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Biomedical subjects

Li Chen

Publications and source records attributed to Li Chen.

At least 127 records · Page 7Linked to original sources

Electrochemical reduction and flow detection of iodate on (Bu4N)2Mo6O19 self-assembled monolayer.

A stable monolayer of the inorganic-organic hybrid polyoxometalate (Bu4N)2Mo6O19, denoted as Mo6O19, was formed on a sodium-3-mercapto-1-propanesulfonate (MPPS)-covered gold electrode surface, interlaced with an anionic poly(dimethyldiallylammonium chloride) (PDDA) binding layer based on the electrostatic self-assembled (ESA) technique. Electrochemical characterization of the Mo6O19 self-assembled thin films on the solid surface by cyclic voltammetry and AC impedance spectroscopy revealed a stable and sensitive electrocatalytic response to the reduction of iodate. Iodate was determined amperometrically through a flow injection cell at the modified electrode in the concentration range of 1.0 x 10(-6) to 1.0 x 10(-1) M with a detection limit of 8 x 10(-8) M (signal-to-noise ratio = 3). Performance was improved to meet practical needs compared with previously reported analogues.

Electrochemistry↗

[A pilot study of spectrum of gene expression of acute leukemia].

OBJECTIVE: To investigate the gene expression of acute leukemia so as to study the pathogenesis of leukemia. METHODS: Five ml of bone marrow was collected from 22 patients with leukemia, 15 males and 7 females, aged 15-86, 17 with acute myelocytic leukemia, 4 with acute lymphocytic leukemia, and 1 with AHL. Mononuclear cells were isolated. Total RNA was extracted and mRNA was purified. DNA microarray technique with 12 848 genes was used to analyze the gene expression profiles. RESULTS: The predicted 45 genes were enormously expressed in 21 patients with acute leukemia, which were consistent with the ALL and AML classification standards reported by Golub and others. 7 genes which were overexpressed in multiple-resistant cell line K562-n/VCR were also overexpressed in 6 cases of refractory acute leukemia. Further analysis showed that 31 genes were upregulated in AML (M(4)-M(6)) and ALL but downregulated in AML (M(1)-M(3)). CONCLUSION: This results support the standard Golub has put forward. The reason that adult patients with ALL and subtypes of AML (M(4)-M(6)) have poorer prognosis in comparison with AMLM(1)-M(3) is attributed to alterations in gene expression. Primary drug resistance may be the major characteristics of refractory leukemia. Analysis of gene expression profile in acute leukemia is significant for classification and prognosis.

Adolescent↗

[Effect of tetramethylpyrazine on the responses of respiration and expression of nNOS in brainstem to hypoxia in rats].

The aim of the present study was to investigate the effect of tetramethylpyrazine (TMP) on the changes of respiration and expression of neuronal nitric oxide synthase (nNOS) in brainstem induced by hypoxia in the rats. Hypoxia was induced by inhalation of 8% O2-balanced N2.The electromyogram (EMG) of diaphragm was monitored to evaluate the respiratory response of the rats to hypoxia. The immunohistochemical staining technique was used to study the change of the expression of nNOS in the brainstem during hypoxia. In the rats of hypoxia group, a successive process of response, excitatory followed by inhibitory, was produced. Twenty min after hypoxia, a significant inhibition of respiration occurred, which was characterized with a marked decrease in the inspiratory duration, the respiratory frequency, and the amplitude of inspiration and a prolongation of expiratory duration (P<0.05). In the rats of pretreated with TMP, the respiratory activity was not obviously depressed (P>0.05). In the rats of hypoxia group, the level of nNOS immunoreactivity was enhanced remarkably in the lateral reticular nucleus, nucleus of trapezoid, hypoglossal nucleus and the facial nucleus compared with the control group (P<0.05). In the rats of pretreated with TMP, the nNOS level increased further in the nuclei mentioned above (P<0.05). The results obtained indicate that TMP can reverse the inhibitory effect of hypoxia on respiration in the rats and that nNOS may be involved in the respiratory protective action of TMP.

Animals↗

Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease.

Alpha-synuclein is phosphorylated at serine 129 (Ser129) in intracellular protein aggregates called Lewy bodies. These inclusion bodies are the characteristic pathologic lesions of Parkinson disease. Here we define the role of phosphorylation of Ser129 in alpha-synuclein toxicity and inclusion formation using a Drosophila model of Parkinson disease. Mutation of Ser129 to alanine to prevent phosphorylation completely suppresses dopaminergic neuronal loss produced by expression of human alpha-synuclein. In contrast, altering Ser129 to the negatively charged residue aspartate, to mimic phosphorylation, significantly enhances alpha-synuclein toxicity. The G protein-coupled receptor kinase 2 (Gprk2) phosphorylates Ser129 in vivo and enhances alpha-synuclein toxicity. Blocking phosphorylation at Ser129 substantially increases aggregate formation. Thus Ser129 phosphorylation status is crucial in mediating alpha-synuclein neurotoxicity and inclusion formation. Because increased number of inclusion bodies correlates with reduced toxicity, inclusion bodies may protect neurons from alpha-synuclein toxicity.

Amino Acid Substitution↗

In vivo insulin signaling through PI3-kinase is impaired in skeletal muscle of adult rat offspring exposed to ethanol in utero.

It is now known that prenatal ethanol (EtOH) exposure is associated with impaired glucose tolerance and insulin resistance in rat offspring, but the underlying mechanism(s) is not known. To test the hypothesis that in vivo insulin signaling through phosphatidylinositol 3 (PI3)-kinase is reduced in skeletal muscle of adult rat offspring exposed to EtOH in utero, we gave insulin intravenously to these rats and probed steps in the PI3-kinase insulin signaling pathway. After insulin treatment, EtOH-exposed rats had decreased tyrosine phosphorylation of the insulin receptor beta-subunit and of insulin receptor substrate-1 (IRS-1), as well as reduced IRS-1-associated PI3-kinase in the gastrocnemius muscle compared with control rats. There was no significant difference in basal or insulin-stimulated Akt activity between EtOH-exposed rats and controls. Insulin-stimulated PKC isoform zeta phosphorylation and membrane association were reduced in EtOH-exposed rats compared with controls. Muscle insulin binding and peptide contents of insulin receptor, IRS-1, p85 subunit of PI3-kinase, Akt/PKB, and atypical PKC isoform zeta were not different between EtOH-exposed rats and controls. Thus insulin resistance in rat offspring exposed to EtOH in utero may be explained, at least in part, by impaired insulin signaling through the PI3-kinase pathway in skeletal muscle.

Animals↗

Reaction pathway for the nonadiabatic reaction of Ca(4s3d 1D)+H2-->CaH(X 2Sigma+)+H.

The reaction pathway and the nascent CaH product distribution in the reaction Ca(4s3d (1)D)+H(2)-->CaH(X (2)Sigma(+))+H are obtained using a pump-probe technique. The Ca atom is first prepared in the 3 (1)D state by a two-photon absorption, and then in brief time delay the laser-induced fluorescence of the reaction product CaH is monitored. The CaH(v=0,1) distributions appear to be single peaked, as characterized by Boltzmann rotational temperature of 807+/-38 K (v=0) and 684+/-77 K (v=1). The vibrational population ratio of CaH(v=0)/CaH(v=1) is determined to be 3.3+/-0.1, while the v=2 population is not detectable. The fractions of the available energy partitioning into rotation, vibration, and translation are estimated to be 0.36+/-0.05, 0.28+/-0.04, and 0.36+/-0.05, respectively. With the aid of the potential energy surfaces calculations, the current reaction should favor a near C(2v) collision configuration. The temperature dependence measurement yields a positive slope, indicative of the reaction occurrence without any potential barrier. The colliding species are anticipated to follow an attractive 1B(2) (or 2A') surface and then transit nonadiabatically to the reactive ground state surface.

Journal Article↗

[Associations of genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with low birth weight in neonates].

OBJECTIVE: To investigate whether genetic polymorphisms in the microsomal epoxide hydrolase gene (EPHX1) and the glutathione S-transferase theta1 gene (GSTT1) are associated with low birth weight in neonates. METHODS: Using standard questionnaires, 246 singleton live born mother-neonates pairs (73 cases were mother-low birth weight neonate pairs and 173 controls were mother-non low birth weight neonate pairs) were investigated by the trained field workers with case-control study at the hospital in Anqing, Anhui Province, China between 1998 and 1999. A total of 246 neonates were genotyped for genetic polymorphisms in the EPHX1 gene and the GSTT1 gene by a polymerase chain reaction-restriction fragment length polymorphism assay. Multiple linear regression models were used to estimate the association of the genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with neonatal low birth weight, adjusting for maternal age, education, parity, neonatal sex and gestational age. RESULTS: EPHX1 His139His homozygote was not associated with low birth weight among neonates, compared with EPHX1 His139Arg heterozygote/Arg139Arg homozygote before and after adjustment confounders. GSTT1 absent genotype group also was not associated with low birth weight among neonates, compared with GSTT1 present genotype group before and after adjustment confounders. When both EPHX1 139 polymorphism and GSTT1 polymorphism were considered, a significant reduction in birth weight was found among neonates with EPHX1 His139His homozygote and GSTT1 absent genotype (OR=3.46, P=0.035). CONCLUSION: The combination between genetic polymorphisms in the EPHX1 gene and the GSTT1 gene in neonates is significantly associated with neonatal low birth weight.

Birth Weight↗

Alpha-synuclein and parkin contribute to the assembly of ubiquitin lysine 63-linked multiubiquitin chains.

Mutations in alpha-synuclein, Parkin, and UCH-L1 cause heritable forms of Parkinson disease. Unlike alpha-synuclein, for which no precise biochemical function has been elucidated, Parkin functions as a ubiquitin E3 ligase, and UCH-L1 is a deubiquitinating enzyme. The E3 ligase activity of Parkin in Parkinson disease is poorly understood and is further obscured by the fact that multiubiquitin chains can be formed through distinct types of linkages that regulate diverse cellular processes. For instance, ubiquitin lysine 48-linked multiubiquitin chains target substrates to the proteasome, whereas ubiquitin lysine 63-linked chains control ribosome function, protein sorting and trafficking, and endocytosis of membrane proteins. It is notable in this regard that ubiquitin lysine 63-linked chains promote the degradation of membrane proteins by the lysosome. Because both Parkin and alpha-synuclein can regulate the activity of the dopamine transporter, we investigated whether they influenced ubiquitin lysine 63-linked chain assembly. These studies revealed novel biochemical activities for both Parkin and alpha-synuclein. We determined that Parkin functions with UbcH13/Uev1a, a dimeric ubiquitin-conjugating enzyme, to assemble ubiquitin lysine 63-linked chains. Our results and the results of others indicate that Parkin can promote both lysine 48- and lysine 63-linked ubiquitin chains. alpha-Synuclein also stimulated the assembly of lysine 63-linked ubiquitin chains. Because UCH-L1, a ubiquitin hydrolase, was recently reported to form lysine 63-linked conjugates, it is evident that three proteins that are genetically linked to Parkinson disease can contribute to lysine 63 multiubiquitin chain formation.

Dimerization↗

Fabrication of a novel Li(x)MoOy film modified electrode and its application as an electrochemical sensor of iodate.

A novel organic gel film modified electrode was simply and conveniently fabricated by casting Li(x)MoOy and polypropylene carbonate (PPC) onto the surface of a gold electrode. The cyclic voltammetry and amperometry studies demonstrated that the Li(x)MoOy film modified electrode has a high stability and a good electrocatalytic activity for the reduction of iodate. In amperometry, a good linear relationship between the steady current and the concentration of iodate was obtained in the range from 3x10(-7) to 1x10(-4) mol L-1 with a correlation coefficient of 0.9997 and a detection limit of 1x10(-7) mol L-1.

Journal Article↗

Synthesis and insecticidal evaluation of propesticides of benzoylphenylureas.

Two series of benzoylphenylurea derivatives were synthesized as candidate propesticides by a nucleophilic addition reaction between 2,6-difluronbenzoyl isocyanate and N-substitutedaniline. The new compounds were identified by 1H NMR spectroscopy, electron ionization-mass spectrometry, and elemental analyses. The bioactivities of the new compounds were evaluated. All of the propesticides reported here were soluble in most organic solvents, and their hydrophobicities were improved obviously. The result of the bioactivities of the new compounds against Oriental armyworm showed that some of the new compounds are good as compared to diflubenzuron and penfluron.

Aniline Compounds↗

Prevalence of antiretroviral drug resistance mutations in chronically HIV-infected, treatment-naive patients: implications for routine resistance screening before initiation of antiretroviral therapy.

BACKGROUND: The prevalence of drug resistance among persons with newly acquired human immunodeficiency virus (HIV) infection is well documented. However, it is unclear to what extent these mutations persist in chronically infected, treatment-naive patients. METHODS: Prevalence of and factors associated with genotypic drug resistance were analyzed retrospectively in a subset of 491 chronically HIV-infected, antiretroviral-naive patients enrolled at 25 cities in the Terry Beirn Community Programs for Clinical Research on Acquired Immune Deficiency Syndrome (AIDS) Flexible Initial Retrovirus Suppressive Therapies trial during 1999-2001. Resistance was defined on the basis of the International AIDS Society 2003 definition, as well as the presence of additional mutations at codons 215 (C/D/E/S) and 69 (A/N/S) in the pol gene. Prevalence of mutations was estimated by use of techniques for stratified random samples. Logistic regression models were used to determine factors associated with resistance. RESULTS: Among the 491 chronically HIV-infected patients (mean CD4 cell count, 269 cells/mm(3); 31% of patients had a prior AIDS diagnosis), 57 (11.6%) had >or=1 resistance mutation, resulting in an estimated prevalence for the cohort of 10.8% (95% confidence interval [CI], 9.5%-12.1%). The prevalence was 8.8% if the 118I mutation was excluded. By drug class, the estimated prevalence of mutations conferring resistance to nucleoside reverse-transcriptase inhibitors was 7.8%, and the prevalence was 3.0% for nonnucleoside reverse-transcriptase inhibitors and 0.7% for protease inhibitors. In a multiple logistic regression analysis, non-Hispanic white subjects were twice as likely than African American subjects to have resistance (odds ratio [OR], 2.1; 95% CI, 1.1-4.1; P=.03), and there was a 40% increase per year in prevalence of mutations by later year of enrollment (OR, 1.4; 95% CI, 1.0-2.1; P=.05). CONCLUSIONS: These results demonstrate the persistence of drug resistance mutations in chronically HIV-infected patients and an increasing prevalence of resistance over time, and they support genotyping of virus at baseline for chronically HIV-infected patients.

Adult↗

The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema.

The Protein Data Bank (PDB) is the central worldwide repository for three-dimensional (3D) structure data of biological macromolecules. The Research Collaboratory for Structural Bioinformatics (RCSB) has completely redesigned its resource for the distribution and query of 3D structure data. The re-engineered site is currently in public beta test at http://pdbbeta.rcsb.org. The new site expands the functionality of the existing site by providing structure data in greater detail and uniformity, improved query and enhanced analysis tools. A new key feature is the integration and searchability of data from over 20 other sources covering genomic, proteomic and disease relationships. The current capabilities of the re-engineered site, which will become the RCSB production site at http://www.pdb.org in late 2005, are described.

Databases, Protein↗

Synthesis, crystal structure and biological activity of aryl [(N,N'-diacyl-N'-tert-butylhydrazino)thio]methylcarbamates.

A series of novel aryl [(N,N'-diacyl-N'-tert-butylhydrazino)thio]methylcarbamates were synthesized by the reaction of aryl (chlorothio)methylcarbamates with N,N'-diacyl-N-tert-butylhydrazines in the presence of sodium hydride. X-Ray single crystal diffraction of 2-isobutylphenyl [(N,N'-dibenzoyl-N'-tert-butylhydrazino)thio]methylcarbamate demonstrated the presence of N-S-N bonding. All of the compounds exhibited excellent larvicidal activities. Toxicity assays indicated that the products had knockdown activities of aryl methylcarbamates at higher concentrations and insect growth regulator activities of diacylhydrazines at lower concentrations.

Animals↗

Nano-composite of poly(L-lactide) and surface grafted hydroxyapatite: mechanical properties and biocompatibility.

In order to improve the bonding between hydroxyapatite (HAP) particles and poly(L-lactide) (PLLA), and hence to increase mechanical properties of the PLLA/HAP composite as potential bone substitute material, the HAP nano-particles were surface-grafted with PLLA and further blended with PLLA. The structure and properties of the composites were subsequently investigated by the mechanical property testing, the differential scanning calorimeter measurements (DSC), the scanning electron microscopy (SEM), the polarized optical microscopy (POM), and the cell culture. The PLLA molecules grafted on the HAP surfaces, as inter-tying molecules, played an important role in improving the adhesive strength between the particles and the polymer matrix. At a low content (approximately 4 wt%) of surface grafted-HAP (g-HAP), the PLLA/g-HAP nano-composites exhibited higher bending strength and impact energy than the pristine PLLA, and at a higher g-HAP content (e.g., 20 wt%), the modulus was remarkably increased. It implied that PLLA could be strengthened as well as toughened by g-HAP nano-particles. The results of biocompatibility test showed that the g-HAP existing in the PLLA composite facilitated both adhesion and proliferation of chondrocytes on the PLLA/g-HAP composite film.

Bone Substitutes↗

DDT serum concentration and menstruation among young Chinese women.

High DDE and DDT concentrations were found to be associated with shortened menstrual cycle length in Laotian immigrants to the United States. We examined this issue in a sample of young Chinese women. A total of 60 women aged 20-24 years were enrolled in three maternal and child health clinics (20 from urban, 20 from suburban, 20 from rural) in Shanghai, China, and vicinity, in 1998. Of these women, 47 who did not use hormonal contraceptives and had valid menstrual cycle characteristics were included in the analysis for associations among serum DDE and DDT concentration and menstrual cycle length, duration of menses, and heaviness of menstrual flow. In univariate analysis, higher p,p'-DDE concentration was associated with longer menstrual cycle length (0.66 day per 10 microg/L, 95% confidence interval [CI]: 0.21, 1.11 day). With adjustment for age, body mass index, education, occupation, and resident location, the estimate was 0.42 day (95% CI: -0.35, 1.19 day). p,p'-DDE was not associated with duration of menses or heaviness of menstrual flow. Neither p,p'-DDT nor o,p'-DDT were associated with menstrual cycle length, duration of menses or heaviness of menstrual flow. The study largely suggests no association between DDE and DDT concentrations and menstrual cycle characteristics in young Chinese women, though the weak-to-no correlation of DDE with menstrual cycle length merits further study.

Adult↗

Prevalence of diabetes mellitus and dyslipidemia among antiretroviral naive patients co-infected with hepatitis C virus (HCV) and HIV-1 compared to patients without co-infection.

OBJECTIVE: An increased prevalence of type 2 diabetes mellitus (DM) has been associated with HCV in the non-HIV infected populations. To describe a similar association among HIV subjects, and explore the biological mechanisms. METHODS: In a cross-sectional analysis, we compared the prevalence of DM (using American Diabetes Association criteria) and insulin resistance (HOMA IR) and dyslipidemia among ARV naive patients with HIV and HIV/HCV infected patients enrolled in CPCRA FIRST (058) and the Metabolic Substudy (061). RESULTS: Among 1389 enrolled in the FIRST study and had HCV serology, the prevalence of diabetes was higher (5.9%) among HCV/HIV as compared to 3.3% among those with HIV alone (p=0.04). Among 417 enrolled in the metabolic substudy, 88 (21%) had HIV/HCV co-infection. As in the main study, the prevalence of DM was higher in HIV/HCV group (9 vs. 3%, p=0.03). The HIV/HCV infected were significantly older (43 vs. 37 years), non-white (83 vs. 70%), with a history of IDU (55 vs. 3%), had higher AST (61 vs. 39 U/l), ALT (55 vs. 43 U/l,) and lower cholesterol levels (3.97 vs. 4.25 mmol/l). By multivariate analysis among subjects <50 years, association between HCV and diabetes remained significant after adjusting for BMI, family history of diabetes (OR=3.7, 95% CI: 1.3-11.1, p=0.02). The insulin resistance (HOMA IR) was not different between the two groups, however, the prevalence of dyslipidemia was lower among HCV co-infected subjects. CONCLUSIONS: Subjects with HIV/HCV co-infection have a higher prevalence of diabetes and thus may need to be screened for it prior to initiation of anti-retroviral therapy, particularly if it is a PI based regimen.

Acquired Immunodeficiency Syndrome↗

Effect of relaxin on myocardial ischemia injury induced by isoproterenol.

The omnipresent 6-kDa polypeptide relaxin (RLX) is emerging as a multifunctional endocrine and paracrine factor in a broad range of target tissues including cardiovascular tissues. To explore the pathophysiological roles of RLX in ischemic cardiovascular diseases, we studied the changes in RLX mRNA level in the myocardium and the effect of RLX supplements in rats with isoproterenol (ISO)-induced myocardial injury. In ISO-treated rats, RLX levels in myocardia and plasma increased 3.7- and 6.9-fold, respectively (P<0.01), the mRNA level increased significantly in myocardia compared with controls. Co-administration of RLX (0.2 and 2.0 microg/kg/d) and ISO increased left-ventricular pressure development and decreased left ventricular end-diastolic pressure (LVDEP) (all P<0.01). Malondialdehyde content in myocardia and lactate dehydrogenase and creatine phosphokinase activities in plasma in RLX-treated rats decreased markedly compared with that in ISO-treated alone rats (P<0.01 or P<0.05). In the high-dose RLX group, fibroblastic hyperplasia was relieved in myocardia, hydroxyproline level was lower, by 33% (P<0.05), and endothelin content in plasma was lower, by 31% (P<0.01) than in the ISO-alone group. Compared with control group, any indexes in sham rats treated with high-dose RLX were unaltered (all P>0.05). These results showed an up-regulation of myocardial RLX during ISO-induced myocardial ischemia injury and the protective effect of RLX on ISO-induced cardiac inhibition and fibrosis, which suggests that RLX could be an endogenous cardioprotective factor in ischemic heart diseases.

Animals↗