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Biomedical subjects

Biao Chen

Publications and source records attributed to Biao Chen.

49 records · Page 3Linked to original sources

[Association between NAD(P)H: quinone oxidoreductase and apolipoprotein E gene polymorphisms in Alzheimer's disease].

OBJECTIVE: To assess the association between NAD(P)H: quinone oxidoreductase 1 (NQO1) C609 T allele and apolipoprotein E (ApoE) polymorphism and sporadic Alzheimer disease (SAD). METHODS: The polymorphisms of NQO1 and ApoE gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 92 SAD patients and 108 normal controls, all of Han nationality. RESULTS: The frequencies of mutant T allele and T/C + T/T genotype at nucleotide position 609 of NQO1 gene were 56% and 89% respectively in the patients with SAD, significantly higher than those in the controls (45% and 71% respectively) with an odds ratio of 1.56 (for mutant T allele) and of 3.301 (for genotype) respectively. The frequency of the ApoE2 allele was significantly lower in the SAD patients than in the controls (chi(2) = 3.753, P < 0.05) and the frequency of ApoE4 was higher in the SAD patients, however, without a statistically significant difference (chi(2) = 1.863, P = 0.172). No significant interaction was found between NQO1 C609T and ApoE polymorphisms in SAD patients. CONCLUSION: NQO1 C609T may be an independent genetic risk factor for SAD in Chinese.

Aged↗

Regulation of GAP-43 expression by chronic desipramine treatment in rat cultured hippocampal cells.

BACKGROUND: The importance of molecular and cellular changes in hippocampus in major depression and in the mechanism of action of antidepressants has become increasingly clear. Identification of novel targets for antidepressants in hippocampus is important to understanding their therapeutic effects. METHODS: We used cDNA microarray to measure the expression patterns of multiple genes in primary cultured rat hippocampal cells. In situ hybridization and Northern and immunoblotting analysis were used to determine brain regional distribution and mRNA and protein levels of target genes. RESULTS: After comparing hybridized signals between control and desipramine treated groups, we found that chronic treatment with desipramine increased the expression of six genes and decreased the expression of two genes. One of the upregulated genes is growth associated protein GAP-43. In situ hybridization revealed that desipramine increased GAP-43 gene expression in dentate gyrus but not other brain regions. Northern and immunoblotting analysis revealed that desipramine increased GAP-43 mRNA and protein levels. GAP-43 expression is also increased by another antidepressant, tranylcypromine, but not by lithium or haloperidol. CONCLUSIONS: Because GAP-43 regulates growth of axons and modulates the formation of new connections, our findings suggest that desipramine may have an effect on neuronal plasticity in the central nervous system.

Animals↗

Preliminary studies on Alzheimer's disease using cDNA microarrays.

Alzheimer's disease (AD) is characterized by a progressive impairment of memory and intellectual functioning. The disease is a complex multi-factorial disease with the involvement of several possible genes. To study AD, a high-density cDNA array was developed to characterize the mRNA expression profile of 14160 genes. The preliminary results support the amyloid cascade hypothesis as the mechanism of the disease.

Alcohol Oxidoreductases↗

Desipramine treatment reduces the long-term behavioural and neurochemical sequelae of early-life maternal separation.

Primate and rodent models of maternal separation have shown that repeated postnatal separation of young from the mother results in long-term changes to neurohormonal systems relevant to depression. To date, however, it remains unclear whether rodents that experience postnatal maternal separation display specific behavioural or biochemical features of depression in adulthood and whether these changes can be prevented by treatment with antidepressant drugs. We report here that maternally separated mice showed significantly shorter swim times on the forced swim test and significantly lower levels of brain-derived neurotrophic factor in dentate gyrus and CA3 regions of the hippocampus compared to control mice when assessed in adulthood. Neither of these differences was apparent in maternally separated mice that received chronic treatment with the antidepressant desipramine after maternal separation. These results suggest that intervention following early stress may eliminate the long-term vulnerability to behavioural and biochemical dysfunction that occurs following this early chronic stress.

Animals↗

[Relationship between the Fnu4HI site polymorphism of monoamine oxidase A gene and Parkinson's disease].

OBJECTIVE: To study the association between the polymorphism of human monoamine oxidase type A (MAO-A) gene and Parkinson's disease(PD). METHODS: Fnu4HI restriction fragment length polymorphism(RFLP) and PCR-RFLP were used to detect the mutation of MAO-A gene. The frequencies of alleles and genotypes at the MAO-A Fnu4HI locus on the X chromosome in different PD group were compared with those of the control group. RESULTS: It was found that the frequencies of G allele in the patients with PD and controls were 0.613 and 0.527 respectively, P=0.039 "the frequencies of TT genotype were 0.303 and 0.415(P=0.014), and the frequencies of GG genotype were 0.564 and 0.451 respectively(P=0.021). When the patients were divided into two groups by age-onset, significant difference in the allelic and genotypic frequencies was observed only between early-onset PD group and control group. And when the PD patients were grouped by sex, significant difference was observed only between male PD group and male control group (the frequencies of G allele being 0.669 and 0.500 respectively, P=0.005). CONCLUSION: This study revealed significant differences between PD group and control group in allelic and genotypic frequencies. The findings supported the hypothesis about an association between MAO-A gene and PD, suggesting that age at onset of PD and gender predisposition might be related to the putative association, and Fnu4HI SNP be a risk factor for PD.

Alleles↗

[Isolation and culture of multipotent mesenchymal stem cells from porcine bone marrow].

OBJECTIVE: To establish a method for the isolation of porcine mesenchymal stem cells (MSCs) from bone marrow and to demonstrate their differentiation ex vivo into various mesenchymal tissue cells. METHODS: MSCs were isolated from bone marrow and purified by centrifuge and in vitro. The proliferation and growth characteristics were observed in primary and passage culture. Cell cycle was analyzed by measuring DNA content with FAC-Scan flow cytometer and cell multipotent was identified with specific staining. RESULTS: The adherent, fibroblast-like cells were confluent in single layer after plating for 12-14 days. The cultured MSCs in vitro differentiated into osteoblasts. The cell cycle analysis showed that 80% of MSCs were in G0/G1 phase. CONCLUSION: Porcine MSCs can be isolated from postnatal bone marrow through their adherent ability. Porcine MSCs may be introduced as a valuable model system to study the mesenchymal lineages for basic research and tissue engineering.

Animals↗

ACT and UCH-L1 polymorphisms in Parkinson's disease and age of onset.

alpha1-Antichymotrypsin (ACT) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have been suggested as susceptibility factors for Parkinson's disease (PD). We replicated these findings in a Chinese case-control sample consisting of 160 PD cases and 160 carefully matched control subjects. Genotypes were determined using polymerase chain reaction and BstN1 or Rsa1 restriction enzyme assay. Analysis showed no significant difference between PD patients and controls for genotype or allele frequencies of the ACT and UCH-L1 S18Y polymorphisms. UCH-L1 S18Y polymorphism carriers, however, were found to be significantly less frequent in early-onset PD patients with a reduced risk of 0.557 (95% C.I. = 0.314-0.985; P = 0.043). These data suggest that ACT polymorphism does not influence the risk for developing PD. UCH-L1 S18Y polymorphism, however, may be a weak protective factor against early-onset PD.

Adult↗

Simvastatin, an HMG-CoA reductase inhibitor, induces the synthesis and secretion of apolipoprotein AI in HepG2 cells and primary hamster hepatocytes.

Clinical studies have recently suggested that statin treatment may beneficially elevate plasma concentrations of high density lipoprotein (HDL)-cholesterol in patients with hyperlipidemia. Here, we have investigated the effect of a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on the synthesis and secretion of apolipoprotein AI (apoAI) in two model systems, HepG2 cells and primary hamster hepatocytes. Cultured cells were incubated with different doses of simvastatin (0.1-10 microM) for a period of 18 h. A dose-dependent increase in synthesis and secretion of apoAI was observed in both cell types. There was a significant increase in the synthesis of apoAI in HepG2 cells (44.3+/-12.1%), and hamster hepatocytes (212+/-2%) after treatment with 10 microM of the statin. The increase in apoAI synthesis appeared to result in a higher level of apoAI secreted into the culture media in both cell types (49.2+/-7.8% in HepG2, 197+/-0.2% in hamster hepatocytes). ApoAI mRNA levels were also significantly increased in both cell types in response to statin treatment. Control experiments with transferrin confirmed specificity of the effect on apoAI secretion. Analysis of a density fraction containing HDL particles in culture media revealed an increase in HDL-associated apoAI of 94.3+/-2.1% in HepG2 cells and 27.0+/-0.03% in hamster hepatocytes following 10 microM simvastatin-treatment. Comparative studies of simvastatin and lovastatin indicated a differential ability to induce apoAI synthesis and secretion, with simvastatin having a more significant effect. Thus, acute statin treatment of cultured hepatocytes (transformed as well as primary) resulted in a significant upregulation of apoAI mRNA and apoAI synthesis, causing oversecretion of apoAI and HDL extracellularly. The stimulatory effect on apoAI synthesis and secretion may thus explain the clinical observation of an elevated plasma HDL-cholesterol level in hyperlipidemic patients treated with certain statins.

Animals↗

Lamotrigine increases gene expression of GABA-A receptor beta3 subunit in primary cultured rat hippocampus cells.

To study the mechanism of action of the novel anticonvulsant and mood stabilizer lamotrigine, we used cDNA array to generate an expression profile of lamotrigine-regulated genes in primary cultured rat hippocampus cells. Gene expression was analyzed using Atlas Rat 1.2 Arrays of approximately 1200 genes. Total RNA was isolated from control and cells treated with lamotrigine at 0.1 mM for one week and reverse-transcribed to cDNA labeled with 32P-dATP. The cDNA probes were hybridized with two identical cDNA array membranes. After comparing hybridized signals between these two membranes, we found that chronic treatment with lamotrigine increased the expression of eight genes and decreased the expression of six genes. One of the upregulated genes is GABA-A receptor beta subunit. This increase in GABA-A receptor beta3 subunit expression was further confirmed by Northern blotting analysis. In situ hybridization revealed that chronic treatment with lamotrigine increased GABA-A receptor beta3 subunit gene expression in CA1, CA3 and dentate gyrus of rat hippocampus. Our findings indicate that lamotrigine may effect GABA-A receptor regulated functions in the central nervous system.

Animals↗

Regulation of ER stress proteins by valproate: therapeutic implications.

OBJECTIVES: This paper reviews results of our studies examining the regulation of endoplasmic reticulum (ER) stress proteins by valproate (VPA). and discusses the possible implications in bipolar disorder. METHODS: Our previous studies in the field are reviewed along with relevant literature. RESULTS: Using differential display PCR, we identified GRP78 as a VPA-regulated gene in rat cerebral cortex. We also showed that other members of the ER stress proteins family, GRP94 and calreticulin, are also upregulated by VPA. Immunohistochemistry identified that ER stress proteins are increased in frontal and parietal cortex, as well as regions of the hippocampus in rat brain following chronic treatment with VPA. CONCLUSIONS: Regulation of ER stress proteins by VPA may prove to be important to the mechanism of action of the drug. The neuroprotective role of these proteins may also prove to be involved in the pathophysiology of bipolar disorder.

Animals↗

Cone-beam volume CT breast imaging: feasibility study.

X-ray projection mammography, using a film/screen combination, or digital techniques, has proven to be the most effective imaging modality currently available for early detection of breast cancer. However, the inherent superimposition of structures makes a small carcinoma (a few millimeters in size) difficult to detect when it is occult or in dense breasts, leading to a high false-positive biopsy rate. Cone-beam x-ray-projection-based volume imaging using flat panel detectors (FPDs) may allow obtaining three-dimensional breast images, resulting in more accurate diagnosis of structures and patterns of lesions while eliminating the hard compression of breasts. This article presents a novel cone-beam volume computed tomographic breast imaging (CBVCTBI) technique based on the above techniques. Through a variety of computer simulations, the key issues of the system and imaging techniques were addressed, including the x-ray imaging geometry and corresponding reconstruction algorithms, x-ray characteristics of breast tissue and lesions, x-ray setting techniques, the absorbed dose estimation, and the quantitative effect of x-ray scattering on image quality. The preliminary simulation results support the proposed CVBCTBI modality for breast imaging in respect to its feasibility and practicability. The absorbed dose level is comparable to that of current mammography and will not be a prominent problem for this imaging technique. Compared to conventional mammography, the proposed imaging technique with isotropic spatial resolution will potentially provide significantly better low-contrast detectability of breast tumors and more accurate location of breast lesions.

Algorithms↗

[The relationship between body mass index, hypertension and all-cause mortality in the populaton over 55 year old in Beijing].

OBJECTIVE: To study the relationship between body mass index (BMI), hypertension and all-cause mortality in the elderly population in Beijing. METHODS: In 1992, a cohort of 3 257 people above 55 years old was selected from 3 different areas of Beijing, i.e. urban and suburbs (both plain and mountain areas). Information on physical condition, history of chronic diseases, self-perceived health, as well as smoking and drinking status was collected. Blood pressure, body height and weight were measured among 2 086 of 3 257 subjects. RESULTS: BMI was decreasing with age, while the prevalence of hypertension increased with age. Meanwhile the prevalence of hypertension increased with age as well as with BMI. There was a reverse relationship between BMI and all-cause mortality, i.e. the risk of death was 39.0% lower for those with BMI = 20.0 - 24.9 kg/m(2) (Hazard ratio: 0.61, 95% Confidence interval: 0.49 - 0.75) and 62% lower for those with BMI >/= 25.0 kg/m(2) (Hazard ratio: 0.38%, 95% Confidence interval: 0.29 - 0.49) than those with BMI < 20.0 kg/m(2). After controlling for age, gender, residential place, hypertension as well as self-perceive health status and cognition function, low BMI remained a significant and independent predictor to death. CONCLUSION: The distribution of BMI was different in elderly from the youth. The findings suggested that it was important to control the body weight among the elderly hypertensives.

Age Factors↗

[A new point mutation on exon 2 of parkin gene in Parkinson's disease].

OBJECTIVE: To detect the relationship between point mutations on exon 2 of parkin gene and sporadic early-onset Parkinson's disease. METHODS: The point mutations on exon 2 of parkin gene were detected using polymerase chain reaction(PCR), agarose electrophoresis, single strand conformation polymorphism(SSCP), DNA sequencing and analysis of restrict enzyme in DNA of 60 Parkinson's disease patients with an onset age under 50 and 120 normal controls. RESULTS: One homozygous mutation (G(237)-->C) on exon 2 was found by sequencing and verified by analysis of restrict enzyme, whereas no mutation was found in normal controls. CONCLUSION: Point mutations on exon 2 of parkin gene are likely to be related to sporadic early-onset Parkinson's disease.

Adult↗