Search PubMed⌕ Search

Biomedical subjects

Wei Lu

Publications and source records attributed to Wei Lu.

At least 73 records · Page 4Linked to original sources
PubMed2006

Establishment of coculture model of blood-brain barrier in vitro for nanoparticle's transcytosis and toxicity evaluation.

AIM: A method of coculture of brain capillary endothelial cells (BCECs) and astrocytes of rats was used to evaluate nanoparticle's blood-brain barrier (BBB) transcytosis and toxicity at the endothelial tight junction. METHODS: A lipophilic fluorescent probe, 6-coumarin, was incorporated in poly (ethyleneglycol)-poly (lactide) nanoparticle using double emulsion/solvent evaporation method. BCECs and astrocytes were firstly isolated from brain of newborn rats and characterized by their morphology and immunocytochemistry staining, separately. Subsequently, a coculture model with BCECs on the top of micro-porous membrane of cell culture insert and astrocytes on the bottom side was established. The permeability of 14C-labeled sucrose and nanoparticle were determined, separately. RESULTS: The mean weight-based diameter of 6-coumarin loaded nanoparticles was (102.4 +/- 6.8) nm, with zeta potential of (-16.81 +/- 1.05) mV. BCECs were positive for factor VIII staining and glial fibrillary acidic protein was expressed in astrocytes. The transendothelial electrical resistance reached up to (313 +/- 23) omega x cm2. The tight junction between BCECs in the coculture model could be visualized by both scanning electron microscopy and transmission electron microscopy. The unchanged paracellular transport of sucrose proved that nanoparticle with concentration lower than 200 microg x mL(-1) did not impact the integrity of BBB endothelial tight junctions. The permeability of 10 microg x mL(-1) 6-coumarin labeled nanoparticle was 0.29 x 10(-3) cm x min(-1). CONCLUSION: This in vitro experimental model of rat BBB was close to resemble the in vivo situation for examination of the permeability of nanoparticle and toxicity evaluation.

Animals↗
PubMed2006

[Epidemiological feature of metabolic syndrome in Shanghai residents aged 15 - 74 years].

OBJECTIVE: To assess the prevalence of the metabolic syndrome in Shanghai residents. METHODS: A cross-sectional study was conducted in Shanghai with a representative sample of 14,327 Chinese adults from 15 to 74 years of age. The sample was randomly selected using stratified cluster sampling. The criteria of International Diabetes Federation (IDF), the US National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines and the China Diabetes Society (CDS), respectively, were applied for diagnosis. RESULTS: Diagnosed by using the IDF criterion, the crude prevalence of metabolic syndrome was 17.51%, and the age and gender-adjusted prevalence was 12.81% (95% CI: 12.26 - 13.36). The prevalence of the metabolic syndrome was higher in females than in males (14.79% and 10.93%, respectively), and higher in urban residents than in rural ones (13.71% and 10.72%, respectively). The age-specific prevalence of the metabolic syndrome increased in both male and female residents and the prevalence of metabolic syndrome in females 45 years of age or elder was significantly increased. The prevalence of having at least 3 parameters of metabolic syndrome was 22.28%. According to the ATP III guideline, the crude and age-adjusted prevalence of metabolic syndrome was 12.03% and 8.62%, respectively. Based on the criterion of CDS, they were 13.98% and 10.41%. CONCLUSION: There is a high prevalence of metabolic syndrome in Shanghai residents. Metabolic syndrome has become a noteworthy public health problem. It suggests that community-integrated control of metabolic syndrome should have its priority.

Adolescent↗
PubMed2006

Generation of 4D CT image data and analysis of lung tumour mobility during the breathing cycle.

The mobility of lung tumours during the breathing cycle is a source of error in radiotherapy treatment planning. Spatio-temporal CT data sets can be used to measure the movement of lung tumours caused by breathing. Because modern CT scanners can only scan a limited region of the body simultaneously at different times, patients have to be scanned in segments consisting of multiple slices. For studying free breathing motion multislice CT scans can be collected simultaneously with digital spirometry over several breathing cycles. The image data set is assembled by sorting the free breathing multislice CT scans according to the couch position and the tidal volume. But artefacts can occur because there are no data segments for exactly the same tidal volume and all couch positions. In this paper, a non-linear registration method is used to interpolate and reconstruct 4D CT data sets from multislice CT scans in high quality. The non-linear registration estimates a velocity field between successive scans, which is used to reconstruct a 4D CT data set by interpolating data at user-defined tidal volumes. By this technique, artefacts can be reduced significantly. Furthermore, the reconstructed 4D CT data sets are used for studying the motion of lung tumours during the respiratory cycle. The reconstructed 4D data sets of 4 patients were used to quantify the individual lung tumour motion as well as to estimate the tumour's appearance probability during a breathing cycle.

Diagnostic Imaging↗
PubMed2006

[Micro-focus X-ray for cochlear implantation research on small animals].

OBJECTIVE: To develop an imaging system suitable for cochlear implant research on small laboratory animals. METHODS: A novel micro-focus X-ray imaging system was developed. The key features of the system were the use of a micro-focus X-ray source (less than 10 micrometers) and an appropriate choice of source-object and object-image distance. The new X-ray modality was evaluated on heads of cats, guinea pigs and rats. RESULTS: It proved to be an useful tool to provide excellent image of small animal cochlea, allowing a clear electrode position to be established, and also helped greatly in detecting the breakage of electrode array. CONCLUSIONS: Experimental studies performed in cats, guinea pigs and rats confirmed that micro-focus radiography was an important tool for cochlear implant research in laboratory

Animals↗
PubMed2005

Novel breathing motion model for radiotherapy.

PURPOSE: An accurate model of breathing motion under quiet respiration is desirable to obtain the most accurate and conformal dose distributions for mobile lung cancer lesions. On the basis of recent lung motion measurements and the physiologic functioning of the lungs, we have determined that the motion of lung and lung tumor tissues can be modeled as a function of five degrees of freedom, the position of the tissues at a user-specified reference breathing phase, tidal volume and its temporal derivative airflow (tidal volume phase space). Time is an implicit variable in this model. METHODS AND MATERIALS: To test this hypothesis, a mathematical model of motion was developed that described the motion of objects p in the lungs as linear functions of tidal volume and airflow. The position of an object was described relative to its position -->P0 at the reference tidal volume and zero airflow, and the motion of the object was referenced to this position. Hysteresis behavior was hypothesized to be caused by pressure imbalances in the lung during breathing and was, in this model, a function of airflow. The motion was modeled as independent tidal volume and airflow displacement vectors, with the position of the object at time t equal to the vector sum -->rP(t) = -->rv(t) + -->rf(t) where -->rv(t) and -->rf(t) were displacement vectors with magnitudes approximated by linear functions of the tidal volume and airflow. To test this model, we analyzed five-dimensional CT scans (CT scans acquired with simultaneous real-time monitoring of the tidal volume) of 4 patients. The scans were acquired throughout the lungs, but the trajectories were analyzed in the couch positions near the diaphragm. A template-matching algorithm was implemented to identify the positions of the points throughout the 15 scans. In total, 76 points throughout the 4 patients were tracked. The lateral motion of these points was minimal; thus, the model was described in two spatial dimensions, with a total of six parameters necessary to describe the 30 degrees of freedom inherent in the 15 positions. RESULTS: For the 76 evaluated points, the average discrepancy (the distance between the measured and prediction positions) of the 15 locations for each tracked point was 0.75 +/- 0.25 mm, with an average maximal discrepancy of 1.55 +/- 0.54 mm. The average discrepancy was also tabulated as a fraction of the breathing motion. Discrepancies of <10% and 15% of the overall motion occurred in 73% and 95% of the tracked points, respectively. CONCLUSION: The motion tracking algorithms are being improved and automated to provide more motion data to test the models. This may allow a measurement of the motion-fitting parameters throughout the lungs. If the parameters vary smoothly, interpolation may be possible, yielding a continuous mathematical model of the breathing motion throughout the lungs. The utility of the model will depend on its stability as a function of time. If the model is only robust during the measurement session, it may be useful for determining lung function. If it is robust for weeks, it may be useful for treatment planning and gating of lung treatments. The use of tidal volume phase space for characterizing breathing motion appears to have provided, for the first time, the potential for a patient-specific mathematical model of breathing motion.

Humans↗
PubMed2005

Reductive and oxidative DNA damage by photoactive platinum(II) intercalators.

Several photoactive platinum alpha-diimine intercalators have been prepared to develop new probes of DNA oxidation and reduction chemistry. Five water-soluble bis(mes')Pt(II) complexes (mes' = N,N,N,3,5-pentamethylaniline) with various aromatic alpha-diimine ligands (dppz = dipyridophenazine, np = naphtha[2,3-f][1,omega]phenanthroline, CN-np = naphtho[2,3-f][1,10]phenanthroline-9-carbonitrile, CN(2)-np = naphtho[2,3-f][1,10]phenanthroline-9,14-dicarbonitrile, and bp = benzo-[f][1,10]phenanthroline) were synthesized. The complex [(np)Pt(mes')(2)]Cl(2) was also characterized by X-ray crystallography, and the crystal structure shows that the ortho-methyl groups of the mes' ligands conveniently block substitution at the vacant sites of platinum without overlapping with the intercalating alpha-diimine ligand. The Pt(II) complexes were found to have excited-state oxidation and reduction potentials of -0.6 to -1.0 and 1.0 to 1.5 V versus NHE, respectively, making them potent photoreductants as well as photooxidants. Many of the complexes are found to promote the photooxidation of N(2)-cyclopropyldeoxyguanosine (d(Cp)G). Photoexcited [(dppz)Pt(mes')(2)](2+) is found to be most efficient in this photooxidation, as well as in the photoreduction of N(4)-cyclopropylcytidine ((Cp)C); these modified nucleosides rapidly decompose in a ring-opening reaction upon oxidation or reduction. Photoexcited [(dppz)Pt(mes')(2)]Cl(2), upon intercalation into the DNA pi stack, is found, in addition, to promote reductive and oxidative damage within the DNA duplex, as is also probed using the kinetically fast electron and hole traps, (Cp)C and (Cp)G. These Pt complexes may therefore offer useful reactive tools to compare and contrast directly reductive and oxidative chemistry in double helical DNA.

Cations, Divalent↗
PubMed2005

A known functional polymorphism (Ile120Val) of the human PCMT1 gene and risk of spina bifida.

Folate binding protein 1 (Folr1) knockout mice with low maternal folate concentrations have been shown to be excellent animal models for human folate-responsive neural tube defects (NTDs). Previous studies using the Folr1 knockout mice revealed that maternal folate supplementation up-regulates the expression of the PCMT1 gene in Folr1 nullizygous neural tube tissue during neural tube closure. PCMT1 encodes the protein repair enzyme l-isoaspartate (d-aspartate) O-methyltransferase (PIMT) that converts abnormal d-aspartyl and l-isoaspartyl residues to the normal l-aspartyl form. PIMT is known to protect certain neural cells from Bax-induced apoptosis. Pcmt1-deficient mice present with abnormal AdoMet/AdoHcy homeostasis. We hypothesized that a known functional polymorphism (Ile120Val) in the human PCMT1 gene is associated with an increased risk of folate-responsive human NTDs. A case-control study was conducted to investigate a possible association between this polymorphism and risk of spina bifida. Compared to the Ile/Ile and Ile/Val genotypes, the homozygous Val/Val genotype showed decreased risk for spina bifida (adjusted odds ratio=0.6, 95% confidence interval: 0.4-0.9). Our results showed that the Ile120Val polymorphism of PCMT1 gene is a genetic modifier for the risk of spina bifida. Val/Val genotype was associated with a reduction in risk for spina bifida.

Adult↗
PubMed2005

Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery.

In this paper, a novel drug carrier for brain delivery, cationic bovine serum albumin (CBSA) conjugated with poly(ethyleneglycol)-poly(lactide) (PEG-PLA) nanoparticle (CBSA-NP), was developed and its effects were evaluated. The copolymers of methoxy-PEG-PLA and maleimide-PEG-PLA were synthesized by ring opening polymerization of D,L-lactide initiated by methoxy-PEG and maleimide-PEG, respectively, which were applied to prepare pegylated nanoparticles by means of double emulsion and solvent evaporation procedure. Native bovine serum albumin (BSA) was cationized and thiolated, followed by conjugation through the maleimide function located at the distal end of PEG surrounding the nanoparticle's surface. Transmission electron micrograph (TEM) and dynamic light scattering results showed that CBSA-NP had a round and regular shape with a mean diameter around 100 nm. Surface nitrogen was detected by X-ray photoelectron spectroscopy (XPS), and colloidal gold stained around the nanoparticle's surface was visualized in TEM, which proved that CBSA was covalently conjugated onto its surface. To evaluate the effects of brain delivery, BSA conjugated with pegylated nanoparticles (BSA-NP) was used as the control group and 6-coumarin was incorporated into the nanoparticles as the fluorescent probe. The qualitative and quantitative results of CBSA-NP uptake experiment compared with those of BSA-NP showed that rat brain capillary endothelial cells (BCECs) took in much more CBSA-NP than BSA-NP at 37 degrees C, at different concentrations and time incubations. After a dose of 60 mg/kg CBSA-NP or BSA-NP injection in mice caudal vein, fluorescent microscopy of brain coronal sections showed a higher accumulation of CBSA-NP in the lateral ventricle, third ventricle and periventricular region than that of BSA-NP. There was no difference on BCECs' viability between CBSA-conjugated and -unconjugated pegylated nanoparticles. The significant results in vitro and in vivo showed that CBSA-NP was a promising brain drug delivery carrier with low toxicity.

Albumins↗
PubMed2005

Synthesis and evaluation of tricyclic pyrrolopyrimidinones as dipeptide mimetics: inhibition of interleukin-1beta-converting enzyme.

The application of a tricyclic pyrrolopyrimidinone scaffold for the synthesis of peptidomimetic inhibitors of interleukin-1beta-converting enzyme (ICE) is reported. The synthesis of the tricyclic scaffold and conversion of it to a variety of target ICE inhibitors were accomplished in 4-5 steps. In vitro biological evaluation of the tricyclic pyrrolopyrimidinones revealed fair to good ICE inhibitors, with the most active compound exhibiting an IC50 of 14 nM in a caspase-1 enzyme binding assay.

Caspase Inhibitors↗
PubMed2005

Discovery of novel conformationally restricted diazocan peptidomimetics as inhibitors of interleukin-1beta synthesis.

A novel diazocan containing dipeptide mimetic was synthesized via reductive N-N bond cleavage of a pyrazolidino-pyrazolidine using Raney-Ni and evaluated as an ICE inhibitor. This versatile 8-membered ring containing scaffold possesses an N-5 ring nitrogen that was used to explore structure-activity relationships in a cell-based assay measuring inhibition of interleukin-1beta.

Caspase Inhibitors↗
PubMed2005

[Proportion of proinsulin two minutes after arginine stimulation: a pilot study].

OBJECTIVE: To seek an easy way to evaluate islet beta cell function. METHODS: 214 residents of Shanghai, aged 20-70, all of Han nationality, were divided into 3 groups according the 1999 WHO standard: 39 in the normal glucose tolerance (NGT) group, aged 52 years +/- 6 years, with the BMI of 22.3 kg/m(2) +/- 0.4 kg/m(2); 29 in the impaired glucose tolerance (IGT) group, aged 54 years +/- 9 years, with the BMI of 24.4 kg/m(2) +/- 0.6 kg/m(2); and 146 in the T2DM group, that was subdivided into 2 subgroups: 43 in the newly diagnosed T2DM (NT2DM) group, aged 52 years +/- 9 years, with the BMI of 24.4 kg/m(2) +/- 0.5 kg/m(2), and 103 in the previously diagnosed T2DM (PT2DM) group, aged 57 years +/- 9 years, with the BMI of 23.5 kg/m(2) +/- 0.3 kg/m(2). Arginine at the dose of 10% 50 ml was injected intravenously in fasting situation. Two, four, and six minutes after blood samples were collected from a needle indwelling in the contralateral vein to examine the levels of plasma glucose (PG), true insulin (TI), and proinsulin (PI). RESULTS: (1) The TI and TI/PG levels of all groups peaked 2 minutes after arginine stimulation and then gradually decreased, however, the levels 6 minutes after stimulation were still higher than the baseline values. The peak values of TI and TI/PG were arranged from high to low in the order of IGT, NGT, NT2DM and PT2DM. The peak values of NT2DM and PT2DM groups were significantly lower than those of the NGT and IGT groups (all P < 0.01). The peak values of the NT2DM group were significantly higher than those of the PT2DM group (both P < 0.01). (2) The PI value of the IGT, NT2DM and PT2DM groups peaked 2 minutes after the stimulation and then gradually decreased with the peak values significantly higher than that of the NGT group (all P < 0.05). The fasting PI/TI and PI/(TI + PI) of the NGT group were all significantly lower than those of the IGT group (both P < 0.05). (3) The changes of PI/TI in each groups manifested almost the mirror image of TI/PG mentioned above, and the lowest PI/TI levels were observed 2 minutes after stimulation. The similar changes of PI/(TI + PI) were found. The lowest points of groups 2 minutes after stimulation was arranged from low to high in the order of NGT, IGT, NT2DM and PT2DM. CONCLUSION: The PI/TI and PI/(TI + PI) values 2 minutes after arginine stimulation may be used as predictors for beta cell function in clinical practice.

Adult↗
PubMed2005

Protein kinase C-epsilon regulates the apoptosis and survival of glioma cells.

In this study, we examined the role of protein kinase C (PKC)-epsilon in the apoptosis and survival of glioma cells using tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-stimulated cells and silencing of PKCepsilon expression. Treatment of glioma cells with TRAIL induced activation, caspase-dependent cleavage, and down-regulation of PKCepsilon within 3 to 5 hours of treatment. Overexpression of PKCepsilon inhibited the apoptosis induced by TRAIL, acting downstream of caspase 8 and upstream of Bid cleavage and cytochrome c release from the mitochondria. A caspase-resistant PKCepsilon mutant (D383A) was more protective than PKCepsilon, suggesting that both the cleavage of PKCepsilon and its down-regulation contributed to the apoptotic effect of TRAIL. To further study the role of PKCepsilon in glioma cell apoptosis, we employed short interfering RNAs directed against the mRNA of PKCepsilon and found that silencing of PKCepsilon expression induced apoptosis of various glioma cell lines and primary glioma cultures. To delineate the molecular mechanisms involved in the apoptosis induced by silencing of PKCepsilon, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that knockdown of PKCepsilon did not affect the expression of Bcl2 and Bax or the phosphorylation and expression of Erk1/2, c-Jun-NH2-kinase, p38, or STAT, whereas it selectively reduced the expression of AKT. Similarly, TRAIL reduced the expression of AKT in glioma cells and this decrease was abolished in cells overexpressing PKCepsilon. Our results suggest that the cleavage of PKCepsilon and its down-regulation play important roles in the apoptotic effect of TRAIL. Moreover, PKCepsilon regulates AKT expression and is essential for the survival of glioma cells.

Amino Acid Sequence↗
PubMed2005

PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking.

PICK1 and ABP/GRIP bind to the AMPA receptor (AMPAR) GluR2 subunit C terminus. Transfer of the receptor from ABP/GRIP to PICK1, facilitated by GluR2 S880 phosphorylation, may initiate receptor trafficking. Here we report protein interactions that regulate these steps. The PICK1 BAR domain interacts intermolecularly with the ABP/GRIP linker II region and intramolecularly with the PICK1 PDZ domain. Binding of PKCalpha or GluR2 to the PICK1 PDZ domain disrupts the intramolecular interaction and facilitates the PICK1 BAR domain association with ABP/GRIP. Interference with the PICK1-ABP/GRIP interaction impairs S880 phosphorylation of GluR2 by PKC and decreases the constitutive surface expression of GluR2, the NMDA-induced endocytosis of GluR2, and recycling of internalized GluR2. We suggest that the PICK1 interaction with ABP/GRIP is a critical step in controlling GluR2 trafficking.

Amino Acid Sequence↗
PubMed2005

A systematic investigation of the synthetic utility of glycopeptide glycosyltransferases.

Glycosyltransferases involved in the biosynthesis of bacterial secondary metabolites may be useful for the generation of sugar-modified analogues of bioactive natural products. Some glycosyltransferases have relaxed substrate specificity, and it has been assumed that promiscuity is a feature of the class. As part of a program to explore the synthetic utility of these enzymes, we have analyzed the substrate selectivity of glycosyltransferases that attach similar 2-deoxy-L-sugars to glycopeptide aglycons of the vancomycin-type, using purified enzymes and chemically synthesized TDP beta-2-deoxy-L-sugar analogues. We show that while some of these glycopeptide glycosyltransferases are promiscuous, others tolerate only minor modifications in the substrates they will handle. For example, the glycosyltransferases GtfC and GtfD, which transfer 4-epi-L-vancosamine and L-vancosamine to C-2 of the glucose unit of vancomycin pseudoaglycon and chloroorienticin B, respectively, show moderately relaxed donor substrate specificities for the glycosylation of their natural aglycons. In contrast, GtfA, a transferase attaching 4-epi-L-vancosamine to a benzylic position, only utilizes donors that are closely related to its natural TDP sugar substrate. Our data also show that the spectrum of donors utilized by a given enzyme can depend on whether the natural acceptor or an analogue is used, and that GtfD is the most versatile enzyme for the synthesis of vancomycin analogues.

Anti-Bacterial Agents↗
PubMed2005

Genetic variation in the proto-oncogene SKI and risk for orofacial clefting.

BACKGROUND: SKI is a proto-oncogene that is required for development of the central nervous system and skeletal muscle, and is involved in specifying selected cranial neural-crest-derived craniofacial structures. To identify genetic variants within the SKI gene and investigate the potential association between SKI polymorphisms and risk for orofacial defects, we initially re-sequenced the gene. METHODS: DNA re-sequencing of all seven exons of the SKI gene was performed on 100 control samples. Subsequently, we genotyped 394 samples (148 CLP cases, 99 CP cases, and 147 control infants) for a novel SNP identified in the DNA re-sequencing effort using restriction fragment length polymorphism (RFLP) analysis. RESULTS: We identified one polymorphism in exon 1 of the SKI gene (257C>G) from controls. This SNP resulted in an amino acid change from alanine to glycine (A62G, GenBank Accession No. NM_003036). Among all samples genotyped by the RFLP method, variants (CG, GG) were found in 10.5% of the cases, compared to a prevalence of 17.7% in the controls. The odds ratio was calculated to be 0.6, with a 95% confidence interval (CI) of 0.3-1.0. CONCLUSION: In a population of California infants with craniofacial defects, a novel polymorphism of the SKI gene was found to be associated with a decreased risk for orofacial defects. The function of this polymorphism and how it might confer protection to the embryo against craniofacial malformations is currently under investigation in our laboratory.

Case-Control Studies↗