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Biomedical subjects

Hong Chen

Publications and source records attributed to Hong Chen.

At least 109 records · Page 6Linked to original sources

Density of platelet collagen receptors glycoprotein VI and alpha2beta1 and prior myocardial infarction in human subjects, a pilot study.

BACKGROUND: Prior studies evaluating whether platelet collagen receptors affect risk of myocardial infarction (MI) have used common polymorphisms thought to affect receptor density, and have yielded conflicting results. Our objective in the current pilot study was to obtain preliminary information on the relationship between platelet collagen receptor density and prior MI. MATERIAL/METHODS: We measured glycoprotein VI (GPVI) and integrin alpha2beta1 density by flow cytometry using FITC-conjugated monoclonal antibodies in consecutive subjects from an outpatient cardiology practice. We used a case-control design to match 77 patients with prior MI to 77 control patients. Matching was performed on the basis of traditional risk factors for MI. RESULTS: The mean GPVI density was 14% higher in those with prior MI (P = 0.098), and the alpha2beta1 density was 6% higher in those with prior MI (P = 0.49). A GPVI or alpha2beta1 density within the lowest decile was associated with a lower MI prevalence (OR = 6.3, 95% CI: 1.3-29.2 P = 0.009). CONCLUSIONS: Our preliminary data suggests that platelet collagen receptor density, when measured directly, may be related to prior myocardial infarction. An appropriately sized clinical study using this methodology is warranted to further investigate whether collagen receptor density serves as a novel risk factor for myocardial infarction.

Aged↗

Microfluidic chip-based liquid-liquid extraction and preconcentration using a subnanoliter-droplet trapping technique.

A robust and simple approach for microfluidic liquid-liquid (L-L) extraction at the subnanoliter-scale was developed for on-chip sample pretreatment. Organic solvent droplets of a few hundred pL were trapped within micro recesses fabricated in the channel walls of a microfabricated glass chip. L-L extraction was performed by delivering aqueous samples through the channel, with the sample stream continuously flowing adjacent to the droplets. The analytes in aqueous streams were enriched within the droplet with high preconcentration factors owing to both phase transfer and dissolution of organic solvent into the bypassing aqueous sample. An aqueous solution of butyl rhodamine B (BRB) and 1-hexanol were used, respectively, as sample and extractant to demonstrate the performance of the system. The fluorescence intensity of the dye extracted into the droplet was monitored in situ by LIF. The system proved to be an efficient means for achieving high enrichment factors of over 1000, with sample consumption of a few microL. Quantitative measurement of the extracted analyte was achieved with a linear response in the range 1 x 10(-9)-8 x 10(-7) M BRB. The precision of the measured fluorescence values for a 10(-7) M BRB standard with a 12.5 min preconcentration period was 6.6% RSD (n = 5).

Journal Article↗

Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer.

Human DAB2IP (hDAB2IP), a novel GTPase-activating protein modulating the Ras-mediated signaling and tumor necrosis factor-mediated apoptosis, is a potent growth inhibitor in human prostate cancer (PCa). Loss of hDAB2IP expression in PCa is due to altered epigenetic regulation (i.e. DNA methylation and histone modification) of its promoter region. The elevated polycomb Ezh2, a histone methyltransferase, has been associated with PCa progression. In this study, we have demonstrated that an increased Ezh2 expression in normal prostatic epithelial cells can suppress hDAB2IP gene expression. In contrast, knocking down the endogenous Ezh2 levels in PCa by a specific small interfering RNA can increase hDAB2IP expression. The association of Ezh2 complex (including Eed and Suz12) with hDAB2IP gene promoter is also detected in PCa cells but not in normal prostatic epithelial cells. Increased Ezh2 expression in normal prostatic epithelial cells by cDNA transfection facilitates the recruitment of other components of Ezh2 complex to the hDAB2IP promoter region accompanied with the increased levels of methyl histone H3 (H3) and histone deacetylase (HDAC1). Consistently, data from PCa cells transfected with Ezh2 small interfering RNA demonstrated that reduced Ezh2 levels resulted in the dissociation of Ezh2 complex accompanied with decreased levels of both methyl H3 and HDAC1 from hDAB2IP gene promoter. We further unveiled that the methylation status of Lys-27 but not Lys-9 of H3 in hDAB2IP promoter region is consistent with the hDAB2IP levels in both normal prostatic epithelial cells and PCa cells. Together, we conclude that hDAB2IP gene is a target gene of Ezh2 in prostatic epithelium, which provides an underlying mechanism of the down-regulation of hDAB2IP gene in PCa.

Apoptosis↗

Differentiation of endometrial stromal cells in vitro: down-regulation of suppression of the cell cycle inhibitor p57 by HOXA10?

Decidualization is a critical step during embryo implantation that is characterized by the differentiation of endometrial stromal cells (ESC) into decidua cells. However, the mechanism of differentiation remains largely unknown. Previously, it has been shown that the null function of homeo box A10 (HOXA10) causes defects in both implantation and decidualization, suggesting that the HOXA10 signalling pathway is likely to be involved in uterine decidualization. In the present study, we determined the expression and subcellular distribution of HOXA10 and its downstream molecule, p57, in ESC during in vitro decidualization induced by a combination of 8-bromo-cAMP and medroxyprogesterone acetate. We demonstrated that the HOXA10 was down-regulated while in contrast, p57 was up-regulated in the process of decidualization. Immunocytochemistry and transient expression of the HOXA10 tagged with green fluorescence protein revealed that there were no differences in the HOXA10 subcellular localization between the induced and non-induced ESC. Our results suggest that the down-regulation of HOXA10 may contribute to increased p57 and that up-regulation of p57 likely plays an important role in ESC differentiation in the process of decidualization. The progesterone receptor pathway may participate in promoting ESC to exit the cell cycle and enter differentiation.

Cell Cycle↗

The association of epsin with ubiquitinated cargo along the endocytic pathway is negatively regulated by its interaction with clathrin.

Monoubiquitination of plasma membrane proteins is a mechanism to control their endocytic trafficking by promoting their interaction with cytosolic adaptor proteins that contain ubiquitin (Ub)-binding domains. Epsin, which contains Ub interaction motifs (UIMs), as well as binding sites for the clathrin coat and clathrin accessory factors, is thought to function as one of such adaptors. The importance of clathrin in the internalization of ubiquitinated cargo, however, has been questioned. Here, we show that a GFP-Ub chimera directly targeted to the plasma membrane via a lipid-based interaction is efficiently taken up by endocytosis and delivered to the same endosomes that accumulate internalized EGF. Internalization of the chimera requires integrity of the UIM binding interface of Ub, but does not require clathrin. Surprisingly, WT epsin showed little colocalization with this chimera, whereas UIM-containing epsin constructs that lack the clathrin and AP2 binding region, strikingly colocalized with this chimera on endocytic vacuoles. In addition, extensive colocalization of WT epsin with the chimera on endocytic structures could be observed in cells where clathrin levels were drastically reduced by RNA interference. Our results reveal an important regulatory mechanism in epsin function. The mutually exclusive colocalization of epsin with membrane-bound Ub or clathrin may play a role in controlling the endocytic route taken by ubiquitinated cargo.

Adaptor Protein Complex 2↗

Glucose biosensor based on platinum microparticles dispersed in nano-fibrous polyaniline.

A sensitive and selective amperometric glucose biosensor based on platinum microparticles dispersed in nano-fibrous polyaniline (PANI) was investigated. Poly (m-phenylenediamine) (PMPD), which was employed as an anti-interferent barrier and a protective layer to platinum microparticles, was deposited onto platinum-modified PANI in the presence of glucose oxidase. The morphology of PANI, Pt/PANI and PMPD-GOD/Pt/PANI were investigated by scanning electron microscopy. The results show that PANI has a nano-fibrous morphology. The enzyme electrode exhibits excellent response performance to glucose with linear range from 2 x 10(-6) to 12 x 10(-3) M and fast response time within 7s. Due to the selective permeability of PMPD, the enzyme electrode also shows good anti-interference to uric acid and ascorbic acid. The Michaelis-Menten constant km and the maximum current density imax of the enzyme electrode were 9.34 x 10(-3) M and 917.43 microA cm(-2), respectively. Furthermore, this glucose biosensor also has good stability and reproducibility.

Aniline Compounds↗

Articular chondrocytes express the receptor for advanced glycation end products: Potential role in osteoarthritis.

OBJECTIVE: The receptor for advanced glycation end products (RAGE) binds multiple ligands, including S100 proteins, high mobility group box chromosomal protein 1 (HMGB-1), and AGEs, all of which are present in articular cartilage. Stimulation of RAGE signaling can lead to MAP kinase activation and increased NF-kappaB activity. The objective of the present study was to determine if chondrocytes express functional RAGE. METHODS: The presence of chondrocyte RAGE was analyzed by immunohistochemistry using normal and osteoarthritic (OA) cartilage from young and old monkeys and humans, immunoblotting of chondrocyte lysates and human cartilage extracts, and reverse transcription-polymerase chain reaction (RT-PCR) analysis of RNA from chondrocytes treated with interleukin-1 (IL-1) and fibronectin fragments. RAGE signaling was evaluated by stimulating chondrocytes with S100B and HMGB-1 and analyzing for activation of the ERK MAP kinase and NF-kappaB. The ability of S100B and HMGB-1 to stimulate matrix metalloproteinase 13 (MMP-13) production was also assessed. A pull-down assay using biotin-labeled S100B was used to demonstrate binding to RAGE. RESULTS: RAGE was detected in sections of monkey knee cartilage and human knee and ankle cartilage. Increased immunostaining for RAGE was noted in cartilage from older adult monkeys and humans and was further increased in OA tissue. RAGE was also detected by immunoblotting and by RT-PCR, where IL-1beta and fibronectin fragments were found to stimulate RAGE expression. Stimulation of chondrocytes with S100B or HMGB-1 increased phosphorylation of the ERK MAP kinase and the p65 subunit of NF-kappaB and increased the production of MMP-13. This signaling was inhibited in cells pretreated with soluble RAGE, and S100B was shown to bind to chondrocyte RAGE. CONCLUSION: Articular chondrocytes express functional RAGE. The increase in RAGE noted in OA cartilage and the ability of RAGE ligands to stimulate chondrocyte MAP kinase and NF-kappaB activity and to stimulate MMP-13 production suggests that chondrocyte RAGE signaling could play a role in OA.

Adult↗

Epidemiological survey of Tourette syndrome in children and adolescents in Wenzhou of P.R. China.

An epidemiological survey on Tourette syndrome (TS) in a developing country is relatively scarce. This study was conducted to investigate the prevalence and distribution of TS in children and juveniles aged 7-16 years in Wenzhou of P.R. China. A total of 9742 children and adolescents were included in this survey. Cross-sectional study with stratified-cluster sampling method was used. The prevalence of TS among school-age children was estimated to be an average of 0.43%. The ratio of male to female was 10.6 to 1 (0.74% for males and 0.07% for females). Pupils in the age range of 7-16 years are more likely to have comorbid disorders. The mean age at onset of TS was 7.7+/-2.7 years, with 45.2% of them at the age of 6-7. The rate of delayed diagnosis, misdiagnosis and misclassification of the syndrome were 78.6, 42.9 and 23.8%, respectively. This survey supports that TS is a common disease prevalent amongst children and juveniles in Wenzhou area of P.R. China, and its incidence was correlated with age and sex and often misdiagnosed and misclassified.

Adolescent↗

Protein repellant silicone surfaces by covalent immobilization of poly(ethylene oxide).

Polydimethylsiloxane elastomers were surface modified with passivating polyethylene oxide (PEO) polymers of different molecular weights, both monofunctional and bifunctional. Following the introduction of Si-H groups on the surfaces by acid-catalyzed equilibration in the presence of polymethylhydrosiloxane, the PEO was linked by platinum-catalyzed hydrosilylation. ATR-FTIR, X-ray photoelectron spectroscopy (XPS) and water contact angle results confirmed that the PEO was successfully grafted to the silicone rubber. Atomic force microscopy and XPS suggested that surface coverage with PEO was very high on the modified surfaces but not complete. The protein-resistant properties of the PEO-modified surfaces were demonstrated by measuring the adsorption of fibrinogen from both buffer and plasma. Fibrinogen adsorption from buffer to the PEO-modified surfaces was reduced by more than 90% compared with controls.

Adhesiveness↗

Immobilization of heparin on a silicone surface through a heterobifunctional PEG spacer.

A novel method of immobilizing heparin on a silicone surface through a heterobifunctional PEG spacer was used yield well defined surfaces with highly active surface immobilized heparin and low non-specific protein adsorption. The heparin surface density achieved using this technique was 0.68 microg/cm2. Sessile drop water contact angles showed increased hydrophilicity of the silicone surface after PEG modification and a further decrease in the contact angles following the grafting of heparin. High specificity for ATIII with little fibrinogen adsorption was noted in plasma adsorption studies. This ATIII adsorption was mediated by the heparin layer, since surfaces modified with PEG only did not adsorb significant quantities of AT. The thrombin resistance of the heparin modified surfaces was demonstrably greater as measured by a chromogenic thrombin generation assay. The results suggest that the heterbifunctional PEG linker results in a high density of active heparin on the surfaces.

Adsorption↗

Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing.

Multicellular organisms initiate adaptive responses when oxygen (O(2)) availability decreases, but the underlying mechanism of O(2) sensing remains elusive. We find that functionality of complex III of the mitochondrial electron transport chain (ETC) is required for the hypoxic stabilization of HIF-1 alpha and HIF-2 alpha and that an increase in reactive oxygen species (ROS) links this complex to HIF-alpha stabilization. Using RNAi to suppress expression of the Rieske iron-sulfur protein of complex III, hypoxia-induced HIF-1 alpha stabilization is attenuated, and ROS production, measured using a novel ROS-sensitive FRET probe, is decreased. These results demonstrate that mitochondria function as O(2) sensors and signal hypoxic HIF-1 alpha and HIF-2 alpha stabilization by releasing ROS to the cytosol.

Basic Helix-Loop-Helix Proteins↗

Effects of dietary pyridoxine on immune responses in abalone, Haliotis discus hannai Ino.

A feeding experiment was conducted to investigate the effects of dietary pyridoxine (PN) on the immune responses of abalone, Haliotis discus hannai Ino. Purified diets supplemented with 0, 40, 800 mg PN kg(-1) or 80 mg kg(-1) of 4-deoxypyridoxine (PN antagonist) were fed to adult abalone (initial weight 45.77 +/- 0.25 g; initial shell length 68.02 +/- 0.78 mm) for 90 days. The air-dried brown kelp, Laminaria japonica, was used as a control diet. Each diet was fed to three replicate groups of abalone in a recirculation system using a completely randomised design. The results showed that weight gain ratio (WGR) of the abalone generally increased with the level of dietary PN supplementation though no significant differences were found among the treatments (P > 0.05). Phagocytic and phenoloxidase activities were significantly higher in abalone fed diets supplemented with 800 mg PN kg(-1) than those fed the PN-free diet or the one with 4-deoxypyridoxine (P < 0.05). Agglutination titre and respiratory burst activity were significantly higher in abalone fed diets supplemented with 40 mg PN kg(-1) than those fed the PN-free diet or the one with 4-deoxypyridoxine (P < 0.05). There were no significant differences in immunological characteristics between the abalone fed the diet containing 40 mg PN kg(-1) and those fed the diet containing 800 mg PN kg(-1) (P > 0.05). L. japonica resulted in significantly lower agglutination titre, respiratory burst and phagocytic activities than the artificial diets supplemented with 40 or 800 mg PN kg(-1) (P < 0.05). Total haemocyte count (THC), serum protein concentration, and the activities of lysozyme and acid phosphatase were not significantly affected by the dietary treatments (P > 0.05). These results demonstrate that dietary deficiency of pyridoxine suppresses the immune functions in H. discus hannai, and further investigations are needed to optimise the dietary level of this vitamin for maintaining the best immune responses in abalone.

Acid Phosphatase↗

Gender, interpersonal transactions, and the perception of pain: an experimental analysis.

UNLABELLED: Two experiments assessed how interpersonal transactions influence responses to cold pressor pain in women versus men. In Experiment 1, 91 young adults (57 women, 34 men) were randomly assigned to either a no transaction (NT) condition in which they coped alone with the cold pressor test or a transaction opportunity (TO) condition in which they also had the option of interacting with an empathetic, reflecting experimenter. Compared to men, women had lower pain tolerance and reported more pain and catastrophizing, although there were no gender differences in support seeking or other ways of coping. Within the TO condition, women were no more likely than men to initiate a transaction, but female speakers were more pain-focused than male speakers, and speaking with the empathetic interaction partner had generally negative effects on pain perception and coping. In Experiment 2, 126 young adults (76 women, 50 men) were randomly assigned to NT, TO, or experimenter-directed (1) Distraction (DT), (2) Reinterpretation (RT), or (3) Encouragement (ET) conditions. Although men had similar levels of pain tolerance across the 5 transaction conditions, women in NT and TO conditions exhibited reduced tolerance compared with those in the DT, RT, and ET conditions. Pain tolerance times among women in DT, RT, and ET conditions were equal to or exceeded those of men in these conditions. Together, findings suggest the nature of interpersonal transactions exerts a greater influence on women's responses to noxious stimulation than those of men. PERSPECTIVE: This study adds to literature indicating that women exhibit reduced tolerance for experimentally induced pain compared with men. These results suggest that the nature of interpersonal transactions also affects women's responses to noxious stimulation, more than those of men.

Adolescent↗

Aberrant methylation of FBN2 in human non-small cell lung cancer.

FBN2, a large modular extracellular matrix glycoprotein, is known to be a key component of human elastic fiber. A loss of FBN2 expression due to promoter methylation was recently identified in pancreatic cancer. We examined FBN2 expression by reverse transcription PCR and aberrant methylation of FBN2 by methylation specific PCR in lung cancer cell lines. Aberrant methylation of FBN2 was present in 55% (6 of 11) of non-small cell lung cancer (NSCLC) cell lines, but it absent in small cell lung cancer cell lines. The concordance between loss of expression and aberrant methylation of FBN2 was 88% (14 of 16) in the cell lines. FBN2 expression was restored after treatment with the demethylating agent, 5-aza-2'-deoxycytidine in all six cell lines tested that lacked FBN2 expression. Among primary NSCLC, 49% (62/126) of cases had FBN2 methylation, but only 7% (5/69) of the corresponding nonmalignant lung tissues had it. Although FBN2 methylation was detected even in patients with early stage disease, it occurred frequently in large tumors (p=0.022), with nodal metastasis (p=0.037), or with advanced stages of NSCLC (p=0.014). Methylation and silencing of FBN2 in tumor cells may play an important role in carcinogenesis, invasion, and metastasis of NSCLC.

Aged↗

Abeta25-35 alters Akt activity, resulting in Bad translocation and mitochondrial dysfunction in cerebrovascular endothelial cells.

The amyloid-beta peptide (Abeta) induces apoptosis in cerebrovascular endothelial cells (CECs), contributing to the pathogenesis of cerebral amyloid angiopathy. We have previously shown that Abeta induces apoptosis in CECs. In the present study, we report that Abeta25-35-induced CEC apoptosis involves the inactivation of Akt, a signaling kinase important in maintaining cell viability. Akt prevents the activation of death-signaling events by facilitating the inactivation of proapoptotic proteins such as Bad. We applied three strategies to show that Abeta25-35 inactivation of Akt is causally related to Abeta25-35-induced CEC death by preventing Bad activation and subsequent mitochondrial dysfunction (reflected by the release of endonuclease G and Smac, two proapoptotic intermembranous proteins of the mitochondria). Wortmannin, a PI3-kinase inhibitor, enhanced Abeta25-35-induced Bad activation, mitochondrial dysfunction and CEC death. Enhancement of Akt activity by a Tat-Akt fusion protein, or by viral gene transfer of a constitutively active mutant of akt, reduced Bad activation, mitochondrial dysfunction, and CEC death. Using a siRNA strategy to knock down the bad gene, we showed that Bad activation is causally related to Abeta25-35-induced mitochondrial dysfunction and CEC death. Together, these results establish that the Akt-Bad cascade is altered by Abeta25-35, resulting in CEC apoptosis.

Amyloid beta-Peptides↗

Dietary protein level and stage of development affect expression of an intestinal peptide transporter (cPepT1) in chickens.

The objective of this study was to evaluate the effect of dietary protein intake and stage of development on chicken intestinal peptide transporter (cPepT1) mRNA abundance. Chicks were sampled at embryonic d 16 (e 16) until the day of hatch (d 0). After hatch, mixed sex Cobb chicks were randomly assigned to diets containing 12, 18, or 24% crude protein (CP). Intakes of the 18 and 24% CP-fed birds were restricted to that consumed by the 12% CP-fed birds. Chickens were sampled on d 0, 1, 3, 5, 7, 10, 14, 21, 28, and 35. The experiment was repeated with the addition of a 4th group with free access to the 24% CP diet. PepT1 mRNA abundance in the duodenum, jejunum, and ileum was quantified by Northern blot. PepT1 mRNA was barely detectable between e 16 and 20 but increased 14- to 50-fold by d 0 (P < 0.001). In chickens fed 12% CP, cPepT1 mRNA abundance decreased throughout the experiment, whereas those fed the restricted 18 or 24% CP diets showed an increase in cPepT1 mRNA abundance (protein x time interaction, P < 0.01). In chicks with free access to the 24% CP diet, cPepT1 mRNA decreased until d 14 but returned to an intermediate level at d 35 (protein x time interaction, P < 0.01). The relative abundance of cPepT1 mRNA varied among intestinal segments with greater abundance occurring in the duodenal or jejunal sections (P < 0.05). Our results indicate that expression of cPepT1 mRNA is regulated by both dietary protein intake and developmental stage.

Animals↗

A comparison of the case-control and case-crossover designs for estimating medical costs of nonfatal fall-related injuries among older Americans.

OBJECTIVES: Although the case-crossover design has been used widely in epidemiological and cost-offset studies as an alternative to the case-control design, it is rarely applied to cost-of-illness studies. In this study, costs for a series of hospitalized and nonhospitalized fall-related injuries were computed using the 2 approaches to allow for a direct comparison of the results. RESEARCH DESIGN: We used claims data from the Medicare fee-for-service 5% Standard Analytical Files. For the case-control design, those who sustained nonfatal fall-related injuries were tracked for 1 year after their first fall, and costs were compared, using regression analysis, to annual costs for a comparison sample of nonfallers. The case-crossover design used a modified regression approach that compared monthly costs of fallers before and after fall. RESULTS: We present unit costs for falls requiring (1) a hospitalization resulting in a live discharge, (2) an emergency department visit not resulting in an admission, and (3) falls requiring office-based or hospital outpatient visits only. Using the case-control design, these costs were $22,260, $3890, and $5040 respectively. Using the case-crossover design, these estimates were reduced to $20,920, $3230, and $4200. CONCLUSIONS: On average, estimates of the costs of fall injuries from the case-control design were between 6% and 17% greater than those from the case-crossover approach. These differences likely result from our inability to control for comorbidity differences between fallers and nonfallers in the case-control design. Under several scenarios, including unobserved heterogeneity between cases and controls, the case-crossover design, although computationally more intensive, produces more accurate results.

Accidental Falls↗

Dental biometrics: alignment and matching of dental radiographs.

Dental biometrics utilizes dental radiographs for human identification. The dental radiographs provide information about teeth, including tooth contours, elative positions of neighboring teeth, and shapes of the dental work (e.g., crowns, fillings, and bridges). The proposed system has two main stages: feature extraction and matching. The feature extraction stage uses anisotropic diffusion to enhance the images and a Mixture of Gaussians model to segment the dental work. The matching stage has three sequential steps: tooth-level matching, computation of image distances, and subject identification. In the tooth-level matching step, tooth contours are matched using a shape registration method, and the dental work is matched on overlapping areas. The distance between the tooth contours and the distance between the dental work are then combined using posterior probabilities. In the second step, the tooth correspondences between the given query (postmortem) radiograph and the database (antemortem) radiograph are established. A distance based on the corresponding teeth is then used to measure the similarity between the two radiographs. Finally, all the distances between the given postmortem radiographs and the antemortem radiographs that provide candidate identities are combined to establish the identity of the subject associated with the postmortem radiographs.

Algorithms↗