Search PubMed⌕ Search

Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 73 records · Page 4Linked to original sources

Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans.

OBJECTIVE: The role of the central melanocortin system in the development of obesity has been extensively studied. Single-nucleotide polymorphisms (SNPs) within several candidate genes have been associated with food intake and obesity-related phenotypes; however, few of these associations have been replicated. SNPs in the agouti-related protein (AGRP) gene coding (Ala67Thr, 199G/A) and promoter (-38C/T) have been reported to be associated with body mass index (BMI), fat mass (FM) and percent body fat, in populations of European and African descent. In this study, we evaluated the association between the functional AGRP -38C/T promoter SNP and weight-related traits, namely BMI, FM and fat-free mass (FFM), as well as diabetes status. DESIGN: An association study of the AGRP -38C/T SNP and indices of obesity and diabetes status. SUBJECTS: A well-characterized population of 538 West Africans from Ghana and Nigeria recruited in the AADM (Africa America Diabetes Mellitus) study (mean age 52 years, 41.3% males, 71% diabetic). MEASUREMENTS: Genotyping of the AGRP -38C/T SNP, BMI, FM, FFM and fasting plasma glucose. RESULTS: Women carrying two copies of the variant T allele had significantly lower BMI (OR=0.47; 95% CI, 0.25-0.87). Also, men with at least one copy of the variant T allele were over two times less likely to be diabetic than other men (OR=0.44; 95% CI, 0.22-0.89). CONCLUSION: Our results replicate previous findings and implicate the AGRP -38C/T SNP in the regulation of body weight in West Africans.

Agouti Signaling Protein↗

Variants in Apaf-1 segregating with major depression promote apoptosome function.

APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 activates caspase 9 and thus initiates a cascade of proteolytic events leading to apoptotic destruction of the cell. Cellular phenotypes were measured using a yeast heterologous expression assay in which human Apaf-1 and other proteins necessary to constitute a functional apoptotic pathway were overexpressed. Apaf-1 variants encoded by APAF1 alleles that segregate with major depression in families linked to chromosome 12 shared a common gain-of-function phenotype in both assay systems. In contrast, other Apaf-1 variants showed neutral or loss-of-function phenotypes. The depression-associated alleles thus have a common phenotype that is distinct from that of non-associated variants. This result suggests an etiologic role for enhanced apoptosis in major depression.

Alleles↗

Obesity intervention in persons with spinal cord injury.

STUDY DESIGN: A single group uncontrolled trial. OBJECTIVES: Despite widespread emphasis on the obesity-related health risks in persons with spinal cord injury (SCI), limited research has been carried out to intervene in this problem. This study was conducted to assess the initial effectiveness of a weight loss program on various health outcomes in persons with SCI. SETTING: A rehabilitation center in Birmingham, Alabama, United States. METHODS: A total of 16 individuals with chronic SCI who were overweight or obese participated in a weight management program that consisted of 12 weekly classes, covering nutrition, exercise, and behavior modification. Various outcomes were examined over a 6-month period (baseline, week 12, and week 24), including body composition measured by dual energy X-ray absorptiometry, physiologic measures, diet behavior, and psychosocial and physical functioning. Of these, 13 participants returned for the week 24 follow-up. RESULTS: Weight loss averaged 3.5+/-3.1 kg (3.8% of the initial weight) at week 12 and 2.9+/-3.7 kg (3.0% of the initial weight) at week 24. There was a significant reduction from baseline values at weeks 12 and 24 in body mass index, anthropometric measurements, and fat mass and improvement in diet behavior and psychosocial and physical functioning, while lean mass and blood albumin and hemoglobin levels were maintained. A correlation analysis showed that a greater weight loss was importantly (r>0.4) associated with a greater reduction in total cholesterol at weeks 12 and 24 and in systolic and diastolic blood pressure at week 24. Several factors were important (r>0.4 or r<-0.4) in determining the success in weight loss, including age, race, marital and employment status, family history of overweight/obesity, level and duration of injury, and cholesterol level at baseline. CONCLUSIONS: This is the first demonstration that a carefully planned program with time-calorie displacement diet is effective for overweight/obese individuals with SCI to lose weight without compromising total lean mass and overall health. It provides foundation for a future large clinical trial for weight loss of persons with SCI or other spinal cord dysfunction.

Adult↗

Antibody-conjugated soybean oil-filled calcium phosphate nanoshells for targetted delivery of hydrophobic molecules.

Hollow calcium phosphate nanoparticles capable of encapsulating poorly water-soluble molecules were produced by self-assembly. Previously reported were solid calcium phosphate nanoparticles and water-filled calcium phosphate nanocapsules suited for encapsulating mostly hydrophilic, but not hydrophobic compounds. Here, calcium phosphate was deposited around 100 nm diameter, 1,2-dioleoyl-sn-glycero-3-phosphate stabilized soybean oil nanoemulsions using either calcium chloride or NaOH titrations to achieve shell thickness between 20-70 nm. The surface was functionalized with carboxylic acid via the addition of carboxyethylphosphonic acid to attach Molecular Probes AB-594C antibody using sulpho-n-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with an efficiency of approximately 70%, while retaining near complete antibody function. Hydrophobic pyrene was encapsulated with an efficiency of 95%, at concentrations much higher than its water solubility limit, and exhibited spectral features characteristic of a hydrophobic environment. These materials can be used in the targeted delivery of many useful, yet poorly water-soluble pharmaceutical and nutraceutical compounds.

Antibodies↗

Transdifferentiation of mouse BM cells into hepatocyte-like cells.

BACKGROUND: During the past few years multiple studies have revealed that adult stem cells, including BM origin stem cells, can be transdifferentiated into various cell types, including hepatocyte-like cells, under proper treatments or in a suitable microenvironment. However, little is known about the mechanism of the transdifferentiation, and the treatments employed seem to be very complicated and require simplification. It is important to determine the suitable conditions in which BM cells would be efficiently differentiated into hepatocytes. METHODS: Mouse BM cells were isolated from femurs and tibias and cultured in IMDM supplemented with 10% FBS. Hepatic differentiation was induced in a differentiation medium containing 20 ng/mL HGF, 10 ng/mL FGF-4, 10 ng/mL Oncostatin M (OSM) and different concentrations of liver-injured mouse sera. The differentiated hepatic cells were characterized by the expression of liver-associated mRNA and proteins and morphologic and functional features. RESULTS: BM cell-derived polygonal cell colonies appeared after several days of culture, and these hepatocyte-like cells expressed AFP, HNF-3beta, CK19, CK18, ALB, TAT and G-6-Pase at mRNA and protein levels, and the cells also had some hepatic cellular functions, such as glycogen storage and urea production. Interestingly, suitable concentrations of sera from liver-injured mice added to this system showed strong stimulation on the in vitro transdifferentiation of mouse BM cells into hepatocytes. DISCUSSION: In the present study we have established an effective hepatic differentiation system by a combination of HGF, FGF-4, OSM and liver-injured mouse sera in vitro. Accordingly, it will be a useful resource not only for understanding the mechanisms of transdifferentiation but also for efficient amplification of hepatocyte progenitor cells of BM origin.

Animals↗

Enhanced immunogenicity and antitumour effects with heterologous prime-boost regime using vaccines based on MG7-Ag mimotope of gastric cancer.

MG7-Ag, gastric cancer-associated antigen, has been shown to be immunogenic and has been used as marker molecule for prognosis. In a previous study, we developed an oral DNA vaccine based on MG7-Ag mimotope. However, we failed to detect cellular immune response using the oral MG7-Ag mimotope DNA vaccine. To induce significant T cell response, we developed a recombinant adenovirus vaccine based on MG7-Ag mimotope and evaluated the efficacy and protective effects of heterologous prime-boost immunization protocol with an oral DNA vaccine previously developed. We found that both vaccines were able to elicit a significant humoral response against MG7-Ag, while the highest serum titre MG7 antibody was detected in mice immunized with the heterologous prime-boost immunization protocol. Enzyme-linked immunospot (ELISPOT) assay demonstrated that the heterologous prime-boost immunization strategy was more efficient in inducing T cell response than the homologous prime-boost strategy. In the tumour challenge assay, 2 of 5 mice immunized with the heterologous prime-boost protocol were tumour free, while none of the mice in homologous prime-boost groups or control groups was tumour free. Those tumour-bearing mice in the heterologous prime-boost regime had smaller tumour masses than their counterparts in the homologous prime-boost groups or control groups. Therefore, our study suggests that vaccines against MG7-Ag induce significant immune response against gastric cancer, and that the heterologous prime-boost protocol using different types of vaccines could achieve better protective effect than the homologous prime-boost protocol.

Adenoviridae↗

B7-H1 expression is upregulated in peripheral blood CD14+ monocytes of patients with chronic hepatitis B virus infection, which correlates with higher serum IL-10 levels.

Chronicity in hepatitis B virus (HBV) infection is maintained by increased type 2 T-helper cell response, possibly because of increased interleukin-10 (IL-10) productions. B7-H1 can negatively regulate T-cell responses via its receptor, programmed death 1. Ligation of B7-H1 to T-cells can result in the preferential secretion of IL-10. In this study, we investigated whether there was an upregulated expression of B7-H1 in peripheral blood mononuclear cells in patients chronically infected by HBV and further explored the correlation between B7-H1 expression and serum interleukin 2, interferon-gamma, IL-10, HBeAg, alanine aminotransferase (ALT) levels and viral load. Fifty-five patients with chronic HBV infection and 20 healthy controls (HCs) were enrolled in the present study. The results showed that in patients with chronic hepatitis B CD14+ monocytes but not CD3+ and CD19+ cells had a significantly increased expression of B7-H1 compared with HCs, which positively correlates with serum IL-10 levels and the presence of HBeAg and negatively correlates with serum ALT levels. In conclusion, chronic HBV patients harbour an increased B7-H1 expression in CD14+ monocytes compared with controls, which may be responsible for the increased serum IL-10 levels. This might be an important way by which HBV evades an adequate immune response, leading to viral persistence and disease chronicity.

Adult↗

Characterization and application of two novel monoclonal antibodies against human OX40: costimulation of T cells and expression on tumor as well as normal gland tissues.

OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is a critical costimulatory receptor during the immune response. Here, we newly generated two specific mouse antihuman OX40 monoclonal antibodies (mAbs) (2G2 and 1F7), whose specificities are quite different from the available OX40 mAb (ACT35) by competition assay. It was also found that both mAbs could enhance the proliferation, activation and differentiation of T lymphocytes primed by anti-CD3 mAb. These results evidenced that both were functional antihuman OX40 mAbs. Furthermore, stained by 2G2 and 1F7, FCM and immunohistochemistry detected the constitutive expression of OX40 on tumor cell lines from epithelium, breast cancer and glioma tissues. Meanwhile, the non-tumor tissues (thyroid gland, stomach gland) were also found OX40 expression. These results suggested that OX40 is not only expressed in activated T cells, but also in some tumors as well as normal gland tissues. Such expression pattern indicated that OX40 may be a valuable surface antigen in unveiling its expression and function outside the immune system. Briefly, these novel antibodies may contribute to the evaluation of the mechanism of tumor metastasis and eventually shed light on further study of tumor immunotherapy and autoimmune diseases.

Animals↗

Production, characterization, and applications of two novel monoclonal antibodies against human interleukin-28A.

Interleukin-28A (IL-28A) is a novel cytokine discovered in recent years and has been shown to have antiviral activity. In this study, IL-28A complementary DNA was inserted into prokaryotic expression vector pET-44 Ek/LIC. The Nus-S-His-tagged IL-28A fusion protein was expressed in Escherichia coli BL21 (DE3) in the soluble fraction. The fusion protein was purified by S-protein agarose affinity chromatography, and the fusion tag was removed from recombinant IL-28A by cleavage with thrombin. To prepare specific monoclonal antibody against human IL-28A, BALB/c mice were immunized with IL-28A, and hybridoma cell lines were obtained by fusing mouse spleen cells with myeloma NS-1 cells. Two strains of hybridoma cells, which produced the anti-human IL-28A antibodies 1B9 and 4B5 were obtained. They are IgM isotype and working in western blot analysis and enzyme-linked immunosorbent assay. In the present study, it was shown for the first time that human umbilical vein endothelial cells treated with interferon-alpha and poly(I:C) express IL-28A protein assessed by flow cytometry and immunofluorescent staining techniques. Immunohistochemistry showed that macrophage-like cells in colon and lung tissue and alveolar epithelial cells in lung tissue contain IL-28A, indicating a novel mechanism for both cell types to carry out their antivirus or antitumor functions.

Animals↗

Disruption of ste23 gene affects composition profile and bioactivity of exopolysaccharide produced by Streptomyces sp. 139.

AIMS: To study the function of the gene ste23 involved in the biosynthesis of Ebosin. METHODS AND RESULTS: In search of databases, the deduced product of the gene ste23 showed high homology to dTDP-4-dehydrorhamnose 3,5-epimerases. ste23 was replaced by a kanamycin resistance gene through double crossover. Compared with Ebosin, an exopolysaccharide (EPS) produced by wild-type Streptomyces sp. 139, the EPS produced by the ste23 mutant (designated EPS1) had a remarkably different monosaccharide composition and significantly diminished rhamnose content, though the molecular mass of EPS1 was similar to that of Ebosin. In addition, EPS1 lost the interleukin 1 (IL-1) antagonist activity in vitro. CONCLUSIONS: ste23 may be involved in the Ebosin biosynthesis in S. sp. 139. and its bioactivity. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first genetic work investigating functions of genes involved in EPS production in streptomyces by gene replacement of the pathway genes.

DNA, Bacterial↗

Characteristics of severe retinopathy of prematurity patients in China: a repeat of the first epidemic?

AIM: To describe the characteristics of babies treated for severe retinopathy of prematurity (ROP) in a tertiary referral unit in China, to provide information to assist in determining screening criteria. METHODS: Information on consecutive babies referred to one eye department for treatment of stage 3 (prethreshold and threshold disease), and stages 4 and 5 ROP between January 2001 and May 2005 were retrieved from medical records. RESULTS: Data from 114 babies were analysed. The number of babies treated increased from nine in 2001 to 52 in 2004. The numbers of infants in each stage of ROP were as follows: stage 3, 40 babies; stage 4, 19 babies, and stage 5, 55 cases. The mean gestational age (GA) was 29.8 (SD 1.9) weeks (range 26-34 weeks) and the mean birth weight (BW) was 1432 (319) g (range 760-2500 g). 31 babies had BWs more than 1500 g (27.2%). 10 cases (8.8%) had GAs more than 32 weeks, and 82 (71.9%) had GAs more than 28 weeks. Overall, 18 (16.2%) infants exceeded UK screening criteria, and 34 (30.4%) exceeded the criteria used in the United States. The median age at presentation was 5.5 months (range 1-72 months). CONCLUSION: Comprehensive screening programmes for ROP are urgently needed in China. Screening criteria recommended by the American Academy of Pediatric Ophthalmology and Strabismus and the Royal College of Ophthalmologists, United Kingdom, may not be suitable for China where bigger, more mature babies are developing severe disease.

Birth Weight↗

RAPD analysis of jasmine rice-specific genomic structure.

Total genomic DNA was extracted from 29 samples of rice seed, including jasmine rice Oryza sativa L. subsp indica 'KDML105', 'KDML105'-derived varieties, nonaromatic Thailand rice, and japonica rice. Polymorphism in RAPD profiles was analyzed to explore the genomic structure specific to jasmine rice. The degree of band sharing was used to evaluate genetic distance between varieties and to construct a phylogenetic tree. RD15, CNTLR85033, and CNT87040 were found to be closest to 'KDML105', which was consistent with the true relation among them. Four RAPD fragments that cooperatively distinguished jasmine rice from others were cloned and sequenced. PCR amplification using pairs of primers designed specifically further confirmed the credibility of the RAPD result. Comparison through Genbank revealed that a 454 bp RAPD band was similar to the first intron of a putative Cf2/Cf5 disease resistance gene and a 1,107 bp RAPD band similar to a wall-associated kinase (wak) gene sequence.

Crosses, Genetic↗

Use of transoesophageal echocardiography during cardiac arrest in patients undergoing elective non-cardiac surgery.

BACKGROUND: Sudden unexpected intraoperative cardiac arrests in patients undergoing elective non-cardiac operations are rare but catastrophic complications. The efficacy and utility of transoesophageal echocardiography (TOE) in the diagnosis and management of these events have not been reported earlier. METHODS: Unexpected intraoperative cardiac arrests in patients undergoing elective non-cardiac operations were prospectively studied during a 6 yr period. In these patients, TOE was performed within 5 min after initiation of external chest compression to identify the causes of the cardiac arrests. RESULTS: Among a total of 125 965 surgical operations, 10 patients who suffered intraoperative cardiac arrests were studied. The causes of the cardiac arrests including myocardial infarction in five, pulmonary embolism in two, and severe hypovolaemia and ventricular arrhythmia without specific pathology in the other two patients were correctly identified using TOE. Seven patients survived. CONCLUSION: We conclude that TOE was useful in cardiac arrest during non-cardiac surgery for identifying or excluding pulmonary embolism and for directing investigations and treatment in those patients who had suffered myocardial infarction.

Adult↗

N-halamine/quat siloxane copolymers for use in biocidal coatings.

A series of copolymers incorporating N-halamine siloxane and quaternary ammonium salt siloxane units has been prepared. The primary function of the quat units was to render the siloxane copolymers soluble in water. The copolymers have been coated onto cotton swatches and evaluated for biocidal efficacy against Staphylococcus aureus and Escherichia coli O157:H7. It was determined that both N-halamine and quat functional groups were effective against S. aureus, but only the N-halamine units were effective against Escherichia coli O157:H7. The copolymers should be useful for applications for which aqueous media is preferred over organic solvents to be used during coating procedures.

Anti-Bacterial Agents↗

DFT and in situ EXAFS investigation of gold/ceria-zirconia low-temperature water gas shift catalysts: identification of the nature of the active form of gold.

A combined experimental and theoretical investigation of the nature of the active form of gold in oxide-supported gold catalysts for the water gas shift reaction has been performed. In situ extended X-ray absorption fine structure (EXAFS) and X-ray absorption near-edge structure (XANES) experiments have shown that in the fresh catalysts the gold is in the form of highly dispersed gold ions. However, under water gas shift reaction conditions, even at temperatures as low as 100 degrees C, the evidence from EXAFS and XANES is only consistent with rapid, and essentially complete, reduction of the gold to form metallic clusters containing about 50 atoms. The presence of Au-Ce distances in the EXAFS spectra, and the fact that about 15% of the gold atoms can be reoxidized after exposure to air at 150 degrees C, is indicative of a close interaction between a fraction (ca. 15%) of the gold atoms and the oxide support. Density functional theory (DFT) calculations are entirely consistent with this model and suggest that an important aspect of the active and stable form of gold under water gas shift reaction conditions is the location of a partially oxidized gold (Audelta+) species at a cerium cation vacancy in the surface of the oxide support. It is found that even with a low loading gold catalysts (0.2%) the fraction of ionic gold under water gas shift conditions is below the limit of detection by XANES (<5%). It is concluded that under water gas shift reaction conditions the active form of gold comprises small metallic gold clusters in intimate contact with the oxide support.

Journal Article↗

Upper limits on a stochastic background of gravitational waves.

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

Journal Article↗