2.The construction of cell-penetrating peptide R8 and pH sensitive cleavable polyethylene glycols co-modified liposomes.
Li ZHANG ; Yang WANG ; Hui-le GAO ; Qin HE
Acta Pharmaceutica Sinica 2015;50(6):760-766
The purpose of the study is to construct R8 peptide (RRRRRRRR) and pH sensitive polyethylene glycols (PEG) co-modified liposomes (Cl-Lip) and utilize them in breast cancer treatment. The co-modified liposomes were prepared with soybean phospholipid, cholesterol, DSPE-PEG2K-R8 and PEG5K-Hz-PE (pH sensitive PEG). The size and zeta potential of Cl-Lip were also characterized. The in vitro experiment demonstrated that the Cl-Lip had high serum stability in 50% fetal bovine serum. The cellular uptake of Cl-Lip under different pre-incubated conditions was evaluated on 4T1 cells. And the endocytosis pathway, lysosome escape ability and tumor spheroid penetration ability were also evaluated. The results showed the particle size of the Cl-Lip was (110.4 ± 5.2) nm, PDI of the Cl-Lip was 0.207 ± 0.039 and zeta potential of the Cl-Lip was (-3.46 ± 0.05) mV. The cellular uptake of Cl-Lip on 4T1 cells was pH sensitive, as the cellular uptake of Cl-Lip pre-incubated in pH 6.0 was higher than that of pH 7.4 under each time point. The main endocytosis pathways of Cl-Lip under pH 6.0 were micropinocytosis and energy-dependent pathway. At the same time, the Cl-Lip with pre-incubation in pH 6.0 had high lysosome escape ability and high tumor spheroid penetration ability. All the above results demonstrated that the Cl-Lip we constructed had high pH sensitivity and is a promising drug delivery system.
Animals
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Cell Line, Tumor
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Cell-Penetrating Peptides
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chemical synthesis
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chemistry
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Cholesterol
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chemistry
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Drug Delivery Systems
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Liposomes
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Mice
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Oligopeptides
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chemical synthesis
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chemistry
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Particle Size
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Phospholipids
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chemistry
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Polyethylene Glycols
3.Cell penetrating peptide TAT and brain tumor targeting peptide T7 dual modified liposome preparation and in vitro targeting evaluation.
Duan-feng YUAN ; Tai-li ZONG ; Hui-le GAO ; Qin HE
Acta Pharmaceutica Sinica 2015;50(1):104-110
The purpose of this study is to prepare T7 and TAT dual modified liposomes (T7-TAT-LIP) to penetrate through blood brain barrier and target to brain tumor cells. The liposomes were prepared with CFPE, T7 modified PEG-DSPE, TAT modified PEG-DSPE, soybean phospholipid, PEG-DSPE and cholesterol. The CFPE was used to track the cellular uptake efficiency. The density of T7 and TAT and the length of PEG were optimized, and then the liposomes were characterized by particle size, zeta potential, morphology and stability. Afterwards, the cellular uptake by bEnd.3 and C6 cells were evaluated. The results showed that the optimized parameters were 6% of T7, 0.5% of TAT, the molecular weight of PEG for T7 was 2000 and the molecular weight of PEG for TAT was 1000. After optimization, the particle size of T7-TAT-LIP was 118 nm, the zeta potential was -6.32 mV and the particles were spherical. The turbidity and particle size of liposomes were not obviously changed after 24 h incubation in PBS at 37 °C. The particle size and polydispersity index were also stable during 1 month incubation at 4-8 °C. The cellular uptake by both bEnd.3 and C6 cells of T7-TAT-LIP was higher than that of T7 or TAT modified liposomes, suggesting dual modified liposomes possessed better blood brain barrier targeting ability and brain tumor targeting ability than the single ligand modified liposomes.
Biological Transport
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Blood-Brain Barrier
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Brain Neoplasms
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drug therapy
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Cell-Penetrating Peptides
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pharmacology
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Cholesterol
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Liposomes
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Particle Size
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Phosphatidylethanolamines
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Polyethylene Glycols
4.Hypolipidemic activity of total phenylpropanoid glycosides fromLigustrum robustum(Roxb.) Blume and its mechanisms on AMPK pathway
Le SUN ; Zhendan HE ; Runmei YANG ; Nannan GAO ; Lijia XU ; Wen JIN
Chinese Pharmacological Bulletin 2017;33(8):1073-1079
Aim To evaluate the hypolipidemic effect of total phenylpropanoid glycoside extracted from Ligustrum robustum(Roxb.)Blume(CNTG)and its mecha-nisms.Methods The 60 hamsters were randomly divided into six groups,namely the control group,the model group,the positive control group(fenofibrate,150 mg·kg-1),the high(1 200 mg·kg-1),medium(600 mg·kg-1)and low(300 mg·kg-1)doses of CNTG groups.Only the control group was given control diet and other groups received high-fat diet.The changes of serum lipid were measured and analyzed in 1st week to ensure the successful establishment of the model.The drugs were administered daily for four weeks and the concentrations of lipids were determined in the 2nd week,3rd week and 4th week respectively.Quantitative real-time PCR and Western blot were used to assay the mRNA and protein expression of related signaling enzymes and proteins.Results Compared with the model group,the concentrations of serum TG,TC,LDL-C(P<0.05,P<0.01)and hepatic TG,TC(P<0.01)were effectively reduced in hamsters in CNTG-treated groups.Mechanism research found that CNTG increased the levels of phospho-AMPKα,LKB1 and phospho-LKB1 in liver(P<0.05).Conclusion CNTG prevents hyperlipidemia via activation of hepatic LKB1-AMPK pathway.
5.A novel method for testing sterility of injections based on biothermodynamics.
Dan GAO ; Dan GAO ; Yong-Shen REN ; Dan YAN ; Cong-En ZHANG ; Zhu-Yun YAN ; Yin XIONG ; Li-Na MA ; Le-Le ZHANG ; Xiao-He XIAO
Acta Pharmaceutica Sinica 2014;49(3):385-391
This study aims at trying to establish a novel method of sterility test for injections based on biothermodynamics, in order to overcome the deficiencies of routine sterility tests such as long detecting cycle, low sensitivity and prone to misjudgments. A biothermodynamics method was adopted to rapidly detect the microorganism contamination of injections by monitoring the heat metabolism during the growth of microbe. The growth rate equal to or greater than zero and the heat power difference of P(i) and P(0) with three folds higher than the noise of baseline were chosen as indexes to study the heat change rule of microbe. In this way, the effectiveness of the new method to detect strains required by conventional sterility test or in injection samples was also investigated. Results showed that the Gram-positive bacteria, Gram-negative bacteria and fungi demanded by sterility testing methodology could be detected by biothermodynamics method within 10 hours, with the sensitivity lower than 100 CFU x mL(-1). Meanwhile, this method was successfully applied to the sterility test of Compound Yinchen injection (FFYC), Shuanghuanglian powder injection (SHL) and Compound Triamcinolone injection (TAND) which were sterilized with different degrees. Therefore, the biothermodynamics method, with advantages of fast detection and high sensitivity, could be a complementary solution for conventional sterility tests.
Anti-Inflammatory Agents
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administration & dosage
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chemistry
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Drug Contamination
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Drugs, Chinese Herbal
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administration & dosage
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chemistry
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Fungi
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isolation & purification
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Gram-Negative Bacteria
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isolation & purification
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Gram-Positive Bacteria
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isolation & purification
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Hot Temperature
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Injections
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Microbiological Techniques
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methods
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Sensitivity and Specificity
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Sterilization
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Triamcinolone
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administration & dosage
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chemistry
6.A method of screening the antitumor lead compounds based on the dynamic bio-response profile of cells.
Li-Na MA ; Le-Le ZHANG ; Yin XIONG ; Yu-Mei HAN ; Cong-En ZHANG ; Dan GAO ; Li MA ; Dan YAN ; Xiao-He XIAO
Acta Pharmaceutica Sinica 2014;49(5):695-700
The study is to report the establishment of a method of screening the antitumor compounds based on the dynamic bio-response profile of cells to make up for the shortages of conventional end-point tests such as tedious operation and low sensitivity. Based on the principle of electric impedance of cells, the real-time cell electronic sensing (RT-CES) system was used to monitor the effect of epirubicin (EPI), cisplatinum (DDP) and carboplatin (CBP) on the growth of HepG2 cells, with the cell index (CI), half maximal inhibitory concentration (IC50) and detachment curve as evaluation indexes. Meanwhile, cell counting kit-8 (CCK-8) and microscopy were applied for verification. The results showed that CI curve could sensitively real-time profile the inhibitory effect of model drugs on HepG2 cells. The IC50 of EPI, DDP and CBP were 0.53 +/- 0.04, 9.79 +/- 0.26 and 597.00 +/- 3.79 microg x mL(-1), respectively. What's more, the significant differences of detachment curves of the three drugs indicated that their functional mechanisms might be different, this is consistent with the literature. The RT-CES system with non-invasive, label-free and real-time characteristics could be used to monitor the bio-response profile of the three drugs to HepG2 cells, allowing to qualitatively and quantitatively distinguish the antitumor activities of the three drugs, and could be a complementary method for the present screening of antitumor compounds.
Antineoplastic Agents
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pharmacology
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Biosensing Techniques
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methods
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Cell Count
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Cell Line, Tumor
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Cisplatin
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pharmacology
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Drug Screening Assays, Antitumor
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Electric Impedance
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Humans
7.Cardiotoxicity study of Shenfu compatibility in rats based on metabonomics.
Jia-le HE ; Jia-wei ZHAO ; Zeng-chun MA ; Qian-de LIANG ; Yu-guang WANG ; Hong-ling TAN ; Cheng-rong XIAO ; Tang XIANG-LIN ; Yue GAO
China Journal of Chinese Materia Medica 2015;40(14):2743-2747
To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity.
Animals
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Biomarkers
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Cardiotoxicity
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Drugs, Chinese Herbal
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toxicity
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Glutathione
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blood
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Least-Squares Analysis
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Male
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Metabolomics
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methods
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Principal Component Analysis
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Rats
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Rats, Wistar
8.Survey on awareness and willingness of breast cancer screening between Han and Mongolian women in Ordos , Inner Mongolia Autonomous Region
Niu LIU ; Xi ZHANG ; Le DANG ; Tao HE ; Duoli LIU ; Chunxiang GAO ; Aihou CHANG ; Meiqing LIU ; Hongmei ZHANG ; Xianzhi DUAN ; Youlin QIAO ; Yuanli LIU
Cancer Research and Clinic 2017;29(3):191-196
Objective To investigate and explore the awareness and willingness of breast cancer screening between Han and Mongolian women in Ordos, Inner Mongolia Autonomous Region, and to analyze the influence factors. Methods The patients answered investigation questionnaires face to face, and the content of questionnaire included demographic information, breast cancer awareness and relevant affecting factors on the awareness and willingness. Results 11162 (88.2 %) Han women and 1495 (11.8 %) Mongolian women were enrolled in the survey, with the average age of (45.4 ±7.1) years old and (45.4 ±6.8) years old. The education level (high school and above) of Han women was lower than that of Mongolian women [4456 women (40.0%) vs. 750 women (50.2%), χ2= 57.041, P< 0.001]. The Main way to delivery information on breast cancer screening in Han and Mongolian women was from their family members or friends [5002 women (44.9%) vs. 688 women (46.1%),χ2=40.699, P<0.001]. The proportions of never attending screening in the Han and Mongolian women were 41.7 % (4640 women) and 45.9 % (683 women), respectively (χ2=14.075, P=0.001). The breast self-examination rate of Han women were higher than that of Mongolian [71.1 % (7926 women) vs. 58.5 % (872 women), χ2= 98.466, P< 0.001]. According to logistics regression analysis, the cognitive level of women with high education level and breast disease history was higher (all P<0.001). Conclusions The cognitive level of breast cancer screening in Han women is better than that in the Mongolian, however, the overall level are low. It is necessary to strengthen the propaganda and education, and to encourage women to actively participate in breast cancer screening.
9.Micro-energy medicine in the treatment of erectile dysfunction:An update
Jun GAO ; Wei-Jie SONG ; Le-Ye HE
National Journal of Andrology 2024;30(1):72-76
Erectile dysfunction(ED)is one of the most common sexual disorders in males,which seriously affects the health of the patient and well-being of the family.The therapeutic strategy of ED is an individualized comprehensive treatment based on phos-phodiesterase inhibitors.At present,as a new option for the treatment of ED,micro-energy medicine has attracted more and more at-tention in its therapeutic effects and advantages.This article presents an overview of the progress in the studies of micro-energy medi-cine in the treatment of ED.
10.Study on Haemophilus influenzae type b: data from autopsy of community acquired pneumonia among children.
Hui-li HU ; Yi-yun HU ; Le-jian HE ; Sang-jie YU ; Wei GAO ; Yong-hong YANG
Chinese Journal of Epidemiology 2005;26(8):604-607
OBJECTIVETo evaluate the status of Haemophilus influenza type b(Hib) on death cases of children from community-acquired pneumonia (CAP) and to estimate the value of direct in-situ polymerase chain reaction (ISPCR) on diagnosis of children CAP, pathogenically.
METHODSOrdinary PCR, Southern blot and direct ISPCR were applied and compared in detecting Hib in 100 paraffin-embedded lung tissues of autopsy children died of CAP.
RESULTSNo major difference on the detection rate of Hib between 50-60s and 80s-2002 was found. The detection rate of Hib by direct ISPCR was higher than the other two methods. By Southern blot, Hib was identified from 8 out of 100 samples (8%), including 4 out of 56 in 1950-60s (7.1%) and 4 out of 44 (9.1%) (chi2 = 0.084, P>0.05) in 1980s-2002. By ISPCR, Hib was identified from 17 out of 100 samples (17%), including 8 out of 56 in 1950-60s (14.3%) and 9 out of 44 (20.5%) with chi2 = 0.665, P > 0.05, in 1980s-2002. Positive cases diagnosed by both Southern blot and ISPCR were 7%.
CONCLUSIONHib was one of the main bacterial pathogens causing CAP and deaths among children. Direct ISPCR was prefertable to be used in pathogenic diagnosis on children pneumonia, in terms of its sensitivity, specificity and localization.
Age Factors ; Autopsy ; Blotting, Southern ; Child, Preschool ; Community-Acquired Infections ; microbiology ; pathology ; Female ; Haemophilus influenzae type b ; genetics ; physiology ; Humans ; Infant ; Lung ; microbiology ; pathology ; Male ; Pneumonia ; microbiology ; pathology ; Polymerase Chain Reaction