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Biomedical subjects

Yi Chen

Publications and source records attributed to Yi Chen.

At least 37 records · Page 2Linked to original sources

Geometric self-sorting in DNA self-assembly.

Two types of DNA star motifs (tiles) can recognize and associate with like tiles to form 2D arrays but exclude unlike tiles even though the local interactions between any two tiles are exactly the same.

Crystallization↗

Chemical functionalization of magnetic carbon-encapsulated nanoparticles based on acid oxidation.

Carbon-encapsulated nickel nanoparticles were used as the representative magnetic carbon-encapsulated nanoparticles for chemical functionalization. After oxidation with the mixed acid of H2SO4/HNO3 under a moderate ultrasonic bath, carboxylic acid groups (-COOH) were effectively generated on the fullerene-like carbon shells, which in turn were utilized to covalently link octadecylamine through an amide reaction. The whole chemical process is well characterized by many methods such as Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, thermogravimetry-differential scanning calorimetry, transmission electron microscopy, and so on, and the self-consistent experimental results were obtained. The results suggested that the magnetic nanoparticles could be well protected, while their magnetic properties could be utilized to guide the transfer of the grafted functional species on the particle surface. This provides many possibilities for potential applications in chemical and biochemical fields.

Journal Article↗

Fingerprint analysis of the fruits of Cnidium monnieri extract by high-performance liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry.

A method incorporating high-performance liquid chromatography (HPLC) with electrospray ionization (ESI) and tandem mass spectrometry (MS), with parallel analysis by HPLC with UV detection using a diode-array detector (DAD) was developed for the qualitative characterization of coumarin and chromone constituents in the fruits of Cnidium monnieri. The chromatographic separations were performed on a Diamonsil C18 column (4.6 mm x 200 mm, 5 microm) with water with 50 mM ammonium acetate and 2% acetic acid (A) and acetonitrile (B) as the mobile phase. According to the characteristic UV spectra, the information of molecular weight and structure provided by ESI-MS/MS, 13 coumarin and 7 chromone components were detected and identified. This method is rapid and reliable for identification of the constituents in the complex herbal system, and the fragmentation patterns proposed could be extended to the similar compounds.

Acetates↗

Gene expression profile analysis of an isogenic tumour metastasis model reveals a functional role for oncogene AF1Q in breast cancer metastasis.

To study the molecular mechanisms underlying breast cancer metastasis, gene expression profile analysis was performed on two well-established breast cancer cell lines with high and low metastatic potentials: MDA-MB-435HM and MDA-MB-435LM. The analysis was conducted using cDNA microarrays containing 8000 genes. Of 60 differentially expressed genes, ALL1-fused gene from chromosome 1q (AF1Q), a putative oncogene not described previously in breast cancer, was identified and found to be over-expressed in MDA-MB-435HM cells compared with MDA-MB-435LM cells. The results indicate that AF1Q may play an important role in breast cancer metastasis. To test this hypothesis, we generated an AF1Q high-expression cell line by stable transfection of AF1Q cDNA into MDA-MB-435LM cells. Results showed that over-expression of AF1Q led to a marked increase in the invasive and metastatic potential of MDA-MB-435LM cells in vitro and in vivo, accompanied by the up-regulation of matrix metalloproteinase-2 (MMP-2), MMP-9, transcription factor Ets-1, and RhoC expression in both mRNA and protein levels. Consistent with this observation, reduced AF1Q expression in MDA-MB-435HM cells by small interfering RNA (siRNA) resulted in a significant decrease in the invasive potential of MDA-MB-435HM cells in vitro and in the protein expression of MMP-2, MMP-9, Ets-1, and RhoC, compared with either parental or non-silencing control cells. These data provide functional evidence that oncogene AF1Q may be a novel mediator of metastasis promotion in human breast cancer through regulation of the MMP pathway and RhoC expression.

Blood Proteins↗

SH-7, a new synthesized shikonin derivative, exerting its potent antitumor activities as a topoisomerase inhibitor.

1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enylfuran-2-caroxylate (SH-7), a new naphthoquinone compound, derived from shikonin, exhibited obvious inhibitory actions on topoisomerase II (Topo II) and topoisomerase I (Topo I), which were stronger than its mother compound shikonin. Notably, the SH-7's inhibitory potency on Topo II was much stronger than that on Topo I. In addition, SH-7 significantly stabilized Topo II-DNA cleavable complex and elevated the expression of phosphorylated-H2AX. The in vitro cell-based investigation demonstrated that SH-7 displayed wide cytotoxicity in diversified cancer cell lines with the mean IC(50) value of 7.75 microM. One important finding is SH-7 displayed significant cytotoxicity in the 3 MDR cell lines, with an average IC(50) value nearly equivalent to that of the corresponding parental cell lines. The average resistance factor (RF) of SH-7 was 1.74, which was much lower than those of reference drugs VP-16 (RF 145.92), ADR (RF 105.97) and VCR (RF 197.39). Further studies illustrated that SH-7 had the marked apoptosis-inducing function on leukemia HL-60 cells, which was validated to be of mitochondria-dependence. The in vivo experiments showed that SH-7 had inhibitory effects on S-180 sarcoma implanted to mice, SMMC-7721, BEL-7402 human hepatocellular carcinoma and PC-3 human prostate cancer implanted to nude mice. Taken together, these results suggest that SH-7 induces DSBs as a Topo II inhibitor, which was crucial to activate the apoptotic process, and subsequently accounts for its both in vitro and in vivo antitumor activities. The well-defined Topo II inhibitory activity, antitumor effects particularly with its obvious anti-MDR action, better solubility and less toxicity make SH-7 as a potential antitumor drug candidate for further research and development.

Animals↗

Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basic fibroblast growth factor, combats tumor angiogenesis and metastasis.

Inhibitors of tumor angiogenesis and metastasis are increasingly emerging as promising agents for cancer therapy. Recently, heparanase inhibitors have offered a new avenue for such work because heparanase is thought to be critically involved in the metastatic and angiogenic potentials of tumor cells. Here, we report that oligomannurarate sulfate (JG3), a novel marine-derived oligosaccharide, acts as a heparanase inhibitor. Our results revealed that JG3 significantly inhibited tumor angiogenesis and metastasis, both in vitro and in vivo, by combating heparanase activity via binding to the KKDC and QPLK domains of the heparanase molecule. The JG3-heparanase interaction was competitively inhibited by low molecular weight heparin (4,000 Da) but not by other glycosaminoglycans. In addition, JG3 abolished heparanase-driven invasion, inhibited the release of heparan sulfate-sequestered basic fibroblast growth factor (bFGF) from the extracellular matrix, and repressed subsequent angiogenesis. Moreover, JG3 inactivated bFGF-induced bFGF receptor and extracellular signal-regulated kinase 1/2 phosphorylation and blocked bFGF-triggered angiogenic events by directly binding to bFGF. Thus, JG3 seems to inhibit both major heparanase activities by simultaneously acting as a substrate mimetic and as a competitive inhibitor of heparan sulfate. These findings suggest that JG3 should be considered as a promising candidate agent for cancer therapy.

Allantois↗

Colloids seeded deposition: growth of titania nanotubes in solution.

The formation of titania nanotubes through CeO2 colloids seeded deposition process in solution has been demonstrated. The interactions among colloidal particles play important roles for the solution "VLS"-type growth of nanotubes. The observation has significance for understanding solution nucleation and for developing new methods for nanomaterials preparation via the disclosed colloids seeded deposition (CSD) mechanism.

Journal Article↗

Synergism of C5N six-membered ring and vapor-liquid-solid growth of CN(x) nanotubes with pyridine precursor.

A series of bamboo-like CN(x)() nanotubes have been synthesized from pyridine precursor by chemical vapor deposition with bimetallic Fe-Co/gamma-Al(2)O(3) catalyst in the range of 550 approximately 950 degrees C. An unusual predomination of pyridinic nitrogen over graphitic nitrogen has been observed for the CN(x)() nanotubes with reaction temperature below 750 degrees C. The pyridinic nitrogen decreases and the graphitic nitrogen increases with rising reaction temperature. A synergism mechanism of C(5)N-six-membered-ring-based growth through surface diffusion and vapor-liquid-solid growth through bulk diffusion was accordingly deduced and schematically presented. This mechanism could not only explain our own experimental results, but also understand the CN(x)()-nanotube-related experimental phenomena in the literature, as well as be in accordance with the basic principle of diffusion kinetics. A promising route to the challenging topic for synthesizing regularly arranged C(5)N or high-N-content CN(x)() nanotubes has also been suggested.

Journal Article↗

Development and validation of a selective and robust LC-MS/MS method for high-throughput quantifying rizatriptan in small plasma samples: application to a clinical pharmacokinetic study.

An analytical method based on liquid chromatography with positive ion electrospray ionization (ESI) coupled to tandem mass spectrometry detection (LC-MS/MS) was developed for the determination of a potent 5-HT(1B/1D) receptor agonist, rizatriptan in human plasma using granisetron as the internal standard. The analyte and internal standard were isolated from 100 microL plasma samples by liquid-liquid extraction (LLE) and chromatographed on a Lichrospher C18 column (4.6mm x 50mm, 5 microm) with a mobile phase consisting of acetonitrile-10mM aqueous ammonium acetate-acetic acid (50:50:0.5, v/v/v) pumped at 1.0 mL/min. The method had a chromatographic total run time of 2 min. A Varian 1200 L electrospray tandem mass spectrometer equipped with an electrospray ionization source was operated in selected reaction monitoring (SRM) mode with the precursor-to-product ion transitions m/z 270-->201 (rizatriptan) and 313.4-->138 (granisetron) used for quantitation. The assay was validated over the concentration range of 0.05-50 ng/mL and was found to have acceptable accuracy, precision, linearity, and selectivity. The mean extraction recovery from spiked plasma samples was above 98%. The intra-day accuracy of the assay was within 12% of nominal and intra-day precision was better than 13% C.V. Following a 10mg dose of the compound administered to human subjects, mean concentrations of rizatriptan ranged from 0.2 to 70.6 ng/mL in plasma samples collected up to 24h after dosing. Inter-day accuracy and precision results for quality control samples run over a 5-day period alongside clinical samples showed mean accuracies of within 12% of nominal and precision better than 9.5% C.V.

Adult↗

Molecularly imprinted solid-phase extraction for rapid screening of mycophenolic acid in human plasma.

A molecularly imprinted solid-phase extraction coupled with high performance liquid chromatography (MISPE-HPLC) method was developed for rapid screening of mycophenolic acid (MPA) in human plasma. MPA imprinted polymers (MPA-MIP) were synthesized and then tested for their performance both in organic and in aqueous solution. MPA was selectively trapped and preconcentrated on the MPA-MIP sorbent using different loading and washing conditions. The good selectivity of MPA-MIP enabled further clean-up of the interfering components in human plasma. For the proposed MISPE-HPLC method, the linearity between responses (peak area) and concentration was found over the range of 1-100microg/ml with a linear regression coefficient (R(2)) of 0.9989. The limit of detection (LOD) and theoretical limit of quantification (LOQ) for MPA in plasma were 0.10 and 0.32microg/ml, respectively. The precisions were 7.3, 3.5 and 4.7% RSD for intra-day assay and 9.2, 4.1 and 5.5% RSD for inter-day reproducibility, respectively, at three concentration levels of MPA in spiked plasma (1, 10 and 100microg/ml). Both recoveries for the extraction (more than 74%) and for the analytical method (more than 87%) were acceptable for screening MPA in plasma samples. Twelve-hour pharmacokinetic profile of MPA for a renal transplant recipient receiving chronic oral dosing of 500mg mycophenolate mofetil (MMF) was investigated. Results indicated that this method could be applied for therapeutic drug monitoring of mycophenolic acid in patient plasma.

Calibration↗

Growth arrest induced by C75, A fatty acid synthase inhibitor, was partially modulated by p38 MAPK but not by p53 in human hepatocellular carcinoma.

C75, a well-known fatty acid synthase (FAS) inhibitor, has been shown to possess potent anti-cancer activity in vitro and in vivo. In this study, we reveal that C75 is a cell cycle arrest inducer and explore the potential mechanisms for this effect in hepatocellular carcinoma (HCC) cell lines with abundant FAS expression: HepG2 and SMMC7721 cells with wt-p53, and Hep3B cells with null p53. The results showed FAS protein expression and basal activity levels were higher in HepG2 cells than in the other two HCC cell lines. Treatment with C75 inhibited FAS activity within 30 min of administration and induced G(2) phase arrest accompanied by p53 overexpression in HepG2 and SMMC7721 cells. By contrast, C75 triggered G(1) phase arrest in Hep3B cells, and RNA interference targeting p53 did not attenuate C75-induced G(2) arrest in HepG2 cells. Similarly, p53 overexpression via p53 plasmid transfection did not affect C75-induced G(1) phase arrest in Hep3B cells. However, we observed a clear correlation between p38 MAPK activation triggered by C75 and the induction of cell cycle arrest in all three HCC cells. Furthermore, treatment with the p38 MAPK inhibitor SB203580 reduced p38 MAPK activity and cell cycle arrest, and also partially restored cyclin A, cyclin B1, cyclin D1 and p21 protein levels. Collectively, it was p38 MAPK but not p53 involved in C75-mediated tumor cell growth arrest in HCC cells.

4-Butyrolactone↗

On-line simultaneous removal of human serum albumin and enrichment of doxazosin using a weak cation-exchange monolithic column.

A weak cation-exchange monolithic column was prepared by modifying the GMA-EDMA (glycidyl methacrylate-co-ethylene glycol dimethacrylate) monoliths with ethylenediamine and monochloracetic acid. The properties of the column were investigated; the column exhibited the ability of low backpressure and fast analysis. Using this monolithic column, trace doxazosin in human serum albumin (HSA) solution and plasma samples has been on-line tested, the extraction efficiency and the maximum loading capacity of the monolithic column were obtained. The results showed that the monolithic column could realize deproteinization and trace drug enrichment simultaneously in the HSA solution and human plasma, which provided a simple, cheap, effective and friendly to environment method for assaying drugs in the blood.

Acetates↗

Separation, identification and rapid determination of liensine, isoliensinine and neferine from embryo of the seed of Nelumbo nucifera Gaertn. by liquid chromatography coupled to diode array detector and tandem mass spectrometry.

An application of mass spectrometric methods has been developed to characterize, prepare and quantitatively analyze three bisbenzylisoquinoline alkaloids (liensinine, isoliensinine and neferine) from embryo of the seed of Nelumbo nucifera Gaertn. Initially, an analytical method based on liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) with positive ionization mode using a MonoChrom C18 column (4.6 mm x 250 mm i.d. 10 microm) has been developed to characterize liensinine, isoliensinine and neferine, and then scaled up to purify them on a 21.4 mm x 250 mm preparative column. The structures of liensinine, isoliensinine and neferine were elucidated by NMR. Finally, a LC-MS/MS determination method, successfully applied to separation within 3 min, was developed for high throughput simultaneous measurement of liensinine, isoliensinine, and neferine in the extract samples. Multiple reaction monitoring (MRM) was used to monitor the transition of the protonated molecules m/z 611, 611, 625 [M+H]+ to the product ions m/z 206, 192, 206 for analysis of liensinine, isoliensinine and neferine. The LC-MS/MS system was linear in the concentration range of 0.0247-6.02 microg/ml with correlation coefficients of r2>0.992. The quantitative method was validated, with an S/N=3 detection limit of 0.15 ng for liensinine, 0.19 ng for isoliensinine and 0.1 2ng for neferine. The mass fractions of liensinine, isoliensinine, and neferine in the crude extract and the phenolic alkaloid sample of embryo of the seed of N. nucifera Gaertn. were 16.5+/-1.1 and 228.6+/-11.9 for liensinine (mg/g), 45.7+/-1.8 and 640.7+/-15.2 for isoliensinine (mg/g), 59.7+/-6.4 and 58.8+/-9.8 for neferine (mg/g).

Alkaloids↗

Operant conditioning of reciprocal inhibition in rat soleus muscle.

Operant conditioning of the H-reflex, the electrical analog of the spinal stretch reflex (SSR), induces activity-dependent plasticity in the spinal cord and might be used to improve locomotion after spinal cord injury. To further assess the potential clinical significance of spinal reflex conditioning, this study asks whether another well-defined spinal reflex pathway, the disynaptic pathway underlying reciprocal inhibition (RI), can also be operantly conditioned. Sprague-Dawley rats were implanted with electromyographic (EMG) electrodes in right soleus (SOL) and tibialis anterior (TA) muscles and a stimulating cuff on the common peroneal (CP) nerve. When background EMG in both muscles remained in defined ranges, CP stimulation elicited the TA H-reflex and SOL RI. After collection of control data for 20 days, each rat was exposed for 50 days to up-conditioning (RIup mode) or down-conditioning (RIdown mode) in which food reward occurred if SOL RI evoked by CP stimulation was more (RIup mode) or less (RIdown mode) than a criterion. TA and SOL background EMG and TA M response remained stable. In every rat, RI conditioning was successful (i.e., change > or =20% in the correct direction). In the RIup rats, final SOL RI averaged 171+/- 28% (mean +/- SE) of control, and final TA H-reflex averaged 114 +/- 14%. In the RIdown rats, final SOL RI averaged 37 +/- 13% of control, and final TA H-reflex averaged 60 +/- 18%. Final SOL RI and TA H-reflex sizes were significantly correlated. Thus like the SSR and the H-reflex, RI can be operantly conditioned; and conditioning one reflex can affect another reflex as well.

Animals↗

Rapid determination of granisetron in human plasma by liquid chromatography coupled to tandem mass spectrometry and its application to bioequivalence study.

A simple, sensitive and rapid method for analysis of granisetron in human plasma, utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS), has been developed and validated to satisfy FDA guidelines for bioanalytical methods. The analyte and internal standard (IS) were isolated from 100microl plasma samples by liquid-liquid extraction (LLE). A Varian 1200l tandem mass spectrometer equipped with an electrospray ionization source was operated in selected reaction monitoring (SRM) mode with the precursor-to-product ion transitions m/z 313.4/138 for granisetron and m/z 270/201 for the IS used for quantitation. The assay exhibited a linear dynamic range of 0.02-20ng/ml for granisetron in human plasma. The lower limit of quantification (LLOQ) was 0.02ng/ml with a relative standard deviation of less than 15%. The mean extraction recovery from spiked plasma samples was 97.9%. The intra-day accuracy of the assay was within 10% of nominal and intra-day precision was better than 15% C.V. A run time of 2.0min for each sample made it possible for high-throughput bioanalysis. The method was employed in a bioequivalence study of two formulations of granisetron hydrochloride 1mg rapidly disintegrating tablets/1mg capsules.

Administration, Oral↗

N-all-trans-retinoyl-L-proline inhibits metastatic potential of hepatocellular carcinoma cells.

Tumor metastasis is usually a serious problem in tumor patients because of the lack of therapeutic approaches. A new compound, N-all-trans-retinoyl-L-proline (ATRP), has been developed and its metastasis inhibition activity has been studied. Low concentrations of ATRP have already been found to inhibit hepatocellular carcinoma cells (HCC) in a dose- and time-dependent manner by inducing the expression of p27(kip). We found that ATRP inhibited metastasis-associated behaviors in Hep3B cells, such as cell migration, invasion, collagen adhesion and gelatinase expression, more significantly than retinoic acid. Further, such inhibitory activities were observed in the regulation of cellular surface fucosylated epitope functions, such as binding of ulex europaeus lectin, expression of Lewis x, y and b, and activity of alpha1,3 fucosyltransferase. Hep3B cells pretreated with ATRP showed a significantly reduced incidence of experimental intrahepatic metastasis in nude mice. We conclude that ATRP is an alternative inhibitor and potential therapeutic agent for HCC metastasis with a different mechanism of action from ATRP.

Animals↗

Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer.

OBJECTIVE: To study severe and rare complications of transarterial chemoembolization (TACE) for liver cancer. METHODS: Clinical records of severe and rare complications following TACE in 1348 cases of liver cancer from January 1997 to February 2004 were studied retrospectively. RESULTS: A total of 2012 TACE procedures were performed for 1348 patients. There were 3 cases of spontaneous rupture of liver cancer, 1 case of perforation of duodenum, 3 cases of liver abscess (1 of them was associated with sepsis), 1 case of pulmonary embolism, 1 case of spasm of the hepatic artery, 40 cases of hepatic artery occlusion, 3 cases of femoral nerve injury, 1 case of bilioma and 1 case of acute renal failure. CONCLUSION: Although the severe complications of TACE are rare, the procedure should be done cautiously including super selection of hepatic artery, slow infusion of lipiodol, careful postoperative observations and early detection and management of complications.

Antineoplastic Agents↗