Objective To study the effect of Tibetan MedicineManu-Xitanggranules on the expression of prostaglandin E2 and TNF-a on adjuvant arthritis (AA) rats.Methods A total of 60 rats were randomly divided into the control group, the model group, the Aspirin group, the low-, medium- and high- dose Manu-Xitang granules groups (each group with 10). Complete Freund's adjuvant method was used for the adjuvant arthritis model except the control group. All the groups started treatment at 8th day, and the treatment last 20 days. The low-, middle- high-dosage groups were treated with 2.0, 1.0, 0.5g/(kg body weight) Manu-Xitang granules, while the the Aspirin group with ASP (0.27 g/kg), control and medol groups with the equal Volume saline. The body weight, the swelling of primary side of arthritis index were observed. The levels of PGE2 and TNF-α were measured by ELISA.Results At 6th, 12th, 18th day, compared with the model group, the body weights in Aspirin group, the low-, middle-, high-dosage groups significantly increased (P<0.05 or P<0.01); at the 6th day, the foot swelling (0.40% ± 0.18%, 0.50% ± 0.25%, 0.55% ± 0.35%vs. 0.85% ± 0.15%) in the Aspirin group, middle-, and high-dosage groups significantly decreased (P<0.05 or P<0.01). And the PGE2 (0.66 ± 0.31vs. 0.39 ± 0.11) and TNF-a (0.72 ± 0.24vs. 0.50 ± 0.15) in the high- dose group were significantly lower than the model group (P<0.05).Conclusions The Tibetan medicineManu-Xitanggranules could treat AA through the changes of PGE2 and TNF-a.

Objective To synthetically evaluate the risk factors of recurrent cerebral infarction in Chinese population.Methods The research literature on the risk factors of recurrent cerebral infarction from the domestic December 2011 published was collected through computers literature retrieval (China Academic Journal,VIP Chinese Science and Technology Academic Journal,Wanfang Database) and literature review.Meta-analysis method was used to synthetically and quantitatively analyze the risk factors of recurrent cerebral infarction reported in China.All of the data were analyzed by STATA 11.0 software.Results The total research literature was 216 studies,and 12 studies were enrolled in this study according to the inclusion and exclusion criteria.All case-control study.There were 1599 cases in case group,2566 cases in control group cumulatively.Meta analysis showed that the summary statistics of sex,hypertension,diabetes,hyperlipemia,smoking,age were 1.58 (1.04-2.39),2.66 (2.02-3.51),2.23 (1.70-2.93),2.22(1.48-3.32),1.94 (1.64-2.29),1.58 (0.55-2.60),respectively.There were significances in statistics (Z =2.16,6.95,5.82,3.87,7.68,3.02,respectively,P ＜ 0.05).Conclusion Hypertension,diabetes,hyperlipemia,smoking,male and age are all the risk factors of recurrent cerebral infarction.

Objective To compare the efficacy of sequential therapy combined with probiotics,pure sequen-tial therapy and standard triple therapy for Helicobacter pylori eradication.Methods Selected the clinical data of 240 patients admitted.The 240 patients were randomly divided into 3 groups.Group A received standard triple thera-py,group B received sequential therapy and Group C received sequential therapy in combination with probiotics. Then,we compared the eradication rate,the score of gastrointestinal tract symptoms before and after treatment,and the side effects among 3 groups.Results The eradication rate was 72.5% in groupA,87.5% in group B,and 96.3% in group C.The eradication rate of group C was significantly better than group A and group B (χ2 =18.531,P <0.001).There was no difference in the score of gastrointestinal tract symptoms before treatment(F =0.206,P >0.05),but they all significantly decreased after treatment among 3 groups(P <0.05),with group C a better result(F =25.581,P <0.05).The side effects of 3 groups were 16.3%,13.8%,3.8%,respectively.There were a significantly differencec between group C and the other 2 groups(χ2 =7.011,P =0.030).Conclusion Sequential therapy in combination with probiotics can achieve a higher eradication rate,improve the score of gastrointestinal tract symptoms, and decrease side effects.

OBJECTIVETo explore the mechanism of protective effect of Sphingosine-1-phosphate(S1P) in cultured neonatal rat cardiomyocytes dining simulated hypoxia/reoxygenation.

METHODSOn the basis of culturing neonatal rat cardiomyocytes, the model of hypoxia-reoxygennation was built by using method of Liquid Paraffin covering, the impact of S1P on apoptosis and p-Akt and mitochondrial membrane potential were studied by using method of Propidine Iodide staining and Western blot and Bhodanmine123 staining.

RESULTSSiP could reduce apoptosis rate (P < 0.01) and stabilize the mitochondrial membrane potential (P < 0.05) and improved the level of p-Akt1 (P < 0.01) in hypoxia/reoxygenation cardiomyocytes significantly. But wonnannin could block these effects of S1P partially.

CONCLUSIONSiP can obviously restrain apoptosis in curtured rat neonatal cardiomyocytes during simulated hypoxia/reoxygenation. Stabilization of mitochondrial membrane potential by P13K-AM signaling pathway is likely to play a role in protective action of S1P.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Cell Hypoxia ; Cells, Cultured ; Female ; Lysophospholipids ; pharmacology ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; cytology ; Oncogene Protein v-akt ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Primary Cell Culture ; Protective Agents ; pharmacology ; Rats ; Signal Transduction ; Sphingosine ; analogs & derivatives ; pharmacology

This study is to investigate the protective effect of rosiglitazone (RSG) against learning and memory impairment of APP/PS1/tau transgenic mice. AD mice model was replicated by using 6-month APP/PS1/tau transgenic mice. The learning and memory ability of mice was evaluated by Morris water maze and Western blotting assays was applied to measure the phosphorylation and O-glycosylation of Tau and neurofilaments (NFs) protein. The results demonstrated that RSG could reverse the learning and memory deficits of 3 x Tg mice significantly. It was also found that RSG could suppress the hyperphosphorylation of Tau and NFs protein levels and increase the glycosylation expression of Tau and NFs proteins in 3 x Tg mice brain. Together, RSG ameliorates cognitive impairments of 3 x Tg mice via the alleviation of the hyperphosphorylated Tau and NFs proteins burden in the brain.
Alzheimer Disease ; Amyloid beta-Peptides ; Animals ; Brain ; drug effects ; Disease Models, Animal ; Glycosylation ; Learning ; drug effects ; Memory ; drug effects ; Memory Disorders ; drug therapy ; Mice ; Mice, Transgenic ; Neurofilament Proteins ; metabolism ; Phosphorylation ; Thiazolidinediones ; pharmacology ; tau Proteins ; metabolism

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by ¹H NMR, ¹³C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC₅₀ = 0.26 μmol·L^-1) was 6.7 times than the lead compound A (IC₅₀ = 1.73 μmol·L^-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

The present study was aimed at investigating the expression of calbindin-D28k (CaBP-D28k) in human fallopian tube, which were collected from 33 childbearing age women undergoing abdominal hysterectomy with adnexectomy for benign disease in the pelvic cavity. These women had normal menstrual cycle and history of normal pregnancy. Isthmus, ampullary and umbrella segments of fallopian tubes were respectively collected. These specimens were divided into 6 groups based on their menstrual cycles: early-proliferative stage (n=6), mid-proliferative stage (n=5), late-proliferative stage (n=5), early-secretory stage (n=7), mid-secretory stage (n=5) and late-secretory stage (n=5). The expressions of CaBP-D28k protein and mRNA in fallopian tubes were determined by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) methods. Positive expressions of CaBP-D28k protein and mRNA were observed in human fallopian tubes. There was no significant difference in the expression of CaBP-D28k protein among the isthmus, ampulla and umbrella segments in the same phase of menstrual cycle (P>0.05). However, in the menstrual cycle, the expression level of CaBP-D28k protein in the epithelium was the lowest during the early- and mid-proliferative stages and increased in both the late-proliferative and early-secretory stages (P<0.05), and then decreased in the mid- and late-secretory stages (P<0.05). The expressed CaBP-D28k protein was disposed to gobbets or dispersed sheets in cytoplasm in the early- and mid- proliferative stages, and showed concentrated granules on the top of cells in the late-proliferative and early-, mid-secretory stages. Then in the late-secretory stage redistribution renewed as in the early- and mid-proliferative stages. The CaBP-D28k mRNA obviously increased in the late-proliferative and early-secretory stages (P<0.05). These findings indicate that the expressions of CaBP-D28k protein and mRNA exist in human fallopian tubes and exhibit a cyclic change.
Calbindin 1 ; metabolism ; Fallopian Tubes ; metabolism ; Female ; Gene Expression ; Humans ; Menstrual Cycle

Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Lactic Acid ; Microspheres ; Nanotechnology ; Polyesters ; Polymers ; Technology, Pharmaceutical ; methods

OBJECTIVETo construct a short hairpin (sh)RNA targeting the gene encoding the MDM2 oncoprotein in order to investigate its role in human hepatocellular carcinoma (HCC) and its potential for use as a gene therapy strategy to inhibit HCC growth in vivo.

METHODSSmall interfering (si)RNAs were designed targeting the MDM2 gene (siMDM2-1 and siMDM2-2) and unrelated sequences (negative control) and cloned into the expression plasmid pGCSilencer-U6-neo-GFP. A HCC mouse model was established by subcutaneous inoculation of HepG2 cells (2 x 10(6) in 0.2 ml) into 20 nude mice. The inoculated mice were divided into four equal groups for tumor-localized injections of saline, negative control siRNA plasmid, siMDM2-1 plasmid, and siMDM2-2 plasmid. Tumor growth was observed daily (by caliper measurement) for one month, when mice were sacrificed by cervical dislocation. The tumor mass was resected for analysis of tumor inhibition rate (% = [(average tumor weight of control group - average tumor weight of treatment group) / average tumor weight of control group x 100]) and effects on MDM2 and p53 mRNA and protein expression (by reverse transcription- PCR and western blotting, both normalized to beta-actin). Significance of between-group differences was assessed by one-way ANOVA or LSD test; pairwise comparisons were made by the Chi-squared test.

RESULTSsiMDM2-1 and siMDM2-2 suppressed the xenografted tumor growth remarkably (60.6% and 54.6% inhibition rates, respectively), significantly reduced the expression ofMDM2 gene (62.8% and 61.6%) and protein (60.7% and 59.5%), and significantly increased p53 gene (47.1% and 45.6%) and protein (45.9% and 44.3%) (all, P < 0.05).

CONCLUSIONshRNA-mediated silencing of the MDM2 gene effectively inhibits HCC tumorigenesis of subcutaneously xenografted HepG2 cells in nude mice, and the mechanism may involve p53.

Animals ; Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Proliferation ; Hep G2 Cells ; Humans ; Liver Neoplasms ; genetics ; pathology ; Male ; Mice ; Mice, Nude ; Plasmids ; Proto-Oncogene Proteins c-mdm2 ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Transfection ; Tumor Suppressor Protein p53 ; metabolism ; Xenograft Model Antitumor Assays

Zuotai (gTso thal) is a typical representative of Tibetan medicines containing heavy metals, but there is still lack of modem safety evaluation data so far. In this study, acute toxicity test, sub-acute toxicity test, one-time administration mercury distribution experiment, long-term mercury accumulative toxicity experiment and preliminary study on clinical safety of Compound Dangzuo were conducted in the hope of obtain the medicinal safety data of Zuotai. In the acute toxicity test, half of KM mice given the lethal dose of Zuotai were not died or poisoned, and LD50 was not found. The maximum tolerated dose of Zuotai was 80 g x kg(-1). In the subacute toxicity test, Zuotai could reduce ALT, AST, Crea levels in serums under low dose (13.34 mg x kg(-1) x d(-1)) and medium dose (53.36 mg x kg(-1) x d(-1)), with significant difference under low dose, and increase the levels of ALT, AST, MDA, Crea in serums under high dose (2 000 mg x kg(-1) x d(-1)); besides, the levels of BUN and GSH in serums reduced with the increase in dose of Zuotai, indicating a significant dose-effect relationship. In the one-time administration distribution experiment, the content of mercury in rat kidney, liver and lung increased after the one-time administration with Zuotai, with a significant dose-dependent relationship in kidney. In the long-term mercury accumulative toxicity experiment, KM mice were administered with equivalent doses of Zuotai for 4.5 months and then stopped drug administration for 1.5 months. Since the 2.5th month, they showed significant mercury accumulation in kidney, which gradually reduced after drug withdrawal, without significant change in mercury content in liver, spleen and brain and ALT, AST, TBIL, BUN and Crea in serum. At the 4.5th month after drug administration, KM mice showed slight structural changes in kidney, liver and spleen tissues, and gradually recovered to normal after drug withdrawal. Besides, no significant difference in weight gain was found between the Zuotai group and the control group. According to the findings of the clinical safety study of Dangzuo, after subjects administered Dangzuo under clinical dose for one month, their serum biochemical indicators, blood routine indicators and urine routine indicators showed no significant adverse change. This study proved that traditional Tibetan medicine Zuotai was slightly toxic, with a better safety in clinical combined administration and no adverse effects on bodies under the clinical dose and clinical medication cycle. However, long-term high-dose administration of Zuotai may have a certain effect on kidney.
Adult ; Animals ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; toxicity ; Female ; Humans ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Medicine, Tibetan Traditional ; Mice ; Middle Aged ; Rats ; Rats, Wistar ; Young Adult