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Biomedical subjects

Jian Shen

Publications and source records attributed to Jian Shen.

At least 37 records · Page 2Linked to original sources
PubMed2005

Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: a study in rats.

PURPOSE: Botulinum toxin A (BoNT-A) is used to manage spasticity in cerebral palsy. BoNT-A cleaves SNAP-25 protein, blocking acetylcholine release and weakening the muscle. Nicotinic acetylcholine receptors (nAChR) including alpha, beta, delta, gamma, and epsilon subunits, and GAP-43 protein are associated with functional recovery of neuromuscular junctions (NMJ) following BoNT-A. To better understand the mechanism behind this functional recovery, this study attempted to (1) document changes in NMJ morphometry following BoNT-A, and (2) determine the gene expression of nAChR subunits, SNAP-25, and GAP-43 protein. METHODS: In this rat study (46 rats), 6 units/kg body weight of BoNT-A was injected into the gastrocnimus. NMJ morphometry and the time course of gene expression of nAChR subunits, SNAP-25, and GAP-43 were evaluated up to 1year post-injection. RESULTS: NMJ morphometry: gutter depth was reduced vs. the control side at two months, and normalizing by 6 months following BoNT. nAChR alpha mRNA and gamma mRNA increased by 3 days, peaked at 7 days and returned to control levels; delta mRNA peaked at 3 days. Epsilon mRNA peaked by 7 days. SNAP-25 mRNA increased from 60 to 90 days, returning to control levels by 6 months. GAP-43 mRNA was unchanged. CONCLUSIONS: Specific nAChR subunit mRNA expression up-regulates and then returns to normal within two weeks, preceding changes in NMJ morphometry. Although GAP-43 participates in nerve sprouting, no increase of GAP-43 mRNA occurred following BoNT-A. Delayed up-regulation of SNAP-25 mRNA might be associated with muscle functional recovery.

Animals↗
PubMed2005

Development of the fecal coliform total maximum daily load using Loading Simulation Program C++ and tidal prism model in estuarine shellfish growing areas: a case study in the Nassawadox coastal embayment, Virginia.

In this study, a linked model system including the Loading Simulation Program C++ (LSPC) and the tidal prism water quality model (TPWQM) was proposed as an alternative tool for total maximum daily load (TMDL) studies. The feasibility of the model system was tested by a case study in the Nassawadox Creek, a Virginia tidal water shellfish growing area. The watershed model, driven by hourly precipitation, simulates hydrology and fecal coliform accumulation and transport processes in the watershed. The simulated surface runoff and subsurface flow as well as fecal coliform loads from the watershed are discharged to the tidal creek. The tidal prism model simulates fecal coliform transport in the Creek. The model results demonstrate the effectiveness in simulating hydrology and fecal coliform concentration in the watershed and its embayment. A series of sensitivity runs was conducted to estimate the load reduction necessary for fecal coliform concentration to meet the water quality standards. The model application to the Nassawadox Creek indicates that the model system is useful in developing fecal coliform TMDLs for estuarine shellfish growing areas.

Animals↗
PubMed2004

[Evaluation of the postoperative quality of life in the elderly over 80 years old who underwent hip hemiarthroplasty for femoral neck fracture].

OBJECTIVE: To evaluate the postoperative quality of life of aged patients (> 80 years old) who underwent hip hemiarthroplasty for femoral neck fracture one year ago. METHODS: From February 1995 to February 2001, 52 elderly patients (> 80 years old) underwent the hip hemiarthroplasty after femoral neck fractures. There were 28 males and 24 females, with the average age of 84.2 years old (ranged from 80 - 95 years old). The fracture type was Garden III or IV, and all the patients underwent the hip hemiarthroplasty of domestic prosthesis. Before the operation, most of them were accompanied with pre-existed diseases. Harris hip score including symptoms and the ability of daily life at the one year after operation was adopted for the follow-up. Postoperative A-P and lateral X-ray of hip joint in different phase were also assayed. RESULTS: Forty-six patients (88.46%) were free of pain and satisfied their operations, only 6 patients (11.54%) complained about slight pain. Twenty-four patients (46.2%) were able to walk without any assistant, 24 patients (46.2%) managed to walk by walker, 4 patients (7.7%) could only lie on the bed or move by wheel chair. Postoperatively, patients with neurological diseases such as Parkinson dementia, Senile dementia, cerebrovascular diseases got poor result of the quality of life. However, the other comorbid diseases such as cardiovascular diseases, diabetes mellitus, chronic renal failure, chronic bronchitis did not affect the result. Thirty-eight patients had the postoperative X-ray when they were followed up. Postoperatively, the X-ray were taken from 3 months to 5 years and 6 months, averaged 54.2 months. Sclerotic line were discovered around the shaft of prosthesis only in 3 patients. No complications such as femoral head central dislocation or hip osteoarthritis were found. CONCLUSION: Operative treatment could be actively adopted for aged femoral neck fracture patients without surgical contraindication, which can contribute to obtain the motion ability, reduce complication caused by lying in bed, and keep a good quality of life.

Aged↗
PubMed2004

Variation in surface energy heterogeneity of graphite due to adsorption of polyoxyethylene sorbitan monooleate.

The heterogeneity of surface energy of graphite before and after adsorption of polyoxyethylene sorbitan monooleate (Tween80) was investigated by the nitrogen adsorption technique. The nitrogen adsorption energy distributions (AEDs) were calculated from the low-pressure isotherm data (i.e., the data of submonolayer adsorption) according to the regularization method. Based on the AED of pristine graphite, two types of dominant energetic surface are identified and assigned respectively to the basal surface and the irregular surface, including the stepped edges and defect sites. When the adsorption amount of Tween80 is raised, both the surface energy and the energy heterogeneity of graphite gradually decline. It is thus demonstrated that Tween80 prefers interacting with and screening higher energetic surfaces to lower ones.

Journal Article↗
PubMed2004

Chemical graft polymerization of sulfobetaine monomer on polyurethane surface for reduction in platelet adhesion.

Surface modification is an effective way to improve the hemocompatibility and remain bulk properties of biomaterials. Recently, polymer tailored with zwitterions was found having good blood compatibility. In this study, the zwitterionic monomer of sulfobetaine was graft polymerized onto polyurethane (PU) surface in a three-step heterogenous system through the vinyl bonds of acrylic acid (AA) or hydroxyethyl methacrylate (HEMA), which was immobilized with hexamethylene diisocyanate (HDI) beforehand. First, PU was activated with isocyanate groups using HDI as coupling agent. Second, AA or HEMA was introduced through reaction of AA or HEMA with NCO groups bonded on PU surface. Last, zwitterionic monomer of sulfobetain was graft polymerized with vinyl group of AA or HEMA using AIBN as polymerization initiator. The reaction process was monitored with ATR-IR spectra and XPS spectra. Variation of graft yield with temperature and monomer feed concentration was investigated and feasible conditions were optimized. The wettability of films was investigated by water contact angle measurement and water absorbance. Platelet adhesion experiment was conducted as a preliminary test to confirm the improved blood compatibility of PU. The number of platelets adhering to PU decreased greatly comparing with the originals after 1 and 3 h of contact with human plate-rich plasma (PRP).

Acrylates↗
PubMed2004

Study of influence on the surface energy heterogeneity of multiwalled carbon nanotubes after the adsorption of poly(acrylic acid).

The heterogeneity of the surface energy of multiwalled carbon nanotubes (MWNTs) before and after the adsorption of poly(acrylic acid) (PAA) at 77 K was investigated by a nitrogen probe adsorption technique in a wide range of pressures. The adsorption energy distributions (AEDs) were calculated from the low-pressure data of isotherms (i.e., the data of submonolayer adsorption) using the regularization method. Based on the AED, two types of dominant energetic surfaces are identified and assigned to the graphite-like carbon and disordered carbon or defects in the pure MWNTs, respectively. While the adsorption amount of PAA is raised, a significant decrease in the contribution of higher-energy surface in AEDs is observed for those PAA-adsorbed MWNTs. It is thus demonstrated that PAA prefers interacting with higher-energy surfaces to lower-energy surfaces in MWNTs. Nitrogen probe adsorption measurements including low-pressure data are shown to be a feasible and effective tool to characterize the heterogeneity of structure and surface properties of porous materials.

Journal Article↗
PubMed2004

Identification of critical amino acid residues of human CYP2A13 for the metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a tobacco-specific carcinogen.

Among all the known human cytochrome P450 enzymes, CYP2A13 has the highest efficiency in catalyzing the metabolic activation (keto aldehyde and keto alcohol formation) of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent lung carcinogen in animals and a suspected human lung carcinogen. As part of the structure-activity relationship (SAR) study, the present work was done to identify the key amino acid residues in CYP2A13 that are responsible for this high catalytic efficiency by using a series of mutants (Ala117Val, His164Gly, Ser208Ile, His372Arg, and Pro465Ser). In these CYP2A13 mutants, the amino acid residues were substituted by the residues at the corresponding positions of CYP2A6, which shares 93.5% amino acid sequence identity with CYP2A13 but is significantly less active (<5%) than CYP2A13 in NNK alpha-hydroxylation. We demonstrated that, except for the His164Gly mutant, all the CYP2A13 mutant proteins showed a significant decrease in the catalytic efficiency (Vmax/Km) for NNK alpha-hydroxylation. The His372 to Arg substitution resulted in a 20-fold increase in the Km value and a 7-fold decrease in the Vmax value for keto aldehyde formation as well as a total loss of detectable keto alcohol formation. The Ala117 to Val substitution, however, only caused a selective decrease in the Vmax value for keto aldehyde formation. The role of these amino acid residues in CYP2A13-catalyzed reactions is clearly substrate-dependent, since the same Ala117Val and His372Arg mutants showed a 9-fold increase in the catalytic efficiency for coumarin 7-hydroxylation. Together with the computational substrate docking, our study provides new SAR in formation of human CYP2A13.

Amino Acid Substitution↗
PubMed2004

Identification of Val117 and Arg372 as critical amino acid residues for the activity difference between human CYP2A6 and CYP2A13 in coumarin 7-hydroxylation.

Human cytochrome P450 (CYP) 2A6 and 2A13 play an important role in catalyzing the metabolism of many environmental chemicals including coumarin, nicotine, and several tobacco-specific carcinogens. Both CYP2A6 and CYP2A13 proteins are composed of 494 amino acid residues. Although CYP2A13 shares a 93.5% identity with CYP2A6 in the amino acid sequence, it is only about one-tenth as active as CYP2A6 in catalyzing coumarin 7-hydroxylation. To identify the key amino acid residues that account for such a remarkable difference, we generated a series of CYP2A6 and CYP2A13 mutants by site-directed mutagenesis/heterologous expression and compared their coumarin 7-hydroxylation activities. In CYP2A6, the amino acid residues at position 117 and 372 are valine (Val) and arginine (Arg), respectively; whereas in CYP2A13, they are alanine (Ala) and histidine (His). Kinetic analysis revealed that the catalytic efficiency (Vmax/Km) of the CYP2A6 Val(117)--> Ala and Arg(372)--> His mutants was drastically reduced (0.41 and 0.64 versus 3.23 for the wild-type CYP2A6 protein). In contrast, the catalytic efficiency of the CYP2A13 Ala(117) --> Val and His(372) --> Arg mutants was greatly increased (2.65 and 2.60 versus 0.31 for wild-type CYP2A13 protein). These results clearly demonstrate that the Val at position 117 and Arg at position 372 are critical amino acid residues for coumarin 7-hydroxylation. Based on the crystal structure of CYP2C5, we have generated the homology models of CYP2A6 and CYP2A13 and docked the substrate coumarin to the active site. Together with the kinetic characterization, our structural modeling provides explanations for the amino acid substitution results and the insights of detailed enzyme-substrate interactions.

Amino Acid Sequence↗
PubMed2004

Various approaches to modify biomaterial surfaces for improving hemocompatibility.

In this paper, the mechanism of thrombus formation on the surface of polymeric materials and the various approaches of modifying biomaterial surfaces to improve their hemocompatibility are reviewed. Moreover, the blood compatibility of the cellulose membrane grafted with O-butyrylchitosan (OBCS) by using a radiation grafting technique was studied. Surface analysis of grafted cellulose membrane was verified by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and electron spectroscopy for chemical analysis (ESCA), which confirmed that OBCS was successfully grafted onto the cellulose membrane surfaces. Blood compatibility of the grafted cellulose membranes was evaluated by platelet rich plasma (PRP) contacting experiments and protein adsorption experiments using blank cellulose membranes as the control. The blood compatibility of OBCS grafted cellulose membranes is better than that of blank cellulose membranes. These results suggest that the photocrosslinkable chitosan developed here has the potential of serving in blood-contacting applications in medical use.

Adsorption↗
PubMed2004

Polyurethane vascular catheter surface grafted with zwitterionic sulfobetaine monomer activated by ozone.

Polyurethane (PU) is a conventional biomedical material with favorable biocompatibility and excellent mechanical properties and widely used in making vascular catheter, but its antithrombogenic property is not good enough to make it as a more demanding applicable biomaterial. Surface modification is an effective way to improve the hemocompatibility for biomaterials. The purpose of present study was to use ozonization method to modify the surface of PU vascular catheter slice to improve its antithrombogenicity by grafting N,N-dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl) ammonium (DMMSA), a zwitterionic sulfobetaine monomer. PU vascular catheter (PUVC) grafted with DMMSA (PUVC-g-PDMMSA) was characterized by ATR-FTIR and XPS. ATR-FTIR and XPS investigation confirmed the graft polymerization. The blood compatibility of the grafted films was evaluated by platelet rich plasma (PRP) platelet adhesion study and scanning electron microscopy (SEM) was used to observe the morphology of platelet using PU vascular catheter (PUVC) as the reference. No platelet adhesion was observed for the grafted PUVC slice incubated with PRP at 37 degrees C for 120 min. It is significant that this new zwitterionic sulfobetaine grafted PUVC have improved antithrobogenicity. It is effective that the inner surface of vascular catheter with inner diameter in only 3mm can be grafted with PDMMSA by using ozonization method.

Betaine↗
PubMed2004

Decision support systems in drug discovery.

Decision support systems have been widely used in drug discovery owing to the complexity of data and information involved. In this article, we review both commercially available packages and publicized in-house made systems. All selected systems should be able to handle chemical structures and to organize information for decision makers, more specifically for medicinal chemists. Although we do not rank these system, pros and cons of these systems will be discussed.

Decision Support Systems, Management↗
PubMed2004

Intratumoral injection of arsenic to enhance antitumor efficacy in human esophageal carcinoma cell xenografts.

To enhance the therapeutic efficacy of anticancer agents and to reduce systemic side effects, it was decided to study the effect of arsenic trioxide directly on solid tumors to observe the anticancer effect of arsenic on tumors and the distribution of arsenic in tumors and other organs. Esophageal carcinoma cells were heterotransplanted in severe combined immunodeficient (SCID) mice in both laterals of the abdominal wall. When both lateral tumors had grown to approximately 10x8x5 mm3, tumor-bearing mice were used for 2 experiments. The right tumors were treated with intratumoral injection of As2O3 in 1, 5 and 10 micro g per day for 10 days sequent. The left tumors were treated with phosphate buffer solution as controls. To explore the distribution of As2O3 remaining in tumor and some organs, a single intratumoral injection of As2O3 was studied with quantitative measurement of arsenic by means of atomic absorption spectrometry. The results revealed that on the 17th day after the 1st injection As2O3-treated tumors were suppressed markedly compared to that of the contrarily lateral tumor accompanied by marked apoptosis and necrosis in tumor cells. The tumor growth inhibition (TGI) was 13.56, 62.37 and 76.92% in 1, 5 and 10 micro g group, respectively. There were no pathological changes in heart, lung, spleen, liver, kidney or brain after arsenic administration. Distribution of As2O3 revealed that As2O3 remained at higher concentration in arsenic-treated tumor tissue than in other organs. Our data suggest that intratumoral delivery of As2O3 efficiently suppresses growth of transplanted esophageal carcinoma without systemic side effects. The protocol of As2O3 intratumoral injection will be its potential clinical utility for therapy of solid tumors.

Animals↗
PubMed2004

The multistage process of carcinogenesis in human esophageal epithelial cells induced by human papillomavirus.

To investigate the multistage process of carcinogenesis, the progressive alteration of the morphology, telomerase, cytogenesis, oncogenes and tumorigenicity in the process of immortalization and malignant transformation of the human fetal esophageal epithelial cell (SHEE) was studied. The SHEE cells were immortalized by gene E6E7 of human papilloma virus (HPV) type 18 in our laboratory and continually cultivated over 100 passages, which had been malignantly transformed. Cells at the 11th, 35th, 65th and 100th passage were examined according to the following criteria: morphological changes of cell growth, contact-inhibition and anchorage-independent growth (AIG); the cell proliferative and apoptotic index; the modal number of chromosomes; c-myc, p53, bcl-2, ras; telomere length and activities of telomerase and tumorigenicity in nude mice or severe combined immunodeficient (SCID) mice. The cells of the 11th passage were well differentiated and the cells of 100th passage were relatively poorly differentiated with polymorphism, while the cells of 35th and 65th had two distinct differentiations. The proliferative indexes were 21.1%, 32.5%, 33.2%, and 40.9% and the apoptotic indexes were 3.3%, 2.7%, 3.5%, 2.7% in the 11th, 35th, 65th and 100th passage respectively. Karyotypes of four cell passages belonged to hyperdiploidy and hypotriploidy. C-myc, ras, p53 genes were low in the 10th and 35th, and high in the 65th and 100th passage, but bcl-2 was low in 4 passages. Telomere length sharply decreased from normal fetal esophagus cells until the 35th passage, but it was stably expressed in the 65th and 100th passage. The activities of telomerase were expressed in cells of the 35th, 65th and 100th passages. The efficiency of AIG varied in different passages of the SHEE cell and was absent in the 11th passage, low efficiency in the 35th passage and 65th passage, and high efficiency in the 100th passage. Transplanted cells of the 65th and 100th passage into SCID mice resulted in tumor formation, but only the 100th passage cells could grow in nude mice. All of these characteristic changes were in dynamic progressive process. These data demonstrate that carcinogenesis of esophageal epithelial cells induced by HPV is the multistage process, which goes through the initial, immortal, premalignant and malignant transformation stages. The generation of esophageal carcinoma is caused by the accumulation of cellular, genetic and molecular changes.

Agar↗
PubMed2004

[Mask lift and facial aesthetic sculpturing].

OBJECTIVE: To improve the outcome of the face-lift with a craniofacial contouring procedure. METHODS: Thirty-seven patients aged 29-53 years (31 in female, 6 in male) were treated through a bicoronal incision. The facial tissue was lifted through a subperiosteal procedure and the facial skeleton was remodeled in three dimensions by osteotomies. RESULTS: The results were satisfactory after the 3-12 months of the follow-ups. CONCLUSIONS: The Face-lift combined with the facial aesthetic sculpturing may be more effective for the aging-face rejuvenating.

Adult↗
PubMed2003

High-yield solvothermal formation of magnetic CoPt alloy nanowires.

One-dimensional (1D) magnetic nanomaterials have attracted much attention recently because of their applications in magnetic recording and spintronics. Nevertheless, it remains a challenge to prepare free-standing magnetic nanowires in high yield. This Communication reports the successful high-yield synthesis of an interesting 1D ferromagnetic CoPt alloy by direct decomposition of platinum acetylacetonate and cobalt carbonyl compound in ethylenediamine solvent through a solvothermal reaction. The CoPt alloy nanowires obtained have a tunable diameter of 10-50 nm and a length along the longitudinal axis of up to several microns, depending on crystallization temperature and reaction time. A unique formation mechanism involving coarsening and ripening under solvothermal conditions was discovered. This research opens new opportunities in synthesizing nanomaterials through low-temperature solvothermal processes.

Journal Article↗