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Biomedical subjects

Feng Li

Publications and source records attributed to Feng Li.

At least 109 records · Page 6Linked to original sources

HMG CoA reductase inhibitors reduce ischemic brain injury of Wistar rats through decreasing oxidative stress on neurons.

Statins possess neuroprotective effect against ischemic damage, but how they protect neurons is not exactly made clear. We speculated that anti-oxidative property of statins is implicated, and investigated statins' influences on the oxidative neuronal damage in the brain after ischemia. After 14 days of atorvastatin, pitavastatin, simvastatin, or vehicle administration, 90 min of middle cerebral artery occlusion was imposed on Wistar rats. The production of 4-hydroxynonenal (HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), both of which are oxidative stress markers, as well as infarction formation were investigated at 1 day after the reperfusion. In the vehicle group, massive infarction was confirmed and HNE and 8-OHdG are robustly produced. In the statins-treated group, the infarction was smaller and the HNE and 8-OHdG production was less prominent than the vehicle group. Among the statins investigated, simvastatin was most effective for reducing oxidative stress and infarction volume, which may be brought by its highly lipophilic property. Reduction of oxidative stress by statins may be one main reason in ameliorating ischemic brain damage in rats.

Aldehydes↗

Distribution patterns and controllable transport of water inside and outside charged single-walled carbon nanotubes.

The density distribution patterns of water inside and outside neutral and charged single-walled carbon nanotubes (SWNTs) soaked in water have been studied using molecular dynamics simulations based on TIP3P potential and Lennard-Jones parameters of CHARMM force field, in conjunction with ab initio calculations to provide the electron density distributions of the systems. Water molecules show different electropism near positively and negatively charged SWNTs. Different density distribution patterns of water, depending on the diameter and chirality of the SWNTs, are observed inside and outside the tube wall. These special distribution patterns formed can be explained in terms of the van der Waals and electrostatic interactions between the water molecules and the carbon atoms on the hexagonal network of carbon nanotubes. The electric field produced by the highly charged SWNTs leads to high filling speed of water molecules, while it prevents them from flowing out of the nanotube. Water molecules enter the neutral SWNTs slowly and can flow out of the nanotube in a fluctuating manner. It indicates that by adjusting the electric charge on the SWNTs, one can control the adsorption and transport behavior of polar molecules in SWNTs to be used as stable storage medium with template effect or transport channels. The transport rate can be tailored by changing the charge on the SWNTs.

Journal Article↗

Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components.

gamma-Secretase, which is responsible for the intramembranous cleavage of Alzheimer beta-amyloid precursor protein and the signaling receptor Notch, is a multiprotein complex consisting of at least four components: presenilin (PS); nicastrin (Nct); APH-1 (anterior pharynx-defective-1); and presenilin enhancer-2 (PEN-2). Presenilin 1 (PS1) is known to be essential for the stability, interaction, and trafficking of the other PS1/gamma-secretase components. However, the precise functions of the other components remain elusive. Here, we investigated the functions of Nct within the PS1/gamma-secretase complex. We demonstrated that the loss of Nct expression in the embryonic fibroblast cells (Nct KO cells) results in dramatically decreased levels of APH-1, PEN-2, and PS1 fragments accompanied by a significant accumulation of full-length PS1. In the absence of Nct, PEN-2 and full-length PS1 are subjected to proteasome-mediated degradation, whereas the degradation of APH-1 is mediated by both proteasomal and lysosomal pathways. Unlike the case of wild type cells in which the gamma-secretase complex mainly locates in the trans-Golgi network, the majority of residual PEN-2, APH-1, and the uncleaved full-length PS1 in Nct KO cells reside in the endoplasmic reticulum, which remain associated with each other in the absence of Nct. Interestingly, significant amounts of full-length PS1 and PEN-2, but not APH-1, are detected on the plasma membrane in Nct KO cells, suggesting the Nct-independent cell surface delivery of the PEN-2.PS1. Finally, the diminished PEN-2 protein level in Nct-deficient cells can be partially restored by overexpression of exogenous PS1, APH-1, or PEN-2 individually or collectively, indicating a dispensable role for Nct in controlling PEN-2 level. Taken together, our study demonstrates a critical role of Nct in the stability and proper intracellular trafficking of other components of the PS1/ gamma-secretase complex but not in maintaining the association of PEN-2, APH-1, and full-length PS1.

Amyloid Precursor Protein Secretases↗

Effect of external cavity length on self-mixing signals in a multilongitudinal-mode Fabry-Perot laser diode.

The effect of external-cavity length on self-mixing signals in a multilongitudinal-mode Fabry-Perot laser diode (FP-LD) was investigated experimentally. It has been shown that the output waveforms of self-mixing signals vary periodically when the length of the external cavity changes. This result agrees well with our theoretical calculations for the self-mixing effect of two adjacent longitudinal modes in a FP-LD. Moreover, the time-averaged output intensities of self-mixing signals has also been measured and compared with theoretical analysis.

Journal Article↗

Development of a new hybrid technique for rapid speciation analysis by directly interfacing a microfluidic chip-based capillary electrophoresis system to atomic fluorescence spectrometry.

This paper represents the first study on direct interfacing of microfluidic chip-based capillary electrophoresis (chip-CE) to a sensitive and selective detector, atomic fluorescence spectrometry (AFS) for rapid speciation analysis. A volatile species generation technique was employed to convert the analytes from the chip-CE effluent into their respective volatile species. To facilitate the chip-CE effluent delivery and to provide the necessary medium for subsequent volatile species generation, diluted HCl solution was introduced on the chip as the makeup solution. The chip-CE-AFS interface was constructed on the basis of a concentric "tube-in-tube" design for introducing a KBH4 solution around the chip effluent as sheath flow and reductant for volatile species generation as well. The generated volatile species resulting from the reaction of the chip-CE effluent and the sheath flow were separated from the reaction mixture in a gas-liquid separator and swept into the AFS atomizer by an argon flow for AFS determination. Inorganic mercury (Hg(II)) and methylmercury (MeHg(I)) were chosen as the targets to demonstrate the performance of the present technique. Both mercury species were separated as their cysteine complexes within 64 s. The precision (relative standard deviation, RSD, n = 5) of migration time, peak area, and peak height for 2 mg.L(-1) Hg(II) and 4 mg.L(-1) MeHg(I) (as Hg) ranged from 0.7 to 0.9%, 2.1 to 2.9%, and 1.5 to 1.8%, respectively. The detection limit was 53 and 161 microg.L(-1) (as Hg) for Hg(II) and MeHg(I), respectively. The recoveries of the spikes of mercury species in four locally collected water samples ranged from 92 to 108%.

Electrophoresis, Microchip↗

Evaluation of automated lung nodule detection on low-dose computed tomography scans from a lung cancer screening program(1).

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the performance of a fully automated lung nodule detection method in a large database of low-dose computed tomography (CT) scans from a lung cancer screening program. Because nodules demonstrate a spectrum of radiologic appearances, the performance of the automated method was evaluated on the basis of nodule malignancy status, size, subtlety, and radiographic opacity. MATERIALS AND METHODS: A database of 393 thick-section (10 mm) low-dose CT scans was collected. Automated lung nodule detection proceeds in two phases: gray-level thresholding for the initial identification of nodule candidates, followed by the application of a rule-based classifier and linear discriminant analysis to distinguish between candidates that correspond to actual lung nodules and candidates that correspond to non-nodules. Free-response receiver operating characteristic analysis was used to evaluate the performance of the method based on a jackknife training/testing approach. RESULTS: An overall nodule detection sensitivity of 70% (330 of 470) was attained with an average of 1.6 false-positive detections per section. At the same false-positive rate, 83% (57 of 69) of the malignant lung nodules in the database were detected. When the method was trained specifically for malignant nodules, a sensitivity of 80% (55 of 69) was attained with 0.85 false-positives per section. CONCLUSION: We have evaluated an automated lung nodule detection method with a large number of low-dose CT scans from a lung cancer screening program. An overall sensitivity of 80% for malignant nodules was achieved with 0.85 false-positive detections per section. Such a computerized lung nodule detection method is expected to become an important part of CT-based lung cancer screening programs.

Adult↗

Prevalence of and risk factors for fatty liver in a general population of Shanghai, China.

BACKGROUND/AIMS: To determine the prevalence and risk factors of fatty liver (FL) among Shanghai adults. METHODS: A cross-sectional ultrasonographic survey with randomized multistage stratified cluster sampling was used. RESULTS: The study included 3175 subjects (1218 men) with a mean age of 52 years. FL was found in 661 (20.82%) subjects. After adjustment by age and sex, FL prevalence was found to be 17.29%, and the prevalences of alcoholic, suspected alcoholic and nonalcoholic FL were determined to be 0.79, 1.15 and 15.35%, respectively. Generally, age, body mass index (BMI), waist circumference, blood pressure, and the prevalences of obesity, diabetes, hypertension and dyslipidemia were all significantly higher in FL patients than in controls; In contrast, the levels of high-density-lipoprotein cholesterol (HDL-C), education and physical activity were markedly lower. Multiple regression analyses showed that only nine factors (male, educational level, waist circumference, BMI, HDL-C, triglyceride, fasting plasma glucose, diabetes and hypertension) were closely related to FL. In excessive drinkers, obesity increased the risk for FL by 4.8-fold, but excessive drinking was associated with only a 1.5-fold increased risk in obese subjects. CONCLUSIONS: FL in Shanghai is highly prevalent and mainly related to multiple metabolic disorders.

Adolescent↗

New liposome-encapsulated-polyoxometalates: synthesis and antitumoral activity.

Liposome-encapsulated polyoxometalates (abbreviated as LEP): incorporating K(6)SiW(11)TiO(40) {(SiW(11)Ti) LEP} have been synthesized and structurally characterized by elemental analysis, and IR, UV-Vis, and NMR spectroscopy. The particle sizes of these complexes ranged from 15 to 60 nm. The polyoxometalate retained the parent structure after encapsulation by the liposome. Based upon in vitro measurements with KB and HeLa cancer cells, the liposome-encapsulation enhances cell-membrane penetration, and the stability and antitumoral activity of the polyoxometalate. The toxicity of the polyoxometalate was reduced when LEPs were employed against HL-60 tumors in vivo.

Animals↗

Protection against hydrogen peroxide-induced cell death in cultured human retinal pigment epithelial cells by 17beta-estradiol: a differential gene expression profile.

It has been demonstrated that estrogen receptors are present in the retinal pigment epithelium (RPE)-choroids complex regardless of sex. This suggests that estrogen could play a functional role in the outer retina, especially the RPE. To gain further insights on the molecular mechanisms differentially activated by 17beta-estradiol (betaE2) in RPE cells, we investigated gene expression changes in response to betaE2 in cultured RPE cells using cDNA microarray technology. A total of 47 genes among 21,329 human genes are significantly altered in response to betaE2 treatment in RPE cells. Among these 47 altered genes, 34 are up-regulated and 13 are down-regulated by betaE2. The products of 34 genes have a known or suspected function. These functions belong to various categories, including caspases; extracellular matrix proteins; metabolism pathway components; GTP/GDP exchangers and G-protein GTPase activity modulators; transcription activators and repressors. Six genes which may contribute to the unique functions of the RPE cells have been validated by both quantitative real-time reverse transcription (RT)-PCR and semi-quantitative RT-PCR. In addition, we also demonstrated that betaE2 quenches H2O2-induced up-regulation of apoptosis-related protein, and protects RPE cell degeneration. These results indicate that estrogen regulates functions of RPE cells and is involved in the maintaining and survival of RPE cells during oxidative stress, and its deficiency during menopause period may be a factor contributing to the development of age-related macular degeneration in elderly women.

Apoptosis↗

Gene cloning, bacterial expression, in vitro refolding, and characterization of a single-chain Fv antibody against PreS1(21-47) fragment of HBsAg.

The murine monoclonal antibody 125E11 is an IgG which recognizes PreS1(21-47) fragment of large hepatitis B surface antigen. It has been successfully used for clinical detection of HBV virion in serum of hepatitis B patients. In present study, the genes of variable region in heavy chain (VH) and light chain (VL) of 125E11 have been cloned. Sequence analysis of cloned VH gene and VL gene showed that they had general characterization of immunoglobin variable region genes. According to Kabat classification, VH gene and VL gene belong to VH10 family, subgroup IIID and Vkappa family subgroup I, respectively. An expression vector of 125E11 single-chain Fv antibody fusion protein, in which VH and VL peptide were connected by a flexible linker (Gly(4)Ser)(3), was constructed. The scFv fusion protein was highly expressed in Escherichia coli mainly in inclusion body form. Using urea and pH gradient gel filtration method, the refolding of scFv was efficiently achieved. The refolding efficiency reached about 11% and 2.7 mg refolded scFv was obtained from 1L of culture. The binding activity and specificity of 125E11 scFv against PreS1(21-47)-containing antigen were also analyzed.

Amino Acid Sequence↗

DCCP and DICP: construction and analyses of databases for copper- and iron-chelating proteins.

Copper and iron play important roles in a variety of biological processes, especially when being chelated with proteins. The proteins involved in the metal binding, transporting and metabolism have aroused much interest. To facilitate the study on this topic, we constructed two databases (DCCP and DICP) containing the known copper- and iron-chelating proteins, which are freely available from the website http://sdbi.sdut.edu.cn/en. Users can conveniently search and browse all of the entries in the databases. Based on the two databases, bioinformatic analyses were performed, which provided some novel insights into metalloproteins.

Animals↗

Controllable self-assembly of nanoparticles for specific delivery of multiple therapeutic molecules to cancer cells using RNA nanotechnology.

By utilizing RNA nanotechnology, we engineered both therapeutic siRNA and a receptor-binding RNA aptamer into individual pRNAs of phi29's motor. The RNA building block harboring siRNA or other therapeutic molecules was fabricated subsequently into a trimer through the interaction of engineered right and left interlocking RNA loops. The incubation of the protein-free nanoscale particles containing the receptor-binding aptamer or other ligands resulted in the binding and co-entry of the trivalent therapeutic particles into cells, subsequently modulating the apoptosis of cancer cells and leukemia model lymphocytes in cell culture and animal trials. The use of such antigenicity-free 20-40 nm particles holds promise for the repeated long-term treatment of chronic diseases.

Animals↗

Computer-aided diagnosis in thoracic CT.

Computer-aided diagnosis (CAD) provides a computerized diagnostic result as a "second opinion" to assist radiologists in the diagnosis of various diseases by use of medical images. CAD has become a practical clinical approach in diagnostic radiology, although, at present, primarily in the area of detection of breast cancer in mammograms. Currently, a large research effort has been devoted to the detection and classification of various lung diseases in thoracic computed tomography (CT) images. We describe in this article the current status of the development of CAD schemes in thoracic CT, including nodule detection, distinction between benign and malignant nodules, and detection, characterization, and differential diagnosis of diffuse lung disease. Observer performance studies indicate that these CAD schemes would be useful in clinical practice by providing radiologists with computer output as a "second opinion."

Humans↗

Hybrid cytomegalovirus enhancer-h1 promoter-based plasmid and baculovirus vectors mediate effective RNA interference.

Plasmid and viral vectors harboring an RNA polymerase (Pol) III promoter would be useful in achieving sustained cellular expression of short interfering RNA (siRNA) to inhibit disease-associated genes. Given that transcription machineries directed by certain Pol II and III promoters may use common factors, we investigated whether the enhancer of the Pol II cytomegalovirus (CMV) immediate-early promoter could improve the efficacy of RNA interference mediated by the Pol III H1 promoter. We constructed a hybrid promoter by appending the CMV enhancer 5' to the H1 promoter. In the context of plasmid vectors, the hybrid promoter provided up to 50% greater inhibition of the expression of target genes than the unmodified H1 promoter and extended the silencing effect beyond that provided by the H1 promoter. Insect baculoviruses can infect a broad range of mammalian cell types. We constructed a baculovector expression cassette in which the synthesis of short hairpin RNA was under the control of the hybrid CMV enhancer-H1 promoter. This recombinant baculovirus vector was capable of suppressing expression of a target gene by 95% in cultured cells and by 82% in vivo in rat brain. These findings indicate that the hybrid CMV enhancer-H1 promoter can be used favorably for RNA interference.

Animals↗

Computer-aided diagnostic scheme for distinction between benign and malignant nodules in thoracic low-dose CT by use of massive training artificial neural network.

Low-dose helical computed tomography (LDCT) is being applied as a modality for lung cancer screening. It may be difficult, however, for radiologists to distinguish malignant from benign nodules in LDCT. Our purpose in this study was to develop a computer-aided diagnostic (CAD) scheme for distinction between benign and malignant nodules in LDCT scans by use of a massive training artificial neural network (MTANN). The MTANN is a trainable, highly nonlinear filter based on an artificial neural network. To distinguish malignant nodules from six different types of benign nodules, we developed multiple MTANNs (multi-MTANN) consisting of six expert MTANNs that are arranged in parallel. Each of the MTANNs was trained by use of input CT images and teaching images containing the estimate of the distribution for the "likelihood of being a malignant nodule," i.e., the teaching image for a malignant nodule contains a two-dimensional Gaussian distribution and that for a benign nodule contains zero. Each MTANN was trained independently with ten typical malignant nodules and ten benign nodules from each of the six types. The outputs of the six MTANNs were combined by use of an integration ANN such that the six types of benign nodules could be distinguished from malignant nodules. After training of the integration ANN, our scheme provided a value related to the "likelihood of malignancy" of a nodule, i.e., a higher value indicates a malignant nodule, and a lower value indicates a benign nodule. Our database consisted of 76 primary lung cancers in 73 patients and 413 benign nodules in 342 patients, which were obtained from a lung cancer screening program on 7847 screenees with LDCT for three years in Nagano, Japan. The performance of our scheme for distinction between benign and malignant nodules was evaluated by use of receiver operating characteristic (ROC) analysis. Our scheme achieved an Az (area under the ROC curve) value of 0.882 in a round-robin test. Our scheme correctly identified 100% (76/76) of malignant nodules as malignant, whereas 48% (200/413) of benign nodules were identified correctly as benign. Therefore, our scheme may be useful in assisting radiologists in the diagnosis of lung nodules in LDCT.

Algorithms↗

Fatty liver and the metabolic syndrome among Shanghai adults.

BACKGROUND AND AIM: To explore the relationship between fatty liver and the metabolic syndrome in the adults of Shanghai and evaluate the value of fatty liver as a marker for risk factor clustering. METHODS: Questionnaires, physical examinations, laboratory tests (blood lipid and glucose) and real-time liver ultrasonographies were performed in Shanghai adults and analyzed using randomized, multistage, stratified cluster sampling. Prevalence of the metabolic syndrome was defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria with the exception of abdominal obesity (waist circumference > 90 cm in men and > 80 cm in women); fatty liver was diagnosed in accordance with the presence of an ultrasonographic pattern consistent with 'bright' liver (brightness and posterior attenuation of liver). RESULTS: The study population consisted of 3175 subjects (1218 men) with a mean (+/- SD) age of 52.4 +/- 15.1 years. Metabolic syndrome and fatty liver were found in 726 (22.87%) and 661 (20.82%) of sampled cases, respectively. After adjustment by age and sex, the prevalence of the metabolic syndrome and fatty liver in the general population of Shanghai were 15.30 and 17.29%, respectively. The risk for fatty liver in subjects with abdominal obesity, diabetes, dyslipidemia and hypertension increased 32.78-fold (95% confidence interval (CI) 14.85-72.35), 31.58-fold (95% CI 14.18-70.35), 22.64-fold (95% CI 10.26-49.99) and 23.25-fold (95% CI 10.54-51.30), respectively, compared with controls, whereas the risk for fatty liver in subjects with metabolic syndrome was increased by 39.33-fold (95% CI 17.77-87.05). After the 661 patients with fatty liver had been stratified by body mass index (BMI), the prevalence of abdominal obesity, hypertension and the metabolic syndrome were increased from 25.0, 47.2 and 36.1%, respectively, in people with normal BMI to 81.0, 73.8 and 55.4%, respectively, in obese persons. However, the prevalence of hypertriglyceridemia, high fasting glucose and low high-density lipoprotein-cholesterol showed no significant changes with increased BMI. Moreover, among fatty liver patients with normal BMI, the detection rate for one or more features of metabolic disorders was as high as 83.3% and that for five features was 2.8%. Compared with obesity (BMI > or = 25 kg/m2) and abdominal obesity, fatty liver had the highest clustering rate, specificity, positive predictive value and attributable risk percentage in detecting risk factor clustering in both sexes. CONCLUSIONS: There is a high prevalence of metabolic syndrome and fatty liver among Shanghai adults. Metabolic disorders are closely related to fatty liver; moreover, fatty liver appears to be a good predictor for the clustering of risk factors for metabolic syndrome.

Adolescent↗