Search PubMed⌕ Search

Biomedical subjects

X Wang

Publications and source records attributed to X Wang.

At least 55 records · Page 3Linked to original sources
PubMed2006

Geographical clustering of pancreatic cancers in the Northeast Nile Delta region of Egypt.

The northeast Nile Delta, Egypt's most polluted region, appears to have a high incidence of pancreatic cancer. We sought to determine whether there is any geographic clustering of pancreatic cancers there and, if so, whether such clustering might be associated with environmental pollution. Using data from the medical records of the Gastrointestinal Surgical Center of Mansoura University in the Dakahleia Province of Egypt and detailed geographical maps of the northeast Nile Delta region, we plotted the residences of all 373 patients who had pancreatic cancer diagnosed between 1995 and 2000. The study region has 15 administrative districts, whose centroid coordinates, population, and number of pancreatic cancer patients were determined for this study. Monte Carlo simulation identified statistically significant clustering of pancreatic cancer in five subdivisions located near the Nile River and Delta plains. This clustering was independent of population size and formed two larger clusters. When data were analyzed by sex, clustering of pancreatic cancer was observed in the same five subdivisions for men but only two subdivisions showed clustering for women. Together, our data suggest that there is clustering of pancreatic cancer cases in the northeast Nile delta region and that this clustering may be related to water pollution. Our data also warrant future studies of the association between water pollution and pancreatic cancer in the region.

Aged↗
PubMed2006

BubR1 is involved in regulation of DNA damage responses.

Defective mitotic spindles or an impaired spindle-kinetochore interaction activates the spindle checkpoint. We have previously shown that BubR1 haplo-insufficiency results in enhanced genomic instability and tumorigenesis in mice. Here we report that BubR1 deficiency also leads to a compromised response to DNA damage. Following treatment with doxorubicin, BubR1(+/-) murine fibroblast cells (MEF) were defective in undergoing G(2)/M arrest. Thus, whereas in the presence of DNA damage BubR1(+/+) MEF cells remained arrested in mitosis, BubR1(+/-) MEFs rapidly exited from mitosis and divided. The impaired mitotic arrest of BubR1(+/-) MEFs was associated with low levels of phospho-histone H2AX, p53, and p21 after DNA damage caused by treatment with both doxorubicin and ultraviolet light (UV). The impaired expression of p53 and p21 was also confirmed in human cell lines with BubR1 knockdown via RNA interference. Affinity pull-down coupled with mass spectrometry identified Poly(ADP-ribose) polymerase 1 (PARP-1) as one of the proteins interacting with BubR1. Reciprocal co-immunoprecipitation analysis confirmed the physical interaction between BubR1 and PARP-1. Our further study revealed that the ability of retaining intact PARP-1 or its cleavage product p89 was compromised in BubR1(+/-) MEFs upon treatment with doxorubicin or UV. Given that PARP-1 mediates DNA damage responses and regulates the activity of p53, our studies suggest that there exists a cross-talk between the spindle checkpoint and the DNA damage checkpoint and that BubR1 may play an important role in mediating the cross-talk.

Animals↗
PubMed2006

Common polymorphisms in SOCS3 are not associated with body weight, insulin sensitivity or lipid profile in normal female twins.

AIMS/HYPOTHESIS: Inhibition of signal transduction by suppressor of cytokine signalling-3 (SOCS-3) potentially influences resistance to insulin and leptin. The aim of this study was to test the association between three single-nucleotide polymorphisms (SNPs) representative of common linkage disequilibrium clusters in SOCS3 (rs4969169, rs12953258 and rs8064821) and obesity measures, insulin sensitivity measures and serum lipids in the general population. METHODS: The three SNPs, which had rare allele frequencies >0.06, were genotyped in 2,777 female twins of European extraction (mean age 47.4+/-12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). RESULTS: Minor allele frequencies were as follows: rs4969169=0.067, rs12953258=0.097 and rs8064821=0.101. Individual SOCS3 SNPs were not associated with general or central obesity, or with two indices of insulin sensitivity (homeostasis model assessment and insulin sensitivity measure). CONCLUSIONS/INTERPRETATION: The results do not indicate that any of the three SNPs studied are associated with obesity, insulin measures or lipid measures.

Adult↗
PubMed2006

Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase.

Glycogen-synthase kinase-3 (GSK-3) and extracellular signal-regulated kinase (ERK) are critical downstream signaling proteins for the PI3-kinase/Akt and Ras/Raf/MEK-1 pathway, respectively, and regulate diverse cellular processes including embryonic development, cell differentiation and apoptosis. Here, we show that inhibition of GSK-3 using GSK-3 inhibitors or RNA interference (RNAi) significantly induced the phosphorylation of ERK1/2 in human colon cancer cell lines HT29 and Caco-2. Pretreatment with the PKCdelta-selective inhibitor rottlerin or transfection with PKCdelta siRNA attenuated the phosphorylation of ERK1/2 induced by the GSK-3 inhibitor SB-216763 and, furthermore, treatment with SB-216763 or transfection with GSK-3alpha and GSK-3beta siRNA increased PKCdelta activity, thus identifying a role for PKCdelta in the induction of ERK1/2 phosphorylation by GSK-3 inhibition. Treatment with SB-216763 increased expression of cyclooxygenase-2 (COX-2) and IL-8, which are downstream targets of ERK1/2 activation; this induction was abolished by MEK/ERK inhibition, suggesting GSK-3 inhibition induced COX-2 and IL-8 through ERK1/2 activation. The transcriptional induction of COX-2 and IL-8 by GSK-3 inhibition was further demonstrated by the increased COX-2 and IL-8 promoter activity after SB-216763 treatment or transfection with GSK-3alpha or GSK-3beta siRNA. Importantly, our findings identify GSK-3, acting through PKCdelta, as a negative regulator of ERK1/2, thus revealing a novel crosstalk mechanism between these critical signaling pathways.

Apoptosis↗
PubMed2006

Intramedullary cervical tuberculoma.

STUDY DESIGN: Case report. OBJECTIVE: To report a rare lesion of intramedullary cervical tuberculoma. SETTING: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, The People's Republic of China. CASE REPORT: A 15-year-old boy presented with pain in the neck and shoulder. Examination showed mild left hemiplegia and pinprink hyperalgesia on the left side up to C3 level. Chest X-ray and CT scan showed patch and dot lesions indicating old tuberculous lesions and MRI showed a ring-enhancing intramedullary lesion at C3/4 level. Tuberculoma resection and antituberculous therapy was given. There was satisfactory recovery clinically. CONCLUSION: Intramedullary cervical tuberculoma is a rare, coexisting systemic tuberculosis and MRI scan helps in obtaining a correct diagnosis; combining surgery with anti-tuberculosis therapy is the treatment of choice.

Adolescent↗
PubMed2006

Low molecular weight polyethylenimines linked by beta-cyclodextrin for gene transfer into the nervous system.

BACKGROUND: Polyethylenimines (PEIs) with high molecular weights are effective nonviral gene delivery vectors. However, the in vivo use of these PEIs can be hampered by their cellular toxicity. In the present study we developed and tested a new PEI polymer synthesized by linking less toxic, low molecular weight (MW) PEIs with a commonly used, biocompatible drug carrier, beta-cyclodextrin (CyD). METHODS AND RESULTS: The terminal CyD hydroxyl groups were activated by 1,1'-carbonyldiimidazole. Each activated CyD then linked two branched PEI molecules with MW of 600 Da to form a CyD-containing polymer with MW of 61 kDa, in which CyD served as a part of the backbone. The PEI-CyD polymer developed was soluble in water and biodegradable. In cell viability assays with sensitive neurons, the polymer performed similarly to low-MW PEIs and displayed much lower cellular cytotoxicity compared to PEI 25 kDa. The gene delivery efficiency of the polymer was comparable to, and at higher polymer/DNA ratios even higher than, that offered by PEI 25 kDa in neural cells. Attractively, intrathecal injection of plasmid DNA complexed by the polymer into the rat spinal cord provided levels of gene expression close to that offered by PEI 25 kDa. CONCLUSIONS: The polymer reported in the current study displayed improved biocompatibility over non-degradable PEI 25 kDa and mediated gene transfection in cultured neurons and in the central nervous system effectively. The new polymer would be worth exploring further as an in vivo delivery system of therapeutic genetic materials for gene therapy of neurological disorders.

Animals↗
PubMed2006

Role of enteral nutrition supplemented with ebselen and EHEC in pancreatitis-associated multiple organ dysfunction in rats.

OBJECTIVES: To investigate potential effects of ebselen and ethylhydroxyethyl cellulose (EHEC) on the acute phase responses and the severity of multiple organ dysfunction associated with acute pancreatitis. METHODS: Acute pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate. The increase of total protein content in the BALF was used as an indication for acute lung injury, plasma amylase for pancreatic damage, plasma bilirubin for acute liver dysfunction, and plasma creatinine for acute kidney dysfunction. Levels of interleukin (IL)-6, macrophage inflammatory protein (MIP)-2 in the BALF were determined by ELISA. RESULTS: There was a dose-related tendency for ebselen or EHEC alone to prevent organ dysfunction and reduce elevated plasma levels of IL-6 and ICAM-1 expression on circulating leukocytes 12 h after AP induction. The combination of ebselen and EHEC significantly prevented pancreatitis-induced multiple organ injury, IL-6 production and ICAM-1 expression in rats and exhibited better effects than either monocompound alone. CONCLUSION: The combination of ebselen and EHEC may be a new potential for treatment of acute severe pancreatitis.

Amylases↗
PubMed2006

Anti-inflammatory effects of inhaled nitric oxide are optimized at lower oxygen concentration in experimental Klebsiella pneumoniae pneumonia.

OBJECTIVE AND DESIGN: To evaluate whether antiinflammatory effects of inhaled nitric oxide (NO) in experimental Klebsiella pneumoniae pneumonia may be affected by oxygen levels in association with cytokine response and NO synthase (NOS) activity. SUBJECTS AND TREATMENT: Healthy adult rats were intratracheally instilled with live Klebsiella pneumoniae to induce pneumonia (P) or with sterile saline as a control (C) group. Group C was allocated to room air (CA) and inhaled NO (CNO, NO = 20 parts per million) groups. Group P was divided into 6 groups (n = 8 - 10) exposed to room air (PA), inhaled NO (PNO), low oxygen (40%, PLO), inhaled NO and low oxygen (PLONO), high oxygen (100%, PHO), and inhaled NO and high oxygen (98%, PHONO). After 24 h exposure, intraalveolar cells, expression of proinflammatory cytokines, nuclear transcription factor (NF-kappaB), myeloperoxidase (MPO) and NOS activities, characteristic of lung inflammatory mechanisms, were measured. RESULTS: All the pneumonia groups had pneumonia whereas CA and CNO had no or mild lung inflammation. Compared to the PA, significantly decreased recruitment of alveolar neutrophils was found in the PNO, along with lower NF-kappaB and MPO activity, tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1). Similar trends were found between the PLONO and PLO in alleviation of lung inflammation. However, PHONO significantly enhanced recruitment of alveolar neutrophils and pulmonary MPO activity associated with increased TNF-alpha. Inhaled NO improved bacterial clearance, reduced total proteins in alveoli, and ICAM-1 expression irrespective of oxygen levels. Inhaled NO and/or low and high oxygen partially restored constitutive NOS activity whereas high oxygen or together with inhaled NO depressed inducible NOS activity. CONCLUSIONS: The overall beneficial effects of inhaled NO in anti-inflammation in the mature lungs with K. pneumoniae pneumonia are in favor of a combination with lower level of oxygen, which warrants clinical verification in the treatment of lung inflammatory injury.

Animals↗
PubMed2006

Impact of biofilm matrix components on interaction of commensal Escherichia coli with the gastrointestinal cell line HT-29.

Commensal Escherichia coli form biofilms at body temperature by expressing the extracellular matrix components curli fimbriae and cellulose. The role of curli fimbriae and cellulose in the interaction of commensal E. coli with the intestinal epithelial cell line HT-29 was investigated. Expression of curli fimbriae by the typical commensal isolate E. coli TOB1 caused adherence and internalization of the bacteria and triggered IL-8 production in HT-29 cells. In particular, induction of IL-8 production was complex and involved curli-bound flagellin. While cellulose alone had no effect on the interaction of TOB1 with HT-29 cells, co-expression of cellulose with curli fimbriae decreased adherence to, internalization and IL-8 induction of HT-29 cells. Investigation of a panel of commensal isolates showed a partial correlation between expression of curli fimbriae and enhanced internalization and IL-8 production. In addition, a high immunostimulatory flagellin was identified. Thus, the consequences of expression of extracellular matrix components on commensal bacterial-host interactions are complex.

Adhesins, Bacterial↗
PubMed2006

The possible study of HuaXi-1 solution for all intra-abdominal organ preservation: a study in rats.

OBJECTIVE: University of Wisconsin (UW) solution continues to be the most commonly used solution for intra-abdominal organs. However, it is expensive. Therefore, we have formulated HuaXi-1 (HX-1) solution. The aim of this research was to assess the effect of HX-1 solution compared to UW, Collins 2, and hypertonic citrate solutions on intra-abdominal organs. METHODS: The effects of HX-1 solution for all intra-abdominal organ preservation were studied in a noncirculated, isolated, perfused rat liver model, in rat pancreas isografts in diabetic rats, and in a kidney autotransplant model. The effects were investigated by measuring hepatic tissue water content, sinusoidal lining cell mortality, Krebs-Henseleits perfusate, aspartate aminotransferase, the number of livers secreting bile during isolated perfusion, blood glucose, glucose tolerance tests, serum insulin of the rat pancreas-transplant recipients, the maximum serum creatinine levels, kidney graft survival rates, and observing the morphological changes in liver, pancreas, and kidneys. RESULTS: HX-1 solution preserved rat liver well for 24 hours as effectively as UW, rat pancreas as well for 48 hours, and dog kidney as well for 72 hours. CONCLUSION: The experimental findings indicated that HX-1 solution was effective to preserve all intra-abdominal organs; it may simplify cold storage of organs for transplantation.

Abdomen↗
PubMed2006

Immunological advantage on small bowel graft induced by simultaneously transplanted liver in porcine auxiliary liver/small bowel transplantation.

BACKGROUND: We developed a new porcine model for auxiliary liver/small bowel transplantation (LSBT). The possible immunological advantage on small bowel graft induced by simultaneously transplanted liver in the large animal was assessed. METHODS: Thirty outbreed long-white pigs were randomized into two groups. Group A animals received LSBT without immunosuppressive treatment (n = 10). Group B animals had segmental small bowel allotransplantation without immunosuppressive treatment (n = 10). The postoperative survival time, initial acute rejection time, and pathological rejection scores were analyzed. RESULTS: There was no remarkable difference in survival time between groups A and B (10.33 days vs 12.89 days, P > .05), but the initial time of acute rejection in intestinal grafts in group A was obviously delayed when compared to group B (8.22 days vs 4.33 days, P < .05), and the rejection scores in group A were remarkably lower than those of group B (0 vs 0.44 on postoperative day (POD) 3, P < .05; 0.22 vs 1.78 on POD 5, P < .05; 1.11 vs 2.56 on POD 7, P < .05). CONCLUSIONS: An immunological advantage on intestinal graft can be induced by simultaneously transplanted liver in auxiliary LSBT. Compared to isolated segmental small bowel allotransplantation, the intestinal graft in LSBT has a delayed initial time of acute rejection and lower acute rejection scores. The liver graft may reduce the risk of intestinal rejection and thus protect the bowel graft.

Acute Disease↗
PubMed2006

Expression of smoothelin in the normal and the overactive human bladder.

PURPOSE: We established the expression pattern of smoothelin, a marker protein for contractile smooth muscle cells, in the human detrusor and investigated its possible impact on bladder overactivity. MATERIALS AND METHODS: Detrusor samples of 13 overactive bladders (sensory urge and detrusor instability) were obtained before botulinum toxin injection and compared to those of 8 normally contractile, nonobstructed bladders obtained during radical cystectomy. Smoothelin mRNA expression patterns were investigated by Northern blot and variant specific reverse transcriptase-polymerase chain reaction as well as by quantitative reverse transcriptase-polymerase chain reaction on laser capture, microdissected smooth muscle. At the protein level smoothelin was investigated by standard and quantitative immunohistochemistry. RESULTS: The bladder muscularis expressed vascular and visceral smoothelin isoforms, and 2 of the known splice variants. In the smooth muscle of patients with detrusor instability and sensory urge a significant 2.4 and 2.2-fold increase, respectively, in smoothelin variant 1 mRNA was observed in comparison to that of normal controls. Analyses at the smoothelin protein level confirmed significant up-regulation in these bladder dysfunctions by a factor of 2.3 and 1.8, respectively. No significant difference in smoothelin expression was observed between detrusor instability and sensory urge. CONCLUSIONS: Increased expression of smoothelin in patients with detrusor instability and sensory urge implies that the etiology of these dysfunctions includes changes in myogenic parameters. In addition, our data support the new classification of the International Continence Society for overactive bladder proposing that sensory urge and detrusor instability represent a single clinical entity.

Cytoskeletal Proteins↗
PubMed2006

Coaxial electrospinning of (fluorescein isothiocyanate-conjugated bovine serum albumin)-encapsulated poly(epsilon-caprolactone) nanofibers for sustained release.

As an aim toward developing biologically mimetic and functional nanofiber-based tissue engineering scaffolds, we demonstrated the encapsulation of a model protein, fluorescein isothiocyanate-conjugated bovine serum albumin (fitcBSA), along with a water-soluble polymer, poly(ethylene glycol) (PEG), within the biodegradable poly(epsilon-caprolactone) (PCL) nanofibers using a coaxial electrospinning technique. By variation of the inner flow rates from 0.2 to 0.6 mL/h with a constant outer flow rate of 1.8 mL/h, fitcBSA loadings of 0.85-2.17 mg/g of nanofibrous membranes were prepared. Variation of flow rates also resulted in increases of fiber sizes from ca. 270 nm to 380 nm. The encapsulation of fitcBSA/PEG within PCL was subsequently characterized by laser confocal scanning microscopy, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) analysis. In vitro release studies were conducted to evaluate sustained release potential of the core-sheath-structured composite nanofiber PCL-r-fitcBSA/PEG. As a negative control, composite nanofiber PCL/fitcBSA/PEG blend was prepared from a normal electrospinning method. It was found that core-sheath nanofibers PCL-r-fitcBSA/PEG pronouncedly alleviated the initial burst release for higher protein loading and gave better sustainability compared to that of PCL/fitcBSA/PEG nanofibers. The present study would provide a basis for further design and optimization of processing conditions to control the nanostructure of core-sheath composite nanofibers and ultimately achieve desired release kinetics of bioactive proteins (e.g., growth factors) for practical tissue engineering applications.

Animals↗
PubMed2006

Tamoxifen-regulated adenoviral E1A chimeras for the control of tumor selective oncolytic adenovirus replication in vitro and in vivo.

Pharmacological control is a desirable safety feature of oncolytic adenoviruses (oAdV). It has recently been shown that oAdV replication may be controlled by drug-dependent transcriptional regulation of E1A expression. Here, we present a novel concept that relies on tamoxifen-dependent regulation of E1A activity through functional linkage to the mutated hormone-binding domain of the murine estrogen receptor (Mer). Four different E1A-Mer chimeras (ME, EM, E(DeltaNLS)M, MEM) were constructed and inserted into the adenoviral genome under control of a lung-specific surfactant protein B promoter. The highest degree of regulation in vitro was seen for the corresponding oAdVs Ad.E(DeltaNLS)M and Ad.MEM, which exhibited an up to 100-fold higher oAdV replication in the presence as compared with the absence of 4-OH-tamoxifen. Moreover, destruction of nontarget cells was six- and 13-fold reduced for Ad.E(DeltaNLS)M and Ad.MEM, respectively, as compared with Ad.E. Further investigations supported tamoxifen-dependent regulation of Ad.E(DeltaNLS)M and Ad.MEM in vivo. Induction of Ad.E(DeltaNLS)M inhibited growth of H441 lung tumors as efficient as a control oAdV expressing E1A. E(DeltaNLS)M and the MEM chimeras can be easily inserted into a single vector genome, which extends their application to existing oAdVs and strongly facilitates in vivo application.

Adenocarcinoma↗
PubMed2006

Gender-related differences in advanced glycation endproducts, oxidative stress markers and nitric oxide synthases in rats.

An age- and blood pressure-associated increase in methylglyoxal (MG) and MG-induced advanced glycation endproducts (AGEs), including N(epsilon)-carboxyethyl-lysine (CEL) and N(epsilon)-carboxymethyl-lysine (CML), in the kidney of spontaneously hypertensive rats (SHR) has been shown. In the present study, gender-related changes in AGEs and nitric oxide synthase were investigated in Sprague-Dawley (SD) and stroke-prone SHR (SHRsp) rats. Immunohistochemical analyses were conducted on kidneys from 24-week-old male and female SD rats as well as SHRsp. The systolic blood pressure of SHRsp was significantly higher than that of SD rats. Male SD rats had more intense kidney staining for CEL than female SD rats. Both male and female SHRsp had more marked CEL and CML staining localized to kidney tubules, as opposed to SD rats. Female rats showed more staining in glomerular vessels than male rats in both SD and SHRsp. Nuclei containing nuclear factor-kappaB (NF-kappaB) p65 and activated macrophages were seen in the kidney from SHRsp, not so much in SD rats, localized to renal tubules in male and glomerular vessels in female SHRsp. A higher protein level of NF-kappaB p65 was found in SHRsp than in SD rats. SD rats had more intense kidney neuronal nitric oxide synthase staining than SHRsp. The intensity of inducible nitric oxide synthase staining was significantly higher in SHRsp than in SD rats, with no gender differences in either strain. SHRsp and male rats exhibited higher AGEs and oxidative stress than SD and female rats, respectively. These differences might partly account for the development of hypertension in SHRsp and the higher vulnerability of male animals to renal pathology.

Animals↗
PubMed2006

Vascular matrix adhesion and the blood-brain barrier.

The integrity of the cerebral microvasculature depends on the interaction between its component cells and the extracellular matrix, as well as reorganized cell-cell interactions. In the central nervous system, matrix adhesion receptors are expressed in the microvasculature and by neurons and their supporting glial cells. Cells within cerebral microvessels express both the integrin and dystroglycan families of matrix adhesion receptors. However, the functional significance of these receptors is only now being explored. Endothelial cells and astrocytes within cerebral capillaries co-operate to generate and maintain the basal lamina and the unique barrier functions of the endothelium. Integrins and the dystroglycan complex are found on the matrix-proximate faces of both endothelial cells and astrocyte end-feet. Pericytes rest against the basal lamina. In the extravascular compartment, select integrins are expressed on neurons, microglial cells and oligodendroglia. Significant alterations in both cellular adhesion receptors and their matrix ligands occur during focal cerebral ischaemia, which support their functional significance in the normal state. We propose that matrix adhesion receptors are essential for the maintenance of the integrity of the blood-brain permeability barrier and that modulation of these receptors contributes to alterations in the barrier during brain injury.

Animals↗
PubMed2006

Multi-class cancer classification using multinomial probit regression with Bayesian gene selection.

We consider the problems of multi-class cancer classification from gene expression data. After discussing the multinomial probit regression model with Bayesian gene selection, we propose two Bayesian gene selection schemes: one employs different strongest genes for different probit regressions; the other employs the same strongest genes for all regressions. Some fast implementation issues for Bayesian gene selection are discussed, including preselection of the strongest genes and recursive computation of the estimation errors using QR decomposition. The proposed gene selection techniques are applied to analyse real breast cancer data, small round blue-cell tumours, the national cancer institute's anti-cancer drug-screen data and acute leukaemia data. Compared with existing multi-class cancer classifications, our proposed methods can find which genes are the most important genes affecting which kind of cancer. Also, the strongest genes selected using our methods are consistent with the biological significance. The recognition accuracies are very high using our proposed methods.

Algorithms↗