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Jian-guo Sun

Publications and source records attributed to Jian-guo Sun.

6 recordsLinked to original sources

Development and validation of a sensitive quantification method for hematoporphyrin monomethyl ether in plasma using high-performance liquid chromatography with fluorescence detection.

A rapid, sensitive, precise and specific method for determination of hematoporphyrin monomethyl ether (HMME), a novel photodynamic therapy (PDT) drug, was developed and validated using high-performance liquid chromatography (HPLC) with fluorescence detection. HMME was isolated from the plasma by a single-step liquid-liquid extraction with ethyl acetate. The analyte and internal standard fluorescein were baseline separated on a Diamonsil C(18) analytical column (4.6 x 150 mm, 5 microm) and analyzed using a fluorescence detector with the excitation and emission wavelengths set at 395 and 613 nm, respectively. The method was linear in the concentration range 0.025-5 microg/mL with a lower limit of quantitation (LLOQ) of 10 ng/mL. The inter- and intra-day accuracies and precisions were all within 10% and the mean recoveries of HMME and fluorescein were 95 +/- 3.7 and 90 +/- 2.3%, respectively. The analyte was stable during all sample storage, preparation and analysis periods. This method was successfully applied to a pharmacokinetic study after a single-dose intravenous administration of HMME (5 mg/kg) to beagle dogs. This method was reproducible and sensitive enough for the pharmacokinetic study of HMME. Based on the results of the pharmacokinetic study, we suggest that a rather long light-avoiding time is essential for patients under HMME therapy.

Animals↗

[Experimental study on transcription regulation of mouse hepcidin gene by NF-kB].

OBJECTIVE: To investigate the involvement of NF-kappaB (NF-kB) regulation of hepcidin gene transcription in acute phase response and its molecular mechanism. METHODS: First, a mouse model of acute phase response was established by intraperitoneal injection of LPS. The relationship between hepcidin expression and dose or time of LPS injection was assessed. Then, electrophoretic mobility shift assay (EMSA) was performed to explore the possibility of the involvement of NF-kB in regulation of hepcidin gene transcription. Next, pAVU6+27-NF-kB, NF-kB p65-specific siRNA expression vector was constructed and transfected into mouse primary hepatocytes using DOTAP liposomal transfection reagents. Hepcidin expression changes after silencing of NF-kB p65 and hepcidin expression after LPS induction were tested. RESULTS: Hepcidin expression showed a time and dose-dependent manner with regard to LPS injection. At 10 h after 50 microg LPS injection, hepcidin expression reached its peak. The result of EMSA exhibited an evident lag band at -53 - -64 bp, indicating regulation of hepcidin gene expression by NF-kB. After mouse primary hepatocytes were transiently transfected with NF-kB p65-specific siRNAs, Western blot showed that inhibition rate of NF-kB expression was 50%-67%. Hepcidin expression of transfected hepatocytes dropped down obviously in comparison with that of untransfected hepatocytes, and could not be induced by LPS. CONCLUSION: Transcription factor NF-kB is likely to be an important molecule in transcription regulation of hepcidin gene. As a key component, p65 subunit binds to hepcidin gene at -53 - -64 bp, and upregulates hepcidin expression.

Acute-Phase Reaction↗

[Pharmacokinetics of oxymatrine and its metabolite in beagle dogs by LC-MS].

OBJECTIVE: To establish LC-MS method in the determination of oxymatrine and its metabolite in plasma and investigate their pharmacokinetics in beagle dogs. METHOD: Lichrospher C18 column (4.6 mm x 250 mm, 5 microm) was used as the analytical column maintained at 25 degrees C. The mobile phase consisted of 10 mmol x L(-1) CH3COONH4 and CH3OH (25:75). Flow rate was 1 mL x min(-1). Electrospray ionization (ESI) was carried out. The ESI ion source was set in positive ion polasity mode. The selective ion monitoring (SIM) was set at m/z 265.1 and 249.2. RESULT: The linearity ranged from 2 to 5000 ng x mL(-1) (r = 0.9991). The detection of oxymatrine and its metabolite were 0.6 and 0.3 ng x mL(-1). The RSD(%) within day and between day was less than 4.7%. The recovery of this method was more than 96.5%. The disposition was conformed to a two-compartment model. The T(1/2), Tmax, Cmax, MRT, AUC(0-->24 h) of oxymatrine were (5.5+/-1.58) h, (1.0+/-0.30) h, (2418.3 +/-970.78) ng x mL(-1), (3.2+/-0.64) h, (5797.4+/-908.16) ng x mL(-1) x h accordingly. The corresponding T(1/2), Tmax, Cmax, MRT, AUC(0-->24 h) of matrine were (9.8+/-2.77) h, (1.9+/-1.09) h, (1532.4+/-494.86) ng x mL(-1), (4.4+/-1.97) h, (5530.5+/-1042.65) ng x mL(-1) x h. CONCLUSION: This assay was highly sensitive, rapid, simple and specific enough for determining concentrations of oxymatrine and its metabolite matrine in plasma of beagle dog.

Administration, Oral↗

[Gene transfection of Livin isoforms into A549 cell line and its effect on cell growth and sensitivity to chemotherapy and radiotherapy].

OBJECTIVE: To express Livin alpha & beta in A549 cells by using gene transfection, and to observe its effect on cell growth and cell sensitivity to chemotherapy drugs and radiation. METHODS: Eukaryotic expression vectors of Livin alpha & beta were transfected into A549 cells and cell clones with stable expression were obtained. Livin alpha & beta expression levels in the transfected A549 cells were assessed at mRNA level and protein level, respectively. Cell growth status was assessed by biological features. MTT was performed to test effects of Livin on sensitivity of the A549 cells to chemotherapy drugs and radiation, and cell cycle analysis was performed to evaluate cell apoptosis. RESULTS: After transfection, positive cells, especially A549 cells expressing Livin, showed an increase of about 20% in colony-forming ability, a shorter doubling time (P < 0.05) and lower sensitivity to chemotherapy drugs and radiation (P < 0.01). Only 0.2% of the cells committed apoptosis with 10 Gy radiation. CONCLUSION: Livin isoforms, especially Livin alpha, are implicated in genesis and development of lung cancer, thus may be an important mechanism for drug resistance of lung cancer cells.

Adaptor Proteins, Signal Transducing↗

[Inhibitory action of berberine on glucose absorption].

AIM: To study the absorption characteristics of berberine and its influence on glucose absorption. METHODS: Rat recirculating perfusion model was used to study berberine absorption characteristics and Caco-2 cell model was used to explore the influence of berberine on disaccharidase, using HPLC to assay the appearance of glucose to indicate enzyme activities. RESULTS: Berberine was found to be hardly absorbed in the intestine (less than 5% in 2.5 h). However, sucrase and maltase activities were found to be inhibited by berberine, its ID50 to sucrase is 1.830 mg.L-1, and showed no dose dependent influence on maltase activity. Berberine also showed influence on glucose absorption. However, this effect is not significant. CONCLUSION: Berberine may act as an alpha-glucosidase inhibitor, which is its main mechanism in diabetes treatment.

Animals↗

[Determination of guanfu base A hydrochloride in plasma by LC-MS method and its pharmacokinetics in dogs].

AIM: To establish an analytical method for determination of guanfu base A (GFA) concentration in plasma and to study its pharmacokinetic profile in dogs. METHODS: Six dogs were given a 7.56 mg.kg-1 dose intravenously. Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography-mass spectrometry (LC-MS) was established to determine the plasma concentration of GFA. Pharmacokinetic evaluation was carried out using the 3P87 program. RESULTS: The calibration curves were linear over the concentration range from 0.42 microgram.mL-1 to 21.2 micrograms.mL-1 (gamma = 0.9994). The intra-day and inter-day precisions were generally good (< 15%) at low, medium and high concentrations. The overall recovery of the analytes was more than 80%. Six dogs were given an i.v. dose of 7.56 mg.kg-1 of GFA hydrochloride, an open three compartment model best described the concentration-time profiles for GFA. The half-lives for the rapid and slow distribution phase and terminal elimination phase (T1/2 pi, T1/2 alpha and T1/2 beta) were 0.07 h, 1.5 h, and 13.5 h, respectively. The total area under the plasma concentration-time curve (AUC), the volume of the central compartment (Vc), and plasma clearance (CLs) were 61.43 micrograms.h.mL-1, 0.37 L.kg-1 and 0.14 L.kg-1.h-1, respectively. CONCLUSION: The analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of GFA.

Aconitum↗