5.Study on the characteristics of antisense oligodeoxy-neucleotides-liposomes complex and cellular uptake.
Hai-liang CHEN ; Zhi CHEN ; Wen-quan LIANG
Acta Pharmaceutica Sinica 2002;37(9):728-732
AIMTo investigate factors affecting the properties of antisense oligodeoxy nucleotides (ASON)-liposomes complex and their cellular uptake.
METHODSThree types of blank liposomes were prepared by reverse-phase evaporation vesicles, and the complex were obtained through physical absorption. The light microscope was used to observe morphology characteristics of the complex. Drug loading capacity was analyzed by agarose gel electrophoresis. The transfected cell percentage and means fluorescence intensity were determined by flow cytometric analysis using M3 myeloma cell as a model.
RESULTSThe neutral liposome showed no aggregation while the cationic liposomes appeared some different extent aggregation in different medium when associated antisense oligodeoxynucleotides. The drug loading capacity depended on the ratio of +/- and the cationic charge density on the lipid membrane. The two kinds of cationic liposomes appeared different principles of loading ASON. As far as cellular uptake, The neutral liposomes showed no improvement of cellular uptake of ASON. However, the cationic liposomes were shown to enhance the cellular uptake of ASON if the appropriate +/- charge ratio was used. The optimal cellular uptake was achieved when +/- charge ratio was at 0.5:1 and 1:1 for SA-I liposome and SA-II liposomes, respectively.
CONCLUSIONThe cationic liposomes improved the loading capacity and cell uptake of antisense oligodeoxynucleotides, which was determined by +/- charge ratio and charge density.
Amines ; metabolism ; Biological Transport ; Drug Carriers ; Drug Delivery Systems ; Humans ; Liposomes ; pharmacokinetics ; Multiple Myeloma ; Oligodeoxyribonucleotides, Antisense ; administration & dosage ; pharmacokinetics ; Random Allocation ; Tumor Cells, Cultured ; metabolism
6.Expression of CD_64 in Neonatal Infection Disease and Its Clinical Significance
xi -xi, XU ; ling-zhi, CHEN ; qing, CHEN ; hai-bin, XU ; man-hua, BAD
Journal of Applied Clinical Pediatrics 2003;0(10):-
Objective To study CD64 expression in neutrophilic granulocyte and its clinical effect in neonatal infection disease. Methods CD64 was detected among 59 neonatal patients(septicemia group 34 patients, local infection group 25 patients)hospitalized in our neonatal department diagnosed as neonatal infection disease in 48 h after hospitalized,2 weeks after therapy, then the results were compared with 27 patients as non - infection disease during the same period. Results CD64 in septicemia group was (6156. 21?3643. 32) molecula per cell,in local infection group was (2176.19 ? 946. 32)molecula per cell, in non- infection group was (2176. 19 ? 946. 32) molecula per cell.There were significant differences among three groups (all P0.05). Conclusions CD64 expression increases in bacterium infection disease. It is more obvious in widespread infection desease.and it can be the mark in early diagnosis of neonatal infection disease.
7.Analysis of effects of arthroscopic treatment for recurrent patellar dislocation by lateral patellar retinacular release outside the synovial bursa of knee joint combined with reconstruction of medial patellofemoral ligament.
Bei LI ; Jian-yi TAN ; Zhi-bin ZENG ; Tie-jun ZHAN ; Hai-qiang CHEN
China Journal of Orthopaedics and Traumatology 2015;28(7):594-598
OBJECTIVETo introduce an arthroscopic technique in managing recurrent dislocation of the patella and its clinical results.
METHODSSixteen patients with recurrent patellar dislocation were reviewed, including 3 males and 13 females. The average age was 17.6 years old (ranged from 14 to 32 years). The patients suffering from patellar sub-luxation averaged 18.5 months (ranged from 6 to 23 months)before operation. These patients were treated with lateral patellar retinacular release outside the synovial bursa of knee joint and medial patellofemoral ligament reconstruction using the semitendinosus tendon free autograft. The Lyshohm scores before and after operation were used to evaluate outcomes at the final follow-up.
RESULTSAll the patients were followed up, and the duration ranged from 6 to 48 months, with an average of 12 months. There was no recurrence. The Q angle decreased from (16.4 ± 3.7)° to (10.1 ± 1.4)°; insall index decreased from 1.37 ± 0.25 to 1.28 ± 0.23; congruence angle decreased from (21.3 ± 2.6)° to (5.86 ± 2.23)°; Lysholm score improved from 76.1 ± 5.2 to 89.8 ± 4.1 at 6 months after operation.
CONCLUSIONCompared with conventional procedure, arthroscopic surgery for recurrent dislocation of the patella achieves excellent outcomes with minimum invasion.
Adolescent ; Adult ; Arthroscopy ; Bursa, Synovial ; surgery ; Female ; Humans ; Knee Joint ; surgery ; Male ; Patellar Dislocation ; physiopathology ; surgery ; Patellar Ligament ; surgery ; Range of Motion, Articular ; Treatment Outcome ; Young Adult
8.Design, synthesis and biological evaluation of novel para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones as human PARP-1 inhibitors.
Hai-Ping YAO ; Zhi-Xiang ZHU ; Ming JI ; Xiao-Guang CHEN ; Bai-Ling XU
Acta Pharmaceutica Sinica 2014;49(4):497-503
Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents
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chemical synthesis
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chemistry
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pharmacology
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Drug Design
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Enzyme Inhibitors
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chemical synthesis
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chemistry
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pharmacology
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Molecular Docking Simulation
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Molecular Structure
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
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Quinazolinones
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chemical synthesis
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chemistry
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pharmacology
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Structure-Activity Relationship
9.HPLC enantioseparation, absolute configuration determination and anti-HIV-1 activity of (±)-F18 enantiomers.
Lei-lei ZHANG ; Hai XUE ; Li LI ; Xiao-fan LU ; Zhi-wei CHEN ; Gang LU
Acta Pharmaceutica Sinica 2015;50(6):733-737
Racemic (±)-F18 (10-chloromethyl-11-demethyl-12-oxo-calanolide A), an analog of nature product (+)-calanolide A, is a new anti-HIV-1 nonnucleoside reverse transcript inhibitor (NNRTI). A successful enantioseparation of (±)-F18 offering (R)-F18 and (S)-F18 was achieved by a chiral stationary phase prepared HPLC. Their absolute configurations were determined by measurement of their electronic circular dichroisms combined with modem quantum-chemical calculations. Further investigation revealed that (R)-F18 and (S)-F18 shared a similar anti-HIV activities, however, (R)-F18 was more potent than (S)-F18 against wild-type virus, K101E mutation and P225H mutation pseudoviruses.
Anti-HIV Agents
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chemistry
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Chromatography, High Pressure Liquid
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HIV-1
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drug effects
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Pyranocoumarins
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chemistry
10.Protective effect of melatonin on oxidative stress inducing hair follicle injury in scald rat.
Jun ZHANG ; Da-Hai HU ; Gang CHEN ; Xiao-Zhi BAI ; Chao-Wu TANG
Chinese Journal of Burns 2009;25(2):129-132
OBJECTIVETo investigate the protective effect of melatonin on residual hair follicle cells of scald rats at early stage.
METHODSEighteen male Sprague-Dawley rats were randomly divided into scald group, treatment group, sham group , with 6 rats in each group. The rats in scald group and treatment group were subjected to 30% TBSA partial thickness scald on the back, and were resuscitated with balanced solution after 1 hour, while those in sham group were immersed in water at 37 degrees C for 25 s to simulate scald, and did not receive fluid replacement. Rats in treatment group were intraperitoneally injected with 10 mg/kg melatonin solution at 1 minute, 8 hours and 12 hours after scald, while those in sham group and scald group were given equal volume of 1% alcohol sodium-isotonic saline instead. Tissue samples were harvested at 6, 12 and 24 post scald hours (PSH) for determination of MDA and GSH levels. Apoptosis of residul hair follicle was detected by TUNEL method and immunohistochemistry of caspase-3.
RESULTSThe level of MDA in scald group at each time point was much higher than that in sham group (P < 0.01) and treatment group (P < 0.05), and it peaked at 12 PSH. The changes in GSH were just opposite to that of MDA. Under fluorescence microscope, the residual hair follicle cells were blue, and the apoptotic cells appeared green. The apoptosis rate in scald group at 6, 12, 24 PSH was obviously higher than that in sham (P < 0.01) and treatment groups (P < 0.05), which was (20.2 +/- 3.4)% vs (4.3 +/- 2.3)% vs (10.9 +/- 3.2)%, (31.2 +/- 3.6)% vs (5.1 +/- 2.5)% vs (19.1 +/- 3.7)%, (22.4 +/- 2.7)% vs (4.1 +/- 2.4)% vs (13.1 +/- 3.4)%, respectively. The score of caspase-3 positive cell in scald group was higher than those in sham group (P < 0.01) and treatment group (P < 0.05).
CONCLUSIONSThere is obvious correlation between oxidative stress and apoptosis rate of hair follicle cells in rats with partial thickness scald. Early administration of melatonin may have anti-apoptosis ability for residual hair follicle cells by attenuation of oxidative stress.
Animals ; Apoptosis ; Burns ; drug therapy ; metabolism ; Hair Follicle ; cytology ; metabolism ; Male ; Melatonin ; therapeutic use ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley