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Biomedical subjects

X Fan

Publications and source records attributed to X Fan.

At least 19 recordsLinked to original sources
PubMed2006

Bone re/modeling is more dynamic in the endothelial nitric oxide synthase(-/-) mouse.

Nitric oxide is a ubiquitous estrogen-regulated signaling molecule that has been implicated in the regulation of bone maturation and remodeling. To better understand the role that bone-cell-secreted nitric oxide plays in ovariectomy-induced modifications of bone turnover, we examined the expression of endothelial NO synthase (eNOS) in bone cells and bone progenitor cells at regular intervals up to 10 wk after acute estrogen deprivation. Ovariectomy led to an anticipated initial decline in bone cell eNOS production, but surprisingly, 17 d after ovariectomy, eNOS expression by bone and marrow stromal cells dramatically rebounded and was maintained at high levels for at least 10 wk after surgery. We examined the long-term consequences of eNOS in the process of ovariectomy-induced bone loss by prospectively analyzing bone mineral density in wild-type and eNOS(-/-) mice for 10 wk after ovariectomy. Ovariectomized eNOS(-/-) mice were observed to undergo an exaggerated state of estrogen-deficiency-induced bone remodeling compared with wild-type controls, suggesting that eNOS may act to mitigate this process. Furthermore, we found that whereas bone formation in estrogen-replete wild-type mice slowed between 14 and 20 wk of age, eNOS knockout mice continued to accrue basal bone mass at a high rate and showed no sign of entering a remodeling stage. Our data suggest that eNOS may play an important role in limiting ovariectomy-induced bone remodeling as well as regulating the transition from basal modeling to remodeling.

Animals↗
PubMed2006

Notch3 signaling initiates choroid plexus tumor formation.

Notch3 has been studied in the context of brain development, but whether it plays a role in the formation of brain tumors is unclear. We demonstrate that the introduction of constitutively active Notch3 into periventricular cells of embryonic day 9.5 mice causes the formation of choroid plexus tumors (CPTs). Tumors arose in the fourth ventricles in 83% of animals and were associated with hydrocephalus. They were microscopically highly similar to choroid plexus papillomas in humans, with an ongoing proliferation rate of 4-6%. Signs of Notch pathway activity were also present in human choroid plexus lesions, and receptor mRNA levels in papillomas were elevated over those in non-neoplastic choroid plexus. Notch2 was overexpressed approximately 500-fold in one case, suggesting that the role of this pathway in CPTs may not be specific to Notch3. Our findings indicate that activated Notch3 can function as an oncogene in the developing brain, and link the Notch pathway to human CPT pathogenesis.

Animals↗
PubMed2006

PPARalpha agonist fenofibrate improves diabetic nephropathy in db/db mice.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPARalpha by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n=8; db/m, n=6) or a diet containing fenofibrate (db/db, n=8; db/m, n=7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P<0.001) and HbA1c levels (P<0.001), and was associated with decreased food intake (P<0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P<0.001) and reduced plasma insulin levels (P<0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P<0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P<0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPARalpha, decreased type I collagen production. Taken together, the PPARalpha agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPARalpha by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.

Albuminuria↗
PubMed2006

Urceolatol, a tetracyclic bromobenzaldehyde dimer from Polysiphonia urceolata.

Urceolatol (1), a novel bromobenzaldehyde dimer, together with one known bromophenol, 3-bromo-4,5-dihydroxy-benzaldehyde (2), were isolated from the red alga Polysiphonia urceolata. The structure and absolute stereochemistry of 1 were elucidated to be (5R,10R)-2,7-dibromo-3,8-dihydroxy-5,10-dimethoxyl-5,10-dihydrochromeno[5,4,3-cde]chromene, on the basis of spectroscopic techniques and X-ray diffraction analysis.

Benzaldehydes↗
PubMed2006

Effect of ICAM-1 and LFA-1 in hyperleukocytic acute myeloid leukaemia.

Acute hyperleukocytic leukemia [AHL; WBC count >100 x 10(9)/l] is associated with a life-threatening complication. The mechanisms of hyperleukocytosis in acute myeloid leukaemia (AML) remain unclear. However, the interaction of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) plays an important role in the adhesion and migration of normal leukocytes and AML cells. Therefore, effects of ICAM-1 and LFA-1 were studied in hyperleukocytic AML. The adhesion of hyperleukocytic AML blasts and human umbilical vein endothelial cells (HUVECs) was significantly increased compared with that of blasts from non-hyperleukocytic AML (WBC < 100 x 10(9)/l). The adhesion of normal neutrophils and HUVECs treated with hyperleukocytic AML blast supernatant was increased significantly. Finally, we determined the ICAM-1 on the surface of HUVECs treated with the supernatant of hyperleukocytic AML blasts and LFA-1 on hyperleukocytic AML blasts by flow cytometry. It showed that the ICAM-1 expression on the surface of the HUVECs treated with hyperleukocytic AML blast supernatant for 24 h could be increased, and the expression of LFA-1 on hyperleukocytic AML was also increased significantly. Our data show that hyperleukocytic AML blasts stimulate the endothelium to secrete more ICAM-1 and promote their own adhesion to vascular endothelium, suggesting that ICAM-1 and LFA-1 may have a role in hyperleukocytic AML.

Adolescent↗
PubMed2005

Hydrothermal synthesis and characterization of a layered cobalt phenylphosphonate, Co(PhPO3)(H2O).

We report the hydrothermal synthesis and characterization of a layered cobalt phenylphosphonate. Unlike most metal phosphonates reported to date, the structure was solved by single crystal X-ray diffraction (SC-XRD). Co(ii) centres are hexa-coordinated by oxygen and the octahedra corner-share into a layer. The layers are capped by phenylphosphonate groups, where the phenyl groups define a hydrophobic bilayer region. The material was also characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA) and SQUID (superconducting quantum interference device) magnetometry. The material undergoes an antiferromagnetic transition at a relatively low Néel temperature of 4.0 K, while the Curie-Weiss temperature of -76.5 K reflects the low-dimensionality of the magnetic structure. The effective magnetic moment of 5.01 micro(B) per Co(2+) verifies a high-spin configuration and an octahedral coordination of the metal centres. This layered material was correctly predicted in the literature from powder data, adds to the structural diversity of the cobalt phosphonates, and may be useful as an intercalation or exfoliation compound.

Journal Article↗
PubMed2005

The mutated subsequence problem and locating conserved genes.

MOTIVATION: For the purpose of locating conserved genes in a whole genome scale, this paper proposes a new structural optimization problem called the Mutated Subsequence Problem, which gives consideration to possible mutations between two species (in the form of reversals and transpositions) when comparing the genomes. RESULTS: A practical algorithm called mutated subsequence algorithm (MSS) is devised to solve this optimization problem, and it has been evaluated using different pairs of human and mouse chromosomes, and different pairs of virus genomes of Baculoviridae. MSS is found to be effective and efficient; in particular, MSS can reveal >90% of the conserved genes of human and mouse that have been reported in the literature. When compared with existing softwares MUMmer and MaxMinCluster, MSS uncovers 14 and 7% more genes on average, respectively. Furthermore, this paper shows a hybrid approach to integrate MUMmer or MaxMinCluster with MSS, which has better performance and reliability.

Algorithms↗
PubMed2005

Long-chain fatty acid uptake is upregulated in omental adipocytes from patients undergoing bariatric surgery for obesity.

OBJECTIVE: To determine the impact of obesity on adipocyte cell size and long-chain fatty acid (LCFA) uptake kinetics in human subjects undergoing laparoscopic abdominal surgery. SUBJECTS: A total of 10 obese patients (BMI 49.8+/-11.9 (s.d.) kg/m(2)) undergoing laparoscopic bariatric surgery, and 10 nonobese subjects (BMI 24.2+/-2.3 kg/m(2)) undergoing other clinically indicated laparoscopic abdominal surgical procedures. MEASUREMENTS: Cell size distribution and [(3)H]oleic acid uptake kinetics were studied in adipocytes isolated from omental fat biopsies obtained during surgery. Adipocyte surface area (SA) was calculated from the measured cell diameters. Plasma leptin and insulin concentrations were measured by RIA in fasting blood samples obtained on the morning of surgery. RESULTS: The mean SA of obese adipocytes (41 508+/-5381 mu(2)/cell) was increased 2.4-fold compared to that of nonobese adipocytes (16 928+/-6529 mu(2)/cell; P<0.01). LCFA uptake in each group was the sum of saturable and nonsaturable components. Both the V(max) of the saturable component (21.3+/-6.3 vs 5.1+/-1.9 pmol/s/50,000 cells) and the rate constant k of the nonsaturable component (0.015+/-0.002 vs 0.0066+/-0.0023 ml/s/50 000 cells) were increased (P<0.001) in obese adipocytes compared with nonobese controls. When expressed relative to cell size, V(max)/mu(2) SA was greater in obese than nonobese adipocytes (P<0.05), whereas k/mu(2) SA did not differ between the groups. CONCLUSION: The data support the concepts that (1) adipocyte LCFA uptake consists of distinct facilitated (saturable) and diffusive processes; (2) increased saturable LCFA uptake in obese adipocytes is not simply a consequence of increased cell size, but rather reflects upregulation of a facilitated transport process; and (3) the permeability of adipocyte plasma membranes to LCFA is not appreciably altered by obesity, and increased nonsaturable uptake in obese adipocytes principally reflects an increase in cell SA. Regulation of saturable LCFA uptake by adipocytes may be an important control point for body adiposity.

Adipocytes↗
PubMed2005

Effect of hydraulic retention time on the efficiency of vertical tubular anaerobic sludge digester treating waste activated sludge.

Treating waste activated sludge at a temperature of 35 degrees C was investigated in vertical tubular anaerobic sludge digester and common anaerobic sludge digester, with the working volume of 2.5 m3 each. Compared with common anaerobic sludge digester, the vertical tubular anaerobic sludge digester greatly improved volatile solids and COD removal efficiencies, the methane production and the stability of the anaerobic digestion system under the same condition of hydraulic retention time. The minimum hydraulic retention time of the vertical tubular anaerobic sludge digester was 5 days, when the organic loading remained at 5.28 kg m(-3) d(-1) (as volatile solids) and the volatile solids removal rate was 41.7%. The suitable hydraulic retention time for vertical tubular anaerobic sludge digester was 5 days, while to get the same COD removal rate it was 10 days for common anaerobic sludge digester. At optimum hydraulic retention time of 5 days, the methane production of the two digesters achieved the maximum difference of 0.06 l g(-1) volatile solids (0.26, 0.20 l g(-1) volatile solids for vertical tubular anaerobic sludge digester and common anaerobic sludge digester, respectively). The advantage of vertical tubular anaerobic sludge digester was especially obvious when the hydraulic retention time was relatively short. Furthermore, it was found that the vertical tubular anaerobic sludge digester in which more anaerobic bacteria lived has significantly intensified the sub-micro mass transfer between the substrate and the microorganisms, which resulted in a remarkable effect on shortening the hydraulic retention time of anaerobic sludge digestion.

Bacteria, Anaerobic↗
PubMed2005

Chemical constituents of the brown alga Dictyopteris divaricata.

A novel sesquiterpene-substituted benzoic acid, named dictyvaric acid (1), together with nine known compounds (2-10), have been isolated from the brown alga Dictyopteris divaricata Okam. The structure of 1 was elucidated as 3-[(decahydro-2-hydroxy-2,5,5,8a-tetramethyl-1-naphthalenyl)-methyl]-4-hydroxybenzoic acid by spectroscopic methods, including IR, FABMS, HR-FABMS, 1D and 2D NMR techniques. All compounds were obtained from this species for the first time.

Benzoates↗
PubMed2005

Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system.

AIMS: Medulloblastoma (MB), a kind of infratentorial primitive neuroectodermal tumour (PNET), is the most frequent malignant brain tumour in childhood. In contrast, supratentorial PNET (sPNET) are very infrequent tumours, but they are histologically similar to MB, although they present a worse clinical outcome. We investigated the differences in genetic abnormalities between sPNET and MB. METHODS AND RESULTS: We analysed 20 central PNET (14 MB and six sPNET) by conventional comparative genomic hybridization (CGH) in order to determine whether a different genetic profile for each tumour exists. Isochromosome 17q was detected in four of the 14 MB cases, but not in any sPNET. Gains at 17q and 7 happened more frequently in MB, and those at 1q in sPNET. Losses at chromosome 10 were detected only in MB, while losses at 16p and 19p happened more frequently in sPNET. A new amplification site, on 4q12, was detected in two MB. CONCLUSIONS: Central PNET are a heterogeneous group of tumours from the genetic point of view. The present and previous data, together with further results from larger series, might contribute to the establishment of specific treatments for supratentorial and infratentorial PNET.

Brain Neoplasms↗
PubMed2004

Molecular biology and clinical implication of hepatitis C virus.

Hepatitis C virus (HCV) was first described in 1989 as the putative viral agent of non-A non-B hepatitis. It is a member of the Flaviviridae family and has been recognized as the major causative agent of chronic liver disease, including chronic active hepatitis, cirrhosis and hepatocellular carcinoma. HCV is a positive RNA virus with a genome containing approximately 9500 nucleotides. It has an open reading frame that encodes a large polyprotein of about 3000 amino acids and is characterized by extensive genetic diversity. HCV has been classified into at least 6 major genotypes with many subtypes and circulates within an infected individual as a number of closely related but distinct variants known as quasispecies. This article reviews aspects of the molecular biology of HCV and their clinical implication.

3' Untranslated Regions↗
PubMed2004

Prostate carcinoma cells that have resided in bone have an upregulated IGF-I axis.

BACKGROUND: Prostate cancer (PC) has a propensity to metastasize to the skeleton, inducing an osteoblastic response in the host. Recent epidemiological studies have suggested that circulating IGF-I may be important for both the pathogenesis and dissemination of PC. We have postulated that tumor secreted IGF-I in conjunction with endogenous IGF-I contributes to the osteoblastic phenotype characteristic of metastatic PC. METHODS: To test this thesis we studied the established LNCaP PC progression model consisting of three genetically related human PC cell lines. RESULTS: Using RIA, we found serum-free conditioned media (CM) of LNCaP and C4-2 had no measurable IGF-I, whereas IGF-I was easily detected in CM from C4-2B cells at 24 hr (i.e., 1.8 +/- 0.53 ng/mg cell protein). Real-time PCR of IGF-I mRNA showed that C4-2B expressed 100-fold more IGF-I mRNA than LNCaP cells. In addition, C4-2B expression of IGF-I mRNA was substantially increased in the presence of exogenous IGF-I to nearly twofold. While IGFBP-3 and IGFBP-1 were not detectable in the CM of any PC line, all cells secreted IGFBP-2. C4-2B cells produced 40% more IGFBP-2 than LNCaP or C4-2 cells (C4-2B at 167 +/- 43 ng/mg cell protein). RANKL, a product of bone stromal cells, was also differentially expressed: LNCaP had threefold higher RANKL mRNA compared to C4-2 and C4-2B and at least equivalent protein expression. CONCLUSIONS: Our results suggest that PC cells that have metastasized to bone have an upregulated IGF-I regulatory system. This suggests an activated IGF-I axis contributes to the host-PC interaction in promoting osteoblastic metastases.

Bone Neoplasms↗
PubMed2004

Nitrate removal from saline water using autotrophic denitrification by the bacterium Thiobacillus denitrificans MP-1.

Autotrophic denitrification of synthetic wastewater by Thiobacillus denitrificans MP-1 isolated from mangrove sediment was investigated in both up-flow packed-bed reactors and fermentor. More than 97.5% and 90% of the nitrate in inflow was removed after 8.8 and 161 hours at 250 and 195 mg l(-1) for the packed-bed reactor and fermentor system, respectively. The nitrate was quickly denitrified at very low flow rates (0.11 m h(-1)) for the packed-bed reactors, but as the flow rate was greater than 0.13 m h(-1), the nitrate removal rate increased as the flow rate increased. In the static fermentor system, the denitrification can be described by a secondary reaction, but at a flow rate between 1.31 to 1.49 m h(-1), the reactor performance can be described using the zero-order reaction in the packed-bed reactor. As the speed increases, the zero-order reaction translates into half-order reaction as the penetration efficiency of nitrate decreases. The mass ratios between the nitrate removed and the sulfate produced were determined to be 6.81 and 9.32 in the reactor column and fermentor, respectively. The results of this study suggest that efficient removal of high concentrations of nitrate in water or wastewater can be achieved effectively using autotrophic bacteria immobilized on surfaces of sulphur granules in packed-bed reactor.

Bioreactors↗
PubMed2003

Effects of recurrent antecedent hypoglycaemia and chronic hyperglycaemia on brainstem extra-cellular glucose concentrations during acute hypoglycaemia in conscious diabetic BB rats.

AIMS/HYPOTHESIS: Our aim was to determine whether the divergent effects of chronic exposure to hyperglycaemia or hypoglycaemia on the glycaemic threshold for auditory brainstem dysfunction are reflected in the extra-cellular fluid (ECF) concentrations of glucose in the inferior colliculus during hypoglycaemia in the diabetic BB rat. METHODS: Microdialysis was used to measure inferior colliculus ECF glucose concentrations under basal and hyperinsulinaemic (20 mU/kg.min) hypoglycaemic conditions. RESULTS: ECF glucose is increased under basal (hyperglycaemic) conditions and decreases during hypoglycaemia in both recurrently hypoglycaemic and chronically hyperglycaemic diabetic BB rats (to 0.5+/-0.1 and 0.8+/-0.2 mmol/L respectively), with no significant differences between groups. In both groups the plasma to ECF glucose ratio doubled during hypoglycaemia. CONCLUSION/INTERPRETATION: Prior exposure to recurrent hypoglycaemia does not lead to increased ECF glucose concentrations in the inferior colliculus of diabetic BB rats. The resistance to impaired brainstem function seen in recurrently hypoglycaemic rats during hypoglycaemia cannot simply be attributed to increased blood-brain barrier glucose transport within this brain region.

Animals↗
PubMed2003

Nucleation of single-walled carbon nanotubes.

The nucleation pathway for single-wall carbon nanotubes on a metal surface is demonstrated by a series of total energy calculations using density functional theory. Incorporation of pentagons at an early stage of nucleation is energetically favorable as they reduce the number of dangling bonds and facilitate curvature of the structure and bonding to the metal. In the presence of the metal surface, nucleation of a closed cap or a capped single-wall carbon nanotube is overwhelmingly favored compared to any structure with dangling bonds or to a fullerene.

Journal Article↗
PubMed2003

Methylglyoxal-bovine serum albumin stimulates tumor necrosis factor alpha secretion in RAW 264.7 cells through activation of mitogen-activating protein kinase, nuclear factor kappaB and intracellular reactive oxygen species formation.

Accumulating evidence suggests that the pathophysiology of diabetes is analogous to chronic inflammatory states. Circulating levels of inflammatory cytokines such as IL-6 and tumor necrosis factor alpha (TNFalpha) are increased in both type 1 and type 2 diabetes. TNFalpha plays an important role in the pathogenesis of insulin resistance in type 2 diabetes. However, the reason for this increase remains unclear. Levels of the dicarbonyl methylglyoxal (MGO) are elevated in diabetic plasma and MGO-modified bovine serum albumin (MGO-BSA) can trigger cellular uptake of TNF. Therefore we tested the hypothesis that MGO-modified proteins may cause TNFalpha secretion in macrophage-like RAW 264.7 cells. Treatment of cells with MGO-BSA induced TNFalpha release in a dose-dependent manner. MGO-modified ribonuclease A and chicken egg ovalbumin had similar effects. Cotreatment of cells with antioxidant reagent N-acetylcysteine (NAC) inhibited MGO-BSA-induced TNFalpha secretion. MGO-BSA stimulated the simultaneous activation of p44/42 and p38 mitogen-activated protein kinase. PD98059, a selective MEK inhibitor, inhibited MGO-BSA-induced TNFalpha release as well as ERK phosphorylation. Pretreatment of cells with NAC also resulted in inhibition of MGO-BSA-induced ERK phosphorylation. MGO-BSA induced dose-dependent NFkappaB activation as shown by electrophoresis mobility shift assay. The MGO-BSA-induced NFkappaB activation was prevented in the presence of PD98059, NAC, and parthenolide, a selective inhibitor of NFkappaB. Furthermore, the NFkappaB inhibitor parthenolide suppressed MGO-BSA-induced TNFalpha secretion. Confocal microscopy using dichlorofluorescein to demonstrate intracellular reactive oxygen species (ROS) showed that MGO-BSA produced more ROS compared with native BSA. MGO-BSA could also stimulate protein kinase C (PKC) translocation to the cell membrane, considered a key signaling pathway in diabetes. However, there was no evidence that PKC was involved in TNFalpha release based on inhibition by calphostin C and staurosporine. Our findings suggest that the presence of chronically elevated levels of MGO-modified bovine serum albumin may contribute to elevated levels of TNFalpha in diabetes.

Animals↗