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Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 73 records · Page 4Linked to original sources
PubMed2006

Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ion-induced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway.

The aim of present study is to explore the cytoprotection of curcumin against 1-methyl-4-phenylpridinium ions (MPP(+))-induced apoptosis and the molecular mechanisms underlying in PC12 cells. Our findings indicated that MPP(+) significantly reduced the cell viability and induced apoptosis of PC12 cells. Curcumin protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by inducing overexpression of Bcl-2, but also reducing the loss of mitochondrial membrane potential (MMP), an increase in intracellular reactive oxygen species (ROS) and overexpression of inducible nitric oxide synthase (iNOS). The selective iNOS inhibitor AG partly blocked MPP(+)-induced apoptosis of PC12 cells. The results of present study suggested that the cytoprotective effects of curcumin might be mediated, at least in part, by the Bcl-2-mitochondria-ROS-iNOS pathway. Because of its non-toxic property, curcumin could be further developed to treat the neurodegenerative diseases which are associated with oxidative stress, such as Parkinson's disease (PD).

1-Methyl-4-phenylpyridinium↗
PubMed2006

Redirecting carbon flux in Torulopsis glabrata from pyruvate to alpha-ketoglutaric acid by changing metabolic co-factors.

The nutrition conditions needed to redirect the carbon flux in Torulopsis glabrata, a pyruvate hyper-production yeast, from pyruvate to alpha-ketoglutaric acid (KG) were investigated in a stirred fermentor. A minor amount of KG (1.3 gl(-1)) was produced when NaOH was used to control the pH, while 12 g KG l(-1) was produced when CaCO(3) was used instead. When thiamine and biotin were included in the medium, 13 g KG l(-1) and 68 g pyruvate l(-1) were produced after 48 h when glucose was nearly consumed (approximately 5 gl(-1)). With fermentation continuing for a further 16 h, the concentration of pyruvate decreased to 31 gl(-1), and KG increased to 30 gl(-1). KG thus accumulated at the expense of pyruvate consumption.

Candida glabrata↗
PubMed2006

A randomized controlled trial of dietary fiber intake on serum lipids.

OBJECTIVE: Clinical trials have indicated that water-soluble fiber from oats reduces serum cholesterol among hypercholesterolemic patients on a low-fat diet. We examined the effect of dietary fiber intake on serum lipids among persons without hypercholesterolemia. DESIGN: Randomized controlled trial. SETTING AND SUBJECTS: We recruited 110 participants who were aged 30-65 years and had a serum cholesterol level < 240 mg/dl from community. INTERVENTION: Study participants were randomly assigned to receive 8 g per day of water-soluble fiber from oat bran or a control intervention. RESULTS: At baseline, the mean levels of serum cholesterol and other measured variables were comparable between the high-fiber and control groups. Over the 3-month intervention, mean changes (95% confidence interval (CI)) in total, HDL-, and LDL-cholesterol were -2.42 mg/dl (-8.90 to 4.05 mg/dl; P = 0.46), -0.24 mg/dl (-2.19 to 1.71 mg/dl; P = 0.81), and -1.96 mg/dl (-7.32 to 3.40 mg/dl; P = 0.47) in the fiber group and -0.02 mg/dl (-5.29 to 5.26 mg/dl; P = 0.99), 1.42 mg/dl (-0.74 to 3.59 mg/dl; P = 0.19), and -0.64 mg/dl (-5.30 to 4.03 mg/dl; P = 0.79) in the control group, respectively. The net changes (95% confidence interval) in total, HDL-, and LDL-cholesterol were -2.40 mg/dl (-10.6 to 5.81 mg/dl; P = 0.56), -1.66 mg/dl (-4.55 to 1.22 mg/dl; P = 0.26) and -1.33 mg/dl (-8.33 to 5.68 mg/dl; P = 0.71), respectively. CONCLUSIONS: Our study does not support the hypothesis that water-soluble fiber intake from oat bran reduces total and LDL-cholesterol in study participants with a normal serum cholesterol level.

Adult↗
PubMed2006

Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors.

We previously reported that oxidative stress and renal tubular damage occur in chronic hyperoxaluric rats. However, the in vivo responses of renal epithelial cells after vitamin E administration and their correlations with calcium oxalate (CaOx) crystal formation have not been evaluated. Male Wistar rats received 0.75% ethylene glycol (EG) for 7, 21, or 42 days to induce CaOx deposition (EG group). Another group of EG-treated rats received 200 mg kg(-1) of vitamin E intraperitoneally (EG+E group) to evaluate its effect on hyperoxaluria. Urinary electrolytes and biochemistry and levels of lipid peroxides and enzymes were examined, together with serum vitamin E levels. Levels of the tubular markers, alpha and mu glutathione S-transferase, proliferating cell nuclear antigen (PCNA), osteopontinin (OPN), and Tamm-Horsfall protein (THP) were also measured, and TUNEL staining was performed to examine the viability of the tubular epithelium. There were no significant differences between the two age-matched controls either untreated or given vitamin E. Compared to untreated controls, tubular cell death was increased at all time points in EG rats with a gradual increase in CaOx crystals, whereas the number of PCNA-positive cells was only significantly increased on day 21. In EG+E rats, tubular cell death was decreased compared to the EG group, and cell proliferation was seen at all time points, while CaOx crystal deposition was decreased, but hyperoxaluria, urinary lipid peroxides, and enzymuria were unaffected. Vitamin E supplement prevented the loss of OPN and THP in renal tissues by EG and the reduction in their levels in the urine. The beneficial effect of vitamin E in reducing CaOx accumulation is due to attenuation of tubular cell death and enhancement of the defensive roles of OPN and THP.

Acetylglucosaminidase↗
PubMed2006

Postprandial mononuclear NF-kappaB activation is independent of the AGE-content of a single meal.

OBJECTIVE: Dietary uptake of Advanced Glycation Endproducts (AGE) is supposed to potentially contribute to inflammatory reactions linked to vascular dysfunction and late diabetic complications. One mechanism by which dietary AGE might exert these effects is by activation of the proinflammatory transcription factor NF-kappa-B. The aim of this study was to analyze the postprandial effects of a casein meal with low or high AGE content on postprandial NF-kappaB activation in peripheral blood mononuclear cells (pBMC) of healthy volunteers. RESEARCH DESIGN AND METHODS: Casein was heated for 40 h at 50 degrees C in the presence of sorbitol or glucose, resulting in either minimal (Sorbitol [S]-casein) or large (glucose [G]-casein) amounts of AGE-modified casein. Nine healthy volunteers ate 250 g of both types of casein, whereas both meals were separated at least by 2 weeks. Plasma and pBMC were taken before and 2 h after each meal. Thereafter, the defined AGE carboxymethyllysine (CML) was determined by ELISA and Western blot. NF-kappaB activation in pBMC was assayed using Electrophoretic Mobility Shift Assays (EMSA) and Western blot analysis. RESULTS: S-casein contained only minor amounts of CML and no pentosidine, while G-casein contained large amounts of both. 2 h after ingestion, the S-casein or the G-casein-meal, both, resulted in a non-significant increase in plasma CML and in the intracellular CML-content of pBMC. This was paralleled by a highly significant increase in postprandial mononuclear NF-kappaB-binding activity. Remarkably, neither the extent of NF-kappaB induction (178% for S-casein, 188% for G-casein), nor composition of the NF-kappaB heterodimer (mainly consisting of NF-kappaB p50/p65) were significantly different after intake of S-casein or G-casein. Consistently, Western blots confirmed an increased NF-kappaBp65 nuclear translocation and a decrease of NF-kappaBp65 in the cytoplasm, while no difference in postprandial NF-kappaB nuclear translocation was observed following intake of S-casein or G-casein. CONCLUSION: Postprandial mononuclear NF-kappaB activation after a single meal is independent of the AGE-content of the ingested protein.

Active Transport, Cell Nucleus↗
PubMed2006

Metabolism of new-generation taxanes in human, pig, minipig and rat liver microsomes.

The novel taxanes SB-T-1102, SB-T-1214 and SB-T-1216 are up to 1000-fold more cytotoxic for resistant tumour cells than clinically used paclitaxel and docetaxel, and the current study has examined the metabolism of these new taxanes in human, rat, pig and minipig liver microsomes. Metabolites were characterized by high-performance liquid chromatography (HPLC)/tandem mass spectrometry (MS/MS) analysis. Metabolic pathways derived from their structures were confirmed by investigating subsequent metabolism of purified metabolites. SB-T-1102, SB-T-1214 and SB-T-1216 were metabolized to 14, 10 and 11 products, respectively. In contrast to docetaxel, side-chain hydroxylation did not occur at their tert-butyl group, but on the isobutyl (SB-T-1102) or isobutenyl (SB-T-1214 and SB-T-1216) chains. Species differences in their metabolism were observed. For example, human and untreated rat microsomes hydroxylated SB-T-1216 preferentially at the side-chain, whereas pig and minipig microsomes preferentially metabolized more at the taxane core. The increased formation of secondary and tertiary metabolites in rat microsomes with high expression of CYP3A1/2 compared with uninduced rats confirmed the role of CYP3A in taxane metabolism. All major products were formed by human cDNA-expressed CYP3A4 and none by CYP1A2, 1B1, 2A6, 2C9 and 2E1, indicating the principal role of CYP3A orthologues in SB-T metabolism. The knowledge of metabolic pathways of the examined agents and of their rates of formation is important due to possible metabolic inactivation of these three novel drugs with a great potential for the therapy of taxane-resistant tumours. The relatively slow metabolism of SB-T-1102 could be favourable for its antitumour efficiency in vivo.

Adolescent↗
PubMed2006

Effect of phospholipid composition on characterization of liposomes containing 9-nitrocamptothecin.

9-Nitrocamptothecin (9-NC), a newly developed camptothecin derivative, had poor solubility in any pharmaceutically acceptable solvents. One way of improving the solubility is to formulate the drug into liposomes. However, 9-NC has low affinity to lipid membranes resulting in a very low drug-to-liposome entrapment. We developed a novel liposome-based 9-NC formulation which was composed of soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC), and cholesterol. Compared with conventional liposomes composed of only SPC and cholesterol, 9-NC/lipid molar ratio increased from 1:72 to 1:18 while incorporation efficiency was still maintained about 80%. In addition, after 9-NC was encapsulated into novel liposomes, pharmacokinetic results revealed an increase in area under the plasma concentration-time curve (AUC) and a decrease in distribution volume of 9-NC following intravenous administration to rats. Increased stability in plasma may account for the improved pharmacokinetic behavior of the novel liposomes. Effect of HSPC/SPC molar ratio on characterization of the novel liposomes was also investigated. Except for drug/lipid molar ratio and encapsulation efficiency, HSPC/SPC molar ratio had only a little effect on other properties of novel liposomes. In conclusion, the study suggests that the novel liposomes can act as promising carriers for hydrophobic substances such as 9-NC.

Animals↗
PubMed2006

Phenotype of early cardiomyopathic changes induced by active immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the human beta-adrenergic receptor.

In the failing human heart, due to idiopathic dilated cardiomyopathy, it has been suggested that the beta1-adrenergic receptor (beta1AR) is a potential pathogenic autoantigen. The aim of the present study was to investigate whether immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the beta1AR (beta1AR EC(II)) was able to induce the early stage of cardiomyopathy and also to investigate immunological and receptor functional parameters at a transcriptional level to permit insights into the autoimmune mechanism in cardiomyopathy. Eleven Whistar Fur rats were immunized with a beta1AR EC(II) peptide (H26R) once a month during 12 months and seven control rats were injected with vehicle according to the same procedure used for the immunized group. Cardiac function, beta1AR autoantibodies and their functional effects on cardiomyocytes were analysed. beta1AR receptor signalling, immunological and cardiomyocyte stretch markers were determined on transcriptional level. In H26R immunized rats, beta1AR autoantibodies were shown to be present and functionally active, cardiac functions in terms of fractional shortening were decreased and beta1-adrenergic receptor kinase (GRK2) mRNA were increased compared with the control group. These data have shown that immunization of rats with a putative antigenic peptide was able to induce an early stage phenotype of cardiomyopathy in the form of cardiac dysfunction and up-regulation of GRK2 as the first step in the desensitization process of the beta1AR, implying the pathological importance of the beta1AR autoantibody.

Animals↗
PubMed2006

Increasing glycolytic flux in Torulopsis glabrata by redirecting ATP production from oxidative phosphorylation to substrate-level phosphorylation.

AIMS: This study aimed at further increasing the pyruvate productivity of a multi-vitamin auxotrophic yeast Torulopsis glabrata by redirecting ATP production from oxidative phosphorylation to substrate-level phosphorylation. METHODS AND RESULTS: We examined two strategies to decrease the activity of F0F1-ATPase. The strategies were to inhibit F0F1-ATPase activity by addition of oligomycin, or to disrupt F0F1-ATPase by screening neomycin-resistant mutant. The addition of 0.05 mmol l(-1) oligomycin to the culture broth of T. glabrata CCTCC M202019 resulted in a significantly decreased intracellular ATP level (35.7%) and a significantly increased glucose consumption rate (49.7%). A neomycin-resistant mutant N07 was screened and selected after nitrosoguanidine mutagenesis of the parent strain T. glabrata CCTCC M202019. Compared with the parent strain, the F0F1-ATPase activity of the mutant N07 decreased about 65%. As a consequence, intracellular ATP level of the mutant N07 decreased by 24%, which resulted in a decreased growth rate and growth yield. As expected, glucose consumption rate and pyruvate productivity of the mutant N07 increased by 34% and 42.9%, respectively. Consistently, the activities of key glycolytic enzymes of the mutant N07, including phosphofructokinase, pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase, increased by 63.7%, 28.8% and 14.4%, respectively. In addition, activities of the key enzymes involved in electron transfer chain of the mutant N07 also increased. CONCLUSIONS: Impaired oxidative phosphorylation in T. glabrata leads to a decreased intracellular ATP production, thereby increasing the glycolytic flux. SIGNIFICANCE AND IMPACT OF THE STUDY: The strategy of redirecting ATP production from oxidative phosphorylation to substrate-level phosphorylation provides an alternative approach to enhance the glycolytic flux in eukaryotic micro-organisms.

Adenosine Triphosphate↗
PubMed2006

Antepartum immunoprophylaxis of three doses of hepatitis B immunoglobulin is not effective: a single-centre randomized study.

To investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIg), currently being used in China, 250 pregnant women who were seropositive for hepatitis B e antigen (HBeAg) were randomly divided into study (117 cases) and control groups (133 cases). Subjects in the study group received HBIg 400 IU intramuscularly once a month at the third, second and first month before delivery; subjects in the control group received no antepartum treatment. All neonates received passive-active immunization after birth. The maternal hepatitis B virus (HBV) markers, hepatitis B surface antigen (HBsAg) titres and HBV deoxyribonucleic acid (DNA) levels were measured at week 28 of gestation (before the antepartum treatment) and at labour; the neonatal serum HBV markers were detected at birth and at 12 months after birth. No side-effects were found in any of the women or their neonates. No statistical differences were seen between the maternal HBsAg and HBV DNA levels of the study and control groups at labour nor the protective efficacy rates of postnatal immunoprophylaxis at 12 months after birth (P > 0.05, respectively). To conclude, antepartum administration of three doses of HBIg for the HBeAg-positive women is inefficacious.

Adult↗
PubMed2006

Chimaeric protein improved immunogenicity compared with fusion protein of Ag85B and ESAT-6 antigens of Mycobacterium tuberculosis.

Antigen 85B (Ag85B) and ESAT-6 are important immunodominant antigens of Mycobacterium tuberculosis, and both are very promising vaccine candidate molecules. In this study, we relied on the T-cell epitopes of Ag85B and ESAT-6 to design a chimaeric protein by inserting ESAT-6 into Ag85B from the amino acids 167-182. We found the ratio of IgG2b/IgG1 and the secretion of interferon (IFN)-gamma in the mice vaccinated with the new protein with adjuvant MPL and TDM were higher than the mice immunized with fusion protein Ag85B-ESAT-6, which have been reported and could induce levels of protective immunity similar to BCG in the mouse model of tuberculosis (TB) infection. These results suggest that the chimaeric protein Ag85B(N)-ESAT-6-Ag85B(C) is a strong candidate for further study and the T-cell epitopes of the antigens should be considered when we design the subunit vaccine.

Acyltransferases↗
PubMed2006

Functional properties and oxidative modulation of A-type K currents in hippocampal granule cells of control and chronically epileptic rats.

A-type K+ channels are crucial determinants of neuronal firing. For example, reducing the amplitude of A-type currents (I(A)) increases seizure susceptibility. We have therefore examined the functional and molecular properties of I(A) in dentate granule neurons following pilocarpine-induced status epilepticus (SE). We found that the levels of various A-type channel subunit mRNAs are unaltered following SE. Furthermore, current density and biophysical properties of I(A) recorded in outside-out and cell-attached patches from dentate granule cells are not modified by SE. However, I(A) in both control and epileptic rats was powerfully regulated by the cellular redox state. I(A) was recorded in outside-out patches with the recording pipette containing either reduced (GSH) or oxidized (GSSG) glutathione. In both control and epileptic rats, the presence of GSSG caused a similar, marked acceleration of recovery from inactivation. Additionally, GSSG produced a small but significant reduction of I(A) amplitudes only in control rats. The inactivation time course of I(A) during depolarizing voltage steps was not modified by GSH or GSSG. Cell-attached recordings, in which the intracellular milieu is conserved, revealed a slow time course of recovery more comparable to that with GSH. In summary, epileptic activity does not produce chronic changes in the molecular and functional properties of the somatic I(A) of dentate granule cells. However, I(A) is powerfully modulated by oxidation in both control and epileptic rats. This finding suggests that the availability of I(A) may be strongly regulated by changes in the GSH/GSSG ratio occurring during prolonged seizure activity or hypoxia.

Animals↗
PubMed2006

Role of colanic acid exopolysaccharide in the survival of enterohaemorrhagic Escherichia coli O157:H7 in simulated gastrointestinal fluids.

AIM: This study evaluated the production of colanic acid (CA) exopolysaccharide (EPS) by Escherichia coli O157:H7 in relation to the pathogen's ability to survive under acidic conditions simulating the environment in the human gastrointestinal tract. METHODS AND RESULTS: Escherichia coli O157:H7 W6-13 and its CA-deficient mutant M4020 were examined for their resistance to bile salts, and their ability to survive in simulated gastric fluid containing pepsin (pH 2.0) and simulated intestinal fluid containing pancreatin (pH 8.0). The effect of acid adaptation at pH 5.5 on the survival of E. coli O157:H7 in simulated gastric fluid was also determined. The results indicated that the survivability of M4020, under conditions simulating the environment in the human gastrointestinal tract, reduced more drastically than the viability of W6-13. The presence of bile salts had a slight effect on both types of E. coli O157:H7 cells. The loss of CA did not change the ability of M4020 to respond to acid adaptation. CONCLUSION: The EPS CA may serve as a protective barrier to E. coli O157:H7 for its survival in the human gastrointestinal tract. SIGNIFICANCE AND IMPACT OF THE STUDY: The study contributes to a better understanding of the EPS affecting the ability of E. coli O157:H7 to combat acid stress.

Escherichia coli O157↗
PubMed2006

Improved glutathione production by gene expression in Escherichia coli.

AIMS: To improve glutathione (GSH) production in Escherichia coli by different genetic constructions containing GSH genes. METHODS AND RESULTS: GSH production was very low in E. coli by the expression of gshI gene. An increase of GSH production was achieved by the expression of both gshI and gshII genes in E. coli. A higher GSH production, namely 34.8 mg g(-1) wet cell weight, was obtained by simultaneous expression of two copies of gshI gene and one copy of gshII gene. CONCLUSIONS: The simultaneous expression of two copies of gshI gene and one copy of gshII gene resulted in a significant increase in GSH production. SIGNIFICANCE AND IMPACT OF THE STUDY: The expression strategy for GSH production described here can be used to increase gene expression and obtain high production rates in other multienzyme reaction systems.

Escherichia coli↗
PubMed2006

Identification of Vibrio harveyi using PCR amplification of the toxR gene.

AIMS: The aim of this study was to develop an effective method for the identification of Vibrio harveyi based on using the toxR gene as a taxonomic marker. METHODS AND RESULTS: Primers for the toxR gene were designed for specificity to V. harveyi, and incorporated in a polymerase chain reaction (PCR). The results of the PCR, which took <5 h from DNA extraction to amplification, revealed positive amplification of the toxR gene fragment in 20 V. harveyi isolates including type strains, whereas DNA from 23 other Vibrionaceae type strains and 13 Vibrio parahaemolyticus strains were negative. The detection limit of the PCR was 4.0 x 10(3) cells ml(-1). In addition, the technique enabled the recognition of V. harveyi from diseased fish. CONCLUSIONS: The PCR was specific and sensitive, enabling the identification of V. harveyi within 5 h. SIGNIFICANCE AND IMPACT OF THE STUDY: The PCR allowed the rapid and sensitive detection of V. harveyi.

Animals↗
PubMed2006

Ultrasound biomicroscopy of Chinese eyes with iridocorneal endothelial syndrome.

AIM: To document the ultrasound biomicroscopic (UBM) findings in Chinese patients with iridocorneal endothelial (ICE) syndrome. METHODS: 21 patients with ICE syndrome and 15 normal subjects underwent UBM. UBM findings of anterior segment were compared between normal subjects and three clinical types of ICE syndrome: progressive iris atrophy (PIA), Chandler's syndrome (CS), and Cogan-Reese syndrome (CRS). RESULTS: Central anterior chamber depth was significantly less in patients with ICE syndrome (2.25 (SD 0.32) mm) than in normal subjects (2.76 (0.32) mm). Peripheral anterior synechiae were observed in all the ICE patients by UBM. Three out of four CRS subjects showed an "arborised" shape of iridocorneal angle. Two eyes out of 10 with CS presented bridge-shaped synechiae. A membrane-like mound was observed in iridocorneal angle in two patients: one with CRS and one with CS. UBM was found to be more effective in detecting peripheral anterior synechiae (PAS) and iris atrophy than slit lamp microscopy and gonioscopy, mainly because of corneal oedema in patients with CS. Four out of 11 patients with unilateral ICE syndrome had shallow or closed anterior chamber angles in their fellow eyes. Two of them successfully responded to laser peripheral iridotomy. CONCLUSIONS: UBM is an effective method to reveal the anterior segment features and provides a useful tool in the diagnosis of ICE syndrome. Different subtypes of ICE syndrome may have different UBM manifestations. UBM can help to identify angle closure in the fellow eye of unilateral ICE syndromes.

Adult↗