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Biomedical subjects

J Xie

Publications and source records attributed to J Xie.

At least 19 recordsLinked to original sources

Effect of albumin on brushite transformation to hydroxyapatite.

Brushite (CaHPO(4) x 2H(2)O) is a precursor to hydroxyapatite [HA, Ca(5)(PO(4))(3)OH]. It has been shown that a modified form of brushite, with potassium substituting for calcium at specific sites, demonstrated accelerated transformation to HA when exposed to nonproteinaceous Hanks' balanced aqueous salt solutions (HBSS). The biocompatibility of a transforming material is related to cellular response to the process, which is initiated by protein adsorption. The effect of adsorbed protein on the kinetics and chemistry of brushite transformation to HA, when exposed to HBSS containing bovine serum albumin (BSA), was examined using Fourier transform IR spectroscopy, X-ray diffraction, and energy dispersive spectrometry techniques. The effect of solution pH was also studied. Results show that, in the presence of a protein-free environment, transformation is faster in buffered medium than in nonbuffered medium. Moreover, curve fitting and second derivatives of the IR spectra show that some bands shift depending on whether the brushite transforms in a buffered or nonbuffered medium. Therefore, variation in pH affects both transformation rate and the associated chemistry. The presence of BSA in either buffered or nonbuffered medium retards the transformation in comparison to the corresponding BSA-free medium. The extent of this retardation increases with the increase in bulk concentration of BSA but does not alter the transformation chemistry. This suggests the retardation on the transformation rate is due to BSA adsorption coverage on the calcium phosphate ceramic. This may be due to the shielding of Ca(2+) and PO(4)(-3) sites, preventing their interaction with the HBSS.

Biocompatible Materials↗

Synthesis and evaluation of a C-glycosyl nucleoside as an inhibitor of chitin synthase.

As part of our ongoing program devoted to inhibit chitin synthases, we have prepared a novel C-glycosyl nucleoside as metabolically stable substrate analog of UDP-GlcNAc. The synthetic strategy relies on the consecutive coupling of nucleoside and amino C-glycosyl moieties with L-tartaric acid. However, this compound inhibited only weakly chitin synthase I, with an IC(50) value of 20 mM.

Chitin Synthase↗

A role of PDGFRalpha in basal cell carcinoma proliferation.

Activation of the hedgehog pathway, through the loss of patched (PTC) or the activation of smoothened (SMO), occurs frequently in basal cell carcinoma (BCC), the most common human cancer. However, the molecular basis of this neoplastic effect is not understood. The downstream molecule Gli1 is known to mediate the biological effect of the pathway and is itself up-regulated in all BCCs. Gli1 can drive the production of BCCs in the mouse when overexpressed in the epidermis. Here we show that Gli1 can activate platelet-derived growth factor receptor alpha (PDGFRalpha) in C3H10T(1/2) cells. Functional up-regulation of PDGFRalpha by Gli1 is accompanied by activation of the ras-ERK pathway, a pathway associated with cell proliferation. The relevance of this mechanism in vivo is supported by a high level expression of PDGFRalpha in BCCs of mice and humans. In the murine BCC cell line ASZ001, in which both copies of the PTC gene are inactivated, DNA synthesis and cell proliferation can be slowed by re-expression of PTC, which down-regulates PDGFRalpha expression, or by downstream inhibition of PDGFRalpha with neutralizing antibodies. Therefore, we conclude that increased expression of PDGFRalpha may be an important mechanism by which mutations in the hedgehog pathway cause BCCs.

Animals↗

Expression of glutathione-S-transferase isozyme in the SY5Y neuroblastoma cell line increases resistance to oxidative stress.

Glutathione-S-transferases (GSTs) are a superfamily of enzymes that function to catalyze the nucleophilic attack of glutathione on electrophilic groups of a second substrate. GSTs are present in many organs and have been implicated in the detoxification of endogenous alpha, beta unsaturated aldehydes, including 4-hydroxynonenal (HNE). Exogenous GST protects hippocampal neurons against HNE in culture. To test the hypothesis that overexpression of GST in cells would increase resistance to exogenous or endogenous HNE induced by oxidative stress, stable transfectants of SY5Y neuroblastoma cells with GST were established. Stable GST transfectants demonstrated enzyme activities 13.7 times (Clone 1) and 30 times (Clone 2) higher than cells transfected with vector alone. GST transfectants (both Clones 1 and 2) demonstrated significantly (p <.05) increased resistance to ferrous sulfate/hydrogen peroxide (20.9% for Clone 1; 46.5% for Clone 2), amyloid beta-peptide (12.2% for Clone 1; 27.5.% for Clone 2), and peroxynitrite (24.3% for Clone 1; 43.9% for Clone 2), but not to exogenous application of HNE in culture medium. GST transfectants treated with 1,1,4-tris (acetyloxy)nonane, a nontoxic derivative of HNE that is degraded to HNE intracellularly, demonstrated a statistically significant (p <.05) increase in viability in a dose-dependent manner compared with SY5Y cells transfected with vector alone. These results suggest that overexpression of GST increases resistance to endogenous HNE induced by oxidative stress or released in the degradation of 1,1,4-tris (acetyloxy)nonane, but not to exogenous application of HNE.

Aldehydes↗

Self-assembly of frameworks with specific topologies: construction and anion exchange properties of M3L2 architectures by tripodal ligands and silver(I) salts.

Three five-component architectures, compounds 3, 4, and 5 were obtained by self-assembly of tripodal 1,3,5-tris(imidazol-1-ylmethyl )-2,4,6-trimethylbenzene (6) and 1,3,5-tris(benzimidazol-2-ylmethyl)benzene (7) ligands with silver(I) salts. The structures of these novel complexes have been determined by X-ray crystallography. The results of structural analysis indicate that these frameworks have same M3L2 components, but different structures. Compounds 3 and 4 are both M3L2 type cage-like complexes, while the 5 is an open trinuclear complex. The complex 3 is a cylindrical cage with simultaneous inclusion of a perchlorate anion inside of the cage as a guest molecule. Such guests can be exchanged for other anions through the open edge of the cage as evidenced by crystal structure of 4. The results demonstrate that the molecular M3L2 type cage can act as a host for anions and provide a nice example of supramolecular architectures with interesting properties and possible applications.

Journal Article↗

Differential gene expression in fully-grown oocytes between gynogenetic and gonochoristic crucian carps.

Silver crucian carp (Carassius auratus gibelio) is a unique triploid bisexual species that can reproduce by gynogenesis. As all other gynogenetic animals, it keeps its chromosome integrity by inhibiting the first meiosis division (no extrusion of the first pole body). To understand the molecular events governing this reproduction mode, suppression subtractive hybridization was used to identify the genes differentially expressed in fully-grown oocytes of the gynogenetic and gonochoristic crucian carp (gyno-carp and gono-carp). From two specific subtractive cDNA libraries, the clones screened out by dot blots and virtual Northern blots were chosen to clone full-length cDNA by RACE. Four differentially expressed genes were obtained. Two are novel genes and are expressed specifically in the oocytes. The gyno-carp stores much more mRNA of cyclin A2, a new member of the fish A-type cyclin gene, in its fully-grown oocyte than in the gono-carp. The last gene is histone H2A. The histone H2As of these two closely related crucian carps are quite different in the C-terminus. Preliminary characterization of the four genes has been analyzed by nucleotide and deduced amino acid sequence and Northern analysis.

Amino Acid Sequence↗

Par-4 is a synaptic protein that regulates neurite outgrowth by altering calcium homeostasis and transcription factor AP-1 activation.

Although Par-4 (prostate apoptosis response-4) is involved in initiation of neurodegenerative cascades associated with certain neurodegenerative disorders, normal physiological roles of Par-4 in neurons have remained elusive. It was recently reported that Par-4 protein levels could be regulated at translational level in synaptic terminals following apoptotic insults, suggesting that Par-4 might play a role in synaptic function. We report that Par-4 is a synaptic protein preferably localized in postsynaptic density (PSD). The expression of Par-4 in synaptosome preparations and PSDs are developmentally and regionally regulated. Synaptic Par-4 is enriched in the cerebral cortex and the hippocampus, but not in the cerebellum. In vitro as well as in vivo experiments demonstrate that the levels of synaptic Par-4 increase as the neurons mature. Overexpression of Par-4 in transfected PC12 cells inhibits nerve growth factor (NGF)-induced cellular differentiation and neurite outgrowth by a mechanism involving aberrant elevation of intracellular calcium levels and suppression of activation of the transcription factor AP-1. The actions of Par-4 were consistently blocked by co-expression of the dominant negative regulator of Par-4 activity (the leucine zipper domain of Par-4). Since the leucine zipper domain of Par-4 (Leu.zip) may mediate protein--protein interactions, the results indicate that the actions of Par-4 require its interaction with other protein(s) or dimerization with itself. These results suggest that Par-4 may play an important role in postsynaptic signal transduction and regulation of cellular pathways associated with cellular differentiation and neurite outgrowth. Identification of Par-4 as a novel synaptic protein may have significant implications in understanding the mechanisms of synaptic functions in physiological and pathological settings.

Animals↗

Energy transfer cassettes for facile labeling of sequencing and PCR primers.

Fluorescence energy transfer (ET) primers and terminators are the reagents of choice for multiplex DNA sequencing and analysis. We present here the design, synthesis and evaluation of a four-color set of ET cassettes, fluorescent labeling reagents that can be quantitatively coupled to a thiol-activated target through a disulfide exchange reaction. The ET cassette consists of a sugar-phosphate spacer with a FAM donor at the 3'-end, an acceptor linked to a modified T-base at the 5'-end of the spacer and a mixed disulfide for coupling to a thiol at the 5'-end. The acceptor dye emission intensities of ET labeled primers produced in this manner are comparable to commercial ET primers. The utility of our ET cassette-labeled primers is demonstrated by performing four-color capillary electrophoresis sequencing with the M13(-21)forward primer and by generating and analyzing a set of single-nucleotide-polymorphism-specific PCR amplicons.

Chromatography, High Pressure Liquid↗

A CaMK IV responsive RNA element mediates depolarization-induced alternative splicing of ion channels.

Calcium regulation of gene expression is critical for the long-lasting activity-dependent changes in cellular electrical properties that underlie important physiological functions such as learning and memory. Cellular electrical properties are diversified through the extensive alternative splicing of ion channel pre-messenger RNAs; however, the regulation of splicing by cell signalling pathways has not been well explored. Here we show that depolarization of GH3 pituitary cells represses splicing of the STREX exon in BK potassium channel transcripts through the action of Ca2+/calmodulin-dependent protein kinases (CaMKs). Overexpressing constitutively active CaMK IV, but not CaMK I or II, specifically decreases STREX inclusion in the mRNA. This decrease is prevented by mutations in particular RNA repressor sequences. Transferring 54 nucleotides from the 3' splice site upstream of STREX to a heterologous gene is sufficient to confer CaMK IV repression on an otherwise constitutive exon. These experiments define a CaMK IV-responsive RNA element (CaRRE), which mediates the alternative splicing of ion channel pre-mRNAs. The CaRRE presents a unique molecular target for inducing long-term adaptive changes in cellular electrical properties. It also provides a model system for dissecting the effect of signal transduction pathways on alternative splicing.

Alternative Splicing↗

Temperature-induced decoupling of phycobilisomes from reaction centers.

Temperature-induced decoupling of phycobilisomes (PBSs) from the reaction centers in the PBS-thylakoid membrane complexes was observed at 0 degrees C. The fluorescence yields of photosystem (PS) I and PSII decreased and that of PBSs increased with selective excitation of PBSs at 0 degrees C, while the yield of PBSs decreased and those of the two photosystems increased with selective excitation of chlorophyll a at room temperature (RT). It indicated that the decoupling of PBSs from the two photosystems led to changes of energy transfer efficiencies, which can be explained by partial detachment of PBSs from thylakoid membrane. The temperature-dependent processes were reversible, i.e. with temperature going up to RT, the complexes could restore to the functionally coupled state with a time constant about 30 s. Based on these results, it could be deduced that PBSs should be in parallel connection with the two photosystems.

Betaine↗

Prostate apoptosis response-4 enhances secretion of amyloid beta peptide 1-42 in human neuroblastoma IMR-32 cells by a caspase-dependent pathway.

Prostate apoptosis response-4 (Par-4) is a leucine zipper protein that promotes neuronal cell death in Alzheimer's disease (AD). Neuronal degeneration in AD may result from extracellular accumulation of amyloid beta peptide (Abeta) 1-42. To examine the effect of Par-4 on Abeta secretion and to reconcile amyloid/apoptosis hypotheses of AD, we generated IMR-32 cell lines that overexpress Par-4 and/or its leucine zipper domain. Overexpression of Par-4 did not significantly affect levels of the endogenously expressed beta amyloid precursor protein but drastically increased the Abeta(1-42)/Abeta(total) ratio in the conditioned media about 6-8 h after trophic factor withdrawal. Time course analysis of caspase activation reveals that Par-4 overexpression exacerbated caspase activation, which is detectable within 2 h after trophic factor withdrawal. Furthermore, inhibition of caspase activity by the broad spectrum caspase inhibitor BD-fmk significantly attenuated the Par-4-induced increase in Abeta 1-42 production. In addition, the effects of Par-4 on secretion of Abeta 1-42 were consistently blocked by co-expression of the leucine zipper domain, indicating that the effect of Par-4 on Abeta secretion may require its interaction with other protein(s). These results suggest that Par-4 increases secretion of Abeta 1-42 largely through a caspase-dependent pathway after apoptotic cascades are initiated.

Amyloid beta-Peptides↗

Qian-Kun-Nin, a Chinese herbal medicine formulation, attenuates mitochondrial oxidant stress in cardiomyocytes.

Qian-Kun-Nin is a Chinese herbal medicine formulation used for several indications, including the treatment of cardiovascular diseases. This formulation contains herbs which possess antioxidant properties. In this study, Qian-Kun-Nin's ability to confer protection to cardiomyocytes against reactive oxygen species (ROS) generated during mitochondrial electron transport inhibition was tested. The intracellular fluorescent probe 2',7'-dichlorofluorescin diacetate (DCFH-DA, sensitive to H(2)O(2) and hydroxyl radicals) was used to assess intracellular ROS, and propidium iodide (PI) was used to assess viability in cultured chick embryonic cardiomyocytes. Qian-Kun-Nin significantly attenuated oxidation of DCFH in cells exposed to the mitochondrial site III inhibitor, antimycin A, consistent with a decrease in oxidative stress. These attenuated oxidant levels were associated with improved cell survival. After antimycin A exposure, Qian-Kun-Nin decreased cell death from 51. 6+/-3.3% in untreated cells to 27.3+/-3.8% in treated cells at 2 h. We conclude that Qian-Kun-Nin attenuates oxidant stress and protects cells from lethal oxidant damage during mitochondrial electron transport inhibition, and thus its therapeutic potential in treating cardiovascular diseases may relate to its antioxidant properties.

Analysis of Variance↗

A placebo controlled evaluation of the antifibrillatory effects of carvedilol.

This article evaluates the antifibrillatory effects of carvedilol 5 mg/kg and vehicle (dimethyl-formamide) over time. Sprague-Dawley rats were anesthetized and intubated. They underwent baseline ventricular fibrillation threshold (VFT) determination and then received 1 of the 2 treatments (n = 10/group) over 8 minutes. VFT and determinations were performed at 2, 7, 15, 30, 45, and 60 minutes postinfusion. Carvedilol significantly increased the VFT at 2, 7, 15, 30 minutes versus baseline and the vehicle control group. Carvedilol significantly reduced the heart rate and the mean arterial pressure at every evaluable time point versus baseline and vehicle control. Carvedilol showed significant antifibrillatory effects versus baseline and vehicle for the first 30 minutes but not thereafter, even though the heart rate and mean arterial pressure remain significantly reduced.

Adrenergic beta-Antagonists↗

Effect of bilateral subthalamic nucleus stimulation on gait in Parkinson's disease.

The fundamental disturbance of the parkinsonian gait is the reduction in walking velocity. This is mainly due to reduction in stride length, while cadence (steps/min) is slightly enhanced. Treatment with L-dopa increases stride length while cadence is unchanged. Chronic stimulation of the thalamus has no effect on Parkinsonian gait. The efficacy of electrical stimulation of the subthalamic nucleus (STN) on gait in advanced Parkinson's disease has been clearly demonstrated clinically. The aim of the present study was to quantify the changes in gait measures induced by STN stimulation and L-dopa and to assess possible differential or additive effects. Eight Parkinson's disease patients (mean +/- SD age 48.1 +/- 7.3 years) with chronic bilateral STN stimulation (mean duration of disease 13.3 +/- 2.4 years, mean stimulation time 15.4 +/- 10.6 months) and 12 age-matched controls were investigated. Subjects walked on a special treadmill with a closed-loop ultrasound control system that used the subject's position to adjust treadmill speed continuously for the actual walking velocity. In an appropriate crossover design, spatiotemporal gait measures and leg joint angle movements were assessed for at least 120 stride cycles in four treatment conditions: with and without stimulation and with and without a suprathreshold dose of L-dopa. With STN stimulation, there were increases of almost threefold in mean walking velocity (from 0.35 to 0.96 m/s) and stride length (from 0.34 to 0.99 m). Cadence remained constant. The range of motion of the major leg joints also increased. L-Dopa alone had a slightly weaker effect, with an increase in walking velocity to 0.94 m/s and in stride length to 0.92 m at a similar cadence. These increased values were in the range of those for healthy age-matched subjects performing the same task. The combination of both treatments further increased the mean walking velocity to 1.19 m/s and stride length to 1.20 m at an unchanged cadence. However, not all patients receiving STN stimulation improved further when they also received L-dopa. These results demonstrate that chronic bilateral STN stimulation, like treatment with L-dopa, improves walking velocity by increasing stride length without changing cadence. STN stimulation almost exclusively affects mechanisms involved in the control of spatial gait measures rather than rhythmicity. The gait measures obtained with STN stimulation alone are in the range of control subjects.

Adult↗

Blood pressure and urinary cations in a low-fat intake Chinese population sample.

BACKGROUND: The relationship between cation intake and blood pressure (BP) in populations with specific dietary habits such as a low fat intake, remains unclear. A low fat intake has been prevalent during human evolution. METHODS: The average of 6 BP readings and heart rate (HR) recordings has been calculated. Dietary intake was measured using the 24 h recall-method. A 24 h urine sample was collected. RESULTS: A highly significant correlation was found between the sodium/potassium ratio (Na/K), after adjustment for age, weight, height, heart rate, alcohol intake and sex and systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). The same applies to the sodium/creatinine (Na/Cr) and potassium/creatinine (K/Cr) ratios, with a positive correlation for Na/Cr and a negative one for K/Cr. The partial regression coefficient was in absolute value about 4-5 times greater for K/Cr than for Na/Cr. Age correlates highly significantly and independently with both SBP and DBP. CONCLUSION: If a Na/K ratio of 1 is considered optimal, by achieving that goal mean SBP could be reduced by about 6 mm Hg and mean DBP by 3 mm Hg in this normotensive population.

Adolescent↗

[Studies on the supercritical-CO2 fluid extraction of complex prescription Danshen-Jiangxiang].

This paper first reported the supercritical-CO2 fluid extraction of complex prescription Danshen-Jiangxiang. With the active constituents and yield of extracts as index, the each other effect of each drug and effect on total complex prescription in extraction were studied. And the effects of pressure and temperature were also studied. The results showed the effects were different in complex prescription extraction and single prescription. Active constituents can be extracted, but a obvious effect exist each other and effects together the yield of extract, extraction rate and content of active constituents of complex prescription extraction, which are concerned in extraction conditions. These study results have important reference on the modernization of traditional Chinese medicines.

Carbon Dioxide↗

[Diagnostic value of five serum markers for liver fibrosis].

OBJECTIVE: To research the diagnostic value of serum hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (CIV), laminin (LN), and transforming growth factor-beta(1) (TGF-beta(1)) for liver fibrosis in patients with chronic hepatitis. METHODS: Serum levels of HA, PCIII, CIV, LN and TGF-beta(1) in 116 patients with chronic hepatitis and cirrhosis were investigated and compared with hepatic histological findings of 87 patients. RESULTS: The correlation between serum HA and histologically assessed grade of inflammatory activity was weak (r=0.393, P<0.05). The correlation between serum HA, PCIII, LN, TGF-beta(1) and histologically assessed stage of liver fibrosis were all moderate (r=0.584, 0.454, 0.441 and 0.612, respectively, P<0.05), while that between serum CIV and histologically assessed stage of liver fibrosis was weak (r=0.319, P<0.05). As shown by the ROC curves in cases of chronic hepatitis, the ability to differentiate patients with cirrhosis from those without cirrhosis was greater for serum HA than that for serum PCIII, CIV, LN, and TGF-beta(1) (the areas under the curves=0.904 vs 0.784, 0.815, 0.805, 0.828, P<0.05). The ability of serum HA, LN and TGF-beta(1) to differentiate patients with extensive liver fibrosis from those with no or mild liver fibrosis exceeded that of serum PCIII and CIV (the areas under the curves=0.849, 0.819, 0.836 vs 0.702, 0.721, P<0.05). To discriminate the stage of liver fibrosis, serum HA and TGF-beta(1) were selected from the five markers by Bayes discriminate analysis. If S(1), S(2) and S(3) were not required to be discriminated, discrimination between the three stages showed significant difference (P<0.05). The predictive accurate percentage was 72.90%. CONCLUSIONS: The five markers all have the ability not only to judge liver cirrhosis, in which the ability of serum HA is the best, but also to differentiate chronic hepatitis with extensive liver fibrosis from that with no or mild liver fibrosis, in which the ability of serum HA, LN, TGF-beta(1) is stronger than the other two. It is useful for detection of serum HA and TGF-beta(1) at the same time to discriminate the histologically assessed stage of fibrosis. Serum HA and TGF-beta(1) can be helpful in discriminating patients of chronic hepatitis with "no liver fibrosis", "liver fibrosis but no cirrhosis" and "liver cirrhosis", but cannot discriminate them accurately as the histologically assessed stage of fibrosis. They cannot displace liver biopsy for the judgement of liver fibrosis.

Adult↗