Biomedical subjects

Jin Chen

Publications and source records attributed to Jin Chen.

At least 55 records · Page 3Linked to original sources

PubMed2005

Electrochemical sensor for immunoassay of carcinoembryonic antigen based on thionine monolayer modified gold electrode.

A sensor based on thionine monolayer modified gold electrode for determination of carcinoembryonic antigen (CEA) in human serum is proposed. The sensor is prepared by covalently binding thionine to a cysteamine self-assembled monolayer with p-phthaloyl chloride as a linkage, which gives a surface coverage of 8.97+/-3.28 x 10(-12)mol/cm(2) for thionine. The electrochemistry of the immobilized thionine displays a surface-controlled electrode process with an average electron transfer rate constant of 1.47+/-0.84 s(-1). Based on an electrochemical enzyme-linked immunoassay by using the immobilized thionine as an electron transfer mediator between the electrode and the horseradish peroxidase (HRP) labeled anti-CEA antibody, a calibration curve with two linear ranges from 0.6 to 17 and 17 to 200 ng/mL and a detection limit of 0.2 ng/mL for CEA determination is obtained in pH 4.2 PBS containing 2.0 mmol/L H(2)O(2) and 0.5 mol/L NaCl. The sensor shows a good accuracy. The precision and reproducibility are acceptable with the intra-assay CV of 4.9% and 5.9% at 10 and 100 ng/mL CEA concentrations, respectively, and the inter-assays CV of 7.8% at 100 ng/mL CEA. The response of thionine modified electrode shows only 1.6% decrease after 100 replicate measurements and the storage stability is acceptable in a pH 7.0 PBS at 4 degrees C for 1 week. The method avoids the addition of electron transfer mediator to the solution, thus is much simpler. The proposed method would be valuable for the diagnosis and monitoring of carcinoma and its metastasis.

Antibodies↗

PubMed2005

The dynamics of hippocampal sensory gating during the development of morphine dependence and withdrawal in rats.

The effects of morphine on hippocampal sensory gating (N40) during the development of morphine dependence and withdrawal were investigated in the double click auditory evoked potential (EP) suppression paradigm. Rats were made dependent upon morphine hydrochloride by a series of injections (every 12 h) over 6 days, followed by withdrawal after stopping morphine administration. Hippocampal gating was examined during the development of dependence and withdrawal. Moreover, the DA antagonist haloperidol was used to assess the contribution of dopamine to hippocampal gating induced by morphine. Our results showed that the morphine-treated rats exhibited significantly disrupted hippocampal gating during the development of morphine dependence and this disrupted gating was partially reversed by haloperidol pretreatment. In contrast, there was significantly enhanced hippocampal gating at the fifth and sixth days of withdrawal. The dynamics of hippocampal gating during the development of morphine dependence and withdrawal suggests the interaction between the hippocampus and opioids.

Acoustic Stimulation↗

PubMed2005

Design, synthesis and structure-activity relationships of novel taxane-based multidrug resistance reversal agents.

A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure-activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonylcinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

High-performance liquid chromatographic assay for the determination of total and free topotecan in the presence and absence of anti-topotecan antibodies in mouse plasma.

A rapid and sensitive high-performance liquid chromatographic (HPLC) assay has been developed to allow determination of total (i.e. bound and unbound) and free (i.e. unbound) topotecan (TPT) in mouse plasma in the presence and absence of anti-TPT antibodies. The chromatographic analysis was carried out using reversed-phase isocratic elution with a Nova-Pak C18 column (3.9 mm x 150 mm, 4 microm) protected by a Nova-Pak C18 guard column (3.9 mm x 20 mm, 4 microm), where 10 mM KH(2)PO(4)-methanol-triethylamine (72:26:2 (v/v/v), pH 3.5) was used as the mobile phase. Topotecan was quantified with fluorescence detection using an excitation wavelength of 361 nm and an emission wavelength of 527 nm. The retention time for the internal standard, acridine, and TPT were 7.4 and 9.0 min, respectively. The lower limit of quantitation (LOQ) for TPT was determined as 0.02 ng in mouse plasma and mouse plasma ultrafiltrate, corresponding to a concentration of 1 ng/ml in 20 microl mouse plasma. The assay was shown to be linear over a concentration range of 1-500 ng/ml. The recoveries of free and total TPT from spiked mouse plasma were within 10% of theoretical values (assessed at 1, 20 and 500 ng/ml). The validated HPLC assay was applied to evaluate TPT pharmacokinetics following administration of TPT to Swiss Webster mice and to hyperimmunized and control BALB/c mice. The assay has been shown to be capable for measuring total and free TPT in mouse plasma with high sensitivity and will allow the testing of the effect of anti-TPT antibodies on the disposition of TPT.

Animals↗

PubMed2005

Hepatoprotection of oleanolic acid is related to its inhibition on mitochondrial permeability transition.

The protective effects of oleanolic acid (OA) on carbon tetrachloride (CCl4)-induced liver mitochondrial damage and the possible mechanisms were investigated. Pretreatment with OA prior to the administration of CCl4 significantly suppressed the increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (4.2- and 19.9-fold, respectively) in a dose-dependent manner in mice. The dissipation of mitochondrial membrane potential (14.8%) and intra-mitochondrial Ca2+ overload (2.1-fold) in livers of CCl4-insulted mice were also dose-dependently prevented by pretreatment with 20, 50 or 100 mg/kg OA. In addition, the effects of OA on liver mitochondria permeability transition (MPT) induced by Ca2+ were assessed by measuring the change in mitochondrial membrane potential, release of matrix Ca2+ and mitochondrial swelling in vitro. The results showed that preincubation with 50 or 100 microg/ml OA obviously inhibited the Ca2+-induced mitochondrial swelling, mitochondrial membrane depolarization and intra-mitochondrial Ca2+ release. It could be concluded that OA has protective effects on liver mitochondria and the mechanisms underlying its protection may be related to its inhibitory action on MPT.

Alanine Transaminase↗

PubMed2005

Antibody-cytotoxic agent conjugates for cancer therapy.

Antibody-based delivery of cytotoxic agents, including toxins, to tumours can dramatically reduce systemic toxicity and increase therapeutic efficacy. The advantage of a monoclonal antibody (mAb) is superior selectivity towards antigens expressed on the surface of cancer cells. Recent advances in biotechnology accelerated progress in the pharmaceutical applications of mAbs. A cytotoxic warhead is attached to a mAb in an immunoconjugate via a linker, which is stable in circulation but efficiently cleaved in the tumour tissue. The warhead, mAb and linker play important roles in the successful design of potent and efficient immunoconjugates. To date, one mAb-cytotoxic agent conjugate has been approved by the FDA and several other candidates are in various stages of clinical trials. This review describes the recent progress in the design and development of mAb-based immunoconjugates of cytotoxic agents, and summarises the criteria for the critical choices of a suitable mAb, linker and cytotoxic agent to design an efficacious immunoconjugate.

Animals↗

PubMed2005

EphA2 receptor tyrosine kinase as a promising target for cancer therapeutics.

Eph receptors are a unique family of receptor tyrosine kinases (RTK) that play critical roles in embryonic patterning, neuronal targeting, and vascular development during normal embryogenesis. Eph RTKs and their ligands, the ephrins, are also frequently overexpressed in a variety of cancers and tumor cell lines. In particular, one family member, EphA2, is overexpressed in breast, prostate, lung, and colon cancers. Unlike traditional oncogenes that often function only in tumor cells, recent data show that Eph receptors mediate cell-cell interactions both in tumor cells and in the tumor microenvironment, namely the tumor stroma and tumor vasculature. Thus, EphA2 receptors are attractive targets for drug design, as targeting these molecules could simultaneously inhibit several aspects of tumor progression. This review focuses on the multiple roles of EphA2 in cancer progression, the mechanisms by which EphA2 inhibition may halt this progression, and the pre-clinical results of EphA2 inhibition in various cancer model systems.

Animals↗

PubMed2005

[The effect of carvedilol on cardiac function and autoantibodies against the cardiac receptors].

OBJECTIVE: To evaluate the effect of carvedilol on the cardiac function and autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors in patients with chronic heart failure (CHF). METHODS: 54 patients with CHF were divided randomly into two groups, one was regular treatment group treated with ACE inhibitor, digoxin and diuretic, another was carvedilol treatment group treated with carvedilol on the basis of above regular treatment. All the patients were followed up for six months and measured the changes of cardiac function and three autoantibodies by echocardiography and enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: (1) After carvedilol treatment, LVEDD and LVESD (57.50 +/- 7.29) mm and (43.17 +/- 8.27) mm were smaller than that in regular treatment group [(64.09 +/- 7.40) mm and (52.93 +/- 8.35) mm], and LVEF [(50.41 +/- 10.91)%] was higher than that [(41.70 +/- 7.45)%] in regular treatment group (P < 0.01). (2) After carvedilol treatment, the positive ratios and average titers of autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors all decreased significantly compared with that of pre-treatment (P < 0.05). The positive ratios of autoantibodies against the three receptors in carvedilol treatment group were lower than those in regular treatment group (P < 0.05). The average titers of autoantibodies against the cardiac beta(1), beta(2) and alpha(1)-adrenergic receptors in carvedilol treatment group (1:72.44, 1:61.66 and 1:67.30) were lower than those in regular treatment group (1:113.24, 1:110.66 and 1:113.24), P < 0.05. CONCLUSIONS: Carvedilol decreased positive ratio and average titer of autoantibodies against the beta(1), beta(2) and alpha(1) receptors accompanied with the obvious improvement of cardiac function though the blockade of beta(1), beta(2) and alpha(1) receptors. It suggests that the autoantibodies might be involved in the process of pathophysiology and development of CHF. Carvedilol can inhibit this process.

Adult↗

PubMed2005

[Effect of dendritic cells co-cultured with cytokine induced killer cells on cytotoxicity against drug resistant K562 cells].

OBJECTIVE: To study the effect of dendritic cells (DC) co-cultured with cytokine induced killer (CIK) cells on cytotoxicity against K562 and K562 drug-resistant (K562/ADM) cells. METHODS: Peripheral blood mononuclear cells (MNC) isolated from healthy adult donors were induced to obtain CIK cells and DC respectively and then these two kinds of cells were co-cultured. The cytotoxicity of the co-cultured cells against K562 and K562/ADM cells was measured with MTT assay. RESULTS: The cytotoxicity CIK cells alone to K562 and K562/ADM cells was (20.0 +/- 1.2)% - (61.1 +/- 2.2)% and (17.5 +/- 2.1)% - (45.2 +/- 3.3)% respectively at low effector to target ratios (2.5 - 20.0). This effect was significantly enhanced by co-culturing with DCs being (25.2 +/- 2.3)% - (70.9 +/- 4.1)% and (22.4 +/- 2.7)% - (62.3 +/- 5.0)%. CONCLUSION: CIK cells showed high cytotoxicity against K562 and K562/ADM cells and the activity could be enhanced by co-culturing with DC.

Cell Proliferation↗

PubMed2004

Reagentless amperometric immunosensor for human chorionic gonadotrophin based on direct electrochemistry of horseradish peroxidase.

A novel amperometric immunosensor for determination of human serum chorionic gonadotrophin (HCG) was constructed by immobilization of HCG with titania sol-gel on a glassy carbon electrode and the direct electrochemistry of horseradish peroxidase (HRP) labeled to HCG antibody (HRP-anti-HCG). The morphologies of the HCG membrane were characterized to be chemically clean, porous and homogeneous. HRP-anti-HCG was functionally conjugated with the immobilized HCG after incubation in phosphate buffer (PBS) containing HRP-anti-HCG. A direct electron transfer of HRP with a rate constant of 1.35+/-0.40 s(-1) was observed at the HRP-anti-HCG-HCG/titania sol-gel membrane modified electrode in 0.1 M PBS pH 7.0. With a competitive mechanism the differential pulse voltammetric peak current of the immobilized HRP decreased linearly with an increasing HCG concentration from 2.5 to 12.5 mIU/ml in the incubation solution. The HCG immunosensor showed a detection limit of 1.4 mIU/ml, a good accuracy and acceptable precision and reproducibility with an intra-assay CV of 4.7% at 5.0 mIU/ml and an inter-assay precision of 8.1% obtained at 10 mIU/ml. The biosensor displayed a good stability in a storage period of 30 days.

Biosensing Techniques↗

PubMed2004

Elastic behavior of adsorbed polymer chains.

Elastic behaviors of single polymer chains adsorbed on the attractive surface are first investigated using Monte Carlo simulation method based on the bond fluctuation model. We investigate the chain size and shape of adsorbed chains, such as mean-square radius of gyration S2, mean-square bond length b2, shape factors sf(i) and delta*, and the orientation of chain segments P2 , to illuminate how the shape of polymer chains changes during the process of tensile elongation. There are some special behaviors of the chain size and shape at the beginning of elongation, especially for strong attraction interaction. For example, mean fraction of adsorbed segments decreases abruptly in the region of small elongation ratio and then decreases slowly with increasing elongation ratio. In fact, the chain size and shape also changes abruptly for small elongation ratio with strong attraction interaction. Some thermodynamics properties are also investigated here. Average Helmholtz free energy increases fast for elongation ratio lambda<1.15, especially with strong attraction, and increases slowly for lambda>1.15. Similar behaviors are obtained for average energy per bond. Elastic force (f ) and energy contribution to force (f(U)) are also studied, and we find that elastic force decreases abruptly for lambda<1.15, and there is a minimum of elastic force for strong attraction interaction, then increases very slowly with increasing elongation ratio. However, there are different behaviors for weak attraction interaction. For energy contribution to force (f(U)), there is a maximum value for strong attraction interaction in the region of lambda<1.15. Some comparisons with the atomic force microscopy experiments are also made. These investigations may provide some insights into the elastic behaviors of adsorbed polymer chains.

Journal Article↗

PubMed2004

Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling.

Trends in increased tuberculosis infection and a fatality rate of approximately 23% have necessitated the search for alternative biomarkers using newly developed postgenomic approaches. Here we provide a systematic analysis of Mycobacterium tuberculosis (Mtb) by directly profiling its gene products. This analysis combines high-throughput proteomics and computational approaches to elucidate the globally expressed complements of the three subcellular compartments (the cell wall, membrane, and cytosol) of Mtb. We report the identifications of 1044 proteins and their corresponding localizations in these compartments. Genome-based computational and metabolic pathways analyses were performed and integrated with proteomics data to reconstruct response networks. From the reconstructed response networks for fatty acid degradation and lipid biosynthesis pathways in Mtb, we identified proteins whose involvements in these pathways were not previously suspected. Furthermore, the subcellular localizations of these expressed proteins provide interesting insights into the compartmentalization of these pathways, which appear to traverse from cell wall to cytoplasm. Results of this large-scale subcellular proteome profile of Mtb have confirmed and validated the computational network hypothesis that functionally related proteins work together in larger organizational structures.

Automation↗

PubMed2004

Reverse endocytosis of transmembrane ephrin-B ligands via a clathrin-mediated pathway.

Eph/ephrin receptors and ligands mediate cell-cell interaction through reciprocal signaling upon juxtacrine contact, and play a critical role in embryonic patterning, neuronal targeting, and vascular assembly. To study transmembrane ephrin-B ligand trafficking, we determined the cellular localization of ephrin-B1-GFP upon engagement by EphB1. Under normal culture conditions ephrin-B1-GFP is localized to the plasma membrane, mostly at the lateral cell borders. Addition of soluble EphB1-Fc receptor induces ephrin-B1-GFP clustering on the cell surface and subsequent internalization, as judged by biochemical studies, electron microscopy, and co-localization with endosomal markers. A dominant-negative mutant of dynamin or potassium depletion blocks ephrin-B1 endocytosis. These results suggest that ephrin-B1 internalization is an active receptor-mediated process that utilizes the clathrin-mediated endocytic pathway.

Animals↗

PubMed2004

Observation of a threshold enhancement in the plambda invariant-mass spectrum.

An enhancement near the m(p)+M(Lambda) mass threshold is observed in the combined pLambda and pLambda invariant-mass spectrum from J/psi-->pK(-)Lambda;+c.c. decays. It can be fit with an S-wave Breit-Wigner resonance with a mass m=2075+/-12(stat)+/-5(syst) MeV and a width of Gamma=90+/-35(stat)+/-9(syst) MeV; it can also be fit with a P-wave Breit-Wigner resonance. Evidence for a similar enhancement is also observed in psi(')-->pK(-)Lambda;+c.c. decays. The analysis is based on samples of 5.8x10(7)J/psi and 1.4x10(7)psi(') decays accumulated in the BES II detector at the Beijing Electron-Positron Collider.

Journal Article↗

PubMed2004

Interspecific variation of plant traits associated with resistance to herbivory among four species of Ficus (moraceae).

BACKGROUND AND AIMS: To understand the defensive characteristics of interspecies varieties and their responses to herbivory damage, four species of Ficus plants (Ficus altissima, F. auriculata, F. racemosa and F. hispida) were studied. They were similar in life form, but differed in successional stages. Of these, Ficus altissima is a late successional species, F. hispida is a typical pioneer and F. auriculata and F. racemosa are intermediate successional species. We addressed the following questions: (1) What is the difference in plant traits among the four species and are these traits associated with differences in herbivory damage levels? (2) What is the difference in the damage-induced changes among the four species? METHODS: Herbivory damage was measured in the field on randomly planted seedlings of the four species of the same age. Defences to herbivory were also tested by feeding leaves of the four species to larvae of Asota caricae in the laboratory. A total of 14 characters such as water content, thickness, toughness, pubescence density on both sides, leaf expansion time, lifetime and the contents of total carbon (C), nitrogen (N), phosphorous (P), potassium (K), magnesium (Mg) and calcium (Ca) were measured. Leaf calcium oxalate crystal (COC) density, total Ca and N content, leaf toughness and height were measured to investigate induced responses to artificial herbivory among the four species. KEY RESULTS: and conclusions Herbivory damage in the four studied species varied greatly. The pioneer species, F. hispida, suffered the most severe herbivory damage, while the late successional species, F. altissima, showed the least damage. A combination of several characteristics such as high in content of N, Ca and P and low in leaf toughness, lifetime and C : N ratio were associated with increased herbivore damage. The late successional species, F. altissima, might also incorporate induced defence strategies by means of an increase in leaf COC and toughness.

Adaptation, Physiological↗

PubMed2004

Gene distribution of cagII in Helicobacter pylori-infected patients of Zhejiang Province.

AIM: To determine the prevalence of genotypes of cagII in Helicobacter pylori (H pylori)-infected patients in Zhejiang Province and investigate the relationship between these genotypes and the types of gastroduodenal diseases. METHODS: One hundred and seventy one clinical isolates were collected from 70 chronic superficial gastritis, 31 chronic atrophic gastritis, 41 gastric ulcer, 21 duodenal ulcer, 3 gastric and duodenal ulcer, and 5 gastric adenocarcinoma patients. Polymerase chain reaction assays were performed for analysis of cagT, ORF13 and ORF10 genes in the cagII region. RESULTS: Of 171 H pylori isolates from Zhejiang patients, 159(93.0%) were positive for all the three loci. One isolate (0.6%) was negative for all the three loci, and 11(6.4%) were partially deleted in cagII. The positive rates of cagT, ORF13 and ORF10 genes were 97.1%, 94.7% and 99.4%, respectively. In the strains isolated from the patients with diseases including chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer and duodenal ulcer, the sitive rates of cagT were 95.7%, 100.0%, 95.1% and 100.0%, respectively. The positive rates of ORF13 were 94.3%, 93.5%, 95.1% and 100.0%, respectively. The sitive rates of ORF10 were 98.6%, 100.0%, 100.0% and 100.0%, respectively. The three genes were all positive in the three H pylori strains isolated from the patients with both gastric and duodenal ulcer. In the five strains isolated from the patients with gastric adenocarcinoma, only one isolate was negative for ORF13. There were no significant differences of the cagT, ORF13 and ORF10 genes among the different gastroduodenal diseases including chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer, duodenal ulcer, both gastric and duodenal ulcer and gastric adenocarcinoma (chi(2)=3.098, P>0.05 for cagT; chi(2)=3.935, P>0.05 for ORF13 and chi(2)=6.328, P>0.05 for ORF10). CONCLUSION: The cagII is not a uniform and conserved entity. Although the genes in cagII are highly associated with the gastroduodenal diseases, the clinical outcome of H pylori infection is not reliably predicted by the three genes in cagII in patients from Zhejiang Province.

Adolescent↗

PubMed2004

EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation.

Angiogenesis is critical for vascular remodeling during development and contributes to the pathogenesis of diseases such as cancer. Targeted disruption of several EphB class receptor tyrosine kinases results in vascular remodeling defects during embryogenesis. The role of EphA class receptors in vascular remodeling, however, is not well-characterized. We recently demonstrated that global inhibition of EphA receptors disrupts endothelial migration induced by ephrin, VEGF or tumor-derived signals, though the specific target remained undefined. Here, we report that EphA2 regulates endothelial cell assembly and migration through phosphoinositide (PI) 3-kinase-mediated activation of Rac1 GTPase in two model systems: primary bovine and murine pulmonary microvascular endothelial cells. EphA2-deficient endothelial cells fail to undergo vascular assembly and migration in response to ephrin-A1 in vitro. Ephrin-A1 stimulation induces PI3-kinase-dependent activation of Rac1 in wild-type endothelial cells, whereas EphA2-deficient cells fail to activate Rac1 upon stimulation. Expression of dominant negative PI3-kinase or Rac1 inhibits ephrin-A1-induced endothelial cell migration. Consistent with in vitro data, EphA2-deficient mice show a diminished angiogenic response to ephrin-A1 in vivo. Moreover, EphA2-deficient endothelial cells fail to assemble in vivo when transplanted into recipient mice. These data suggest that EphA2 is an essential regulator of post-natal angiogenesis.

Adenoviridae↗

PubMed2004

Elastic behavior of short compact polymers.

In this paper, we investigate the elastic behaviors of short compact polymers using the enumeration calculation method and the HP model on a two-dimensional square lattice. Both the mean-square end-to-end distance R(2) and the ratio of R(2)/S(2) increase with lambda. However, when the elongation ratio becomes larger, the curves of R(2)/S(2) become smooth and they are close to the limit of 10.50 for different compact polymers. We also investigate the changes of interior conformations in the process of tensile elongation through calculating the probabilities of three bond angles (i.e., 90 degrees, 180 degrees, and 270 degrees). The average energy and Helmholtz free energy per bond are both negative and increase with elongation ratio lambda. In the meantime, the elastic force per bond (f ) also increases with elongation ratio lambda, and the energy contribution to the elastic force (f(U)) increases first and then drops, and there exists the maximum of f(U) in the region of lambda=1.40-1.80 for different sequences. The entropy contribution to force (f(S)) is close to zero at a small elongation ratio lambda and then increases with lambda. Some comparisons with different sequences (including nonfolding and folding sequences) are also made.

Journal Article↗