1.Construction of biotin-modified polymeric micelles for pancreatic cancer targeted photodynamic therapy.
Chun-yue DENG ; Ying-ying LONG ; Sha LIU ; Zhang-bao CHEN ; Chong LI
Acta Pharmaceutica Sinica 2015;50(8):1038-1044
In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy.
Animals
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Antineoplastic Agents
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chemistry
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Biotin
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Drug Carriers
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chemistry
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Drug Screening Assays, Antitumor
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Humans
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Micelles
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Pancreatic Neoplasms
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drug therapy
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Photochemotherapy
2.The effect of TSPG in vivo on transplantation of neural stem cells in treatment of Parkinson's disease mouse.
Chinese Journal of Applied Physiology 2009;25(1):133-137
AIMTo observe the effect for the model of PD and the transplantation of NSCs after injection of TSPG into mouse in advance.
METHODSFirstly, we divided the mouse into 5 groups. For the group of 1-4, we established the model of PD with MPTP. For the group of 5, before the establishment of the model, we injected TSPG into mouse in advance for prevention. And then, we evaluated the effect by paralysis agitans score standard and praxiology marker. Secondly, we obtained the NSCs from the 7-12 week embryo cerebral cortex. Then we transplanted NSCs which pretreated by TSPG into the striatum of the 5 groups. After 60 days, we obtained the brain section, and detected the TH by ICC to analyse the differentiation status of NSCs.
RESULTSThe prevention of TSPG could decrease the neural cells damage by MPTP, and could protect the nervous system. After we transplanted NSCs into the striatum of Parkinson' s disease mouse, we found that for the group of 5, the paralysis agitans, auto-activity and memory function had the most distinct amelioration. And the number of dopaminergic neurons increased most transparently in brain section, and the neurons contact was the most enriched with the adjacent nervous cells.
CONCLUSIONTSPG can decrease the neural cells damage and can produce a marked effect in treatment of PD by transplanting NSCs invivo.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Combined Modality Therapy ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells ; transplantation ; Panax ; chemistry ; Parkinson Disease, Secondary ; chemically induced ; therapy ; Random Allocation ; Saponins ; isolation & purification ; therapeutic use
3.The effect of AGS3 on the I(A) of newborn rat prefrontal cortical neurons pretreated by chronic morphine.
Ying ZHAO ; Li-sha WU ; Ye YANG
Chinese Journal of Applied Physiology 2010;26(2):191-194
OBJECTIVEThe effect of chronic morphine treatment on the I(A) (transient outward K+ current) of prefrontal cortical neurons of newborn rat. On this basis, we use AGS3 antibody to inhibit the function of AGS3, for observing the impact of AGS3 on the I(A), thus further explore the mechanism of AGS3 protein in morphine addiction.
METHODSBy using whole-cell patch-clamp technique, I(A) was recorded. In the whole-cell configuration, observed the impact of morphine on the current density-voltage curve (I-V) of I(A) and the effect of AGS3 antibody with three different concentrations on the I(A) of morphine treated rat prefrontal cortical neurons.
RESULTSMorphine increased the I(A). When the test potential was + 55 mV, different concentrations of AGS3, 10(-3) microg/L, 10(-2) micdrog/L and 10(-1) microg/L acted on morphine treated rat prefrontal cortical neurons, the enhanced IA by morphine was inhibited.
CONCLUSIONMorphine increases the I(A), AGS3 protein may participate in signal transduction pathway involved with I(A).
Animals ; Animals, Newborn ; Antibodies, Monoclonal ; pharmacology ; Carrier Proteins ; immunology ; metabolism ; Female ; Male ; Morphine ; adverse effects ; Neurons ; metabolism ; Patch-Clamp Techniques ; Potassium Channels ; drug effects ; Prefrontal Cortex ; metabolism ; Rats ; Rats, Sprague-Dawley ; Substance-Related Disorders ; metabolism ; physiopathology
5.Study on molecular target promoting human neural stem cells of ginsenoside Rg1 by gene chip.
Ying-Bo LI ; Xiang-Qin ZHAO ; Ying-Hong JIANG ; Di CHEN ; Sha-Li WANG
China Journal of Chinese Materia Medica 2013;38(16):2701-2705
OBJECTIVETo screen out main molecular target promoting human neural stem cells (NSCs) of ginsenoside Rg1 by using the gene chip technology.
METHODFirst, MTT assay was adopted to screen out the optimal concentration of Rg1-promoted NSC proliferation (120 mg x L(-1)). Then, on the 7th day after the Rg1-promoted NSC proliferation, the expression of target genes was observed by the gene chip technology. The most important target gene and signal transduction pathways were screened out through the data calculations.
RESULTOn the 7th day after the Rg1-promoted NSC proliferation, obtained 440 differential genes, 266 significantly upregulated genes and 174 significantly down-regulated genes. HES1 gene, CAMP (cyclic adenosine monophosphate)-PKA (protein kinase A) and PI3K (phosphatidylinositol 3 kinase)-AKT signal transduction pathways were closely related to the NSC proliferation.
CONCLUSIONThe differentially expressed genes screened out by gene chip may provide new clues for studies on molecular mechanism of ginsenoside Rg1-promoted NSCs proliferation.
Cell Proliferation ; drug effects ; Ginsenosides ; pharmacology ; Humans ; Neural Stem Cells ; cytology ; drug effects ; metabolism ; Oligonucleotide Array Sequence Analysis ; RNA ; genetics ; isolation & purification
6.Expression of extracellular matrix metalloproteinase inducer in the unstable plaque of patients with acute coronary syndrome.
Bin WANG ; Sha-sha XU ; Jian-jun JIANG ; Xian-ben LU ; Ying-sheng XUE ; Jiao-chen WANG ; Ya-fei MI ; Min ZHU ; Wei-li GE ; Li-jiang TANG
Chinese Journal of Cardiology 2012;40(5):416-420
OBJECTIVETo observe the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the unstable plaque of patients with acute coronary syndrome (ACS), and the impact of leukotriene B4 (LTB4) on the EMMPRIN expression in macrophages.
METHODSThe EMMPRIN expression was detected by immunohistochemistry in 11 unstable plaques from patients with ACS. Protein expression of EMMPRIN was evaluated by Western blot on macrophages differentiated from THP-1 which were stimulated with LTB4 in the absence or presence of LTB4 antagonist U75302. There are 8 study groups: 1-THP-1, 2-8-the macrophages derived from THP-1, 2-6-macrophages were stimulated by LTB4 (0, 10(-10), 10(-9), 10(-8) and 10(-7) mol/L) for 24 h, 7-8-the macrophages were pretreated by 10(-6) mol/L or 10(-7) mol/L U75302 2 h before the LTB4 (10(-7) mol/L) stimulation.
RESULTSAbundant EMMPRIN expression was detected in macrophages and smooth muscle cells of unstable plaques from ACS patients. As to the THP-1 derived macrophages, EMMPRIN expression was significantly upregulated in a concentration-dependent manner in LTB4 stimulated groups, which was significantly higher in group 3-6 than in the THP-1 group (group 1) and macrophages group (group 2) (all P < 0.05) and pretreatment with U75302 significantly reduced the LTB4 induced upregulation of EMMPRIN in a dose-dependent manner (P < 0.05).
CONCLUSIONEMMPRIN expression is enhanced in macrophages and smooth muscle cells on unstable coronary artery plaques from ACS patients. LTB4 could stimulate EMMPRIN expression on THP-1 derived macrophages suggesting that LTB4 and EMMPRIN might be both involved in the formation and progression of unstable plaques, future studies are warranted to explore if LTB4 and EMMPRIN antagonists are effective or not for treating patients with ACS.
Acute Coronary Syndrome ; metabolism ; pathology ; Basigin ; metabolism ; Cell Line ; Humans ; Leukotriene B4 ; metabolism ; pharmacology ; Macrophages ; drug effects ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Plaque, Atherosclerotic ; metabolism
7.Effects of television viewing on body fatness among Chinese children and adolescents.
Ning WANG ; Feng XU ; Li-qiang ZHENG ; Xin-gang ZHANG ; Yang LI ; Guo-zhe SUN ; Xiao-fan GUO ; Sha-sha YU ; Ying-xian SUN
Chinese Medical Journal 2012;125(8):1500-1503
BACKGROUNDNumerous studies have shown that time spent on television (TV) viewing is positively associated with obesity. The aim of this study was to examine the potential association between excessive TV viewing and obesity, especially abdominal obesity, among children and adolescents in mainland of China.
METHODSA total of 4708 children and adolescents aged 6 to 16 years were recruited for the study. Anthropometric measures were conducted by trained personnels. A self-report questionnaire was designed to gather information on TV time, physical activity, diet habits, maternal body mass index (BMI), birth weight, and on general demographics, including age and gender, and socio-economic status.
RESULTSThe prevalence of obesity in this group was 6.5%. Linear regression analysis indicated that high TV viewing time (≥ 1.5 h/d) was significantly associated with higher BMI, waist circumference (WC), and waist-to-height ratio (WHtR). In addition, the high TV time group had 1.3 times the odds of obesity as compared to the low TV time group. Likewise, high TV viewing time increased the OR value 1.32 and 1.21 times higher in WC- and WHtR-defined obesity. Within the non-obesity group, high TV viewing time was also positively associated with higher WC and WHtR. All these correlations remained significant after adjustment for the confounding variables.
CONCLUSIONSExcessive TV viewing might increase the risk of obesity among Chinese youth. Reducing TV viewing time may be beneficial to improve health outcomes, both in the short- and long term. This finding should be taken into account in future designs of intervention policies to prevent childhood and adolescent obesity in China.
Adolescent ; Body Mass Index ; Child ; China ; epidemiology ; Female ; Habits ; Humans ; Logistic Models ; Male ; Obesity ; epidemiology ; Prevalence ; Television ; Waist Circumference
8.The infection status of Leptospira in rodents on the Heixiazi island of Heilongjiang province, China,in 2011.
Zhen-dong WANG ; Sha-sha WANG ; Li-juan LIU ; Yu YANG ; Ming LI ; Tian-yu GUO ; Ying-qun FU ; Yong HOU ; Xiao-hong SUN ; Bao-liang XU ; Jing WANG
Chinese Journal of Preventive Medicine 2013;47(6):510-513
OBJECTIVETo study the infection status of Leptospira in rodents on Heixiazi island Heilongjiang province in 2011.
METHODSA total of 356 rodents were captured by night trap on the Heixiazi island from April to October 2011. The kidney tissue samples were collected by asepsis operation and the genomic DNA were extracted from them. Leptospira strains were confirmed by polymerase chain reaction(PCR) amplification of the 482 bp 23 S rDNA gene. Fifteen PCR products selected by the month were purified and sequenced by the methods of Sanger dideoxy, the sequences then compared with other Leptospira strains in Genebank, and phylogenetic analyses were drafted by software Mega 4.0.
RESULTSAmong 356 rodents, the dominant species were Clethrionomys rutilus (39.3%, 140/356) and Apodemus agrarius (36.0%, 128/356). The infection rate of Leptospira was 11.0%, with 39 rodent samples detected positive. All the rodent species were infected except for Rattus norvegicus. The infection rate was 9.4% (12/128) in Apodemus agrarius, 12.9%(18/140) in Clethrionomys rutilus, 10.8%(7/65) in Microtus fortis Buchner. No significant difference was found between the infection rate and the species of rodents by chi square test(χ(2) = 1.92, P > 0.05). Among months, the infection rate was 5.6% (4/72) in May, 8.8% (5/57) in June, 12.8% (5/39) in July, 9.8% (5/51) in August, 33.3% (11/33) in September, 22.5% (9/40) in October,but no infection in April. There was significant difference in infection in different months (χ(2) = 32.92, P < 0.05). All the Leptospira in rodents on the Heixiazi island were in the same phylogenetic branch with a high similarity of 97.1%-99.6%, close with the Australia strain U90865 by the similarity above 96.3%.
CONCLUSIONLeptospira is probably prevalent in rodents on the Heixiazi island, and the phylogene of the strains were similar. The infection rate in rodents was significantly different in months but not in hosts.
Animals ; China ; Leptospira ; isolation & purification ; Leptospirosis ; prevention & control ; Murinae ; microbiology ; Phylogeny ; Rats
9.Expression and clinical significance of Semaphorin4D in non-small cell lung cancer and its impact on malignant behaviors of A549 lung cancer cells.
Sha-sha RUAN ; Rui-chao LI ; Qi HAN ; Jing LIU ; Gui-ling LI ; Ying-qiu SONG ; Gang WU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2014;34(4):491-496
This study aimed to explore Semaphrin4D (Sema4D) expression and clinical significance in non-small cell lung cancer (NSCLC), and to define the roles and mechanisms of Sema4D in regulating the malignant behaviors of A549 cells by small interfering RNA (siRNA). Firstly, immunohistochemistry revealed that Sema4D was more frequently expressed in NSCLC than in lung benign lesion (P<0.05) and its overexpression was associated with low differentiation (P<0.05), poor pTNM staging (P<0.05) and occurrence of lymph node (LN) metastasis (P<0.05). Endogenous Sema4D expression was suppressed by Sema4D siRNA in A549 cells overexpressing Sema4D. Protein levels of Sema4D, total Akt and p-Akt were examined by Western blotting. Cell proliferation, migration and invasion abilities were measured by MTT assay and Transwell assay respectively. Results showed that Sema4D siRNA significantly suppressed phosphorylation of AKT in A549 cells, but it did not alter total AKT expression. In addition, efficient down-regulation of SemaD significantly inhibit cell proliferation (P<0.05), migration (P<0.05) and invasion (P<0.05) in A549 cells. These findings suggest that Sema4D might serve as a reliable tool for early prediction of NSCLC poor prognosis. Sema4D could play an important role in promoting tumor proliferation, migration and metastasis in the NSCLC, by influencing the Akt protein phosphorylation. Inhibition of Sema4D may be a useful approach for the treatment of NSCLC.
Aged
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Antigens, CD
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biosynthesis
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Carcinoma, Non-Small-Cell Lung
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metabolism
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mortality
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pathology
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Disease-Free Survival
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Lung Neoplasms
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metabolism
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mortality
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pathology
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Lymphatic Metastasis
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Male
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Middle Aged
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Neoplasm Invasiveness
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Phosphorylation
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Proto-Oncogene Proteins c-akt
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metabolism
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Semaphorins
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biosynthesis
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Survival Rate
10.Idiopathic CD4+ T-lymphocytopenia in a child with disseminated cryptococcosis.
Ming XU ; Hong SHI ; Xiao-Hui LI ; Min ZHOU ; Sha LI ; Yi WANG ; Cheng XIE ; Ying LIU ; Jinshu LI ; Wei SHEN
Chinese Journal of Pediatrics 2005;43(1):60-61