Biomedical subjects

Yu Chen

Publications and source records attributed to Yu Chen.

At least 109 records · Page 6Linked to original sources

PubMed2006

Arsenic exposure from drinking-water and carotid artery intima-medial thickness in healthy young adults in Bangladesh.

Epidemiological studies have linked high levels (>200 microg/L) of chronic exposure to arsenic in drinking-water with elevated risks of several vascular diseases. In this pilot study, the association between low-level arsenic exposure and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy, normotensive, relatively young individuals (mean age 35 years) participating in the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh. Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75 mm). Although the differences in average arsenic exposure between the two groups were not statistically significant, the findings suggest a possible association between low-level arsenic exposure from drinking-water and carotid atherosclerosis, warranting the need for larger studies.

Adult↗

PubMed2005

Embryonic stem cells cultured in biodegradable scaffold repair infarcted myocardium in mice.

Our previous findings demonstrated that directly injecting embryonic stem cells (ESCs) into ischemic region of the heart improved cardiac function in animals with experimental myocardial infarction (MI). Tissue engineering with stem cells may provide tissue creation and repair. This study was designed to investigate the effectiveness of grafting of ESC-seeded biodegradable patch on infarcted heart. MI in mice was induced by ligation of the left coronary artery. Mouse ESCs were seeded on polyglycolic-acid (PGA) material patches. Three days after culture, an ESC-seeded patch was transplanted on the surface of ischemic and peri-ischemic myocardium. Eight weeks after MI operation and patch transplantation, hemodynamics and cardiac function were evaluated in four (sham-operated, MI, MI + cell-free patch, and MI + ESC-patch) groups of mice. The blood pressure and left ventricular function were significantly reduced in the MI animals. Compared with MI alone and MI + cell-free patch groups, the animals received MI + ESC-seeded patches significantly improved blood pressure and ventricular function. The survival rate of the MI mice grafted with MI + ESC-seeded patches was markedly higher than that in MI alone or MI + cell-free patch animals. GFP-positive tissue was detected in infarcted area with grafting of ESC-seeded patch, which suggests the survivors of ESCs and possible myocardial regeneration. Our data demonstrate that grafting of ESC-seeded bioabsorbable patch can repair infarcted myocardium and improve cardiac function in MI mice. This novel approach of combining stem cells and biodegradable materials may provide a therapeutic modality for repairing injured heart.

Absorbable Implants↗

PubMed2005

Celecoxib could reverse the hypoxia-induced Angiopoietin-2 upregulation in gastric cancer.

We investigated the potential effect of Cyclooxygenase-2 (Cox-2) on hypoxia-induced Angiopoietin-2 (Ang-2) expression in gastric cancer cells. Our results revealed that hypoxia augmented Cox-2 and Ang-2 expressions. Also, the hypoxia-induced Ang-2 could be mimicked by CoCl(2) treatment while genestein treatment could partially counteract the hypoxia-induced Ang-2 expression. Celecoxib but not Cox-1 inhibitor sc-560 reversed the hypoxia-induced Ang-2 expression, while this effect could be partially restored by addition of exogenous PGE2. Our findings suggest that the hypoxia-elevated Ang-2 expression in gastric cancer cells may be mediated by both Cox-2-derived PGE2 and HIF-1alpha pathways, while celecoxib could counteract the hypoxia-induced Ang-2 expression.

Angiopoietin-2↗

PubMed2005

Malignant hypertension in patients with idiopathic IgA nephropathy.

BACKGROUND: Idiopathic IgA nephropathy is one of the main causes of secondary malignant hypertension, especially in Chinese population. But little information has been available about malignant hypertension secondary to IgA nephropathy (IgANMHT). The purpose of this study is to evaluate the clinico-pathological features and outcomes of IgANMHT patients. METHODS: A case control retrospective study was carried out in 45 cases of IgANMHT and 26 cases of primary malignant hypertension (PMHT) diagnosed by renal biopsy. Their clinical features and pathological findings were investigated. Their average follow-up time was 37.4 months. Univariate analysis and multivariate Cox regression analysis were performed to select variables to predict renal survival. RESULTS: In the study, 1.2% of all the IgA nephropathy patients presented malignant hypertension. The amounts of urine protein excretion and red blood cells in IgANMHT patients were significantly higher, while the levels of serum creatinine were significantly lower than those in PMHT patients. The glomerular injury in IgANMHT patients was more severe than that in PMHT patients. The two characteristic vascular lesions of primary malignant hypertension, proliferative endoarteritis and fibrinoid necrosis were also found in IgANMHT patients but with less severity. Renal survival of IgANMHT patients was significantly higher than that of PMHT patients (p = 0.0043). However, log-rank test showed no significant difference in the renal survival between IgANMHT and PMHT patients with similar SCr levels at admission. Multivariate Cox regression analysis revealed that a high amount of urine protein excretion(> or =1.5 g/24 h), mesangial proliferation and elevated serum creatinine (> or =2 mg/dl) were statistically independent risk factors for renal prognosis (RR = 1.90, 2.72, 2.84, respectively). Conversely, strict blood pressure control had a favorable effect on renal prognosis. CONCLUSION: The clinico-pathological features and outcomes of IgANMHT patients were different from those of PMHT patients. The renal survival of IgANMHT patients was poor, which was determined by many factors. Early control of proteinuria, early monitoring and strictly controlling blood pressure may contribute to the renal survival.

Adolescent↗

PubMed2005

Hypertonic saline enhances neutrophil elastase release through activation of P2 and A3 receptors.

Hypertonic saline (HS) holds promise as a novel resuscitation fluid for the treatment of trauma patients because HS inhibits polymorphonuclear neutrophil (PMN) activation and thereby prevents host tissue damage and associated posttraumatic complications. However, depending on conditions of cell activation, HS can increase PMN degranulation, which could exacerbate tissue damage in trauma victims. The cellular mechanism by which HS increases degranulation is unknown. In the present study, we tested whether HS-induced ATP release from PMN and feedback via P1 and/or P2 receptors may be involved in the enhancement of degranulation by HS. We found that HS enhances elastase release and ERK and p38 MAPK activation when HS is added after activation of PMN with formyl peptide (fMLP) or phorbol ester (PMA). Agonists of P2 nucleotide and A3 adenosine receptors mimicked these enhancing effects of HS, whereas antagonists of A3 receptors or removal of extracellular ATP with apyrase diminished the response to HS. A1 adenosine receptor antagonists increased the enhancing effect of HS, whereas A1 receptor agonists inhibited elastase release. These data suggest that HS upregulates degranulation via ATP release and positive feedback through P2 and A3 receptors. We propose that these feedback mechanisms can serve as potential pharmacological targets to fine-tune the clinical effectiveness of HS resuscitation.

Adenosine Triphosphate↗

PubMed2005

[Effects of ethanol on the function of cultured hepatocytes].

OBJECTIVE: To develop a novel culture system to investigate the effects of ethanol on the function of cultured hepatocytes. METHODS: Sandwich configuration was used to culture hepatocytes and the effects of ethanol on functions of bile excretion and protein synthesis as well as the morphology of cultured hepatocytes were observed. RESULTS: Bile canaliculi-like structures decreased and anastomatic networks disappeared in ethanol treated hepatocytes. The ability for hepatocytes to internalize, metabolize and excrete compounds into bile was indicated by FDA metabolizing in the hepatocytes. In hepatocytes without ethanol, the bile excretion was showed clearly, but in ethanol-interfered hepatocytes, no bile excretion was observed. After ethanol was given, the level of protein secretion decreased and with the time going, it became lower and lower. CONCLUSION: Hepatocytes can be seriously damaged by ethanol. The study provides a new model to investigate the mechanism of some liver diseases caused by ethanol.

Animals↗

PubMed2005

A novel approach to structural alignment using realistic structural and environmental information.

In the era of structural genomics, it is necessary to generate accurate structural alignments in order to build good templates for homology modeling. Although a great number of structural alignment algorithms have been developed, most of them ignore intermolecular interactions during the alignment procedure. Therefore, structures in different oligomeric states are barely distinguishable, and it is very challenging to find correct alignment in coil regions. Here we present a novel approach to structural alignment using a clique finding algorithm and environmental information (SAUCE). In this approach, we build the alignment based on not only structural coordinate information but also realistic environmental information extracted from biological unit files provided by the Protein Data Bank (PDB). At first, we eliminate all environmentally unfavorable pairings of residues. Then we identify alignments in core regions via a maximal clique finding algorithm. Two extreme value distribution (EVD) form statistics have been developed to evaluate core region alignments. With an optional extension step, global alignment can be derived based on environment-based dynamic programming linking. We show that our method is able to differentiate three-dimensional structures in different oligomeric states, and is able to find flexible alignments between multidomain structures without predetermined hinge regions. The overall performance is also evaluated on a large scale by comparisons to current structural classification databases as well as to other alignment methods.

Algorithms↗

PubMed2005

Biochemical properties of C78SC96S rhFGF-2: a double point-mutated rhFGF-2 increases obviously its activity.

Fibroblast growth factor-2 (FGF-2) is a multifunctional polypeptide that affects many cellular functions and phenomena. The wild-type recombinant human fibroblast growth factor rhFGF-2(W) and the mutant C78SC96S rhFGF-2(M) were expressed in Escherichia coli and their products were purified. The results by the means of fluorescence spectroscopy and CD spectrums, suggested that due to its decreased hydrophobicity rhFGF-2 is not deposited as an inclusion body. The mitogenic activity of the expressed rhFGF-2(M) on 3T3 fibroblasts was shown to be 10-fold more than the expressed rhFGF-2(W) of which the biological activity was a little less than that of the standard rhbFGF(W), indicating that the increased biological activity was due to the change of its secondary structure, dimerization and affinity binding to FGF receptor (FGFR).

3T3 Cells↗

PubMed2005

Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs.

BACKGROUND/AIMS: We developed a bioartificial liver (BAL) based on a direct hemoperfusion typed nonwoven fabric bioreactor containing porcine hepatocytes. In this study, the efficacy of our BAL was evaluated with a pig fulminant hepatic failure (FHF) model. METHODS: FHF was induced with intravenous administration of D-galactosamine (1.3 g/kg) in each pig. Twelve hours post D-galactosamine injection, fifteen pigs were divided into: a BAL group (n = 5), in which pigs received the BAL treatment with 1.0 to 1.3 x 10(9) hepatocytes for 6 h, a sham BAL group (n = 5), in which pigs received the BAL treatment without hepatocytes, and a FHF group (n = 5), in which pigs only received intensive care. Parameters related to liver function and animal survival up to 168 h were determined. RESULTS: In the BAL group, blood ammonia and plasma lactate levels were lower, and serum glucose levels and Fischer index were higher than those in the other two groups. Survival time of pigs in the BAL group was significantly prolonged as compared with the sham BAL and the FHF group. CONCLUSIONS: The BAL based on a nonwoven fabric bioreactor containing porcine hepatocytes appears to be effective in the treatment of FHF in pigs.

Animals↗

PubMed2005

LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages.

Mutations in the human LIS1 gene cause the smooth brain disease classical lissencephaly. To understand the underlying mechanisms, we conducted in situ live cell imaging analysis of LIS1 function throughout the entire radial migration pathway. In utero electroporation of LIS1 small interference RNA and short hairpin dominant negative LIS1 and dynactin cDNAs caused a dramatic accumulation of multipolar progenitor cells within the subventricular zone of embryonic rat brains. This effect resulted from a complete failure in progression from the multipolar to the migratory bipolar state, as revealed by time-lapse analysis of brain slices. Surprisingly, interkinetic nuclear oscillations in the radial glial progenitors were also abolished, as were cell divisions at the ventricular surface. Those few bipolar cells that reached the intermediate zone also exhibited a complete block in somal translocation, although, remarkably, process extension persisted. Finally, axonal growth also ceased. These results identify multiple distinct and novel roles for LIS1 in nucleokinesis and process dynamics and suggest that nuclear position controls neural progenitor cell division.

Animals↗

PubMed2005

Small interfering RNA knocks down heat shock factor-1 (HSF-1) and exacerbates pro-inflammatory activation of NF-kappaB and AP-1 in vascular smooth muscle cells.

OBJECTIVES: Heat shock and elevated expression of heat shock proteins suppress activation of the pro-inflammatory transcription factor NF-kappaB. We hypothesized that knocking down the expression of heat shock factor-1 (HSF-1) with RNAi technology would exacerbate angiotensin (Ang) II-induced inflammatory injury in vascular smooth muscle cells (VSMC). METHODS: Rat aorta A10 cells and human intestinal smooth muscle cells were grown without transfection or with transfection with HSF-1 small interfering RNA (siRNA), or negative control siRNA. Cells were stimulated with Ang II (100 nM) to activate the NF-kappaB signaling pathway. RESULTS: HSF-1 siRNA significantly knocked down HSF-1 expression, and one of the downstream heat shock proteins (Hsp), Hsp27, in both cells lines. HSF-1 siRNA also affected cells stressed with heat shock or Ang II treatment. Ang II induced activation of NF-kappaB and AP-1 in untransfected VSMCs, however, Ang II induced significantly higher activities of these pro-inflammatory transcription factors in HSF-1 siRNA transfected cells. Control siRNA had no apparent effect on HSF-1 and Hsp27 expression and Ang II-induced NF-kappaB and AP-1 activation. CONCLUSIONS: These data indicate that the knock down of HSF-1 exacerbates Ang II-induced inflammation in VSMCs, and suggests that heat shock proteins protect against inflammatory injury by suppression of pro-inflammatory transcription factors such as NF-kappaB and AP-1.

Angiotensin II↗

PubMed2005

Monitoring dopamine release from single living vesicles with nanoelectrodes.

Carbon fiber nanoelectrodes (tip diameter = ca. 100 nm) have been first used to monitor real-time dopamine release from single living vesicles of single rat pheochromocytoma (PC12) cells. The experiments show that active and inactive release sites exist on the surface of cells, and the spatial distributions have been differentiated even in the same active release zone. It is first demonstrated that multiple vesicles can sequentially release dopamine at the same site of the cell surface, which possibly plays the main role in the dopamine release from PC12 cells.

Action Potentials↗

PubMed2005

Alpha-catenin expression is decreased in patients with gastric carcinoma.

AIM: To assess the expression of alpha-catenin in gastric carcinoma and to determine the role of alpha-catenin expression in gastric carcinogenesis. METHODS: alpha-catenin expression was assessed by semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining in 49 gastric carcinomas, 26 adjacent non-cancerous mucosae, and gastric biopsy specimens from 11 healthy controls. RESULTS: mRNA levels of alpha-catenin were reduced or absent in 34 of 49 (69%) gastric carcinoma tissues and in 5 of 26 (19%) tumor-free gastric mucosae of carcinoma patients, respectively. Of the carcinoma samples with altered alpha-catenin mRNA levels, alpha-catenin expression was negative in 20 and decreased in 14 cases. Up to 69% of tumors were stained abnormally for alpha-catenin. Of the 34 cases whose mRNA expression of alpha-catenin was reduced, 32 (94%) showed abnormal immunostaining patterns, while only 2 showed a normal alpha-catenin expression. The frequency of reduced expression of alpha-catenin mRNA was 14% in well-differentiated carcinomas, higher than that in poorly differentiated carcinomas (86%). A significant correlation was not shown between alpha-catenin expression and both depth of invasion and lymph node metastasis. Moreover, there was no statistical difference between loss or down-regulation of alpha-catenin mRNA and Helicobacter pylori (H. pylori) infection. CONCLUSION: Downregulation of alpha-catenin expression is common in gastric carcinoma, and alpha-catenin expression may be used as a differentiation marker. Downregulation of alpha-catenin expression may be an early event in tumorigenesis. Reduced alpha-catenin expression is not correlated with H. pylori infection.

Adult↗

PubMed2005

Specific inhibition of HIV-1 replication by short hairpin RNAs targeting human cyclin T1 without inducing apoptosis.

RNA interference (RNAi), a sequence-specific RNA degradation mechanism mediated by small interfering RNA (siRNA), can be used not only as a research tool but also as a therapeutic strategy for viral infection. We demonstrated that intracellular expression of short hairpin RNA (shRNA) targeting human cyclin T1 (hCycT1), a cellular factor essential for transcription of messenger and genomic RNAs from the long terminal repeat promoter of provirus of human immunodeficiency virus type 1 (HIV-1), could effectively suppress the replication of HIV-1. We also showed that downregulation of hCycT1 did not cause apoptotic cell death, therefore, targeting cellular factor hCycT1 by shRNAs may provide an attractive approach for genetic therapy of HIV-1 infection in the future.

Apoptosis↗

PubMed2005

{alpha}-Syntrophin regulates ARMS localization at the neuromuscular junction and enhances EphA4 signaling in an ARMS-dependent manner.

EphA4 signaling has recently been implicated in the regulation of synapse formation and plasticity. In this study, we show that ankyrin repeat-rich membrane spanning (ARMS; also known as a kinase D-interacting substrate of 220 kD), a substrate for ephrin and neurotrophin receptors, was expressed in developing muscle and was concentrated at the neuromuscular junction (NMJ). Using yeast two-hybrid screening, we identified a PDZ (PSD-95, Dlg, ZO-1) domain protein, alpha-syntrophin, as an ARMS-interacting protein in muscle. Overexpression of alpha-syntrophin induced ARMS clustering in a PDZ domain-dependent manner. Coexpression of ARMS enhanced EphA4 signaling, which was further augmented by the presence of alpha-syntrophin. Moreover, the ephrin-A1-induced tyrosine phosphorylation of EphA4 was reduced in C2C12 myotubes after the blockade of ARMS and alpha-syntrophin expression by RNA interference. Finally, alpha-syntrophin-null mice exhibited a disrupted localization of ARMS and EphA4 at the NMJ and a reduced expression of ARMS in muscle. Altogether, our findings suggest that ARMS may play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EphA4.

Animals↗

PubMed2005

RANTES gene single nucleotide polymorphisms and expression in patients with chronic hepatitis B virus infection.

BACKGROUND: Regulated on activation, normal T-cell expressed and secreted (RANTES) plays a critical role in T-lymphocyte activation and proliferation. The process is involved in both acute and chronic phases of inflammation. The present study was to ascertain the possible correlations between chronic hepatitis B virus (HBV) infection and the RANTES gene polymorphisms and their expression. METHODS: The study included 130 HBV negative healthy donors and 152 patients with chronic hepatitis B (CHB) virus infection. The polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLPs) were used to detect RANTES gene single nucleotide polymorphisms (SNPs). RANTES levels in the platelet depleted plasma were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: RANTES alleles -403G, -28C and In1.1T were the predominant alleles in the subjects studied. No significant correlation was found between CHB infection and the RANTES alleles, while a significant correlation was found between CHB infection and increased RANTES expression in platelet depleted plasma (P < 0.05). CONCLUSIONS: SNPs in RANTES gene do not affect chronic HBV infection or the outcome of interferon-alpha treatment in patients positive for HBV "e" antigen (HBeAg+). However, patients with CHB infection express the higher levels of plasma RANTES, which is thus associated with CHB infection.

Alleles↗

PubMed2005

Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis.

Recent studies point to important interactions between proinflammatory cytokines and neurohumoral mediators in heart failure. Here we investigate the influence of the beta-adrenergic system on cytokines and neurohumoral factors and the sequelae of viral myocarditis. In an experimental model with virus-infected BALB/c mice, we studied the acute and chronic effects of epinephrine and propranolol on myocardial morphology, cytokine gene expression, and survival. BALB/c mice were inoculated with the encephalomyocarditis virus (EMCV) or sham inoculated with saline and followed for 30 days. Epinephrine increased the severity of inflammatory cell infiltration and myocardial necrosis induced by EMCV. Gene expression of TNF-alpha, IL-6, and IL-10 was markedly enhanced by epinephrine in EMCV-inoculated mice. Survival rate after 30 days was reduced to 40% in epinephrine-treated EMCV-inoculated mice compared with 70% in untreated EMCV-inoculated mice (P < 0.05). Treatment with the beta-blocker propranolol significantly decreased mortality, myocardial necrosis, and infiltration of inflammatory cells in EMCV-inoculated mice. Propranolol also suppressed gene expression of TNF-alpha, IL-6, and IL-10. A single dose of epinephrine 120 days after EMCV inoculation caused sudden death in 70% of infected mice; propranolol significantly reduced incidence of death to 33%. These results indicate that acute and chronic stages of viral myocarditis are modulated by the beta-adrenergic system and its interactions with proinflammatory cytokines.

Acute Disease↗

PubMed2005

Candidate multi-peptide-vaccine against classical swine fever virus induced potent immunity with serological marker.

Our previous study proposed a protective multi-peptide-vaccine (MPV) with Freund's adjuvant against classical swine fever virus (CSFV). In this study, another candidate MPV, using aluminum adjuvant, was further examined. All immunized pigs kept healthy during the experimental period, while the control group rapidly showed clinical symptoms and died. Moreover, anti-sera from MPV-immunized pigs could interact with peptides involved in the MPV, in contrast to anti-sera from non-immunized or infected ones. This property permits MPV-immunized pigs to be easily differentiated from infected ones with simple serological method. Therefore, this new MPV is suitable to act as a candidate marker vaccine against CSFV.

Adjuvants, Immunologic↗