OBJECTIVEThe present study was undertaken to design antisense oligodeoxynucleotides (AS-ODNs) of glial glutamate transporter-la (GLT-1a) and to evaluate the effectiveness of the designed AS-ODNs on the expression of GLT-1a.

METHODSFive sequences of GLT-1a AS-ODNs were designed according to the C terminus specific sequences of GLT-1a mRNA using antisense design software of IDT Com- pany. Western blot analysis was used to evaluate the inhibition effects of the five GLT-1a AS-ODNs on the expression of GLT-la.

RESULTSThe sequence of GLT-1a AS-ODNs with sequence of 5'-GGTTCTTCCTCAACACTGCA-3' could specifically inhibit the expression of GLT-1a in the hippocampal CA1 subfield of rats, while it had no effect on the expression of GLT-1b. This sequence showed similar inhibition on the expression of GLT-la in sham and ceftriaxone (Cef)-treated rats. It could also significantly inhibit the cerebral ischemic preconditioning (CIP)-induced up-regulation in the expression of GLT-1a. The magnitude of the inhibition in sham, Cef- or CIP-treated rats was similar by more than 60%.

CONCLUSIONFrom the designed five sequences of GLT-1a AS-ODNs, we obtained an effective sequence which can specifically inhibit the expression of GLT-1a.

Animals ; CA1 Region, Hippocampal ; metabolism ; Excitatory Amino Acid Transporter 2 ; antagonists & inhibitors ; metabolism ; Ischemic Preconditioning ; Oligonucleotides, Antisense ; genetics ; RNA, Messenger ; Rats ; Up-Regulation

Objective To observe the effects of an enriched environment (EE) on cognitive functioning and the synaptic plasticity of mice modeling post-stroke cognitive impairment (PSCI) and explore the possible mechanisms involved.Methods Mice modeling PSCI and sham-operated mice were randomly divided into 3 groups:sham-operated mice in a standard environment (the Sham+SE group),PSCI mice in a standard environment (the PSCI+SE group) and PSCI mice in an enriched environment (the PSCI+EE group).The cognitive functioning of all of the mice was quantified using a Morris water maze and their hippocampal long-term potentiation (LTP) was recorded using an electrophysiological method.The level of synaptophysin was detected using Western blotting.Synaptic ultrastructure in the hippocampus was imaged using electron microscopy.Results Compared with the Sham +SE group,the PSCI+SE group showed significantly poorer water maze performance and failed induction of contralateral LTP.Their average level of synaptophysin was significantly lower,and significant adverse changes in the synaptic ultrastructure of the hippocampus were observed,including a decreased number of synapses.The average width of the synaptic cleft,postsynaptic density and the interface curvature of the synapses were all less desirable.All of the measurements of the PSCI+EE group improved significantly compared to those of the PSCI+SE group,but were still significantly poorer than those of the Sham+SE group.Conclusions An enhanced environment can improve the cognitive functioning of mice modelling PSCI.It may be that an EE can improve synaptic plasticity in the hippocampus contralateral to the stroke.

Aim To explore the effect of genetic poly-morphisms of POR on the stable warfarin maintenance doses in Han Chinese patients receiving mechanical heart valve replacement. Methods The association between POR gene polymorphisms and warfarin doses of 185 Han Chinese patients were investigated through ANOVA or t test. SNPs of POR and VKORC1 were de-tected by Sequenom? DNA MassArray genotyping method. CYP2C9*3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP ) . Patients ’ clinical characteris-tics, INR value and daily dose were obtained from their medical records. Statistical analysis was performed by SPSS 21. 0 software. Results No mutant carriers of POR rs17148944 , POR rs56256515 and rs72553971 were found in this study. The genotype frequencies of other SNPs were in accordance with Hardy-Weinberg e-quilibrium. In the group of patients with CYP2C9*1*1 , the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(3. 50 ± 1. 07) mg·d-1 vs (3. 14 ± 0. 94) mg· d-1,P =0. 03. Also, in the group of patients with CYP2 C9*1*1 and VKORC1 rs9934438 G allele carri-ers, the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(4. 76 ± 0. 90) mg·d-1 vs (4. 08 ± 1. 03) mg· d-1 ,P=0. 04. No significant difference was found in different genotypes of POR rs2868177 . Conclusion These results illustrate that POR rs17685 T carrier is closely associated with a higher warfarin maintenance dose, suggesting that this SNP is useful for clinical guidance of warfarin.

Objective To explore the efficacy and safety of tacrolimus among Chinese Takayasu arteritis (TAK) patients. Methods This was a single center, prospective study of active TAK patients treated with tacrolimus. Clinical manifestations, white blood cell count, hemoglobin level, erythrocyte sedimentation rate (ESR), hypersensitivity C reactive protein (hsCRP), alanine and aspartate aminotransferase and serum creatinine were recorded before and during tacrolimus treatment. Vascular changes were repeated every 6 months during tacrolimus treatment. All data were analyzed by statistical product and service solutions (SPSS) 20.0 statistical software, unpaired t test and Fisher exact probability and Kruskal-Wallis H test were used for statistical analysis. Results A total of 19 consecutive patients with an average age of (26 ±6) years were analyzed in this study. Sixteen of them were women. Pulselessness, fatigue, asymmetric blood pressure and fever were the most common clinical findings. Cervical and subclavian artery were more vulnerable. The most common artery involvement pattern was Numano type Ⅰ, followed by type Ⅱa and type Ⅴ. The median tacrolimus dosage was 2(2, 3) mg. Tacrolimus was effective in 9 out of the 19 patients. Patients who responded to tacrolimus tended to have lower mean ESR [(33±29) mm/1 h vs (42±20) mm/1 h, t=-0.776, P=0.448] and hsCRP [(20 ±31) mg/L vs (54 ±45) mg/L, t=-1.758, P=0.099] levels. However, no statistical significance was observed. During tacrolimus treatment, no drug related side effect was observed. Conclusion Tacrolimus is an alternative and effective therapy for some of the TAK patients.

Although gene therapy was regarded as a promising approach for glioma treatment, its therapeutic efficacy was often disappointing because of the lack of efficient drug delivery systems. Mesenchymal stem cells(MSCs) have been reported to have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy. Therefore, in this study, we attempted to treat glioma by using MSCs as a vehicle for delivering replication-competent adenovirus. We firstly compared the infectivity of type 3, type 5, and type 35 fiber-modified adenoviruses in MSCs. We also determined suitable adenovirus titer in vitro and then used this titer to analyze the ability of MSCs to deliver replication-competent adenovirus into glioma in vivo. Our results indicated that type 35 fiber-modified adenovirus showed higher infectivity than did naked type 3 or type 5 fiber-modified adenovirus. MSCs carrying replication-competent adenovirus significantly inhibited tumor growth in vivo compared with other control groups. In conclusion, MSCs are an effective vehicle that can successfully transport replication-competent adenovirus into glioma, making it a potential therapeutic strategy for treating malignant glioma.
Adenoviridae ; Animals ; Brain Neoplasms ; pathology ; therapy ; Cell Line, Tumor ; Genetic Vectors ; Glioma ; pathology ; therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Oncolytic Virotherapy ; Random Allocation ; Virus Replication ; Xenograft Model Antitumor Assays

Adenosine Triphosphatases ; chemistry ; Antineoplastic Agents ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; Drug Screening Assays, Antitumor ; Female ; Humans ; Liver Neoplasms ; pathology ; Luminescence ; Luminescent Measurements ; Male ; Middle Aged ; Tumor Cells, Cultured

Animals ; Carbon Tetrachloride ; H(+)-K(+)-Exchanging ATPase ; metabolism ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; pathology ; Male ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

Objective To investigate the differences in distribution of platelet endothelial aggregation receptor 1 (PEAR1) between Chinese cardiovascular patients and healthy population. Methods This study used method of Sequenom Mass ARRY to detect differences in distribution of PEAR1 gene between Chinese cardiovascular patients and healthy population. Results A total of 203 patients with cardiovascular disease and 106 healthy volunteer were enrolled. Nineteen sites were detected and all of them are variants in PEAR1 locus. There is no statistical difference of distribution between patients and healthy volunteers(P > 0. 05). Conclusion PEAR1 gene have multiple polymorphic sites in Chinese people.

OBJECTIVETo explore the molecular mechanism and prevention of retinoic acid syndrome (RAS).

METHODSSDF-1 alpha mRNA from healthy adult lung tissue was measured by RT-PCR, CXCR4 protein expression on the cell membrane of APL cells induced by ATRA (APL-ATRA) was tested by FCM, and the rotary cell culture system (RCCS) was used to build a modal for in vitro stimulation of APL-ATRA infiltrating human lung tissue. The ability of APL-ATRA in adhesion, migration and infiltration was observed by interference from DEX, Ara-C and DNR.

RESULTSThe APL-ATRA cells could evidently infiltrate into normal lung tissue. Mean fluorescence intensity (MFI) of CXCR4 on the cell membrane of APL-ATRA cells was 30.6 +/- 1.8, which was much higher than that on unspecialized APL cells (9.8 +/- 4.2). SDF-1 alpha mRNA expression was detected positive in all 6 lung tissue. Contrary to the control groups, DEX could dramatically restrain the ability of APL-ATRA cells in adhesion and migration [(27.2 +/- 2.6)% vs. (46.0 +/- 3.0)%, (28.1 +/- 4.0)% vs. (48.2 +/- 3.0)%], while Ara-C and DNR could distinctly depress the ability in adhesion, migration and infiltration [(28.1 +/- 3.0)%, (30.2 +/- 3.2)% vs. (46.0 +/- 3.0)%; (29.0 +/- 4.0)%, (23.0 +/- 5.2)% vs. (48.2 +/- 3.0)%; (16.8 +/- 7.6)%, (17.1 +/- 6.0)% vs. (43.6 +/- 5.0)%].

CONCLUSIONIn vitro APL-ATRA cells can infiltrate into the human lung tissue. High expression of CXCR4 on APL-ATRA and SDF-1 alpha in the lung tissue may be one of the molecular mechanisms of the lung infiltration and RAS. DEX, Ara-C and DNR can dramatically restrain the ability of APL-ATRA cells in adhesion, migration and infiltration.

Adolescent ; Adult ; Cell Adhesion ; Cell Culture Techniques ; Cell Movement ; Chemokine CXCL12 ; genetics ; metabolism ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Receptors, CXCR4 ; genetics ; metabolism ; Tretinoin ; adverse effects ; Tumor Cells, Cultured

Objective To grasp the distribution status of Oncomelania hupensis snails in Poyang Lake area,so as to provide the evidence for formulating and adjusting the schistosomiasis prevention and control strategy in lake areas. Methods The vec-tor grid was created and sampled randomly by 200 m × 200 m in the spatial database of grassland,and the distribution of snails was investigated in the selected grid by using the method of mechanical sampling by 50 m × 50 m. At the same time,the eleva-tion of investigation points was extracted based on the topographic map of Poyang Lake. Results Totally 949 and 210 investiga-tion points were collected from the south and north of Poyang Lake areas,accounting for 3.04%and 3.21%of all the investiga-tion points in the respective region. The number of investigation points,the appearance rate of snail frame,and the average den-sity of alive snails were 15231,8.15%,and 0.463/0.1 m2,respectively. The elevation of snail distribution area of the south and north Poyang Lake areas were 11-16 m and 9-16 m respectively. The elevation of concentrated snail belts of the south Poyang Lake area were 12-13 m and 15-16 m,and the elevation of concentrated snail belts of the north Poyang Lake area was 12-14 m. Conclusions The distribution of snails is in the range of 9-16 m. The suitable habitats of snail breeding are moving from the south Poyang Lake area to the north Poyang Lake area,and from high elevation to low elevation. In the future,the schistosomia-sis prevention and control measures could be formulated based on the geographical characteristics of current snail distribution in order to consolidate the achievements of schistosomiasis control.