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Biomedical subjects

Ying Wang

Publications and source records attributed to Ying Wang.

At least 163 records · Page 9Linked to original sources

Autoantibodies closely relate to the elevation level of in vivo hydrogen peroxide and tissue damage in systemic lupus erythematosus.

Recent studies have shown that antibodies efficiently catalyze the conversion of molecular singlet oxygen (1O2) plus water to hydrogen peroxide (H2O2). H2O2 is toxic to cells and is a cause of further free radical generation that are implicated in the pathogenesis of a variety of diseases. Systemic lupus erythematosus (SLE) is one of the most serious autoimmune diseases which are characterized by the production of various autoantibodies and subsequent tissue damage. However, the correlation of autoantibodies, H2O2, and tissue lesion in SLE has not been yet investigated. To address this issue, in the present study, we induced autoantibodies and kidney tissue damage by using SLE animal model as described previously. We detected the level of H2O2 in SLE mice and found the increase of in vivo H2O2 was accompanied and closely correlated with the production of anti-dsDNA and antihistone antibodies. Importantly, there was onefold increase of H2O2 in the mice kidneys with apparent glomerulonephritis and IgG deposits. These results suggest that the induced autoantibodies possess catalytic activity. The produced autoantibodies lead to the production and elevation of H2O2, which results in subsequent renal damage and the pathogenesis of SLE. Our findings provide an insight into the understanding of SLE mechanism and provide a potential approach for therapeutic intervention of SLE.

Animals↗

Epigallocatechin gallate supplementation alleviates diabetes in rodents.

As the prevalence of type 2 diabetes mellitus is increasing at an alarming rate, effective nutritional and exercise strategies for the prevention of this disease are required. Specific dietary components with antidiabetic efficacy could be one aspect of these strategies. This study investigated the antidiabetic effects of the most abundant green tea catechin, epigallocatechin gallate (EGCG, TEAVIGO), in rodent models of type 2 diabetes mellitus and H4IIE rat hepatoma cells. We assessed glucose and insulin tolerance in db/db mice and ZDF rats after they ingested EGCG. Using gene microarray and real-time quantitative RT-PCR we investigated the effect of EGCG on gene expression in H4IIE rat hepatoma cells as well as in liver and adipose tissue of db/db mice. EGCG improved oral glucose tolerance and blood glucose in food-deprived rats in a dose-dependent manner. Plasma concentrations of triacylglycerol were reduced and glucose-stimulated insulin secretion was enhanced. In H4IIE cells, EGCG downregulated genes involved in gluconeogenesis and the synthesis of fatty acids, triacylgycerol, and cholesterol. EGCG decreased the mRNA expression of phosphoenolpyruvate carboxykinase in H4IIE cells as well as in liver and adipose tissue of db/db mice. Glucokinase mRNA expression was upregulated in the liver of db/db mice in a dose-dependent manner. This study shows that EGCG beneficially modifies glucose and lipid metabolism in H4IIE cells and markedly enhances glucose tolerance in diabetic rodents. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus.

Acyl-CoA Oxidase↗

Agrin is involved in lymphocytes activation that is mediated by alpha-dystroglycan.

It is well established that agrin, an extracellular matrix protein, plays a crucial role in the formation of neuromuscular junctions. Recent evidence indicates that agrin also contributes to immunological synapse formation. However, little is known about how agrin induces the activation of lymphocytes and whose receptors mediate its regulatory effects on these cells. In the present study, agrin was detected in lymphocytes. Up-regulation of agrin expression was involved in lymphocyte activation whereas down-regulation of its expression led to inhibition of both antigen-specific and nonspecific lymphocyte activation, indicating an intrinsic role for agrin in the activation of lymphocytes. Unexpectedly, unlike that found in muscle cells where there is coexpression of muscle-specific kinase (MuSK) and alpha-dystroglycan receptors for agrin, only alpha-dystroglycan could be detected in lymphocytes. Confocal examination showed that alpha-dystroglycan colocalized with agrin in forming the immunological synapse. Down-regulation of alpha-dystroglycan expression inhibited lymphocyte activation even in the presence of agrin. However, agrin involved in down-regulation of alpha-dystroglycan receptors did not increase the inhibitory effect on lymphocytes activation. The anti-alpha-dystroglycan antibody also induced lymphocytes activation. Taken together, these findings strongly indicate that agrin and alpha-dystroglycan mediate lymphocyte activation. Furthermore, agrin-involved lymphocyte activation is mediated by alpha-dystroglycan.

Agrin↗

Prognostic value of interleukin 6, procalcitonin, and C-reactive protein levels in intensive care unit patients during first increase of fever.

To investigate the prognostic value of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) in critically ill patients during the first increase of fever, serum levels were measured in 38 patients admitted to intensive care unit of the Department of Medicine, Klinikum Grosshadern, University of Munich, immediately after increase of body temperature more than 38.3 degrees C. Ten healthy controls were also included for comparison. The onset of fever was accompanied by elevated circulating levels of all the 3 markers in comparison with healthy controls. However, only IL-6 levels were significantly higher (P < 0.05) in nonsurvivors (n = 21) compared with survivors. Sensitivity, specificity, positive, and negative predictive values calculated from median levels was higher for IL-6 compared with PCT and CRP. Areas under receiver characteristic operating curves revealed the highest area under the curve for IL-6 in contrast to PCT and CRP. These data suggest that IL-6 rather than PCT or CRP may be an early predictor of mortality in patients with onset of fever and identify patients, who need intensive monitoring to initiate appropriate therapy at an early stage.

Adult↗

Genomic distribution and functions of uptake signal sequences in Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans is naturally competent for transformation, with a transformation system similar to that of Haemophilus influenzae that preferentially takes up DNA bearing uptake signal sequences (USS) with the same 9-base USS core. This study examined the function of the extended 29-base USS, which comprises a highly conserved 1st region (containing the 9-base core) and 2nd and 3rd semi-conserved AT-rich regions, in transformation of A. actinomycetemcomitans. Transformation frequency was not affected by either location (in middle or at 5' end) or quantity (one or two) of USS in donor DNA. Relative transformation efficiencies (in comparison to the positive control) were 28-67 % for linear DNA with single-base mutations in the USS 1st region, and 47 % and 73 %, respectively, for linear DNA with USS that contained either a non-consensus 2nd or a non-consensus 3rd region. Plasmids with a stand-alone 1st or a stand-alone 2nd-3rd region exhibited 21 % and 6 % relative transformation efficiencies, respectively. It was also noted that A. actinomycetemcomitans and H. influenzae were similar in the frequencies and distribution patterns of USS in their genomes. In conclusion, all three regions of the extended 29-base USS are required for optimum transformation in A. actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans↗

Inhibitory effects of Triptolide on interferon-gamma-induced human leucocyte antigen-DR, intercellular adhesion molecule-1, CD40 expression on retro-ocular fibroblasts derived from patients with Graves' ophthalmopathy.

PURPOSE: To explore the effects of Triptolide, the principal active diterpenoid from the Chinese Medicinal Herb Tripterygium Wilfordii Hook F that has immunosuppressive and anti-inflammatory properties, on cell proliferation, hyaluronic acid (HA) synthesis, and the expressions of human leucocyte antigen-DR (HLA-DR), intercellular adhesion molecule-1 (ICAM-1) and CD40 on cultured retro-ocular fibroblasts (RFs) from patients with Graves' ophthalmopathy. METHODS: After two to five passages, cultured RFs were incubated for 48 h within a medium alone or in the presence of recombinant human interferon-gamma (IFN-gamma) and various concentrations of Triptolide. Cell viability was assessed by MTT (3-[4.5-dimethylahiazol-2-yl]-2,5-diphenyltetrazolium Bromide). RFs proliferation was assessed by [(3)H]-thymidine incorporation assay. Flow cytometry was used to investigate the amount of HLA-DR, ICAM-1 and CD40. HA synthesis was measured by radioimmunoassay. RESULTS: Cell viability was not detrimentally affected when incubated with Triptolide from 0.01 microg/L to 10 microg/L for 48 h, and decreased with 20 microg/L Triptolide. The incorporation of [(3)H]-thymidine of RFs was 55 476 +/- 15 842 cpm incubated with medium alone or 18 352 +/- 3568 cpm with 10 microg/L Triptolide (t = 5.600, P < 0.01). Initially, the percentage of positive cells of HLA-DR, ICAM-1 and CD40 on RFs were 4.75 +/- 2.13%, 17.53 +/- 10.12% and 6.38 +/- 2.23%, respectively, and the synthesis of HA was 100 +/- 12%. Compared with basal values, 48-h incubation with IFN-gamma (100 U/mL) significantly enhanced the amount of HLA-DR, ICAM-1 and CD40, and HA synthesis. The values were 60.58 +/- 10.12% (t = 13.224, P < 0.01), 62.66 +/- 18.17% (t = 5.315, P < 0.01), 57.67 +/- 13.61% (t = 9.110, P < 0.01) and 164 +/- 22% (t = 9.238, P < 0.01), respectively. Triptolide 0.01 microg/L had little effect on IFN-gamma-induced HLA-DR, ICAM-1 and CD40 amounts, as well as HA synthesis. When the concentration ranged from 0.1 microg/L to 10 microg/L, Triptolide inhibited IFN-gamma-induced RFs activation in a dose-dependent manner. It was also found that Triptolide had the same inhibiting effects on IFN-gamma-induced RFs and skin fibroblasts from patients with normal individual conditions. CONCLUSIONS: Triptolide could inhibit IFN-gamma-induced activation of RFs derived from patients with Graves' ophthalmopathy.

Adult↗

Microbial desulfurization of gasoline by free whole-cells of Rhodococcus erythropolis XP.

Rhodococcus erythropolis XP could grow well with condensed thiophenes, mono-thiophenic compounds and mercaptans present in gasoline. Rhodococcus erythropolis XP was also capable of efficiently degrading the condensed thiophenes in resting cell as well as biphasic reactions in which n-octane served as a model oil phase. Free whole cells of R. erythropolis XP were adopted to desulfurize fluid catalytic cracking (FCC) and straight-run (SR) gasoline oils. About 30% of the sulfur content of FCC gasoline and 85% of sulfur in SR gasoline were reduced, respectively. Gas chromatography analysis with atomic emission detection also showed depletion of sulfur compounds in SR gasoline. Rhodococcus erythropolis XP could partly resist the toxicity of gasoline and had an application potential to biodesulfurization of gasoline.

Biodegradation, Environmental↗

Identification of melanoma-specific peptide epitopes by HLA-A2.1-restricted cytotoxic T lymphocytes.

HLA-A2.1-associated peptides, extracted from human melanoma cells, were used to study epitopes for melanoma-specific HLA-A2.1-restricted cytotoxic T lymphocytes (CTLs) by epitope reconstitution, active peptide sequence characterization and synthetic peptide verification. CTL were generated from tumor-involved nodes by in vitro stimulation, initially with autologous melanoma cells and subsequently with allogeneic HLA-A2.1 positive melanoma cells. The CTLs could lyse autologous and allogeneic HLA-A2.1 positive melanomas, but not HLA-A2.1 negative melanomas or HLA-A2.1 positive non-melanomas. The lysis of melanomas could be inhibited by anti-CD3, anti-HLA class I and anti-HLA-A2.1 monoclonal antibodies. HLA-A2.1 molecules were purified from detergent-solubilized human melanoma cells by immunoaffinity column chromatography and further fractionated by reversed phase high performance liquid chromatography. The fractions were assessed for their ability to reconstitute melanoma-specific epitopes with HLA-A2.1 positive antigen-processing mutant T2 cells. Three reconstitution peaks were observed in lactate dehydrogenase release assay. Mass spectrometry and ion-exchange high performance liquid chromatography analysis were used to identify peptide epitopes. Peptides with a mass-to-charge ratio of 948 usually consist of nine amino acid residues. The data from reconstitution experiments confirmed that the synthetic peptides contained epitopes and that the peptides associated with HLA-A2.1 and recognized by melanoma-specific CTL were present in these different melanoma cells. These peptides could be potentially exploited in novel peptide-based antitumor vaccines in immunotherapy for CTL.

Antibodies, Monoclonal↗

Selective biodegradation of S and N heterocycles by a recombinant Rhodococcus erythropolis strain containing carbazole dioxygenase.

The carbazole dioxygenase genes were introduced into a dibenzothiophene degrader. The recombinant Rhodococcus erythropolis SN8 was capable of efficiently degrading dibenzothiophene and carbazole simultaneously. SN8 could also degrade various alkylated derivatives of carbazole and dibenzothiophene in FS4800 crude oil by just a one-step bioprocess.

Biodegradation, Environmental↗

Selective deletion of Pten in pancreatic beta cells leads to increased islet mass and resistance to STZ-induced diabetes.

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase. PTEN inhibits the action of phosphatidylinositol-3-kinase and reduces the levels of phosphatidylinositol triphosphate, a crucial second messenger for cell proliferation and survival, as well as insulin signaling. In this study, we deleted Pten specifically in the insulin producing beta cells during murine pancreatic development. Pten deletion leads to increased cell proliferation and decreased cell death, without significant alteration of beta-cell differentiation. Consequently, the mutant pancreas generates more and larger islets, with a significant increase in total beta-cell mass. PTEN loss also protects animals from developing streptozotocin-induced diabetes. Our data demonstrate that PTEN loss in beta cells is not tumorigenic but beneficial. This suggests that modulating the PTEN-controlled signaling pathway is a potential approach for beta-cell protection and regeneration therapies.

Animals↗

Polymorphisms in the two helicases ERCC2/XPD and ERCC3/XPB of the transcription factor IIH complex and risk of lung cancer: a case-control analysis in a Chinese population.

The transcription factor IIH (TFIIH) helicases ERCC2/XPD and ERCC3/XPB are responsible for opening the DNA strand around the lesion site during nucleotide excision repair process. Genetic variants in these two genes may be markers for interindividual variability in DNA repair capacity and thus predisposition to cancer risk. In this case-control study of 1,010 incident lung cancer cases and 1,011 age and sex frequency-matched cancer-free controls in a Chinese population, we genotyped eight tagging polymorphisms of ERCC2 and ERCC3 using the high-throughput Taqman platform to determine their associations with risk of lung cancer. Although none of the eight polymorphisms was individually associated with lung cancer risk, we found that genetic variants in ERCC2 and ERCC3 jointly contributed to lung cancer risk in a dose-response manner. Compared with those with 0 to 1 "at-risk" locus, subjects carrying >1 at-risk loci were at increased risk for lung cancer [adjusted odds ratio (OR), 1.29; 95% confidence interval (95% CI), 0.98-1.70 for 2 at-risk loci; adjusted OR, 1.38; 95% CI, 1.02-1.85 for 3 at-risk loci; and adjusted OR, 1.51; 95% CI, 1.09-2.10 for > or =4 at-risk loci, respectively; P(trend) = 0.015]. This combined effect was slightly more evident in young subjects (<60 years), males, current smokers, and those with family history of cancer, particularly for histologic type of adenocarcinomas. No evidence for interaction was found. These findings indicate that these tagSNPs of the ERCC2 and ERCC3 along with their surrounding regions may serve as biomarkers of susceptibility to lung cancer, which warrant further validation by other population-based and phenotypic studies to determine the biological relevance of these tagSNPs.

Adenocarcinoma↗

Schnurri transcription factors from Drosophila and vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism.

Bone Morphogenetic Proteins (Bmps) are secreted growth factors that play crucial roles in animal development across the phylogenetic spectrum. Bmp signaling results in the phosphorylation and nuclear translocation of Smads, downstream signal transducers that bind DNA. In Drosophila, the zinc finger protein Schnurri (Shn) plays a key role in signaling by the Bmp2/Bmp4 homolog Decapentaplegic (Dpp), by forming a Shn/Smad repression complex on defined promoter elements in the brinker (brk) gene. Brk is a transcriptional repressor that downregulates Dpp target genes. Thus, brk inhibition by Shn results in the upregulation of Dpp-responsive genes. We present evidence that vertebrate Shn homologs can also mediate Bmp responsiveness through a mechanism similar to Drosophila Shn. We find that a Bmp response element (BRE) from the Xenopus Vent2 promoter drives Dpp-dependent expression in Drosophila. However, in sharp contrast to its activating role in vertebrates, the frog BRE mediates repression in Drosophila. Remarkably, despite these opposite transcriptional polarities, sequence changes that abolish cis-element activity in Drosophila also affect BRE function in Xenopus. These similar cis requirements reflect conservation of trans-acting factors, as human Shn1 (hShn1; HIVEP1) can interact with Smad1/Smad4 and assemble an hShn1/Smad complex on the BRE. Furthermore, both Shn and hShn1 activate the BRE in Xenopus embryos, and both repress brk and rescue embryonic patterning defects in shn mutants. Our results suggest that vertebrate Shn proteins function in Bmp signal transduction, and that Shn proteins recruit coactivators and co-repressors in a context-dependent manner, rather than acting as dedicated activators or repressors.

Animals↗

Morphologic research of microcirculation patterns in human and animal melanoma.

OBJECTIVE: The pattern and distribution of microcirculation of malignant melanoma were studied in human malignant melanoma tumor samples and in an animal model by staining of paraffin-embedded sections and transelectron microscopy. METHODS: Blood supply models for melanoma were studied with immunohistochemical and periodic acid-Schiff (PAS) double-staining technique. New sections were made from 190 paraffin-embedded melanoma samples, and immunohistochemical staining of the platelet-endothelial cell adhesive molecule (CD31 antigen) and PAS staining were conducted to confirm different microcirculation patterns of melanoma. Furthermore, malignant melanoma cells B16 and LiBr were injected into the groin of C57 mice and into the abdominal cavity of SCID mice, respectively. Tumors with vasculogenic mimicry (VM) were stained with PAS and CD31 to study the morphology and distribution of VM in mice melanoma. A diluted suspension of activated carbon was injected into the circulation of mice previously inoculated in the groin with B16 melanoma cells. Tumor tissue with VM was observed under electron microscopy. RESULTS: There were three kinds of microcirculation pattern in human and animal melanoma. The walls of VM were positive for PAS staining and negative for CD31 staining in the tumor tissues. The distribution of VM and mosaic vessels was not uniform and appeared in patches. VM along with endothelium-dependent vessels and mosaic vessels sustained the blood supply for the tumors. The results from electron microscopy validated the presence of three patterns. CONCLUSIONS: The results obtained using activated carbon as a tracer showed that VM and mosaic vessels connect with the host blood circulation. VM and mosaic vessels exist in malignant melanoma. Tumor cells can obtain oxygen and nutriment through VM and mosaic vessels besides endothelium-dependent vessels.

Animals↗

Electrocatalytic reduction of nitrate in water with a palladium-modified copper electrode.

A highly active electrocatalytic electrode for nitrate reduction was prepared by the electro-deposition of palladium onto a copper electrode. The capacity of nitrate reduction by a palladium-modified copper electrode has been studied using cyclic voltammetry (CV). The existence of a reduction peak at -0.605 V versus saturated calomel electrode in 0.1-M sodium nitrate + 0.1-M perchloric acid solution (pH = 0.86) can be found in the CV measurement. The influence of solution properties, such as pH, nitrate concentration, and other anions in solution, on nitrate reduction was determined in detail. Results showed that nitrate reduction was suppressed in alkaline solution, while it was beneficial to nitrate reduction in acid or neutral solution. At low nitrate concentrations (0.01 to 0.5 M), nitrate reduction current increased with increasing nitrate concentration, but was hindered by sulfate. At high nitrate concentrations (1 to 5 M), no significant difference on nitrate reduction was observed. Compared with other different electrodes prepared in our work (copper, titanium, and palladium-modified titanium electrodes), the palladium-modified copper electrode showed the highest electrocatalytic capacity and stability in the nitrate-reduction process.

Catalysis↗

Asthma educational seminar targeting Medicaid providers.

BACKGROUND: Medicaid-insured children have high risk of asthma but are less likely to receive care in keeping with national guidelines. We targeted providers who care for a large proportion of Medicaid-insured children and presented a 2-session multimedia asthma-education seminar that emphasizes communication and teaching techniques, to enhance providers' asthma-care teaching skills. METHODS: Five Medicaid-approved health maintenance organizations recruited pediatric primary-care providers. Providers were surveyed at baseline, 6 months, and 12 months to determine if they reported changes in their use of certain asthma-care communication techniques. RESULTS: Fifty-three of 70 participating providers completed the program and initial survey. They reported that 50% (median) of their patients were insured by Medicaid. At baseline, providers reported they were very confident of their asthma knowledge; however, they were less confident in interactions with patients/families regarding asthma self-management skills. Providers reported use of written plans less than half of the time. The response rate was 60% at 6 months and 71% at 1 year. Twenty-eight providers completed all 3 surveys. They reported significantly more frequent use of communication and counseling techniques that involved patient/parent asthma education and self-management skills at the 6-month point, that were partly sustained at 1 year. Reported provision of written asthma plans to patients had increased significantly at 6 months, but that increase was not sustained at the 1-year point. CONCLUSIONS: The seminar significantly enhanced knowledge of specific communication techniques related to asthma-teaching goals and reported use of asthma action plans to enhance self-management skills; however, these practices appear to need frequent reinforcement.

Asthma↗

[Expression, structure prediction and functional analysis of murine single-chain fragment variable antibody against human cervical cancer].

OBJECTIVE: To amplify and express the gene encoding murine single-chain fragment variable (scFv) antibody against human cervical cancer and predict the secondary structure and three-dimensional structure of the antibody. METHODS: The gene fragments coding for the variable region of the heavy and light chains of scFv antibody against human cervical cancer were amplified respectively using recombinant DNA techniques from CsA125 hybridoma cells, and spliced together using a flexible linker to the antibody. The scFv genes were then cloned into the expression vector pCANTAB 5E and expressed in E.coli HB2151 and TG1, respectively. The scFv antibody obtained was assayed using SDS-PAGE, Western blotting, and immunohistochemical analysis, with its secondary structure and three-dimensional structure predicted with Swiss-model and 3dpssm. The physicochemical properties of the antibody were analyzed with Antheprot software. RESULTS: The expressed scFv antibody was soluble and phage-displayed. The specific binding capacity of the soluble and phage-displayed scFv antibody to the surface-associated antigen of human cervical cancer cell line were further confirmed. The scFv antibody had a relative molecular mass of 32,000 as was consistent to theoretical prediction, with pI of 7.215 and characterized to belong to alpha+beta protein. The antibody contained many protein kinase C phosphorylation sites and casein kinase II phosphorylation sites in both the VH and VL domains. Computer graphic modeling indicated that the linker was isolated from the VH and VL domains, which formed a hydrophobic pocket in the molecule to facilitate antigen binding. CONCLUSIONS: The soluble and phage displayed scFv antibody expressed in E. coli against human cervical cancer shows high and specific affinity to the cervical cancer cell line surface-associated antigen. The construction and analysis of the molecular model of the antibody may facilitate further studies in engineering of the antibody and exploration of the mechanism of the antigen-antibody interaction.

Amino Acid Sequence↗