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Biomedical subjects

Wei Lu

Publications and source records attributed to Wei Lu.

At least 55 records · Page 3Linked to original sources

Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration.

In order to improve the absorption of nanoparticles in the brain following nasal administration, a novel protocol to conjugate biorecognitive ligands-lectins to the surface of poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles was established in the study. Wheat germ agglutinin (WGA), specifically binding to N-acetyl-D-glucosamine and sialic acid, both of which were abundantly observed in the nasal cavity, was selected as a model lectin. The WGA-conjugated nanoparticles were prepared by incorporating maleimide in the PLA-PEG molecular and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothialane thiolated WGA. Coupling of WGA with the PEG-PLA nanoparticles was confirmed by the existence of gold-labeled WGA-NP under TEM. The retention of biorecognitive activity of WGA after the covalent coupling procedure was confirmed by haemagglutination test. The resulting nanoparticles presented negligible nasal ciliatoxicity and the brain uptake of a fluorescent marker-coumarin carried by WGA functionized nanoparticles was about 2 folds in different brain tissues compared with that of coumarin incorporated in the unmodified ones. Thus, the technique offered a novel effective noninvasive system for brain drug delivery, especially for brain protein and gene delivery.

Administration, Intranasal↗

Fine tuning photoluminescence properties of CdSe nanoparticles by surface states modulation.

Fine control of the photoluminescence properties of CdSe nanoparticles (NPs) dispersed in CHCl3 is achieved by simple adjustment of the NPs concentration, and the wavelength of photoluminescence emission of CdSe NPs can be tuned within the nanometer accuracy. The mechanism of the process is proposed to be relevant to the modulation of the surface states of NPs by the concentration. This solution-based approach offers an attractive and complementary process to the conventional band gap engineering of semiconductor NPs with fine tunable optical properties.

Journal Article↗

Integrated optical filter arrays fabricated by using the combinatorial etching technique.

A combinatorial etching technique is developed to fabricate integrated narrow bandpass filters on a single substrate. It is highly efficient for fabrication of integrated filter arrays in optical regions. A monolithic filter array has been fabricated by using the technique with a two-step deposition process. The filter contains 32 elements in the near-infrared region. The relative full width at half-maximum (FWHM) sigmalambda/lambda of the filter elements is less than 0.2%. Such a narrow bandpass filter array can be utilized in many optical applications.

Journal Article↗

Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases.

Miltirone analogues were synthesized and evaluated for inhibitory activity against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25 inhibitory activity, and several exhibited higher selectivity for Cdc25 than for PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against the tumor cell lines A549 and HCT-116, producing IC(50) values in the micromolar range.

Cell Line, Tumor↗

Electron transport in self-assembled polymer molecular junctions.

A molecular junction of a poly(p-phenyleneethynylene)s derivative with thioacetate end groups (TA-PPE) was fabricated by self-assembling. Nanogap electrodes made by electroplating technique was used to couple thiol end groups of TA-PPE molecules. Room temperature current-voltage characteristics of the molecular junction exhibited highly periodic, repeatable, and identical stepwise features. First-principles calculations suggest that one possibility for the equidistant step is due to the opening of different conducting channels that corresponds to the unoccupied molecular orbitals of the polymer in the junction. It is interesting to see that an 18 nm long polymer is of quantized electronic structures and behaves like a quantum transport device.

Journal Article↗

Allelotyping analysis at chromosome arm 8p of high-grade prostatic intraepithelial neoplasia and incidental, latent, and clinical prostate cancers.

In this study, we used 7 informative microsatellite markers at 8p22, 23.1, and 23.2 in Japanese patients to compare frequency of loss of heterozygosity (LOH) in 53 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 38 cases (38 lesions) of incidental prostate cancer (IPC), 31 cases (41 lesions) of latent prostate cancer (LPC), and 102 cases (168 lesions) of clinical prostate cancer (CPC). The frequency of LOH at 8p22-23.2 with at least 1 marker was 0%, 33%, 57%, and 51% in the HGPIN, IPC, LPC, and CPC cases, respectively. No statistically significant difference was found at 8p22-23.2 between the types of prostate cancer. However, the frequency of 8p22 deletion was significantly higher in CPC and LPC cases than in IPC cases (P = 0.0003) or lesions (P = 0.0017). The frequency of LOH at 8p22 and 8p23.1 loci in high-grade tumors was significantly higher than in low-grade tumors in both the LPCs/IPCs and CPCs (P < 0.05). Allelic loss at 8p22 was significantly more frequent in CPC than in IPC (P = 0.002) and in pT4 CPC than in earlier-stage CPC (P = 0.038). These findings suggest that deletion of 8p is an important event in both the initiation and metastasis of prostate cancer. The extremely high frequency of LOH at 8p22-23.1 in high-grade tumors suggests the existence of a novel putative tumor-suppressor gene associated with the progression of prostate cancer. These results should be useful in identifying the target gene of deletion at 8p.

Alleles↗

Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation.

BACKGROUND: The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. METHODS: Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-gamma ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. RESULTS: Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-gamma producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. CONCLUSIONS: Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

Animals↗

First-principles study of electrochemical gate-controlled conductance in molecular junctions.

A first-principles computational method is developed to study the electrochemical gate-controlled conductance in molecular junctions. It has been applied to a single molecular field-effect transistor made by a perylene tetracaboxylic diimide molecule connected to gold electrodes and has successfully reproduced the experimentally observed huge gate voltage effect on the current. It is found that such a significant gain is a result of the large polarization of the molecule induced by the huge local electrical field generated by the electrochemical gate. The resonant electron tunneling through unoccupied molecular orbitals is shown to be the dominant transport process.

Computer Simulation↗

High-performance transparent conducting oxide nanowires.

We report the growth and characterization of single-crystalline Sn-doped In2O3 (ITO) and Mo-doped In2O3 (IMO) nanowires. Epitaxial growth of vertically aligned ITO nanowire arrays was achieved on ITO/yttria-stabilized zirconia (YSZ) substrates. Optical transmittance and electrical transport measurements show that these nanowires are high-performance transparent metallic conductors with transmittance of approximately 85% in the visible range, resistivities as low as 6.29 x 10(-5) Omega x cm and failure-current densities as high as 3.1 x 10(7) A/cm2. Such nanowires will be suitable in a wide range of applications including organic light-emitting devices, solar cells, and field emitters. In addition, we demonstrate the growth of branched nanowire structures in which semiconducting In2O3 nanowire arrays with variable densities were grown epitaxially on metallic ITO nanowire backbones.

Journal Article↗

The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles in rats.

The aim of this study was to encapsulate nimodipine (NM) within methoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) nanoparticles and to investigate its brain targeting efficiency following intranasal administration. NM-loaded nanoparticles, prepared through an emulsion/solvent evaporation technique, were characterized in terms of size, zeta potential, NM loading and in vitro release. The nanoparticles were administered intranasally to rats, and the concentrations of NM in blood, cerebrospinal fluid (CSF) and brain tissues were monitored. The contribution of the olfactory pathway to the uptake of NM in the brain was determined by calculating the brain/plasma concentration ratios and "brain drug direct transport percentage (DTP)" following intranasal administration of the nanoparticles and the solution formulation. The results showed that MPEG-PLA nanoparticles had a mean particle size of 76.5 +/- 7.4 nm, a negative surface charge and a 5.2% NM loading. In vitro release was moderate under sink conditions. The intranasal administration of nanoparticles resulted in a low but constant NM level in plasma. The ratio of AUC values of the nanoparticles to the solution was 1.56 in CSF. The olfactory bulb/plasma and CSF/plasma concentration ratios were significantly higher (P < 0.05) after application of nanoparticles than those of the nasal solution, except the ratio in olfactory bulb at 5 min. Furthermore, nasally administered nanoparticles yielded 1.6-3.3-fold greater DTP values in CSF, olfactory bulb and other brain tissues compared to nasal solution. Thus, MPEG-PLA nanoparticles demonstrated its potential on improving the efficacy of the direct nose-brain transport for drugs.

Administration, Intranasal↗

Field data: a study on trend and prediction of fatal traffic injuries prevalence in Shanghai.

OBJECTIVE: The main objectives of the study are to analyze fatal traffic-injury trends in 1987-2003 in Shanghai and predict its prevalence in near future and provide scientific data for the local governmental decision on developing practical working methods on traffic-injury prevention and control. METHODS: In this study, epidemiological method and Grey dynamic model GM (1,1) were introduced to analyze and forecast traffic-injury mortality rates respectively. RESULTS: There was an apparent increasing trend of traffic-related injuries in Shanghai from 1987 to 2003 with the rate of growth in motorization. The average rates of annual increase are 3.59% in fatalities (from 7.78 per 100,000 population to 14.18 per 100,000 population) during the period. Pedestrians were the most common type of victims (29.6%), followed by bicyclists (25.1%), and motorcyclists (24.1%). Males accounted for the majority of all victims, over 69%. The population of high-school and lower high-school education level represented 66.4% victims of total road-traffic injuries. And if no special factors effect its development, the traffic fatalities would be up to 17.84 per 100,000 population in 2010, when calculating from equations we found and validated Y(t) = 359.90 x e0.027(t-1)-352.13, (t = 1, 2, ..., N) for Shanghai. CONCLUSION: Our data indicate the risk of fatal traffic injuries has increased in recent years and will go on growing in the near future in Shanghai. The findings showed that Grey dynamic model GM (1,1) is eligible on the prediction and can be a tool for injuries forecasting, implementing effective policies, programs, and interventions for reducing traffic injuries in the big cities.

Accidents, Traffic↗

Analysis of gene expression profile in colon cancer using the Cancer Genome Anatomy Project and RNA interference.

OBJECTIVE: To investigate the changes in the gene expression profile in colon cancer to further identify gene markers that may be useful in the management of this disease. METHODS: Data from serial analysis of gene expression (SAGE) collected by the Cancer Genome Anatomy Project (CGAP) were used to detect the difference in gene expression between normal tissue and colon cancer, and were further confirmed in a sample of 20 patients using RT-PCR. To identify the functions of differential genes in regulating the cell growth of colon cancer, RNA interference (RNAi) was used to block one of these genes in the colon cancer cell line HCT-116. RESULTS: Expression changes of greater than twofold in two SAGE libraries of colon cancer compared to two of normal tissue were observed for 216 tags of a total of 195,160 transcript tags (54 up-regulated genes and 136 down-regulated genes). Subsequent analysis of 17 genes by RT-PCR confirmed the reliability of this analysis. RNAi-mediated blockage of one of these genes, transforming growth factor (TGF)beta1, significantly reduced the growth of a colon cancer cell line. CONCLUSIONS: The combination of CGAP analysis and RNAi provides an excellent system to rapidly define the specific genes that are up-regulated in cancer to impact the growth of cancer cells. Further study on these differential overexpressed genes may provide gene markers for the detection and treatment of colon cancer.

Biomarkers, Tumor↗

A comparison between amplitude sorting and phase-angle sorting using external respiratory measurement for 4D CT.

Respiratory motion can cause significant dose delivery errors in conformal radiation therapy for thoracic and upper abdominal tumors. Four-dimensional computed tomography (4D CT) has been proposed to provide the image data necessary to model tumor motion and consequently reduce these errors. The purpose of this work was to compare 4D CT reconstruction methods using amplitude sorting and phase angle sorting. A 16-slice CT scanner was operated in ciné mode to acquire 25 scans consecutively at each couch position through the thorax. The patient underwent synchronized external respiratory measurements. The scans were sorted into 12 phases based, respectively, on the amplitude and direction (inhalation or exhalation) or on the phase angle (0-360 degrees) of the external respiratory signal. With the assumption that lung motion is largely proportional to the measured respiratory amplitude, the variation in amplitude corresponds to the variation in motion for each phase. A smaller variation in amplitude would associate with an improved reconstructed image. Air content, defined as the amount of air within the lungs, bronchi, and trachea in a 16-slice CT segment and used by our group as a surrogate for internal motion, was correlated to the respiratory amplitude and phase angle throughout the lungs. For the 35 patients who underwent quiet breathing, images (similar to those used for treatment planning) and animations (used to display respiratory motion) generated using amplitude sorting displayed fewer reconstruction artifacts than those generated using phase angle sorting. The variations in respiratory amplitude were significantly smaller (P < 0.001) with amplitude sorting than those with phase angle sorting. The subdivision of the breathing cycle into more (finer) phases improved the consistency in respiratory amplitude for amplitude sorting, but not for phase angle sorting. For 33 of the 35 patients, the air content showed significantly improved (P < 0.001) correlation with the respiratory amplitude than with the phase angle, suggesting a stronger relationship between internal motion and amplitude. Overall, amplitude sorting performed better than phase angle sorting for 33 of the 35 patients and equally well for two patients who were immobilized with a stereotactic body frame and an abdominal compression plate.

Algorithms↗

A semi-automatic method for peak and valley detection in free-breathing respiratory waveforms.

The existing commercial software often inadequately determines respiratory peaks for patients in respiration correlated computed tomography. A semi-automatic method was developed for peak and valley detection in free-breathing respiratory waveforms. First the waveform is separated into breath cycles by identifying intercepts of a moving average curve with the inspiration and expiration branches of the waveform. Peaks and valleys were then defined, respectively, as the maximum and minimum between pairs of alternating inspiration and expiration intercepts. Finally, automatic corrections and manual user interventions were employed. On average for each of the 20 patients, 99% of 307 peaks and valleys were automatically detected in 2.8 s. This method was robust for bellows waveforms with large variations.

Algorithms↗

Potent antitumor activity of 10-methoxy-9-nitrocamptothecin.

The present data showed that 10-methoxy-9-nitrocamptothecin (MONCPT), a family of camptothecin analogues, possessed high antitumor activity in vitro and in vivo. Cytotoxicity assays showed that MONCPT was a potential and highly efficient antitumor compound with IC50 values of 0.1 to 500 nmol/L in nine tumor cell lines. The high cytotoxic potency of MONCPT was paralleled with its ability to increase the cellular accumulation of DNA damage. DNA relaxation assay also showed that MONCPT exerted high potency as a topoisomerase I inhibitor. Moreover, administration of MONCPT (5-20 mg/kg) for 15 to 17 days significantly inhibited tumor growth in human androgen-independent prostate tumor (PC3) and human non-small cell lung tumor (A549) xenografts; the inhibition rates ranged from 29.6% to 98%. The cytotoxic effect of 1,000 nmol/L of MONCPT in PC3 cells was associated with causing an arrest in G0-G1 phase, whereas that of 10 and 100 nmol/L MONCPT was relative to a persistent block in G2-M phase. Furthermore, down-regulation of CDK2, CDK4, and cyclin D1 was observed in PC3 cells treated with 1,000 nmol/L of MONCPT, whereas overexpression of CDK7, CDK1, and cyclin B1 was seen in PC3 cells treated with 10 and 100 nmol/L of MONCPT. These results suggested that cell cycle regulation might contribute to the anticancer properties of MONCPT and strongly support the further anticancer development of MONCPT.

Animals↗

Preparation of bupleurum nasal spray and evaluation on its safety and efficacy.

Radix Bupleuri is widely used in traditional medicine for the treatment of fever, pain, and inflammation associated with influenza or the common cold. The essential oil extracted from the herb is generally claimed to play the major role in the efficacious treatment of fever. The purpose of the present study was to formulate an intranasal delivery system for the essential oil in an aqueous solution used in the form of nasal spray. From 450 g Radix Bupleuri was extracted the essential oil in the amount of about 0.2 ml, which was slightly water-soluble and viscous with low-fluidity. In order to dissolve the essential oil evenly in the aqueous solution, tween-80 (TW-80, used in 10% (w/v) solution), propylene glycol (PG) and diethylene glycol monoethyl ether (TC) were selected as the favorable solubilizing agents, whose amount was respectively determined by L16(4(5)) orthogonal design. An aqueous solution with clarity and no ciliotoxicity was prepared when TW-80 8% (v/v), PG 14.4% (v/v) and TC 14.4% (v/v) were added. Employed to evaluate the acute toxicity, the rats grew well and were kept active and healthy within 14 d after an intranasal administration of this preparation at the dose of oil from 10 g Bupleuri/kg (50-fold higher than the clinical dose), indicating that there would be no serious toxicity at the normal dose. Intranasal administration of this preparation to 2 kg rabbits with fever induced by subcutaneous injection of turpentine decreased body temperature markedly (0.5, 0.8 and 1.0 degrees C respectively at the dose of oil from 1, 2 and 4 g Bupleuri/body). In addition, the administration significantly reduced fever in 200 g rats induced by intramuscular injection of colicine suspension (0.6 degrees C at the dose of oil from 0.8 g Bupleuri/body). The results suggest that the formulation of nasal spray for the essential oil from Radix Bupleuri can be potentially effective in the treatment of fever.

Administration, Intranasal↗

[Apoptosis of in vitro cultured BMMNC from MDS patients induced by arsenic sulfide].

The aim of this study was to investigate the inhibition effect of arsenic sulfide (As2S2) on the growth of in vitro cultured BMMNC from MDS patients and to explore its possible cellular and molecular mechanisms. The apoptosis of MDS cells induced by As2S2 solution of different concentrations were studied with MTT, flow cytometry, and RT-PCR. The results showed that (1) low concentration of As2S2 (0-0.6 mg/L) had no marked inhibition effect on proliferation of MDS cells; (2) after treatment with 1.5-50 mg/L of As2S2, both low risk MDS cells and high risk MDS cells presented typical features of apoptosis with a dose-dependent manner, the expression of bcl-2 mRNA and the ratio of bcl-2/bax obviously decreased after As2S2 treatment (P < 0.05); (3) BMMNC from MDS patients had higher apoptosis ratio than that of BMMNC from control. It is concluded that BMMNC excessive apoptosis exists in MDS patients; low concentration of As2S2 (0-0.6 mg/L) shows no inhibition effect on proliferation of MDS cells; high concentration of As2S2 (1.5-50 mg/L) induces apoptosis of MDS cells.

Adult↗

[Clinical study on crossed disparity and uncrossed disparity in intermittent exotropia before and after surgery].

OBJECTIVE: To understand the clinical variety of zero disparity, crossed disparity and uncrossed disparity in intermittent exotropia before and after strabismus surgery. METHODS: 100 cases of intermittent exotropia were involved in the study. Before and after surgery, zero disparity stereo-acuity, crossed disparity and uncrossed disparity stereo-acuity were examined with stereogram designed by Yan Shaoming, distance fusion range and distance stereo-acuity were examined with traditional and random dot synoptophore stereogram. The patients were divided into four groups based on the results of the stereogram examination before surgery. RESULTS: In the 100 cases, there was no coexistence of zero disparity and uncrossed disparity, no coexistence of crossed and uncrossed disparity, and no existence of only crossed disparity or only uncrossed disparity. Postoperative zero disparity, crossed disparity, uncrossed disparity, distance fusion range and distance stereo-acuity improved significantly compared with the preoperative results for each group (P < 0.01). The comparison of distance fusion range was not prominent before and after strabismus surgery in the 4 groups (P > 0.05). The distribution of distance stereo-acuity was prominent after strabismus surgery in the 4 groups (P < 0.01). Distance stereo-acuity rebuilding after surgery in group 1 and group 2 was better than that in group 3 and group 4. CONCLUSIONS: (1) In the cases with intermittent exotropia, zero disparity stereo-acuity, crossed disparity and uncrossed disparity stereo-acuity are abnormal. The sequential damage of stereopsis is uncrossed disparity, crossed disparity and zero disparity. The sequential rebuilding of stereopsis is zero disparity, crossed disparity and uncrossed disparity. (2) The serious damage or disappearance of uncrossed disparity stereo-acuity is the indication of intermittent exotropia surgery for perfect binocular vision rebuilding.

Adolescent↗