2.Preparation and in vitro evaluation of borneol and folic acid co-modified doxorubicin loaded PAMAM drug delivery system.
Jing-jing LI ; Man-man GUO ; Shun-ping HAN ; Yue SUN ; Wei-dong FEI ; Xiu-iing XU ; Fan-zhu LI
Acta Pharmaceutica Sinica 2015;50(7):899-905
A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.
Biological Transport
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Blood-Brain Barrier
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Bornanes
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chemistry
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Cell Line, Tumor
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Dendrimers
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Doxorubicin
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pharmacology
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Drug Carriers
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chemistry
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Drug Delivery Systems
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Folic Acid
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chemistry
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Glioma
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Humans
3.Cross-sectional survey on healthcare-associated infection in Miao and Dong Autonomous Prefecture of Guizhou Province in 2014
Liyuan CHEN ; Zhongyan QIU ; Huai YANG ; Xia MU ; Yan XU ; Jing CHEN ; Tingxiu YANG ; Man ZHANG ; Man ZHANG ; Hongyan WU
Chinese Journal of Infection Control 2016;(1):10-14
Objective To investigate the current situation of healthcare-associated infection(HAI)in hospitals of Miao and Dong Autonomous Prefecture of Guizhou Province,and provide basis for formulating prevention and con-trol measures of HAI.Methods According to the unified plan of the National HAI Surveillance Network,26 hospi-tals in Miao and Dong Autonomous Prefecture of Guizhou Province were performed cross-sectional survey on HAI prevalence rate,antimicrobial use,and specimen bacterial culture rate.Results A total of 3 tertiary and 23 seconda-ry hospitals were investigated,7 799 inpatients were included,the prevalence rate of HAI was 2.54%(n =198), and case prevalence rate was 2.65% (n=205).HAI mainly distributed in intensive care unit (29.63%);the main infection site was lower respiratory tract (44.44%);HAI mainly caused by gram-negative bacteria,the major pathogens were Escherichia coli ,Pseudomonas aeruginosa ,and Klebsiella pneumoniae .The usage rate of antimi-crobial agents was 45.66%,secondary hospitals was higher than tertiary hospitals (53.65% vs 31 .14%,χ2 =148.53,P <0.001 ).74.02% of antimicrobial agents were for therapeutic purpose,19.77% for prophylaxis,and 6.21 % for both prophylactic and therapeutic application;81 .02% of patients received one agent,17.21 % received two,and 1 .77% received three and more agents;among patients who received antimicrobials for therapeutic as well as for both therapeutic and prophylactic purpose,only 29.37% were sent specimens for pathogenic detection.Conclusion The prevalence rate in this region is lower than national average level,antimicrobial usage rate is lower than national standard,management of key departments and key sites should be strengthened,antimicrobial agents,especially used in secondary hospitals should be used rationally.
4.Point prevalence of healthcare-associated infection and antimicrobial use in Buyi autonomous prefecture hospitals in Guizhou Province
Liyuan CHEN ; Zhongyan QIU ; Huai YANG ; Xia MU ; Yan XU ; Jing CHEN ; Tingxiu YANG ; Man ZHANG ; Man ZHANG ; Hongyan WU
Chinese Journal of Infection Control 2016;15(3):155-159
Objective To explore the status of healthcare-associated infection(HAI)in hospitals in Buyi autono-mous prefecture of Guizhou Povince,and provide basis for formulating HAI control measures.Methods A survey was conducted by combined methods of bed-side survey and medical record reviewing,prevalence rates of secondary and above hospitals in Buyi autonomous prefecture in Guizhou Province between September 10 and October 5,2014 were surveyed.Results 6 577 hospitalized patients should be investigated,6 541(99.45%)were actually investiga-ted.The prevalence rate and case prevalence rate of HAI were 1 .83% (n=120)and 1 .94%(n=127)respectively. The top three departments of HAI distribution were intensive care unit (26.32%),neurosurgery (6.10%),and neonatal intensive care unit(5.13%);the main infection site was lower respiratory tract(n=39,30.71 %),followed by skin-soft tissue (n=24,18.90%)and superficial incision (n=23,18.11 %).58 pathogenic isolates were detec-ted,gram-negative bacteria were the major pathogens (n=44),gram-positive bacteria and fungi were 10 and 3 iso-lates respectively.Antimicrobial usage rate at survey day was 42.12%,64.75% of which were for therapeutic, 26.83% for prophylactic,and 8.42% for therapeutic+prophylactic use;the percentage of mono-drug,two drugs combination,and three or more drugs combination use were 79.53%,19.89%,and 0.58% respectively;bacterial detection rate in patients receiving therapeutic as well as therapeutic+prophylactic antimicrobial use was 13.76%. Conclusion Survey on prevalence of HAI is helpful for understanding the current status of HAI,monitoring on HAI in key departments of hospital and key sites of patients should be strengthened to reduce the occurrence HAI effectively.
5.A novel spliceosome encoding isoform of suppresser of fused in human pancreatic cancer
Qing XU ; Xiaohua MAN ; Jun GAO ; Zhaoshen LI ; Yanfang GONG ; Hongyu WU ; Jing JIN
Chinese Journal of Pancreatology 2013;13(4):231-234
Objective To investigate spliceosome of suppresser of fused(SUFU),a major member of hedgehog signaling pathway in human pancreatic cancer.Methods SUFU fragment was amplified by using reverse transcription and 3' RACE.After sequencing,a new exon was discovered,and then nSUFU was amplified by RT-PCR.nSUFU and SUFU were transfected into SW1990 by liposomes,and then the expressions of SUFU protein encoded by new spliceosome in SW1990 cells and pancreatic cancer tissues were detected by Western blot.Results PCR products by 3'RACE were of 600 bp,after sequencing and comparison with Blast data of NCBI,it was detected that a new exon was inserted between SUFU mRNA isoforml (NM_016169.3) exon 10 and exon 11.After verification with SW1990,it was noted the entire new spliceosome containing new exon was of 1400 bp.SW1990 with nSUFU transfection strongly expressed nSUFU protein,and pancreatic cancer tissues expressed both SUFU and nSUFU protein.Conclusions A new spliceosome of SUFU,which can encode SUFU protein,is present in pancreatic cancer tissue and cell.
6.Role of extracellular regulated kinase signal transduction pathway in the pathogenesis of acute necrotizing pancreatitis
Xingang SHI ; Yongchun XU ; Xiaohua MAN ; Jing JIN ; Yanfang GONG ; Zhenxing TU ; Zhaoshen LI
Chinese Journal of Pancreatology 2010;10(2):116-119
Objective To investigate the changes of extraceUular regulated kinase 1/2 (ERK1/2) phosphorylation and assess the effects of blocking the ERK1/2 phosphorylation on rats with acute necrotizing pancreatitis (ANP). Methods The ANP model was induced by retrograde injection of 5% sodium tanrocholate into the biliary and pancreatic duct. 5 rats were treated as normal control. Other 75 Sprague-Dawley (SD) rots were randomly divided into sham operations(SO) group (n =25), ANP group (n =25) and PD98059 group (n =25). The rats were sacrificed at 15 min, 30 min, 1 h, 3 h and 6 h after ANP induction, the blood and pancreatic sample were taken. Pathological changes of pancreas were observed with light microscope and scored. The serum level of TNF-α and IL-1β was determined by ELISA. MPO activities in pancreas were measured by enzyme chemistry assay. Western blotting was performed to determine the phosphorylations of ERK1/2 in the pancreas homogenates. Results There was no significant pathologic changes in rats of SO group;but significant injuries occurred in ANP group, the pathologic score at 3 h was 9.9 ± 0.4;the extent of injuries attenuated in PD98059 group, the pathologic score at 3 h was 4.0 ± 0.4 (P < 0.05). The serum levels of TNF-α at 3 h in SO, ANP and PD98059 groups were (65.8 ± 20.5) pg/ml, (286.5 ± 50.3) pg/ml, (180.4±32.9)pg/ml, respectively;the serum levels of IL-1β at 3 h in SO, ANP and PD98059groups were (85.8 ± 25.5) pg/ml, (293.8 ± 46.3) pg/ml, (200. 5 ± 33.6) pg/ml, respectively;MPOactivities in pancreas were (0. 19 ± 0.02)U/g, (0.61±0.05)U/g, (0.52±0.03) U/g, and the values in ANP and PD98059 groups were significantly higher than those in SO group, while the values in PD98059 group were significantly lower than those in ANP group (P < 0.01). The expression of ERK1/2 phosphorylation in normal pancreas was 1100 ± 141, the expressions of ERK1/2 phosphorylation in ANP group at 15 min, 30 min were 5300 ± 486, 5621 ± 384, respectively;the expressions began to decrease 1 h later and returned the similar level as SO group at 6 h;the expressions of ERK1/2 phosphorylation in PD98059 group at 15 min, 30 rain were 4200 ± 370, 3600 ± 290, respectively;which were signifieanfly lower than those in ANP group (all P value < 0. 01). Conclusions The ERK1/2 signal transduetion pathway plays an important role in the pathogenesis of ANP. Inhibition of ERK1/2 phosphorylation by PD98059 may decrease the production of IL-1β, TNF-α and pancreatic MPO, attenuate the extent of pancreatic pathologic injuries.
7.Effect of sevoflurane pretreatment on renal ischemia-reperfusion-induced apoptosis in kidney in rats
Jing WANG ; Jianbo YU ; Lirong GONG ; Haidong LI ; Man WANG ; Yue ZHANG ; Fen ZHOU ; Jin XU
Chinese Journal of Anesthesiology 2011;31(3):360-363
Objective To investigate the effects of sevoflurane pretreatment on renal ischemia-reperfusion (I/R)-induced apoptosis in kidney in rats. Methods Thirty pathogen-free male SD rats weighing 220-260 g were randomized into 3 groups (n=10 each):group control (group C);group I/R and group sevoflurane(group S). Renal I/R was induced by clamping the left renal pedicle for 45 min in I/R and S groups. In group S inhalation of 2.2% sevoflurane in O2 was started at 30 min before operation and maintained throughout the experiment.Venous blood samples were taken at 3 h of reperfusion for determination of serum BUN and Cr concentrations. The animals were then sacrificed and the left kidneys were removed for microscopic examination, detection of apoptosis(by TUNEL)and determination of heme oxygenase-1(HO-1) mRNA and protein expression (by RT-PCR and Western blot).Results Renal I/R significantly increased serum BUN and Cr concentrations, apoptotic index(percentage of apoptotic cells) and the severity of necrosis of renal proximal convoluted tubules (0=normal,4=necrosis of whole segment of proximal convoluted tubules).Sevoflurane inhalation attenuated the I/R-induced changes mentioned above.HO-1 mRNA and protein expression was up-regulated by I/R and HO-1 mRNA expression was further up-regulated by sevoflurane inhalation.Conclusion Sevoflurane pretreatment can protect kidney against I/R injury by attenuating cell apoptosis.Up-regulation of HO-1 mRNA expression may be involved in the mechanism.
8.Comparability of 5 items of hepatitis B in ELISA by using water bath box and rapid incubation
Xucai DONG ; Huanhuan SHI ; Fang CHENG ; Man WANG ; Jing XU ; Huizhong ZHANG
International Journal of Laboratory Medicine 2015;(7):923-924
Objective To investigate and evaluate the comparison results of five items of hepatitis B in ELISA by using water bath box and rapid incubation .Methods 92 patients with hepatitis B in our hospital from June 2012 to June 2013 were randomly se‐lected and 184 cases of healthy physical examination were randomly selected as the controls .The water bath and rapid incubation were adopted to conduct ELISA for simultaneously detecting 5 items of hepatitis B in samples .Results The results of two groups had higher positive coincidence rate .The average OD value of specimens in the water bath was higher .But the specimen S/CO value in the fast average incubation was higher ,its co value was higher than that of the water bath .Conclusion The rapid incubation can be introduced for improving the work efficiency in the daily work ,but the specimen with weak reactiveresult needs to be re‐de‐tected by using the water bath and making records .The fast incubation device is best for only use of the HBsAg reaction ,because the other four reaction process time is shorter ,and there are some non‐conformity results .
9.Relationship between three thrombophilic gene mutations and unexplained recurrent early spontaneous abortion
Li XU ; Xiao-Man LIU ; Hong-Yan ZHANG ; Jing ZHAO ; Qi-Wei QI ; Yun-Fei CHANG ;
Chinese Journal of Obstetrics and Gynecology 2001;0(03):-
Objective To explore the relationship of methylenetetrahydrofolate reductase (MTHFR)gene C677T,factor V(FV)gene G1691A and prothrombin(PT)gene G20210A polymorphisms to unexplained recurrent early spontaneous abortion(URESA).Methods One hundred and twelve patients with URESA and 100 women with at least 1 normal pregnancy and without any miscarriage were analyzed for MTHFR,FV and PT gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results MTHFR gene T/T genotype and T allele frequencies were increased in URESA patients[38.4%(43/112)and 59.8%(134/224)]versus controls[18.0%(18/100)and 43%(43/100),P
10.Effects of histone deacetylase 1 gene silencing on cell cycle regulation of pancreatic cancer cell line PaTu8988
Daojian GAO ; Xiaohua MAN ; Min XU ; Yuqi ZHANG ; Jun GAO ; Yanfang GONG ; Hongyu WU ; Jing JIN ; Gouming XU ; Zhaoshen LI
Chinese Journal of Pancreatology 2011;11(5):315-317
Objective To investigate the effects of histone deacetylase 1 (HDAC1) gene silencing on cell cycle of pancreatic cancer cell line PaTu8988 and possible mechanism.Methods The PaTu8988 cells were routinely cultured and divided into control group,negative control siRNA group (c-siRNA),HDAC1 siRNA 15 nmol/L group and HDAC1 siRNA 30nmol/L group.After Liposomes 2000 transfection for 48 h,the Western blotting was used to detect the efficiency of HDAC1 gene silencing on protein levels and the expression of p21 protein.Cell cycle was evaluated by using flow cytometry.Results Compared with that of control group,the expression of HDAC1 protein in PaTu8988 cell of HDAC1 siRNA 30nmol/L group was significantly decreased,and the expression of p21 protein was significantly increased; the percentage of G2/M phase cells were significantly decreased[(21.48 ±3.67)% vs.(28.28 ±2.94) %,P<0.05]; while the percentage of S phase cells were significantly increased[( 50.20 ± 6.85 ) % vs.( 32.49 ± 2.78 ) %,P < 0.05].Conclusions HDAC1 siRNA can efficiently and specifically inhibit the expression of HDAC1 in PaTu8988 cells,and can induce S phase cells arrest,which may be related with up-regulation of p21 protein expression.