1.Effects of PEG stress on flavonoids accumulation and related gene expression in suspension of Scutellaria baicalensis.
Zhaochun YANG ; Yuan YUAN ; Min CHEN ; Lingfei SHUAI ; Qian XIAO ; Shufang LIN
China Journal of Chinese Materia Medica 2011;36(16):2157-2161
OBJECTIVETo study the effects of PEG stress on baicalin, baicalein accumulation induced by an increased concentration of PEG solution and the related genes' expression in suspension of Scutellaria baicalensis.
METHODThe content of baicalin, baicalein in suspension of S. baicalensis was determined by HPLC. The related genes' expression was analyzed by semi-quantitative PCR.
RESULTThe content of proline in suspension of S. baicalensis was promoted by PEG treatment. Ten percent PEG treatment promoted the expression of PAL and the content of baicalein in experimental material via a drought stress. 20% PEG solution treatment promoted the expression of UBGAT. At the same time, the increased activity of APX inhibited the progress of eliminating reactive oxygen by baicalein, which induced the transformation from baicalein to baicalin.
CONCLUSIONActive ingredient in suspension of S. baicalensis was promoted significantly via a stress of light concentration of PEG solution.
Flavonoids ; metabolism ; Gene Expression ; Polyethylene Glycols ; pharmacology ; Scutellaria baicalensis ; drug effects ; metabolism ; Suspensions
2.Management of toxicities associated with pegaspargase in treatment of patients with lymphoid malignancy: experience from 443 cases in a single center.
Jia CONG ; Lei YANG ; Jin YE ; Li Qiang WEI ; Xin LI ; Jing Wen WANG
Chinese Journal of Hematology 2018;39(8):654-660
Objective: To summarize the adverse effects of pegaspargase in the treatment of lymphoid malignancies and management experience. Methods: Clinical data of patients who received chemotherapy including pegaspargase in the Department of Hematology of Beijing Tongren hospital during August 2011 to December 2015 were retrospective analyzed, and the adverse effects of pegaspargase and the management experience was summarized. Results: A total of 129 patients with 443 times of pegaspargase used during this period. The common adverse reactions included allergic reactions in 2 cases (1.6%), acute pancreatitis in 19 (14.7%) including 6 acute symptomatic pancreatitis and 13 chemical pancreatitis with elevated pancreatin, hypertriglyceridemia in 15 cases(11.6%), hyperglycemia in 85 (65.9%), hypoglycemia in 7 (5.4%), elevated aminotransferase in 25 (19.4%), hyperbilirubinemia in 21 (15.5%), hypoalbuminemia in 62 (48.1%), prolonged APTT in 61 (47.3%), prolonged PT in 22 (17.1%), prolonged TT in 15 (11.6%), hypofibrinogen in 75 (58.1%), thrombus in 11 (8.5%) and bleeding in 3 (2.3%). The above adverse reactions were improved by symptomatic treatment of anti allergy, inhibition of secretion of pancreatic juice, lipid lowering, hypoglycemic, liver preservation, supplementation of plasma and hemostasis, respectively. Some serious adverse reactions affected the application of pegaspargase, even lead to discontinuation of the aspartate. Conclusion: Though adverse effects associated with pegaspargase are extensive, most patients can successfully complete the chemotherapy containing the pegaspargase with close monitoring and timely treatment.
Asparaginase/metabolism*
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Humans
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Polyethylene Glycols/metabolism*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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Retrospective Studies
3.Preparation of recombinant cutinase and its application in surface modification of poly (ethylene terephthalate).
Yao ZHANG ; Sheng CHEN ; Dan WU ; Miao HE ; Kongliang ZHU ; Jian CHEN ; Jing WU
Chinese Journal of Biotechnology 2011;27(7):1057-1064
Fermentation and induction conditions for recombinant Escherichia coli expressing Thermobifida fusca cutinase were optimized in flasks and 3L fermenter. Surface modification of poly (ethylene terephthalate) fibers with cutinase was also discussed. The results showed that, cutinase yield reached 128 U/mL by adding 2 g/L inducer lactose and 0.5% glycine. In the fed-batch culture in a 3 L fermenter, the maximum biomass cutinase activity was up to 506 U/mL, which is the highest bacterial cutinase activity reported by far. Recombinant cutinase was used to modify polyester fibers and terephthalic acid substance was detected by using UV analysis. The dyeing and wetting properties of cutinase treated fibers were higher than untreated fibers. Combined utilization of cutinase and Triton X-100 can significantly improve the hydrophilicity of polyester. This is the first report of surface modification on polyester fibers by bacterial cutinase.
Actinomycetales
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enzymology
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genetics
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Carboxylic Ester Hydrolases
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biosynthesis
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chemistry
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genetics
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Escherichia coli
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genetics
;
metabolism
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Fermentation
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Polyethylene Glycols
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chemistry
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Polyethylene Terephthalates
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Recombinant Proteins
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biosynthesis
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genetics
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Surface Properties
4.Quantitative characterization of adsorbed bovine serum albumin on modified surfaces of poly(ether urethane) materials using ATR-FT-IR spectroscopy.
Dongan WANG ; Jian JI ; Linxian FENG ; Jiacong SHEN
Journal of Biomedical Engineering 2002;19(1):4-9
Attenuated total reflection (ATR) FT-IR spectroscopy was used to quantitatively characterize the extent of bovine serum albumin (BSA) adsorbed on the surface-coating-modified poly(ether urethane) (PEU) matrix. The two surface modifying additives (SMA) were respectively a tri-block-coupling-polymer of stearyl poly (ethylene oxide)-4,4'-methylene diphenyl diisocyanate-stearyl poly(ethylene oxide), for short MSPEO, and another similar block-coupling polymer with the Cibacron Blue F3G-A endgroups, for short cibaMPEO. The experiments of static BSA adsorption were composed by two parts. One was static isothermal adsorption, and the other was static adsorption kinetics. The quantitative characterization was based on the optical principles of FT-IR, method of experiment and index of the apparatus, by which the enhancement of BSA adsorption on the SMA-modified surfaces was confirmed.
Adsorption
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Animals
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Biocompatible Materials
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Cattle
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Polyethylene Glycols
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Polyurethanes
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Serum Albumin, Bovine
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metabolism
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Spectroscopy, Fourier Transform Infrared
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Stearates
5.Influence of wall polymer and preparation process on the particle size and encapsulation of hemoglobin microcapsules.
Wei QIU ; Guang-Hui MA ; Fan-Tao MENG ; Zhi-Guo SU
Chinese Journal of Biotechnology 2004;20(2):245-251
Methoxypoly (ethylene glycol)- block-poly (DL-lactide) (PELA) microcapsules containing bovine hemoglobin (BHb) were prepared by a W/O/W double emulsion-solvent diffusion process. The P50 and Hill coeffcient were 3466 Pa and 2.4 respectively, which were near to the natural bioactivity of bovine hemoglobin. The results suggested that polymer composition had significant influence on encapsulation efficiency and particle size of microcapsules. The encapsulation efficiency could reach 90% and the particle size 3 - 5 microm when the PELA copolymer containing MPEG 2000 block was used. The encapsulation efficiency and particle size increased with the concentration of PELA. Increasing the concentrations of NaCl in outer aqueous solution resulted in the increase of encapsulation efficiency and the decrease of particle size. As the concentration of stabilizer in outer aqueous solution increased in the range of 10 g/L to 20 g/L, the particle size reduced while encapsulation efficiency was increased, further increase of the stabilizer concentration would decrease encapsulation efficiency. Increasing of primary emulsion stirring rate was advantageous to the improvement of encapsulation efficiency though it had little influence on the particle size. The influence of re-emulsion stirring rate was complicated, which was not apparent in the case of large volume of re-emulsion solution. When the wall polymer and primary emulsion stirring rate were fixed, the encapsulation efficiency decreased as the particle size reduced.
Animals
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Biocompatible Materials
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chemistry
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Capsules
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Cattle
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Hemoglobins
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metabolism
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Lactates
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chemistry
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Particle Size
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Polyethylene Glycols
;
chemistry
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Technology, Pharmaceutical
;
methods
6.Mechanisms and strategies for targeting drugs to myocardial ischemic regions.
Acta Pharmaceutica Sinica 2010;45(7):827-832
The ischemic heart disease has been endangering human health seriously. Although there are many kinds of anti-ischemic drugs, most of them are lacking in tissue specificity, which together with a remarkably reduced blood circulation in the ischemic zone often lead to a quite low drug distribution in the targets. Myocardial ischemia can cause a lot of pathophysiological changes, such as the enhanced permeability of the endothelial cell membrane, the up-regulated expression of various cell adhesion molecules on endothelium, the exposure of intracellular antigenic components, the decrease of pH within the ischemic zone, and so on. To date, some of these changes have been exploited with limited success to gain the passive, active and physicochemical targeting of diagnostic or therapeutic drugs to myocardial ischemic regions. However, more effective delivery strategies are still eagerly needed. Here, we reviewed and discussed the potential targeting-delivery mechanisms and strategies, used or may be used in the future, for myocardial ischemic regions.
Animals
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Antibodies, Monoclonal
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immunology
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Capillary Permeability
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Drug Carriers
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Drug Delivery Systems
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methods
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Genetic Therapy
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Humans
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Liposomes
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chemistry
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metabolism
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Myocardial Ischemia
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therapy
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Myocardium
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metabolism
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pathology
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Polyethylene Glycols
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metabolism
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Ultrasonics
7.The Efficacy of an Acrylic Intraocular Lens Surface Modified with Polyethylene Glycol in Posterior Capsular Opacification.
Hyeon Il LEE ; Mee Kum KIM ; Jung Hwa KO ; Hyun Ju LEE ; Won Ryang WEE ; Jin Hak LEE
Journal of Korean Medical Science 2007;22(3):502-507
To investigate if the surface modification of intraocular lens (IOL) is efficient in the prevention of posterior capsular opacification (PCO), the acrylic surface of intraocular lens (Acrysof(R)) was polymerized with polyethylene glycol (PEG-IOL). The human lens epithelial cells (1x10(4) cells/mL) were inoculated on PEG grafted or unmodified acrylic lenses for the control. The adherent cells on each IOL surface were trypsinized and counted. The every PEG-IOL was implanted in 20 New Zealand rabbits after removal of crystalline lens. The formations of PCO were checked serially through retroilluminated digital photography, and the severity scores were calculated using POCOman(R). The cell adherence patterns on each IOL were examined by scanning electron microscopy. As a result, the mean number of adherent cells of PEG-IOL (3.2+/-1.1x10(3)) tended to be smaller than that of the acrylic controls (3.6+/-1.9x10(3)) without a statistical significance (p=0.73). However, the mean severity of PCO formation in PEG-IOL was significantly lower than that in the control during the third to sixth weeks after surgery. Scanning electron microscopy revealed that the more patch-like cells were found firmly attached to the IOL surface in control than in the PEG-IOL. Conclusively, PEG polymerization to the acrylic IOL would possibly lessen the formation of PCO after cataract removal.
Acrylic Resins/chemistry
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Biocompatible Materials
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Cataract/metabolism/*therapy
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Cell Adhesion
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Humans
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Lens Implantation, Intraocular/*methods
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Lens, Crystalline/cytology/ultrastructure
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Microscopy, Electron, Scanning
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Polyethylene Glycols/*chemistry/metabolism
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Time Factors
8.Effect of polyethylene glycol on the regeneration of the callus of Pogonatherum paniceum under different culture conditions.
Wen-Guo WANG ; Xiao-Guang ZHAO ; Sheng-Hua WANG ; Fang CHEN
Chinese Journal of Biotechnology 2007;23(2):337-342
This paper studied the effect of polyethylene glycol (PEG) on regeneration and free proline accumulation of callus of Pogonatherum paniceum (Lam.) Hack. under motionless liquid culture condition and shake liquid culture condition. Callus of P. paniceum had the ability to resist the stress of PEG. The effects of PEG stress and culture conditions on the callus of P. paniceum appeared mainly in two aspects, delaying regeneration time and debasing regeneration rates. The shake liquid culture mainly delayed the regeneration time and PEG stress mainly debased the regeneration rates. Free proline accumulated in the two culture conditions, and the contents of proline were positively correlated with PEG concentrations and culture time. After stress removal, most of the callus could recover the ability of regeneration, and the free proline might pay an important part in the inhibition and recovery. So it must be chosen a more than 300 g x L(-1) PEG concentration and long than 3 weeks culture time in the selection of drought-resistant mutants of P. paniceum. The motionless liquid culture was more suitable for selection of drought-resistant mutants.
Dose-Response Relationship, Drug
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Poaceae
;
drug effects
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metabolism
;
physiology
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Polyethylene Glycols
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pharmacology
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Proline
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metabolism
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Regeneration
;
drug effects
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Time Factors
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Tissue Culture Techniques
9.Immobilization of lipase labeled with fluorescent probe and its stability.
Jiayin XU ; Chi ZHANG ; Xijin SONG ; Jie WANG
Chinese Journal of Biotechnology 2010;26(1):100-107
The lipase labeled with the fluorescein isothiocyanat (FITC) was immobilized on the derivatives of the polyethylene glycol. The article discussed the effect of factors on the characters of lipase and analyzed the relationships among the activity of lipase, conformation, and fluorescence spectrum while the activity and the fluorescence spectrum of immobilized lipase were determined. The results demonstrated that polyethylene glycol 400-diacrylate could form appropriate network to improve the activity of enzyme. Adding ligand induced the lipase's catalytic conformation to increase the activity twice more than before. The active centre of lipase could be released by the extraction of ligand thus increasing the activity. After immobilization, the stability of labeled lipase improved greatly: immobilized lipases retained more than 70% and 60% of initial activity under conditions of 90 degrees C and strong acid or alkali, respectively. After immersing immobilized lipases into guanidine hydrochloride or urea for 15 days, the lipases retained upwards of 70% activity. The fluorescence spectrum could obviously reflect the changes of the activity and conformation of lipase. The fluorescence intensity was the minimum in the optimal pH and temperature. In the denaturing agent it declined as time passed. These results indicated that the unfolded processes of immobilized lipases are different under different conditions.
Dextrans
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chemistry
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Enzyme Stability
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Enzymes, Immobilized
;
chemistry
;
metabolism
;
Fluorescein-5-isothiocyanate
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analogs & derivatives
;
chemistry
;
Fluorescent Dyes
;
chemistry
;
Lipase
;
chemistry
;
metabolism
;
Polyethylene Glycols
;
chemistry
;
Protein Unfolding
;
drug effects
10.Site-specific monoPEGylated interferon alpha2a mediated by microbial transglutaminase.
Xiwu HUI ; Weirong CAO ; Di ZHANG ; Wenli GE ; Shuli LI ; Yingui LI
Chinese Journal of Biotechnology 2020;36(4):750-762
PEGylation is considered one of the most successful techniques to improve the characteristics of protein drugs including to increase the circulating half-life of proteins in blood and to decrease their immunogenicity and antigenicity. One known PEG modification method is to attach PEG to the free amino group, typically at lysine residues or at the N-terminal amino acid with no selectivity, resulting in a heterogeneous product mixture. This lack of selectivity can present problems when a therapeutic PEGylated protein is being developed, because predictability of activity and manufacturing reproducibility are needed for regulatory approval. Enzymatic PEGylation of proteins is one route to overcome this limitation. Transglutaminases (TGase) are enzyme candidates for site-specific PEGylation. We use human interferon alpha 2a (IFN α2a) as a test case, and predict that the potential modification residues are Gln101 by computational approach as it contains 12 potential PEGylation sites. IFN α2a was PEGylated by Y shaped PEG40k-NH2 mediated by microbial transglutaminase. Our results show that the microbial transglutaminase mediated PEGylation of IFN α2a was site-specific only at the site of Gln101 in IFN α2a, yielding the single mono-conjugate PEG-Gln101-IFN α2a with a mass of 59 374.66 Da. Circular dichroism studies showed that PEG-Gln101-IFN α2a preserved the same secondary structures as native IFN α2a. As expected, the bioactivity and pharmacokinetic profile in rats of PEG-Gln101-IFN α2a revealed a significant improvement to unmodified IFN α2a, and better than PEGASYS.
Animals
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Antiviral Agents
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Humans
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Interferon alpha-2
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metabolism
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Interferon-alpha
;
biosynthesis
;
pharmacokinetics
;
Polyethylene Glycols
;
pharmacokinetics
;
Protein Structure, Secondary
;
Rats
;
Recombinant Proteins
;
biosynthesis
;
pharmacokinetics
;
pharmacology
;
Reproducibility of Results
;
Transglutaminases
;
metabolism