Biomedical subjects

Guanghui Chen

Publications and source records attributed to Guanghui Chen.

10 recordsLinked to original sources

PubMed2006

Tandem chain walking polymerization and atom transfer radical polymerization for efficient synthesis of dendritic nanoparticles for bioconjugation.

A tandem polymerization methodology, chain walking polymerization (CWP) followed by atom transfer radical polymerization, was developed for efficient synthesis of nanoparticles for bioconjugation. Using the chain walking palladium-alpha-diimine catalyst (catalyst 1), dendritic polymers bearing multiple initiation sites were synthesized and used as macroinitiators for subsequent Cu(I)-mediated ATRP. Control of molecular weight and size of the water-soluble core-shell polymeric nanoparticles was achieved by tuning reaction conditions. Addition of an N-acryloyloxysuccinamide (NAS) monomer at the end of the ATRP afforded NHS-activated polymer nanoparticles. Conjugation with both small dye molecules and protein (ovalbumin) yielded nanoparticle conjugates with relatively high dye or protein per particle ratio. With the efficient synthesis and good biocompatibility, these nanoparticles may find many potential applications in bioconjugation.

Copper↗

PubMed2006

General strategies for nanoparticle dispersion.

Traditionally the dispersion of particles in polymeric materials has proven difficult and frequently results in phase separation and agglomeration. We show that thermodynamically stable dispersion of nanoparticles into a polymeric liquid is enhanced for systems where the radius of gyration of the linear polymer is greater than the radius of the nanoparticle. Dispersed nanoparticles swell the linear polymer chains, resulting in a polymer radius of gyration that grows with the nanoparticle volume fraction. It is proposed that this entropically unfavorable process is offset by an enthalpy gain due to an increase in molecular contacts at dispersed nanoparticle surfaces as compared with the surfaces of phase-separated nanoparticles. Even when the dispersed state is thermodynamically stable, it may be inaccessible unless the correct processing strategy is adopted, which is particularly important for the case of fullerene dispersion into linear polymers.

Journal Article↗

PubMed2006

Augmentation of revascularization and prevention of plasma leakage by angiopoietin-1 and vascular endothelial growth factor co-transfection in rats with experimental limb ischaemia.

BACKGROUND: Angiopoietin-I (Ang I) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors. In the current study, we tested the hypothesis that co-expression of AngI and VEGF could have an effect on development of leakage-resistant vessels. METHODS AND RESULTS: Expression plasmids, pcD2 (control plasmid), pcD2/AngI, pcD2NEGF121, or pcD2/AngI +pcD2NEGF121, were injected intramuscularly into an ischaemic hindlimb rat model, followed by electroporation. Collateral vessel development and skeletal muscle atrophy were assessed before and 7, 14, 28 days after treatment. Capillary density was significantly increased in the rats transfected with AngI or VEGF compared with that in the rats transfected with pcD2 alone (P < 0.05). Rats transfected with AngI + VEGF had the highest capillary density (P < 0.05). The mean perimeter ratio of ligated hindlimb to non-ligated hindlimb was lower with pcD2 treatment rats compared with that in the rats transfected with AngI, VEGF or AngI +VEGF (P < 0.01). Limb necrosis was observed in two of 33 control rats, but none in the AngI and/orVEGF gene-transferred rats. The amount of extravasated Evans blue in rat ligated hindlimb muscle (7 days after treatment) treated with both AngI and VEGF was significantly less compared with that in the rats transfected with VEGF alone (P < 0.01). CONCLUSIONS: The current study demonstrated that co-expression of AngI and VEGF genes in the ischaemic muscle effectively develops leakage-resistant vessels in the rat model. Therefore, this approach may provide a more appropriate therapeutic strategy in ischaemic vascular diseases.

Angiopoietin-1↗

PubMed2004

Transition metal-catalyzed one-pot synthesis of water-soluble dendritic molecular nanocarriers.

Here, we report the first example of transition metal-catalyzed one-pot synthesis of water-soluble dendritic molecular nanocarriers behaving like unimolecular micelles. Using the palladium-alpha-diimine chain walking catalyst, copolymerization of ethylene and comonomer 3 afforded, in one step, amphiphilic copolymer 1 having a hydrophobic core and a hydrophilic shell. A much larger amphiphilic core-shell copolymer 2 was synthesized by a two-step approach: a copolymer having many free hydroxyl groups was first prepared, which was subsequently coupled to poly(ethylene glycol) (PEG) to afford the copolymer 2. Light-scattering, fluorescence, and UV/vis spectroscopic studies with Nile Red in aqueous solution showed unimolecular micellar properties for both copolymers 1 and 2. The dye encapsulation capacity for the core-shell copolymers is nearly proportional to the molecular weight of the hydrophobic core. The unimolecular micellar properties coupled with the good water solubility and biocompatibility of the PEG moieties make these molecular nanocarriers promising candidates for many applications including drug delivery and controlled drug release.

Journal Article↗

PubMed2004

Cardio: a web-based knowledge resource of genes and proteins related to cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading killer for human. In order to understand the linkage between cardiovascular diseases and genes or proteins, it is essential to construct a database to organize the body of knowledge. While the existing molecular biological databases focus on the sequence and structural aspects of biological macromolecules, i.e. DNAs, RNAs and proteins, Cardio is the web-based system we built to provide a knowledge environment with visual interface to integrate information about major cardiovascular diseases in relation to genes and proteins. METHODS: We collected the information from the web by using a group of software we developed and used a relational database management system to manage the information of these data. RESULTS: Cardio consists of six sections: GENE, PROTEIN, DISEASE, DRUG, LINKS, and REFERENCE. Each section contains relevant information about the topic. Using a phenotype-driven approach, we can identify genetic mechanisms underlying the physiology and pathophysiology of specific cardiovascular disease, such as atherosclerosis, hypertension, heart failure, and stroke. CONCLUSION: The website titled "Database of Genes and Proteins Related to Cardiovascular Disease (Cardio)" is available at along with additional information on cardiovascular disease, supplementary materials and related figures.

Cardiovascular Diseases↗

PubMed2004

Cross-cultural comparison of mild cognitive impairment between China and USA.

Individuals with mild cognitive impairment (MCI) are at increased risk for dementia of Alzheimer's type (DAT), vascular dementia (VaD), Lewy Body (LBD) and Fronto-temporal dementias (FTD). Risk factors and conversion rates of MCI to dementia have not been thoroughly investigated in developing countries. Chinese and English versions of Mini-Mental State Examination were administered serially among well-matched subjects from two clinics located in Xi'an, China and Houston, USA. Subtle cognitive impairments were weighed according to MCI criteria as defined previously. Subjects with MCI were followed for an additional 3 years after their identification. Diagnoses of VaD and DAT were made according to established criteria. During screening period, 73 American and 65 Chinese individuals were identified with MCI. After 3 years of MCI follow-up, of the 73 American MCI subjects, 35 (47.9%) developed DAT and 15 (20.5%) developed VaD. Of the 65 Chinese MCI subjects, 12 (18.5%) developed DAT and 19 (29.2%) developed VaD. According to Kaplan-Meier analysis, Chinese MCI subjects, despite their lower educational level, are 1.7 times less likely to progress to DAT and 2.3 times more likely to progress to VaD than American subjects within 3 years of MCI being identified (p<0.01). Data suggest that progression rates of MCI vary considerably among subjects from two countries. American MCI subjects are more prone to DAT, while Chinese subjects are more prone to VaD. Differences in genetic factors, cultures, educational levels, and preventive treatments of vascular risk factors are proposed as responsible for this uneven geographic distribution for different types of dementia.

Aged↗

PubMed2003

Synthesis of functional olefin copolymers with controllable topologies using a chain-walking catalyst.

The branching topology of ethylene polar copolymers was for the first time successfully controlled by copolymerization of ethylene with polar olefins using a palladium-bisimine chain-walking catalyst, in which ethylene pressure and comonomer concentration were used to control the competition between isomerization (chain-walking) and monomer insertion processes. Although the overall branching density changes very slightly, the topology of the copolymers becomes more dendritic as the ethylene pressure and comonomer feed concentration are decreasing. This provides a straightforward one-pot synthesis to access a full range of functional copolymers having controllable branching topologies. To demonstrate the utility of this methodology, dendritic functional copolymers having hydroxyl, epoxide, and carbohydrate groups were prepared in a one-pot polymerization as potential functional materials.

Journal Article↗

PubMed2003

Effects of certain vasoactive peptides on pathogenesis of vascular restenosis.

OBJECTIVE: To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty. METHODS: In rat aortic artery restenosis model produced by denudation of aortic endothelia, we observed changes of endothelin (ET), angiotensin II (AII), calcitonin gene-related peptide (CGRP) and adrenomedullin (Adm) in plasma and aorta with radioimmunoassay and expression of hypertension-related gene (HRG-1) with semi-quantitative RT-PCR, and studied the effects of these peptides on intimal hyperplasia, intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore, in cultured cells, we studied the effects of these peptides on vascular smooth muscle cell (VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with 3H-TdR incorporation and RT-PCR respectively. RESULTS: After angioplasty, the levels of ET and AII in plasma and aorta significantly increased, accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty, the levels of ET in plasma and aorta increased by 69% and 124% respectively, compared with sham group (P < 0.01); and the level of aortic AII increased by 80% (P < 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme (ACE) could significantly inhibit the proliferation of VSMC and neointima formation. Compared with the sham group, on day 3 after angioplasty, the CGRP levels in plasma and aorta increased by 64% and 89% respectively (P < 0.01) and the Adm levels in plasma and tissue increased by 129% and 102% respectively (P < 0.01). On day 10, intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima formation induced by balloon aortic injury (by 66% and 79% respectively, P < 0.01). In addition, ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase (MAPK) activity, while CGRP and Adm potentiated the expression of HRG-1 and inhibited MAPK. CONCLUSIONS: ET and AII can stimulate the proliferation of injured intima while CGRP and Adm have an anti-hyperplasia effect after angioplasty. These 4 peptides are involved in the regulation of VSMC proliferation and affect the development of vascular restenosis by regulating the expression of HRG-1 and MAPK activity.

Adrenomedullin↗

PubMed2003

[Adenovirus-mediated transfer of TIMP-4 gene inhibits neointimal formation after balloon injury].

OBJECTIVE: To investigate the effects of human tissue inhibitor of matelloproteinase-4 (TIMP-4) on vascular smooth muscle cells (VSMCs) migration and the neointimal formation after balloon injury in rats. METHODS: The cultured VSMCs were transfected with an adenoviral vector containing human TIMP-4 gene, AdTIMP-4. Effect of TIMP-4 on VSMC migration was investigated by monolayer cell scrape. AdTIMP-4, control adenoviral vector or PBS was transduced into the rat carotid artery from the adventitial after carotid artery injury. Cell number within the internal elastic lamina 4 days after gene transfer was counted and neointima/media area ratio 28 days after gene transfer was calculated. RESULTS: The migration distance of VSMCs infected with AdTIMP-4 was inhibited markedly. Morphometric analysis demonstrated a statistically significant reduction in the number of cells migrated into neointima compared with controls [(32.5 +/- 4.8) cells per section, (33.8 +/- 7.0) cells per section and (8.2 +/- 2.4) cells per section for uninfected, AdGFP-treated and AdTIMP-4-treated arteries, respectively]. There was a reduction of intima/media ratio of TIMP-4-treated group by 66.5% compared with control groups 28 days after gene transfer (P < 0.01). There was no statistical difference between the control adenoviral vector group and PBS group. CONCLUSION: Adenoviral mediated gene transfer of TIMP-4 inhibits migration of VSMC and significantly reduces neointimal hyperplasia in the rat carotid balloon injury model. The TIMP-4 gene transfer is a potential therapeutic approach to preventing neointimal formation after balloon injury.

Adenoviridae↗

PubMed2002

Cholesteryl ester transfer protein levels and gene deficiency in Chinese patients with cardio-cerebrovascular diseases.

OBJECTIVE: To detect cholesteryl ester transfer protein (CETP) levels, frequencies of CETP D442G and I 14A mutations and characteristics of abnormal lipids in patients with cardio-cerebro vascular diseases. METHODS: Ninety-four myocardial infarction (MI) patients, 110 stroke patients and 335 healthy controls were selected. The CETP concentration was determined using ELISA. The CETP activity was measured using a substrate of (14)C-radiolabeled discoidal bilayer particles. The CETP gene mutations were detected by PCR-RFLP. RESULTS: The CETP concentrations in the MI and stroke group, were higher than those in the controls. The gene mutation frequencies of D442G in the MI, stroke and control group were 3.5%, 3.6% and 5%, respectively, and the frequencies of I 14A were 1.05%, 0.91% and 1%, respectively. One case of D442G homozygote was detected in the healthy group. The frequency of two CETP gene mutations showed no significant difference among the patients and controls. The CETP concentration and activity in subjects with CETP mutations were one-third of those in the control group. The level of HDL-C, apo-A1 increased in the mutation subjects, while the TG level decreased. CONCLUSIONS: The CETP level increased significantly in patients with cardio-cerebrovascular diseases. The carriers of CETP deficiency had CETP and lipid abnormalities.

Carrier Proteins↗