Search PubMed⌕ Search

Biomedical subjects

X Xin

Publications and source records attributed to X Xin.

At least 19 recordsLinked to original sources

Glucose-induced Akt1 activation mediates fibronectin synthesis in endothelial cells.

AIMS/HYPOTHESIS: Increased expression and decreased degradation of extracellular matrix (ECM) proteins are key features of chronic diabetic complications. Fibronectin, a predominant ECM protein, has been shown to be overexpressed in all target organs of diabetic complications and in endothelial cells cultured in high levels of glucose. The present study was designed to elucidate the role of protein kinase B (Akt/PKB) in glucose-induced fibronectin mRNA expression and protein production in vascular endothelial cells. METHODS: Human umbilical vein endothelial cells were cultured in the presence of high glucose to study Akt/PKB activation. The upstream and downstream mediators in the Akt/PKB pathway were also investigated using dominant negative transfections and specific inhibitors of signalling pathways. Cells were subjected to real time RT-PCR, western blotting, and confocal microscopy to assess Akt1/PKBalpha activation and fibronectin mRNA expression and protein production. To detect transcription factor activation, electrophoretic mobility shift assay was carried out. RESULTS: Our data demonstrate that fibronectin mRNA expression and protein production that are induced by high glucose are mediated via activation of Akt/PKB, which is modulated by mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase C. Glucose-induced fibronectin mRNA expression and protein production are also mediated by Akt1/PKBalpha-dependent activation of the transcription factors nuclear factor-kappaB and activating protein-1. CONCLUSIONS/INTERPRETATION: Our study provides insight into the mechanical basis of glucose-induced increases in fibronectin mRNA expression and protein production. High levels of glucose may increase fibronectin mRNA expression and protein production by activating Akt/PKB.

Cell Survival↗

Torsional vibrational modes of tryptophan studied by terahertz time-domain spectroscopy.

The low-frequency torsional modes, index of refraction, and absorption of a tryptophan film and pressed powders from 0.2 to 2.0 THz (6.6-66 cm(-1)) were measured by terahertz time-domain spectroscopy at room temperature. It was found that there were two dominated torsional vibrational modes at around 1.435 and 1.842 THz. The associated relaxation lifetimes ( approximately 1 ps) for these modes of the tryptophan molecule were measured. Using a density-functional calculation, the origins of the observed torsional vibrations were assigned to the chain and ring of the tryptophan molecule.

Coated Materials, Biocompatible↗

Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression.

AIMS: Dietary fatty acid profile, independent of caloric percent of fat, is a major regulator of body adiposity. This study examined the effects of dietary fat amount and types on fat storage and hypothalamic gene expression in the mouse model of chronic diet-induced obesity. METHODS: The dietary interventions were in twofold: (1) the obesity was induced by a 13-week obesogenic fat diet compared with a low-fat (LF) diet, and (2) the reversibility was tested by using high n-3 polyunsaturated fat (PUFA) and LF diets. Fifty-four C57Bl/6 mice were fed a high-fat (59% in kcal) diet for 13 weeks and then classified as diet-induced obese (DIO) or diet-resistant (DR) mice according to upper and lower tertiles of body weight gain. The DIO mice were then subdivided into three groups for a 6-week secondary dietary intervention. Two of the groups were switched to either a high n-3 PUFA (DIO-n3) or a low-fat (10% in kcal, DIO-LF) diet, whereas the third (controls) and DR mice continued on the initial high-fat diet. Food efficiency was calculated as weekly body weight gain per gram of food intake. RESULTS: After switching the DIO mice to the n-3 PUFA or LF diet, their body weights were reduced to the level of the DR and LF mice. The food efficiencies were, from the highest to lowest, in the order: DIO>LF>DR>DIO-LF>DIO-n3. Using quantitative in situ hybridization, we found that the DIO mice had higher levels of leptin receptor (LR, +290%, p<0.005) and neuropeptide Y (NPY, +25%, p<0.05) mRNA expression in the hypothalamic arcuate nucleus (Arc) than the DR mice, whereas the level of pro-opiomelanocortin (POMC) mRNA expression was significantly reduced (-45%, p<0.01). All effects that were essentially returned to DR levels by the change to the n-3 PUFA diet and, with the exception of a failure to normalize Arc NPY mRNA levels, by the change to LF diet. CONCLUSIONS: Taken together, the present results show that both change in level and quality of dietary fat can potently alter hypothalamic neuropeptide expression and result in effective amelioration of diet-induced obesity. Interestingly, the n-3 PUFA diet when fed to already obese mice produced a pattern of hypothalamic gene expression similar to that in obesity resistant (DR) mice. It remains to be determined if the effects of n-3 fatty acids on brain neuropeptide gene expression are direct or indirect.

Adipose Tissue↗

Prevalence of diabetes and impaired fasting glucose in the Chinese adult population: International Collaborative Study of Cardiovascular Disease in Asia (InterASIA).

AIMS/HYPOTHESIS: To estimate the prevalence of diagnosed and undiagnosed diabetes and impaired fasting glucose in the general adult population of China. METHODS: The International Collaborative Study of Cardiovascular Disease in ASIA, conducted from 2000 to 2001, included a nationally representative sample of 15 540 adults, aged 35 to 74 years. An overnight fasting blood specimen was collected to measure serum glucose and information on history of diabetes and use of hypoglycaemic medications was obtained by a standard questionnaire. Undiagnosed diabetes (fasting glucose > or =7.0 mmol/l) and impaired fasting glucose (6.1-6.9 mmol/l) were defined using the American Diabetes Association criteria. RESULTS: Prevalence of self-reported diagnosed diabetes, undiagnosed diabetes, and impaired fasting glucose in Chinese adults were 1.3%, 4.2%, and 7.3%, respectively. Overall, 5.2% or 12.7 million men and 5.8% or 13.3 million women in China aged 35 to 74 years had diabetes (self-reported diagnosis plus undiagnosed diabetes). The age-standardized prevalence of diabetes was higher in residents of northern compared to southern China (7.4% vs 5.4%, p<0.001) and in those living in urban compared to rural areas (7.8% vs 5.1%, p<0.001). CONCLUSIONS/INTERPRETATION: Our results show that the prevalence of diabetes in the adult population in China is much higher than previously reported. Three out of every four diabetes patients are undiagnosed, indicative of a lack of population-based screening programmmes and a relatively rapid and recent increase in incidence of diabetes. These results indicate that diabetes has become a major public health problem in China and underscore the need for national strategies aimed at prevention and treatment of diabetes.

Adult↗

[Job strain and hypertension risk in Capital Steel and Iron Company in Beijing].

OBJECTIVE: To assess the relation between the scales of Job Demand control Model (or "Job strain") and the prevalence of hypertension. METHODS: A standardized questionnaire base-line survey was conducted among 1,556 male and female employees aged 18-65 in two factories of the Capital Steel and Iron Company, Beijing, in 1997 to investigate the socio-demographic factors and job strain so as to identify the major risks of hypertension. RESULTS: The prevalence of hypertension increased from 6.5% to 21.2% with an age-adjusted relative prevalence ratio (95% CI) of 3.26 (2.30, 4.41) when the job strain pattern changed from high control and low demand to moderate control and moderate demand and further to low control and high demand among the male employees. After adjustment for confounding effects from age, education, body mass index, smoking, alcohol consumption, and physical activity, the odds ratio (95% CI) was attenuated to 2.31 (1.45, 3.81). Such a phenomenon was not typical among females. CONCLUSION: The risk of hypertension was elevated with the increase of job strain in men.

Adolescent↗

Hepatocyte growth factor enhances vascular endothelial growth factor-induced angiogenesis in vitro and in vivo.

Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis in both physiological and pathological processes. Hepatocyte growth factor (HGF) is a mesenchyme-derived mitogen that also stimulates cell migration, and branching and/or tubular morphogenesis of epithelial and endothelial cells. In the present study, we tested the hypothesis that simultaneous administration of HGF and VEGF would synergistically promote new blood vessel formation. HGF acted in concert with VEGF to promote human endothelial cell survival and tubulogenesis in 3-D type I collagen gels, a response that did not occur with either growth factor alone. The synergistic effects of VEGF and HGF on endothelial survival correlated with greatly augmented mRNA levels for the anti-apoptotic genes Bcl-2 and A1. Co-culture experiments with human neonatal dermal fibroblasts and human umbilical vein endothelial cells demonstrated that neonatal dermal fibroblasts, in combination with VEGF, stimulated human umbilical vein endothelial cells tubulogenesis through the paracrine secretion of HGF. Finally, in vivo experiments demonstrated that the combination of HGF and VEGF increased neovascularization in the rat corneal assay greater than either growth factor alone. We suggest that combination therapy using HGF and VEGF co-administration may provide a more effective strategy to achieve therapeutic angiogenesis.

Animals↗

Vibrational spectra and normal coordinate analysis of a weak ligand complex, Co(p-DMABA)2Cl2 x 2H2O.

The complex Co(p-DMABA)2Cl2 x 2H2O (p-dimethylaminobenzaldehyde, p-DMABA) was prepared from the solid-state reaction of a weak ligand p-DMABA and CoCl2 x 6H2O at lower heating temperature (60 degrees C). It is very difficult to obtain the title complex using solution reaction method, less than isolating single crystals. In order to determine the crystal structure of the title compound, we have to rely on the X-ray powder diffraction data. That is, the crystal structure can be solved directly from powder data, which crucial step is to constitute the structure model. Indirect spectroscopic methods, such as infrared and Raman spectroscopes, and further vibrational assignments made with the aid of normal coordinate calculations by using a modified Urey-Bradley force field, were analyzed to proposed molecular structure. One hundred and fifty-seven internal coordinates were established and 129 theoretical vibrational frequencies were calculated. An appropriate set of internal coordinates and force constants in the course of calculation were introduced, so that the calculated vibration frequencies are good agreement with the observed values. The average difference and the maximum deviation between theoretic and experimental frequencies are 2.44 and 8.0 cm(-1), respectively. Thus the normal coordinate analysis is a powerful tool to the molecular structure. Other structural and spectral properties are also discussed in this paper. The purpose of the present paper is to obtain a good structural model. This model was used as starting model for crystal structure determination from powder X-ray diffraction (XRD) data.

Crystallization↗

Novel polymorphisms in human macrophage inflammatory protein-1 alpha (MIP-1alpha) gene.

Human macrophage inflammatory protein-1 alpha (MIP-1alpha) is a chemotactic cytokine, which binds to macrophages, T cells, and B cells affecting their activation. We found novel polymorphisms at four sites within MIP-1alpha gene in Japanese population: C to T in exon 2; A to G in intron 2; C to G and A to G in exon 3. They occurred on the same allele. Although MIP-1alpha effectively suppresses the replication of HIV-1 in vitro, we observed no statistically significant difference in the allele frequency of this polymorphism between HIV-1-infected and uninfected individuals in Japanese population. Since an increased transcription level of MIP-1alpha has been reported to be associated with inflammatory diseases such as atopic dermatitis, we also investigated the frequency of these polymorphisms among patients with atopic dermatitis, HIV-1-infected individuals (with a normal IgE level), and healthy donors. A small increase in ratio of homozygotes to other genotypes was observed in patients with atopic dermatitis (P = 0.04).

Alleles↗

Leakage and aggregation of phospholipid vesicles induced by the BH3-only Bcl-2 family member, BID.

BID is a BH3 domain-only member of the Bcl-2 family that acts as an apoptotic agonist in programmed cell death. After cleavage by caspase-8, the N-terminal of BID (N-BID) stays in the cytosol while the C-terminal of BID (C-BID) translocates to mitochondria, leading to cytochrome c release in vivo and in vitro. We have previously reported that BID or truncated BID (tBID) can induce the release of entrapped trypsin and cytochrome c from large unilamellar vesicles (LUVs). Further studies have been performed and are presented here; the results demonstrate that C-BID, like BID and tBID, induces vesicle leakage, whereas N-BID or the BID mutants BID (D59A) and BID (G94E) fail to have any significant effects. The affinity of the above-mentioned proteins for soybean phospholipid LUVs (SLUVs) decreased in an order similar to their leakage-inducing capability: tBID > BID > BID (D59A), while N-BID and BID (G94E) were unable to bind to the vesicles at all. BID-induced leakage was dependent on the lipid composition of vesicles. Acidic phospholipid (e.g. phosphatidic acid or phosphatidylglycerol) was necessary for BID-induced leakage while the presence of phosphatidylethanolamine or cholesterol reduced the leakage. It was also found C-BID is better able to penetrate the soybean phospholipid monolayer than BID or tBID. A further finding was that tBID, but not full-length BID, could stimulate the aggregation of SLUVs. Finally, Bcl-x(L), an apoptotic antagonist in programmed cell death, can prevent the aggregation of LUVs induced by tBID, but not the release of entrapped trypsin. It is postulated that two separate domains of tBID are responsible for inducing leakage and aggregation of phospholipid vesicles.

BH3 Interacting Domain Death Agonist Protein↗

Insulin-like growth factor-I and Bcl-X(L) inhibit c-jun N-terminal kinase activation and rescue Schwann cells from apoptosis.

We previously reported that Schwann cells undergo apoptosis after serum withdrawal. Insulin-like growth factor-I, via phosphatidylinositol-3 kinase, inhibits caspase activation and rescues Schwann cells from serum withdrawal-induced apoptosis. In this study, we examined the role of c-jun N-terminal protein kinase (JNK) in Schwann cell apoptosis induced by serum withdrawal. Activation of both JNK1 and JNK2 was detected 1 h after serum withdrawal with the maximal level detected at 2 h. A dominant negative JNK mutant, JNK (APF), blocked JNK activation induced by serum withdrawal and Schwann cell apoptosis, suggesting JNK activation participates in Schwann cell apoptosis. Serum withdrawal-induced JNK activity was caspase dependent and inhibited by a caspase 3 inhibitor, Ac-DEVD-CHO. Because insulin-like growth factor-I and Bcl-X(L) are both Schwann cell survival factors, we tested their effects on JNK activation during apoptosis. Insulin-like growth factor-I treatment decreased both JNK1 and JNK2 activity induced by serum withdrawal. LY294002, a phosphatidylinositol-3 kinase inhibitor, blocked insulin-like growth factor-I inhibition on JNK activation, suggesting that phosphatidylinositol-3 kinase mediates the effects of insulin-like growth factor-I. Overexpression of Bcl-X(L) also resulted in less Schwann cell death and inhibition of JNK activation after serum withdrawal. Collectively, these results suggest JNK activation is involved in Schwann cell apoptosis induced by serum withdrawal. Insulin-like growth factor-I and Bcl family proteins rescue Schwann cells, at least in part, by inhibition of JNK activity.

Animals↗

Naturally occurring deletional mutation in the C-terminal cytoplasmic tail of CCR5 affects surface trafficking of CCR5.

CCR5 is an essential coreceptor for the cellular entry of R5 strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(-) is a single-nucleotide deletion mutation which is observed exclusively in Asians (M. A. Ansari-Lari, et al., Nat. Genet. 16:221-222, 1997). This mutant gene produces a CCR5 which lacks the entire C-terminal cytoplasmic tail. To assess the effect of CCR5-893(-) on HIV-1 infection, we generated a recombinant Sendai virus expressing the mutant CCR5 and compared its HIV-1 coreceptor activity with that of wild-type CCR5. Although the mutant CCR5 has intact extracellular domains, its coreceptor activity was much less than that of wild-type CCR5. Flow cytometric analyses and confocal microscopic observation of cells expressing the mutant CCR5 revealed that surface CCR5 levels were greatly reduced in these cells, while cytoplasmic CCR5 levels of the mutant CCR5 were comparable to that of the wild type. Peripheral blood CD4(+) T cells obtained from individuals heterozygous for this allele expressed very low levels of CCR5. These data suggest that the CCR5-893(-) mutation affects intracellular transport of CCR5 and raise the possibility that this mutation also affects HIV-1 transmission and disease progression.

Amino Acid Sequence↗

Vascular endothelial cell growth factor-driven endothelial tube formation is mediated by vascular endothelial cell growth factor receptor-2, a kinase insert domain-containing receptor.

Vascular endothelial cell growth factor (VEGF) binds to 2 related receptor tyrosine kinases, known as kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase (Flt-1). The KDR has been shown to mediate VEGF-stimulated endothelial cell mitogenesis, migration, and permeability. The Flt-1 receptor has been suggested to mediate VEGF-stimulated endothelial branching morphogenesis, a process whereby endothelial cells, in the presence of a 3D milieu composed of extracellular matrix components and a mixture of growth factors, undergo a morphological transition into a tubular network with many lumina. In the present study, we have used 2 independent endothelial cell tube formation models and highly selective VEGF mutants for the KDR and Flt-1 receptors. We demonstrate that KDR, not Flt-1, stimulation is responsible for the induction of endothelial tubulogenesis. In addition, we demonstrate a modulatory role for Flt-1 in VEGF-mediated tube formation. We also report that VEGF-driven endothelial tube formation is inhibited by selective inhibitors of mitogen-activated protein kinase activation and p38 protein kinase.

Blood Vessels↗

Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials.

Alcohol drinking has been associated with increased blood pressure in epidemiological studies. We conducted a meta-analysis of randomized controlled trials to assess the effects of alcohol reduction on blood pressure. We included 15 randomized control trials (total of 2234 participants) published before June 1999 in which alcohol reduction was the only intervention difference between active and control treatment groups. Using a standard protocol, information on sample size, participant characteristics, study design, intervention methods, duration, and treatment results was abstracted independently by 3 investigators. By means of a fixed-effects model, findings from individual trials were pooled after results for each trial were weighted by the inverse of its variance. Overall, alcohol reduction was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressures of -3.31 mm Hg (-2.52 to -4.10 mm Hg) and -2.04 mm Hg (-1.49 to -2.58 mm Hg), respectively. A dose-response relationship was observed between mean percentage of alcohol reduction and mean blood pressure reduction. Effects of intervention were enhanced in those with higher baseline blood pressure. Our study suggests that alcohol reduction should be recommended as an important component of lifestyle modification for the prevention and treatment of hypertension among heavy drinkers.

Adult↗

Expression of alpha-adrenoceptor subtypes by smooth muscle cells and adventitial fibroblasts in rat aorta and in cell culture.

Previous radioligand binding reports of vascular alpha-adrenoceptor (AR) density have been limited to total alpha1- or alpha2-ARs. Studies using whole blood vessel homogenates have not differentiated among receptor or mRNA expression by medial smooth muscle cells (SMCs) versus adventitial fibroblasts (AFBs). Therefore, we used quantitative reverse transcription-polymerase chain reaction and radioligand binding to measure alpha-AR subtypes in media, adventitia, and cultured SMCs and AFBs from rat aorta. Both media and adventitia expressed alpha1A-, alpha1B-, alpha1D-, and alpha2D-AR mRNAs, but in markedly different abundances. Total alpha1-AR density was the same for media and adventitia (Bmax = 101 +/- 10 versus 96 +/- 16 fmol/mg of protein). However, densities for alpha1A-, alpha1B-, and alpha1D-AR subtypes in media were 19 +/- 2, 26 +/- 4, and 55 +/- 2%, and in adventitia were 44 +/- 3, 37 +/- 5, and 19 +/- 2%. No alpha2B- or alpha2C-AR transcripts were detected in either layer or in cultured SMCs or AFBs. Total alpha1-AR densities in cultured SMCs and AFBs (Bmax = 111 +/- 4 and 48 +/- 6 fmol/mg of protein, respectively) were similar to media and adventitia, with alpha1B- and alpha1D-AR transcript levels and receptors largely sustained. However, alpha1A- and alpha2D-AR expression in cultured SMCs and AFBs was strongly reduced, compared with media and adventitia, an effect not prevented by 30 different culture conditions. Like SMCs, exposure of AFBs to norepinephrine induced protein synthesis and proliferation of AFBs. This is the first study to quantitate alpha-AR subtype expression in media and adventitia and in cultured SMCs and AFBs. In addition, we report the intriguing finding that AFBs express alpha1-ARs in similar abundance as medial SMCs and that norepinephrine induced them to proliferate.

Adrenergic alpha-Agonists↗

[Morphological changes and quantitative DNA analysis of Schwann cells in peripheral nerves after high voltage electrical injury].

OBJECTIVE: To explore the characteristics and the mechanism of the injury of Schwann cells and nerve fibres of the peripheral nerves inflicted by high voltage electricity. METHODS: Rabbits injured by high voltage electricity were employed as the model. Thirty rabbits were randomly divided into control (9) and experimental (21) groups. The dynamic quantitative DNA analysis and the change of the morphology and structure of the sciatic nerve were observed with LM and EM on 0, 3, 7, 10, 14 and 21 postburn days (PBDs), respectively. RESULTS: There was continuous degeneration of the axon and medullary sheath of sciatic nerve tissue and its neogenesis was inhibited. The DNA synthesis in Schwann cell initiated on 3 postburn day (PBD). The distribution of the current was heterogeneous on the cross section of peripheral nerve fibres. CONCLUSION: The obvious features of peripheral nerve injured by high voltage electricity included delayed initiation of the DNA synthesis of Schwann cell and the secondary necrosis and inhibition of neogenesis process of Schwann cell.

Animals↗

[Detecting human papillomavirus type 6/11 with fluorescence quantitative PCR].

BACKGROUND: To study the human paillomavirus type 6/11 (HPV6/11) infectious status of patients with vaginitis. METHODS: Fluorescence quantitative PCR (FQ-PCR) was used to measue HPV 6/11 DNA in 129 secretion samples. RESULTS: 47 samples were positive with a positive rate of 36.43%; 39 of 47 samples had over 105 copy/ml of the virus. CONCLUSIONS: Middle and old aged patients do not go to hospital until their virus infectious state becomes serious. FQ-PCR is suitable for clinical application because of its high sensitivity, rapidity and accuracy.

Adult↗

[Significance and expression of transforming growth factor beta in human nasal polyp tissue].

OBJECTIVE: To explore the pathogenesis of nasal polyposis and the expression of transforming growth factor beta (TGF-beta) in human inflammatory nasal polyps. METHODS: TGF-beta 1-3 in nasal polyp tissues and inferior turbinate mucosa of twenty-five polyposis patients were detected with immunohistochemistry alkaline phosphatase and anti-alkaline phosphatase (APAAP) method. The inferior turbinate mucosa of eight healthy volunteers were selected as control. Six polyp tissues were estimated with double immunolabeling and Western-blot analysis to compare the characterization of the TGF-beta isoforms expression and the proportion of macrophages and eosinophils in nasal polyp tissues. RESULTS: The expression of TGF-beta 1-3 in nasal polyps was significantly higher than that in nasal mucosa and indetecable in nasal mucosa from healthy volunteers; TGF-beta 1 was the main isoform detected in nasal polyps; TGF-beta positively was accompanied by numerous macrophage and eosinophil infiltration. CONCLUSIONS: TGF-beta mainly TGF-beta 1 is strongly expressed in nasal polyps and its mucosa, where it could be produced by macrophages and eosinophils. TGF-beta could induce modification of epithelium and connective tissue and therefore be involved in the pathogenesis of nasal polyposis.

Eosinophils↗