1.Regulation of organic anion transporting polypeptides expression and activity.
Man-man ZHAO ; Dan LI ; Yan LI
Acta Pharmaceutica Sinica 2015;50(4):400-405
Organic anion transporting polypeptides (OATP), a member of solute carrier (SLC) superfamily, is considered as an important transmembrane uptake transporters. OATP is involved in the transport of a variety of endo- and xenobiotics (bile acids, bilirubin, prostaglandin, thyroid hormones, steroid hormone conjugates), drugs and toxins in a Na+ and ATP independent manner. Multiple factors (eg. hormones, proinflammatory cytokines, drugs) can affect the distribution, expression and activity of OATPs, leading to an altered accumulation of OATP substrates and related food-drug and drug-drug interactions. Changes in the distribution and expression of OATPs in malignant tissues may be related to the pathological process of cancer, while the modulation epigenetic mechanism also contributes to its distribution patterns. This review describes the factors that can affect the expression or function of OATPs, which may provide a valuable reference for drug development and the clarification of pathogenesis.
Biological Transport
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Humans
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Neoplasms
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Organic Anion Transporters
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physiology
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Xenobiotics
3.cDNA microarray in the gene expression pattern in lymphatic metastasis of colon carcinomas
Man LI ; Zuowei ZHAO ; Yang ZHANG
Cancer Research and Clinic 2006;0(10):-
Objective To analyze differential gene expression profiles by cDNA microarray in colon carcinomas with or without lymphatic metastasis. Methods cDNA microarray was prepared by spotting polymerase chain reaction (PCR) products of 16 000 human genes onto specially treated glass slides. The cDNA probes were prepared by labeling cancer tissue mRNA and lymphatic metastasis tissue mRNA with Cy3-dUTP and Cy5- dUTP through reverse transcription. The mixed probes were ,then hybridized to the cDNA microarray. The chips were scanned by Agilent fluorescence scanner and analyzed by gene Pix QuantArray. Results Among the 16 000 target genes, 999 genes were screened out for differences in gene expression level in the cases with colon carcinoma and lymphatic metastasis, among which 537 were up-regulated and 462 down-regulated. There were many genes evolved in the metastasis of colon carcinoma, including oncogenes, tumor-suppressor genes, adhesion molecular, matrix metalloproteinases, signal transduction factors, metabolism, immune associated genes, etc. Conclusion The genes, being closely associated with carcinoma metastasis, could be considered as potential markers to predict metastasis and targets for antimetastasis intervention.
4.Clinical Significance of Changes in NT-proBNP, Hcy and Partial Coagulation-Fibrinolytic Indexes with Acute Cerebral Infarction
Yu WANG ; Xiue LI ; Man ZHAO ; Ya ZHAO ; Ning LI
Journal of Modern Laboratory Medicine 2017;32(3):89-91
Objective To Analyze the examination meaning of b-type brain natriuretic peptide precursor (NT-proBNP),homocysteine and coagulation-fibrinolysis indexes for patients with acute cerebral infarction.Methods Selected 40 patients with acute cerebral infarction (experimental group) to hospital from March 2014 to May 2015 and 40 healthy check-up cases (control group).Then,compared the indicators in blood between the two groups of patients,namely homocysteine (Hcy),NT-proBNP,activated clotting time live enzymes enzyme (APTT),original activator inhibitory factor (PAI-1) and tissuetype fibrinolytic enzyme original activator (tPA).Meanwhile,also compared these indicators for the experimental group before and after treatment.Results Before treatment,the levels of Hcy,t-PA,NT-proBNP,PAI-1 and ATPP for experiment group were 17.7±3.6 μmol/L,29.4±7.9 μmol/L,3 212.8±2 511.4 ng/L,130.1±17.8 μmol/L and 37.8±4.5 s,respectively.The levels of Hey,t-PA,NT-proBNP,PAI-1 and ATPP for control group were 7.2± 2.1 μmol/L,15.1 ± 3.7 μmol/ L,198.7 ± 1 14.8 ng/L,67.8 ± 7.9 μmol/L and 37.8 ± 4.5 s,respectively.After treatment,the levels of Hcy,t-PA,NT-proBNP,PAI-1 and ATPP for experiment group were 12.2±1.5 μmol/L,18.2±2.3 μmol/L,348.7±194.8 ng/L,78.6±9.8 μmol/L and 32.2±4.5 s,respectively.Before treatment,the indicator of APTT for experiment patients was significantly shorter than it after treatment and that of the control group.The other four indicators were significantly higher than them after treatment and those of the control group.The differences were statistically significant (P <0.05).Conclusion Hcy,NT-proBNP,APTT,PAI-1,and t-PA had closely relation with the occurrence of acute cerebral infarction development,and they can be helpful to evaluate disease progression and predict prognosis for patients with acute cerebral infarction.
5.Chemokine Receptor 5 of Human Brain Microvascular Endothelial Cells Takes Part in Amyloid beta Induced T Lymphocytes Transendothelial Migration
Li ZHU ; Man LI ; Weidong ZHAO ; Yuhua CHEN
Journal of China Medical University 2010;(6):410-412,431
Objective To investigate the function of chemokine receptor 5(CCR5)in human brain microvascular endothelial cells(HBMEC)during T lymphocytes transendothelial migration induced by amyloid beta(Aβ).Methods The in vitro model of blood-brain barrier was established with cultured HBMEC monolayer.The ability of T lymphocytes transendothelial migration induced by Aβ was analyzed by Transwell and Millicell-ERS endothelia volt-ohmmeter.Results Aβ could promote T lymphocytes to migrate through the HBMEC monolayer.Over-expression of CCR5 in HBMEC promoted T lymphocytes to migrate through HBMEC monolayer.Expression of CCR5 mutant in HBMEC inhibited the transendothelial migration of T lymphocytes.Conclusion CCR5 of HBMEC is involved in T lymphocytes transendothelial migration induced by Aβ.
6.Application of quadruple bags-separated umbilical cord blood stem cells in 8 cases
Linna ZHAO ; Jianbin LI ; Yong MAN ; Hong SHAN ; Hongliang JIAO
Chinese Journal of Tissue Engineering Research 2009;13(32):6397-6400
BACKGROUND:Separating umbilical cord blood stem cells using tubes has low efficiency,and microbial contamination easily occurs during this process,therefore,safety cannot be ensured in clinical application.lt is urgent to find a method for separating umbilical cord blood stem cells to treat femoral head necrosis.OBJECTIVE:To establish a high efficient,safe,and clinically valuable method to separate umbilical cord blood stem cells.DESIGN,TIME AND SETTING:A self-control experiment was performed at the First Department of Surgery,Zhengzhou Second People's Hospital,Institute of Blood Constituent Application,Henan Red Cross Blood Centre between February 2006 and August 2007.PARTICIPANTS:Eight male patients with femoral head necrosis,averaging 40.6 years of age,were included in this study.Of these patients,4 had the history of hormone application.An average of 90 mL umbilical cord blood was harvested from each healthy normal full term neonate from Maternal and Children Health Care Hospital of Zhengzhou City.The quadruple bags used for separating umbilical cord blood stem cells consisted of 1 main bag,1 empty bag,and 2 physiological saline bags,provided by Shandong Weigao Holding,China.METHODS:Within 6 hours after collection,umbilical cord blood was centrifuged in the empty bag of quadruple bag,which was connected with an aseptic filling machine.After centrifugation,partial blood plasma was discarded,and the remaining erythrocytes were thoroughly mixed by adding hetastarch.Five minutes later,the mixture was diluted with physical saline at 1:1.Umbilical cord blood was slowly added into the main bag (at 1:1),in which,human lymphocyte separating medium was pre-added.After cantrifugation,the upper layer of solution,i.e.,monocyte-rich solution,was transferred into another empty bag.Within 24hours of preservation,after suspension with umbilical blood plasma,umbilical cord monocytes were transfused into patients with femoral head necrosis via superficial vein on the hand back,monocytes≥1×108/portion,2 portions once.There were three treatment courses,each involving three transfusion sessions,one session every 4 days,and a 2-3-month interval between two treatment courses.MAIN OUTCOME MEASURES:Cell recovery rate and cell viability of umbilical cord blood monocytes and improvements in clinical symptoms.RESULTS:The separation of quadruple bags could obtain umbilical cord blood monocytes with high recovery rate.Furthermore,microbial contamination hardly occurred in the process of separation.Hip joint pain relieved or disappeared to different extents in all 8 patients,with an effective rate of 100%.Abduction and internal rotation of hip joint,ambulation distance,and gait were markedly improved.At 6 months after cell transplantation,5 patients presented with changed bone density in femoral head necrosis regions,2 showed normal femoral head morphology,and the remaining 1 exhibited no obvious changes.Joint effusion was reduced or disappeared in 12 hips.Magnetic resonance images showed that femoral head morphology had been improved in various degrees in 9 hips,but no changes in 3 hips.No complications,fever,or allergies occurred during and after cell transplantation.CONCLUSION:The method of separating stem cells from umbilical cord blood in junction with aseptic interface technology is highly effective,safe,and clinically valuable.Multiple intravenous transfusions of umbilical cord blood stem cells provide a novel approach for systemic treatment of femoral head necrosis.
7.Effect and mechanism of acrylamide on learning and memory and long-term potential in female Wistar rats
Man ZHANG ; Tao MENG ; Wenjin ZHAO ; Bin LI
Chinese Journal of Pharmacology and Toxicology 2017;31(1):87-93
OBJECTIVE To investigate the accumulated effect and the mechanism of repeated sc administration of acrylamide (AM) on learning and memory after 28 d,and the effect of AM on the amplitude of population spike(PS) potential after a single sc administration of AM. METHODS Female Wistar rats were sc adminstered with AM 10, 20 and 40 mg · kg-1 once a day for 28 d, and weighted every week. The ability of study and memory was evaluated, The morris water maze was used from 22nd to 28th day,followed by step down test on the 29th and 30th day. The escape latent period and the number of errors in those two days were recorded. Rats from normal control group and AM 40 mg·kg-1 group were taken to have their N-methyl-D-aspartate receptor (NR) and calmodulin-dependent protein kinaseⅡ (CaMKⅡ) protein levels detected by Western blotting. Additionally, some other female Wistar rats were sc administered with a single dose of AM 40 mg · kg-1 ,before the changes in PS potential amplitude induced by high frequency stimulation were recorded by long-term potential (LTP). RESULTS Compared with normal control group, the relative body mass gain was significantly decreased in AM exposure groups(P<0.01). Additionally, the escape latency period was significantly increased in AM 20 and 40 mg·kg-1 groups compared with normal control group, while the crossing frequency was not significantly different betmeen these four groups. Compared with the first day of step down test, the number of errors was significantly decreased(P<0.01) and the escape latency period was significantly extended(P<0.01) in normal control group on the 2nd day. However, the number of errors and the escape latency period did not significantly change in the AM groups between the two days. The results of Western blotting showed that the protein expressions and phosphorylation of NR2A and NR2B, as well as the phosphorylation of CaMKⅡ in AM 40 mg · kg-1 group were significantly increased compared with normal control group. LTP result showed that AM 40 mg·kg-1 significantly inhibited the amplitude of PS potential after a single percutaneous administration. CONCLUSION AM can inhibit the PS amplitude by inhibiting the release of glutamate, increasing the expressions and activities of NR,and inhibiting PS potential, thus affecting the hippocampal synaptic plasticity, and the function of learning and memory.
8.Association between rs1079727 polymorphism in the DRD2 gene and the distractibility in the school-age children
Yuling LI ; Hongyan GUAN ; Xiaoli CHEN ; Man ZHAO
Chinese Journal of Behavioral Medicine and Brain Science 2014;23(12):1083-1086
Objective To understand the association between rs1079727 polymorphism in the DRD2 gene and the distractibility in the school-age children.Method The rs1079727 polymorphisms were genotyped using Sequenom Mass Array and the distractibility was measured based on the Middle Childhood Temperament Questionnaire (MCTQ) in 121 children aged from 8 to 12 years,in order to analyze the function of rs1079727 polymorphism and its interaction with gender or the delivery mode on the distractibility.The results were analyzcd with oneway ANOVA and logistic regression analysis.Results There was association between the distractibility and rs1079727 polymorphism or delivery mode respectively.The means of distractibility for the genotypes of GG (4.37 ±0.53) and AG (4.27±0.69) were significantly higher than that of the genotype of AA(4.01±0.67) (P<0.05).The proportion of high distractibility in the cesarean children (48.28%) was significantly higher than that in the natural labor children (33.90%) (P<0.05).The child distractibility occurred through an interaction between rs1079727 polymorphism and gender/delivery mode.The girls with G alleles possessed increased risk of distractibility (OR=2.231,P<0.05),and the natural labor children with A alleles were tend to be associated with low distractibility(OR =0.048,P<0.01).Condusion The distractibility based the temperament for the school-age children might be influenced by delivery mode,rs1079727 polymorphism and its interaction with gender/delivery mode.
9.Prediction and prevention of stroke-associated pneumonia
Qian LI ; Yuping LENG ; Yidong SHEN ; Man ZHAO ; Yi CHAI
International Journal of Cerebrovascular Diseases 2015;23(1):71-74
Pneumonia is one of the most common medical complications after stroke.Stroke-associated pneumonia (SAP) can not only increase the length of hospital stay and medical cost of patients,but also an important risk factor for mortality and morbidity in patients with stroke.All these indicate that the importance of prediction and prevention of SAP.This article reviews the advances in research on the prediction and prevention of SAP.
10.Small cell carcinoma of the bladder: dagnosis and treatment of 18 cases
Du SHI ; Chuize KONG ; Zhenhua LI ; Wei ZHAO ; Xiaojun MAN
Chinese Journal of Urology 2016;37(8):607-610
Objective To study the clinical features,diagnosis and management of small cell carcinoma of the bladder (SCCB).Method The clinical data of 18 cases of patients with small cell carcinoma of the bladder were analyzed retrospectively and the literature were reviewed.There were 16 males and 2 females,ages 54 to 81 years (median age,61 years).Clinical manifestations included gross hematuria in 11 cases,urgency in 2 cases,dysuria in 2 cases and postoperative review after TURBT of bladder urothelial carcinoma in 3 cases.The median tumor size was 3.35cm (ranged,1.0 to 6.0 cm).2 cases underwent TURBT and intravesical chemotherapy regularly were followed after surgery.3 cases underwent partial cystectomy,intravenous chemotherapy combined with radiotherapy was followed in one case,the other 2 cases refused the following therapy.13 cases underwent radical cystectomy,intravenous chemotherapy was followed in 2 cases,pelvic radiotherapy was followed in 2 csaes and intravenous chemotherapy combined with radiotherapy was followed in 2 cases,the other 7 cases refused the following therapy.Results 11 cases were pure SCCB,7 cases were mixed SCCB,all with urothelial carcinoma.T1N0M0 in 3 cases,T2N0.1M0 in 4 cases,and T3N0-2M0 in 11 cases.The duration of follow-up was from 5 to 35 months after surgery.9 cases died of tumor metastasis,9 cases are still alive,except 1 case with lymph node metastasis,the other 7 cases are free of tumor recurrence or metastasis.Conclusions SCCB is rare,with high malignant degree and poor prognosis.The prognosis of the pure SCCB may be worse than the mixed SCCB.The diagnosis depends on pathology examination.Radical cystectomy is the main treatment method,the strategy of bladder-preserving may be an attempt for proper SCCB patients.Adjuvant therapy plus surgery may be better.