PubMed Health⌕ Search

Biomedical subjects

Jing Chen

Publications and source records attributed to Jing Chen.

At least 55 records · Page 3Linked to original sources
PubMed2006

CD38 is required for the peripheral survival of immunotolerogenic CD4+ invariant NK T cells in nonobese diabetic mice.

T cell-mediated autoimmune type-1 diabetes (T1D) in NOD mice partly results from this strain's numerical and functional defects in invariant NK T (iNKT) cells. T1D is inhibited in NOD mice treated with the iNKT cell superagonist alpha-galactosylceramide through a process involving enhanced accumulation of immunotolerogenic dendritic cells in pancreatic lymph nodes. Conversely, T1D is accelerated in NOD mice lacking CD38 molecules that play a role in dendritic cell migration to inflamed tissues. Unlike in standard NOD mice, alpha-galactosylceramide pretreatment did not protect the CD38-deficient stock from T1D induced by an adoptively transferred pancreatic beta cell-autoreactive CD8 T cell clone (AI4). We found that in the absence of CD38, ADP-ribosyltransferase 2 preferentially activates apoptotic deletion of peripheral iNKT cells, especially the CD4+ subset. Therefore, this study documents a previously unrecognized role for CD38 in maintaining survival of an iNKT cell subset that preferentially contributes to the maintenance of immunological tolerance.

ADP Ribose Transferases↗
PubMed2006

[Relationship between visceral adipose tissue and prevalence of metabolic syndrome MS in patients with MS, and hypertension and/or diabetes].

OBJECTIVE: To investigate the relationship between the visceral adipose (VA) accumulation and the prevalence of metabolic syndrome (MS) in patients with MS, and hypertension and/or diabetes. METHODS: VA area was measured by computed tomography (CT) in 564 patients with with MS, and hypertension and/or diabetes, 308 males and 256 females. Body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were assessed. Receiver operating characteristic (ROC) curve was used as index for analysis. RESULTS: (1) The VA of the patients with MS was 116 cm(2) +/- 38 cm(2), significantly higher than those of the patients with hypertension and diabetes (72 cm(2) +/- 34 cm(2) and 64 cm(2) +/- 34 cm(2) respectively, both P < 0.01). ROC curve analysis showed that the optimal cut-off points of VA for hypertriglyceridemia, hypo-high density lipoproteinemia, abdominal obesity and MS was 91 - 107 cm(2) for men; and 70 - 72 cm(2) for women. (2) The anthropometric parameters to the corresponding optimal cut-off points of VA were as follow: BMI, WC, and WHP were 25 kg/m(2), 89 cm, and 0.95 - 0.96 for men; and 24 - 25 kg/m(2), 82 - 84 cm, and 0.91 for women. Both the cut-off points of VA in assessing hyperglycemia and in assessing hypertension could not be found out. (3) The prevalence of MS was significantly increased when VA >or= 55 cm(2) in women and when VA >or= 70 cm(2) in men respectively. CONCLUSION: There is a gender difference in the accumulation of the VA tissue. Even in the subjects with overweight, abdominal obesity and dyesmetabolism have appeared in patients. The prevalence of MS is significantly increased with the intra-abdominal fat accumulation.

Adipose Tissue↗
PubMed2006

Uptake and UV-photooxidation of gas-phase PAHs on the surface of atmospheric water films. 1. Naphthalene.

The adsorption and photochemical reaction of naphthalene vapor at the air-water interface of water films (22 microm and 450 microm) were studied in a horizontal flow reactor. Experiments were conducted in the regime where gas-phase mass transfer resistance did not limit the uptake. The equilibrium uptake was dependent on water film thickness only below 1 microm. Bulk water-air and air-to-interface partition constants were estimated from the experiments. The equilibrium partition constant between the water film and air decreased with increasing temperature. Photochemical reaction products were isolated in the water film after exposure to UV light. Four main oxygenated products were identified (1,3-indandione, 1(3H)-isobenzofuranone (phthalide), 2H-1-benzopyran-2-one (coumarin), and 1-naphthol). The initial rates of product formation were 46 to 154% larger for the thin film (22 microm) compared to both a thick film (450 microm) and bulk aqueous phase photooxidation. The atmospheric implications of reactions in water films are discussed.

Journal Article↗
PubMed2006

Aldosterone promotes fibronectin production through a Smad2-dependent TGF-beta1 pathway in mesangial cells.

Accumulating evidence demonstrates that aldosterone can cause extra-cellular matrix (ECM) accumulation, in addition to regulating sodium and potassium homeostasis. Increased extra-cellular matrix production by renal glomerular mesangial cells has been suggested to be involved in pathogenesis of glomerular sclerosis. The present studies examine whether aldosterone is also produced in renal mesangial cells, and the effect of aldosterone on ECM accumulation in these cells. In cultured renal mesangial cells, aldosterone synthase (CYP11B2), mineralocorticoid receptor (MR), and 11beta-HSD2 mRNA expressions were detected by RT-PCR. The ability of renal mesangial cells to produce aldosterone was confirmed by directly detecting aldosterone in culture medium via radioimmunoassay. Real-time RT-PCR showed that the expression of CYP11B2 mRNA in mesangial cells was significantly enhanced by AngII (P<0.001) and by potassium (P<0.05). Exposure of the cultured mesangial cells to aldosterone significantly increased fibronectin production from 12.4+/-1.9 to 74.6+/-16.8ng/ml (P<0.05). The aldosterone induced fibronectin production was abolished by aldosterone receptor antagonist spironolactone. Aldosterone also increased the TGF-beta1 reporter luciferase activity from 0.8+/-0.1 to 1.7+/-0.1 (P<0.05). Immunoblot showed TGF-beta1 protein expression was increased following aldosterone treatment. Blocking TGF-beta1 signaling pathway by knocking down Smad2 significantly blunted the aldosterone induced fibronectin production. The present studies indicate that renal mesangial cell is a target of local aldosterone action, which promotes ECM protein fibronectin production via TGF-beta1/Smad2 signaling pathway.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2006

A newly proposed mechanism for arginine-assisted protein refolding--not inhibiting soluble oligomers although promoting a correct structure.

Arginine has been demonstrated to be capable of suppressing aggregation during protein refolding. However, the pathway and the mechanism for arginine to participate in and to assist refolding process still remains unclear. In this study, arginine-assisted refolding of recombinant consensus interferon (rIFN-con1) was investigated. It was found that although arginine minimized the formation of protein precipitate, it failed to prevent the formation of the soluble oligomeric species. The amount of the oligomers increased with the increase in arginine concentration. This phenomenon has not been reported. On the other hand, arginine was able to promote the yield of correctly refolded rIFN-con1, which was more than 2 times higher than that in the absence of arginine. A proposed mechanism is the stabilization of different soluble species by arginine, which slowed down the conformational movement. The stabilization effect on native-like structure formation overwhelmed the oligomeric promotion effect, which resulted in a composite effect of increased refolding yield for rIFN-con1 when arginine concentration was below 0.5M.

Arginine↗
PubMed2006

[Prognostic value of early treatment response in children with acute myeloid leukemia].

OBJECTIVE: To assess the prognostic value of early treatment response in children with acute myeloid leukemia (AML). METHODS: Sixty-one children with AML, 37 male and 24 female, aged 96 months (6 - 154 months), underwent treatment according to the protocol AML-XH-99 with a total treatment course of 15 months and were followed up for 12 months (1 - 74 months). Bone marrow smear was made 48 hours after the end of the first course of induction treatment. Then the children were divided into 2 groups according to the number of bone marrow blast cells: group with the number of blast cells > or = 0.15 and group with the number of blast cells < 0.15. Second bone marrow smear was made when complete remission was achieved after the end of the treatment course. Then the children were divided into 2 groups according to the number of bone marrow blast cells: group with the number of blast cells of 0.00 and group with the number of blast cells between 0.00 and 0.05. The probability of event-free survival (EFS) was estimated by Kaplan-Meier analysis. Log-rank test was used to compare the 5-year EFS (pEFS) of different groups. The differences in the biological features were compared by Chi-square analysis or Fisher exact test. RESULTS: The pEFS of the group with the number of blast cells > or = 0.15 was 18% +/- 15%, significantly shorter than that of the group with the number of blast cells < 0.15 (49% +/- 11%, P = 0.079). The 3 patients without morphologically identifiable blast all survived 5 years after complete remission had been achieved, and the pEFS of the 39 patients with the number of blast cells between 0.00 and 0.05 was 53% +/- 10%. The pEFS of the patients among which complete remission was achieved after the first course of treatment (n = 39) was 54% +/- 10%, significantly higher than that of the patients without complete remission after the first course of treatment (10% +/- 9%, P = 0.0002). Multiple factor analysis showed that achievement of complete remission after the first course of treatment and existence of central nervous system leukemia were both independent prognostic factors with the hazard ratios of 4.007 and 7.050 respectively and the 95% confidential intervals of 1.019 to 6.163 and 0.018 to 0.547 respectively (P = 0.045 and P = 0.008). The number of blasts 48 hours after the end of the first course of induction treatment was highly correlated with the rate of complete remission after the first treatment course (P = 0.000 028 8). CONCLUSION: With important prognostic significance, early treatment response, such as the number of blasts 48 hours after the end of the first course of induction treatment can predict whether complete remission can be achieved.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

A novel type of PTD, common helix-loop-helix motif, could efficiently mediate protein transduction into mammalian cells.

Protein transduction domains (PTDs), such as HIV TAT PTD, have been widely used as delivery tools into living cells. Here we reported for the first time that the helix-loop-helix (HLH) domain of basic helix-loop-helix (bHLH) family was a novel type of PTD. Efficient internalization has been obtained with HLH domains derived from bHLH proteins, NeuroD/BETA2, Neurogenin3, and Mitf, in various cell types including stable cell lines and primary cells. Cellular uptake of HLH PTD was barely or slightly inhibited by the metabolic, phagocytosis, clathrin- or caveolar-endocytosis formation inhibitors, but significantly and substantially reduced by heparin and macropinocytosis inhibitor, which suggested important roles of cell surface glycosaminoglycans and macropinocytosis during the protein transduction. Furthermore, NeuroD proteins still preserved transcription activation after internalized into cells. Our results demonstrated a new motif of PTD different from previous models as cationic residues cluster or amphipathic helix. The HLH domain is also the characteristic of the bHLH family, which implied a large number of PTDs could be discovered in this family to fit different purposes, and some of them could be directly recruited to penetrate cell membrane according to their crucial roles in development such as NeuroD and Ngn3.

Animals↗
PubMed2006

Mitochondrial complex I activity is significantly decreased in a patient with maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy associated with mitochondrial DNA C3310T mutation: a cybrid study.

Mitochondrial respiratory function in a patient with maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy associated with heteroplasmic mitochondrial DNA (mtDNA) C3310T mutation, which replaces the second amino acid of NADH dehydrogenase 1 (ND1) from a hydrophobic Proline to a hydrophilic Serine, was investigated. Mitochondrial respiratory function solely due to mtDNA C3310T mutation was investigated in cybrid system by the fusion of mtDNA-deleted (rho(0)) HeLa cells and exogenous mtDNA either from the proband or from controls. Total oxygen consumption of the proband cybrid cells was significantly decreased compared with those of controls (2.468+/-0.475 versus 2.871+/-0.484 micromol/h/10(7) cells, p=0.0392). Mitochondrial respiratory chain complex I activity of the proband cybrid cells was also significantly decreased compared with those of controls (0.191+/-0.080 versus 0.288+/-0.113 micromol/h/mg protein, p=0.0223). Furthermore, ATP content in the proband cybrid cells was also significantly decreased compared with those in controls (1.119+/-0.344 versus 1.419+/-0.378 pmol/10(5) cells, p=0.044). The present study indicates that mtDNA C3310T mutation may be a pathogenic mutation of maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy in the proband and the family.

Blotting, Southern↗
PubMed2006

Differential expression of mouse orexin receptor type-2 (OX2R) variants in the mouse brain.

We have identified two novel mouse orexin type-2 receptor (OX2R) splice variants: OX2alphaR and OX2betaR. Here, we have mapped in detail the differential gene expression of OX2alphaR and OX2betaR in the mouse brain. Using RT-PCR and in situ hybridization, we show that OX2alphaR is expressed in various areas of the mouse brain and has low expression in caudal part of cerebellum. OX2betaR is expressed in detectable levels, with the exception of striatum, midbrain and anterior part of cerebellum/pons. Our novel findings demonstrate the differential expression of OX2R splice variants in the mouse brain.

Animals↗
PubMed2006

From biochemistry to morphogenesis in myxobacteria.

Many aspects of metazoan morphogenesis find parallels in the communal behavior of microorganisms. The cellular slime mold D. discoideum has long provided a metaphor for multicellular embryogenesis. However, the spatial patterns in D.d. colonies are generated by an intercellular communication system based on diffusible morphogens, whereas the interactions between embryonic cells are more often mediated by direct cell contact. For this reason, the myxobacteria have emerged as a contending system in which to study spatial pattern formation, for their colony strutures rival those of D.d. in complexity, yet communication between cells in a colony is carried out by direct cell contacts. Here I sketch some of the progress my laboratory has made in modeling the life cycle of these organisms.

Animals↗
PubMed2006

Aryl hydrocarbon receptor activation produces heart-specific transcriptional and toxic responses in developing zebrafish.

Proper regulation of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, is required for normal vertebrate cardiovascular development. AHR hyperactivation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during zebrafish (Danio rerio) development results in altered heart morphology and function, culminating in death. To identify genes that may cause cardiac toxicity, we analyzed the transcriptional response to TCDD in zebrafish hearts. Zebrafish larvae were exposed to TCDD for 1 h at 72 h after fertilization (hpf), and the hearts were extracted for microarray analysis at 1, 2, 4, and 12 h after exposure (73, 74, 76, and 84 h postfertilization). The remaining body tissue was also collected at each time for comparison. TCDD rapidly induced expression in 42 genes within 1 to2hof exposure. These genes function in xenobiotic metabolism, proliferation, heart contractility, and pathways that regulate heart development. Furthermore, these expression changes preceded signs of cardiovascular toxicity, characterized by decreased stroke volume, peripheral blood flow, and a halt in heart growth. This identifies strong candidates for important AHR target genes. It is noteworthy that the TCDD-induced transcriptional response in the hearts of zebrafish larvae was substantially different from that induced in the rest of the body tissues. One of the biggest differences included a cluster of genes that were down-regulated 12 h after exposure in heart tissue, but not in the body samples. More than 70% of the transcripts in this heart-specific cluster promote cellular growth and proliferation. Thus, the developing heart stands out as being responsive to TCDD at both the level of toxicity and gene expression.

Animals↗
PubMed2006

Estimated fluence-to-absorbed dose conversion coefficients for use in radiological protection of embryo and foetus against external exposure to photons from 50 keV to 10 GeV.

In the literature, no conversion coefficients are available for use in radiological protection of the embryo and foetus against external exposure to photons. This study used the Monte-Carlo code MCNPX to determine mean absorbed doses to the embryo and foetus when the mother is exposed to external photon fields. Monoenergetic photons ranging from 50 keV to 10 GeV were considered. The irradiation geometries included antero-posterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT), and isotropic (ISO). At each of these standard irradiation geometries, absorbed doses to the foetal brain and body were calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months. Photon fluence-to-absorbed-dose conversion coefficients were estimated for the four prenatal ages.

Body Burden↗
PubMed2006

Activation of FIP1L1-PDGFRalpha requires disruption of the juxtamembrane domain of PDGFRalpha and is FIP1L1-independent.

Genetic abnormalities that result in expression of chimeric tyrosine kinase proteins such as BCR-ABL1 and ETV6-PDGFRbeta are common causes of hematopoietic malignancies. The paradigm for constitutive activation of these fusion tyrosine kinases is enforced homodimerization by self-association domains present in the fusion partner proteins. The unique interstitial deletion on chromosome 4q12 that leads to expression of the FIP1L1-PDGFRalpha fusion tyrosine kinase was recently identified as a cause of chronic eosinophilic leukemia. In this report, we demonstrate that FIP1L1 is completely dispensable for PDGFRalpha activation in vitro and in vivo. Instead, truncation of PDGFRalpha between two conserved tryptophan residues in the juxtamembrane (JM) domain is required for kinase activation and transforming potential of FIP1L1-PDGFRalpha. The presence of a complete JM domain in FIP1L1-PDGFRalpha is inhibitory, but this autoinhibition can be overcome by enforced homodimerization. Similar effects of the JM domain in the context of PDGFRbeta were observed. These results suggest that disruption of the autoinhibitory JM domain is an alternative, dimerization-independent mechanism by which chimeric tyrosine kinases are constitutively activated and induce leukemogenesis.

Animals↗
PubMed2006

One novel quinoxaline derivative as a potent human cyclophilin A inhibitor shows highly inhibitory activity against mouse spleen cell proliferation.

Cyclophilin A (CypA) is a ubiquitous cellular enzyme playing critical roles in many biological processes, and its inhibitor has been reported to have potential immunosuppressive activity. In this work, we reported a novel quinoxaline derivative, 2,3-di(furan-2-yl)-6-(3-N,N-diethylcarbamoyl-piperidino)carbonylamino quinoxaline (DC838, 3), which was confirmed to be a potent inhibitor against human CypA. By using the surface plasmon resonance (SPR) and fluorescence titration techniques, the kinetic analysis of CypA/DC838 interaction was quantitatively performed. CypA peptidyl prolyl cis-trans isomerase (PPIase) activity inhibition assay showed that DC838 demonstrated highly CypA PPIase inhibitory activity. In vivo assay results showed that DC838 could inhibit mouse spleen cell proliferation induced by concanavalin A (Con A). Molecular docking simulation further elucidated the specific DC838 binding to CypA at the atomic level. The current work should provide useful information in the discovery of immunosuppressor based on CypA inhibitor.

Animals↗
PubMed2006

[PLAC1/CP1 gene expression and autologous humoral immunity in gastric cancer patients].

OBJECTIVE: To investigate PLAC1/CP1 as a potential candidate gene in gastric cancer therapy. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the expression of PLAC1/CP1 mRNA in gastric cancer tissues and paired adjacent non-cancerous tissues resected from 28 patients with gastric cancer. Specific antibodies against PLAC1/CP1 were also detected by ELISA method in gastric cancer patients. RESULTS: Fourteen (50%,14/28) out of the 28 gastric cancer samples were PLAC1/CP1 mRNA positive. Of the 28 serum samples tested,eight (29%,8/28) displayed positive seroreactivity against PLAC1/CP1 antigen, accounting for 57% (8/14) of PLAC1/CP1 mRNA positive samples. CONCLUSION: PLAC1/CP1 mRNA was expressed in high frequency and induced spontaneous antibody responses in gastric cancer patients. PLAC1/CP1 may be a valuable candidate antigen in gastric cancer immunotherapy.

Antibodies, Neoplasm↗
PubMed2006

Targeted disruption of CD38 accelerates autoimmune diabetes in NOD/Lt mice by enhancing autoimmunity in an ADP-ribosyltransferase 2-dependent fashion.

Ubiquitously expressed CD38 and T cell-expressed ADP-ribosyltransferase 2 (ART2) are ectoenzymes competing for NAD substrate. CD38 exerts pleiotropic actions in hemopoietic and nonhemopoietic compartments via effects on calcium mobilization. ART2 is an ADP-ribosyltransferase on naive CD4+ and CD8+ T cells. ART2-catalyzed ADP-ribosylation of the P2X7 purinoreceptor elicits apoptosis. Transfer of a genetically disrupted CD38 allele into the autoimmune diabetes-prone NOD/Lt background accelerated diabetes onset in both sexes, whereas transfer of a disrupted ART2 complex had no effect. However, the fact that the accelerated pathogenesis mediated by CD38 deficiency required ART2 activity was demonstrated by combining both ART2 and CD38 deficiencies. Reciprocal bone marrow reconstitution studies demonstrated accelerated diabetes only when CD38-deficient bone marrow was transferred into CD38-deficient recipients. Neither decreases in beta cell function nor viability were indicated. Rather, the balance between T-effectors and T-regulatory cells was disturbed in CD38-deficient but ART2-intact NOD mice. In these mice, significant reductions in total viable CD8+ T cells were observed. This was accompanied by an age-dependent increase in a diabetogenic CD8 clonotype. This in turn correlated with impaired T-regulatory development (10-fold reduction in Foxp3 mRNA expression). These changes were corrected when CD38 deficiency was combined with ART2 deficiency. Both ART2-deficient and CD38/ART2 combined deficient T cells were resistant to NAD-induced killing in vitro, whereas CD38-deficient but ART2-intact T cells showed increased sensitivity, particularly the CD4+ CD25+ subset. Unexpectedly, diabetes development in the combined CD38/ART2 stock was strongly suppressed, possibly through epistatic interactions between genes linked to the targeted CD38 on Chromosome 5 and the ART2 complex on Chromosome 7.

ADP Ribose Transferases↗
PubMed2006

[Transduction of heme oxygenase-1 gene to human Islet cells via adenovirus vector enhances anti-apoptosis function and insulin release].

OBJECTIVE: To investigate the effects of heme oxygenase-1 (HO-1) gene on human islets in vitro, and to explore the potential value of gene therapy in clinical islet transplantation. METHODS: Adenovirus vector carrying human HO-1 gene (Ad-HO-1) or EGPF (Ad-EGFP) were established respectively. Human cadaveric pancreases were isolated, purified, cultured, and divided into 3 groups to be transfected with Ad-HO-1, Ad-EGFP or blank vector. Human tumor necrosis factor and cyclohexamide (CHX) were added into the culture fluid of the pancreatic islets. 48 hours later the pancreatic islets were digested into single cells. Flow cytometry was used to detect the apoptosis. Glucose of the concentration of 16.7 mmol/L was added into the culture fluid of the 3 groups of islet cells. After 1-hour co-incubation radioimmunochemistry was used to detect the level of insulin in the supernatant. RESULTS: After stimulation of glucose the insulin concentration in the supernatant of the Ad-HO-1 group was 270 mIU/L +/- 89 mIU/L, significantly higher than those of the Ad-EGFP group (189 mIU/L +/- 88 mIU/L) and control group (182 mIU/L +/- 59 mIU/L, both P < 0.05). The apoptotic ratio of the Ad-HO-1 group was 63.1% +/- 10.9%, significantly lower than that of the control group (90.9% +/- 11.3%, P < 0.01) after treatment with TNFalpha and CHX. CONCLUSION: Transfection of Ad-HO-1 into human islets improves anti-apoptotic function in cultured human islets and promotes insulin release of human pancreatic islets.

Adenoviruses, Human↗