)][Mo(4)O(12)(OH)(2)]] (IN(-) = isonicotinate ion, 2,2'-bpy = 2,2'-bipyridine), 1, has been hydrothermally synthesized and structurally characterized, and this compound is built from an unprecedented tetranuclear molybdenum oxide cluster covalently bonded to two types of copper complex fragments, [Cu(II)(2,2'-bpy)](2+) and [Cu(II)(IN)(2)], via terminal oxygen atoms of [MoO(6)] octahedra. Crystal data for compound 1: monoclinic, space group C2/c, a = 16.4755 A, b = 10.3714 A, c = 17.4382 A, alpha = 90.0000 degrees, beta = 94.8098 degrees, gamma = 90.0000 degrees; V = 2969.24 A(3); Z = 2. Variable temperature magnetic susceptibility indicates that both ferromagnetic and antiferromagnetic interactions exist in 1.

Journal Article↗

PubMed2003

Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42.

BACKGROUND: Mammalian Diaphanous-related formins (Drfs) act as Rho small GTPase effectors during growth factor-induced cytoskeletal remodeling and cell division. While both p140 mDia1 (herein called Drf1) and p134 mDia2 (Drf3) have been shown to bind in vitro to activated RhoA-C, and Drf3 has also been shown to bind to Cdc42, little is known about the cellular function of these GTPase effector pairs. Thus, we have begun targeting the murine Drf genes to address their various contributions to small GTPase signaling in cytoskeletal remodeling and development. RESULTS: Drf1 +/+, +/-, and -/- cell lines were derived from embryonic stem cells. While some Drf1 +/- lines had fewer actin stress fibers, several Drf1 +/- and -/- cells were more motile and had more abundant lamella and filopodia. Because the apparent "gain-of-function" corresponded with elevated levels of Drf3 protein expression, we hypothesized that the effects on the actin cytoskeleton were due to Cdc42 utilization of Drf3 as an effector. In this study, we found that inactive Drf3 variants and microinjected Drf3 antibodies interfered with Cdc42-induced filopodia. In addition, we observed that Drf3 contains a previously unidentified CRIB-like motif within its GTPase binding domain (GBD). By fluorescent resonance energy transfer (FRET) analysis, we demonstrate that this motif is required for Cdc42 binding and Drf3 recruitment to the leading edge and, surprisingly, to the microtubule organizing center (MTOC) of migrating fibroblasts. CONCLUSIONS: Our observations extend the role of the mammalian Drfs in cell signaling and demonstrate that Cdc42 not only activates Drf3, but guides the effector to sites at the cell cortex where it remodels the actin cytoskeleton.

Actins↗

PubMed2003

The TNF2 allele is a risk factor to severe aplastic anemia independent of HLA-DR.

Severe aplastic anemia (SAA) is a disease with an autoimmune component. The susceptibility to the development of SAA is strongly associated with genes in the major histocompatibility complex (MHC). The gene for tumor necrosis factor-alpha (TNF-alpha) is encoded in the MHC locus and TNF-alpha is involved in the pathogenesis of SAA. A TNF-alpha variant with a polymorphism at position -308 in its promoter region (-308A), which is designated TNF2, has been demonstrated to be linked to a number of autoimmune diseases. In this study, the TNF-alpha -308 promoter polymorphism and HLA-DRB1 alleles were analyzed in 75 SAA patients, 55 mild aplastic anemia patients (MAA), and 128 controls. In SAA the phenotype frequencies of TNF2, HLA-DR3, and -DR2 were significantly higher in comparison to controls. Stratification analysis confirmed that the TNF2 allele contributes to the susceptibility to SAA independently of HLA-DR3 or -DR2. The results indicated that TNF2 might act as an independent risk factor for SAA.

Adolescent↗

PubMed2003

Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura.

The treatment of chronic idiopathic thrombocytopenic purpura (ITP) is difficult in those unresponsive to corticosteroids and/or splenectomy. We attempted to induce durable response in 21 patients with refractory ITP by applying mycophenolate mofetil (MMF) (1.5-2.0 g/d), a novel immunosuppressive agent. Overall response rate was 62% (13 of 21), including 24% (five of 21) in complete response (CR), 29% (six of 21) in partial response (PR), and 10% (two of 21) in minor response (MR). The response rates for non-splenectomized and splenectomized ITP patients were 64% (nine of 14) and 57% (four of seven), respectively (P > 0.05). 39% (five of 13) responders relapsed as a result of dose reduction or withdraw of MMF, and 61% (eight of 13) responders maintained their effectiveness for a median of 24 wk. Sustained response was observed in three patients in whom MMF was withdrawn. MMF was well tolerated with only slight nausea and diarrhea recorded in 3 of 21 cases. No premature withdrawal was found in this study. CD3+ peripheral blood mononuclear cells (PBMC) and CD19+ PBMC were significantly reduced 12 wk after MMF administration in the responders. Platelet-associated antibodies against glycoproteins GPIIb/IIIa were detected in 13 of 21 (62%) patients before MMF treatment, and antibody levels were significantly decreased in responders 12 wk after MMF administration. This suggested that MMF might correct the immunologic abnormalities underlying the destruction of circulating platelets in ITP. We conclude that MMF could be used as a second-line agent for the treatment of steroid-resistant ITP before or after splenectomy and thereby is worth of further evaluation in randomized studies.

Adult↗

PubMed2003

[Purification of eutrophicated water body by Vetiveria zizanioids].

Studies on the purification efficiency of eutrophicated water body by Vetiveria Zizanioids on floating-beds showed that V. zizanioids had a great ability to remove TN, NH4(+)-N, TP, PO4(3-), COD, and BOD, and had a significant effect on improving water quality. It was proved that V. zizanioids could be used to purify the eutrophicated water body.

Eutrophication↗

PubMed2003

[Study on autoimmune thrombocytopenic purpura related antibody].

OBJECTIVE: To investigate a specific and sensitive assay for the diagnosis of autoimmune thrombocytopenic purpura (AITP). METHODS: Glycoprotein specific autoantibodies in platelet eluate and plasma were detected by a modified monoclonal antibody immobilization of platelet antigens assay (MAIPA). RESULTS: The overall positive rate of specific autoantibodies against platelet GPIIb/IIIa and GPIb/IX in plasma was 38.89% and in eluated platelet membrane was 68.52%. The difference between them was significant (corrected chi(2) = 19.39, P < 0.005). The proportion of positive MAIPA results between primary AITP and secondary AITP was not significantly different. There was a significant inverse correlation between antibody level and platelet count. CONCLUSION: Detection of eluated GP-specific autoantibodies by MAIPA is highly specific and much more sensitive as compared with the measurement of their plasma counterparts in the diagnosing and therapeutic monitoring of AITP.

Adolescent↗

PubMed2003

Effect of arsenic trioxide on cytokine expression by acute promyelocytic leukemia cells.

OBJECTIVE: To detect the expression of cytokines by acute promyelocytic leukemia (APL) cells before and after exposure to arsenic trioxide. METHODS: Diagnoses were performed according to the FAB cytological classification criteria and cytogenetic criteria. Bone marrow or blood samples from APL patients were collected in heparinized tubes, then primary APL cells were separated by traditional Ficoll-Hypaque density centrifugation and purified after adherence to plastic surfaces. IL-1(beta), IL-6, IL-8, TNF alpha and G-CSF levels in the leukemia cell culture supernatants were detected by ELISA. At the same time, nitro blue tetrazolium (NBT) reduction test was used to detect the differentiation of APL cells. RESULTS: After 96 hours exposure to arsenic trioxide, 10 - 6 mol/L in vitro or 10 mg/d in vivo, APL cells showed a significant increase of IL-1(beta) (P < 0.05) and G-CSF (P < 0.05) production, and a significant decrease of IL-6 (P < 0.05) and IL-8 (P < 0.05). However, there was no obvious variation of TNF alpha when compared with APL cells without exposure to arsenic trioxide. On the other hand, the proliferation ratio of APL cells in vitro was statistically correlated to the IL-1(beta) secretion ratio or G-CSF secretion ratio. The cell number ratio in patients with detectable IL-1(beta) or G-CSF was higher than that without detectable IL-1(beta) or G-CSF. CONCLUSION: IL-1(beta) and G-CSF secretion may play an important role in the proliferation of APL cells after exposure to arsenic trioxide.

Arsenic Trioxide↗

PubMed2002

Effects of B7-blocking agent and/or CsA on induction of platelet-specific T-cell anergy in chronic autoimmune thrombocytopenic purpura.

Chronic autoimmune thrombocytopenic purpura (AITP) is characterized by platelet-specific autoantibody production that is influenced by enhanced antiplatelet T-helper cell reactivity. Costimulatory signals are absolutely required for T-cell activation and play key roles in the decision between tolerance and immunity. In this study we cultured T cells isolated from patients with chronic AITP to investigate the effects of the B7-blocking agent cytologic T-lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig), and cyclosporin A (CsA), alone or in combination, on induction of platelet-specific T-cell anergy. The data showed that in most cases CTLA4-Ig and/or CsA could induce tolerance toward platelet antigens based on anergy. It could be overcome by stimulation with unrelated antigens, demonstrating its platelet specificity. The anergy is associated with lack of interleukin 2 (IL-2) and withheld by exogenous IL-2, emphasizing the pivotal role of IL-2 suppression in the induction of platelet-specific anergy. We also prospectively evaluated the efficacy of CsA therapy in patients with refractory AITP and observed that the response to CsA treatment in vivo was associated with the inhibiting sensitivity of platelet-reactive T cells to CsA in vitro. This suggests that the sensitivity of T cells to CsA in vitro could serve as a reliable parameter in predicting the efficacy of CsA for patients with refractory AITP. CTLA4-Ig may become a promising new therapeutic agent for the treatment of chronic AITP, and the combination of CTLA4-Ig and CsA would be a more powerful strategy for the management of refractory AITP.

Abatacept↗

PubMed2002

Inhibition of caspases protects cerebellar granule cells of the weaver mouse from apoptosis and improves behavioral phenotype.

The homozygous mouse mutant weaver exhibits a massive loss of cerebellar granule neurons postnatally. The death of these cells is associated with a single amino acid mutation in the G protein-activated inwardly rectifying potassium channel, Girk2. Evidence suggests that both the mutated Girk2 channel and the calcium channel-associated N-methyl-d-aspartate receptor play important roles in the apoptotic death of weaver cerebellar granule cells, but the downstream events associated with this process are unknown. In this study, we demonstrate that the consequences of the mutation result in caspase activation. In addition, our results show that caspase inhibition in vivo decreases caspase activation and granule cell apoptosis and significantly improves behavioral deficits associated with the weaver's phenotype.

Animals↗