Assessment of Benchmark Dose in BEAS-2B Cells by Evaluating the Cell Relative Viability with Particulates in Motorcycle Exhaust / 生物医学与环境科学（英文）

Objective@#This study aimed to use an air-liquid interface (ALI) exposure system to simulate the inhalation exposure of motorcycle exhaust particulates (MEPs) and then investigate the benchmark dose (BMD) of MEPs by evaluating cell relative viability (CRV) in lung epithelial BEAS-2B cells.@*Methods@#The MEPs dose was characterized by measuring the number concentration (NC), surface area concentration (SAC), and mass concentration (MC). BEAS-2B cells were exposed to MEPs at different concentrations @*Results@#Our results reveal that BMD of NC and SAC were estimated by the best-fitting Hill model, while MC was estimated by Polynomial model. The BMDL for CRV following ALI exposure to MEPs were as follows: 364.2#/cm @*Conclusion@#These results indicate that MEPs exposure

Effect of Olaparib on Ovarian Cancer SKOV3 Cell Line Proliferation by Inhibiting the PI3K/AKT/mTOR Signaling Pathway / 中国药学杂志

OBJECTIVE: To analyze the involvement of PI3K/AKT/mTOR signaling pathway on the inhibiting the proliferation of ovarian cancer SKOV3 cell line by olaparib. METHODS: The SKOV3 cells were randomly divided into five groups: control group, olaparib low dose group (10 mg•L-1), olaparib medium dose group (30 mg•L-1), olaparib high dose group (90 mg•L-1), and PI3K protein inhibitor LY294002 group (10 mg•L-1). In addition to the control group, the rest of the cells were incubated with the corresponding doses of the compounds. DAPI and Western blotting were used to analyze the expression of apoptotic protein. qPCR, Western blotting and immunocytochemistry were adopted to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins. RESULTS: After olaparib treatment, the proliferation of ovarian cancer SKOV3 cells was significantly inhibited (P<0.05). Apoptotic bodies in SKOV3 cells increased gradually, and the expression of caspase 3 and caspase 9 increased gradually (P<0.05), PI3K, AKT and mTOR expression gradually decreased (P<0.05) after olaparib medication. With the increase of olaparib level, the above effects were more obvious (P<0.05). CONCLUSION: Olaparib has an inhibitory effect on ovarian cancer SKOV3 cells, and it may play a role by inhibiting the PI3K/AKT/mTOR signaling pathway.

Biochemical Assessment of the Effects of Aqueous Stem Bark Extract of Anogeissus leiocarpus on Wistar Strain Rats.

Aqueous stem bark extract of Anogeissus leiocarpus was phytochemically screened indicating the presence of alkaloids, tannins, anthraquinones, saponins and phenols. Antimicrobial activity of the aqueous extract using Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae as test organisms showed varying zones of inhibition with 10 mm zone of inhibition exhibited by Staphylococcus aureus and Escherichia coli respectively. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration of extract were 16 μg/ml and 32 μg/ml respectively. Treatment of experimental animals with the aqueous stem bark extract for a period of six weeks and subsequent assessment of its effect biochemically revealed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatase (ACP), and lactate dehydrogenase (LDH) levels were significantly higher than normal suggesting certain degree of liver injury. Glucose, cholesterol, total and direct bilirubin as well as total protein levels were significantly higher than normal values with respect to animals treated with 500mg/kg body weight suggesting a dose dependent effect of the extract on the animals. Urea and creatinine levels were slightly lower than normal. Overall, the result of this study showed that the effect of the extract was more pronounced on the liver than the kidney as depicted by the photomicrographs.

Effects of 3, 5, 2', 4'-tetrahydroxychalcone on serum uric acid levels and the content of hepatic XOD/XDH in mice / 中国药学杂志

OBJECTIVE: To investigate the time- and dose-dependent effects of 3, 5, 2', 4'-tetrahydroxy chalcone (P40) on the levels of uric acid and the contents of hepatic xanthine dehydrogenase (XDH) and xanthine oxidase (XOD) in the hyperuricemic mice induced by potassium oxonate. METHODS: The hyperuricemic mice were induced by an intraperitoneal injection of uricase inhibitor potassium oxonate. Serum uric acid levels were determined by using tie phosphotungstic acid method. The contents of hepatic XOD and XDH were determined using commercially available Elisa kits. Allopurinol was as a positive control. RESULTS: When orally administrated to the oxonate-induced hyperuricemic mice, compound P40 at doses of 0.5, 1.0, 2.0, 4.0 mg · kg-1 and the allopurinol at a doses of 1.0 mg · kg-1 significantly decreased the uric acid levels and reduced the concentration of XOD compared with model group. As for the study of time-dependent effects: after administration of allopurinol 30 min or P40 60 min effectively reduced serum uric acid levels compared to the model group, respectively. Administration with P40 and allopurinol for 15, 30, 60, 90 min can reduce the concentration of XDH and XOD, compared with model group. CONCLUSION: P40 could reduce the serum uric acid levels in oxonate-induced hyperuricemic mice by reducing the contents of hepatic XDH/XOD.

Cardio-protective properties of Momordica charantia in Albino Rats.

Momordica charantia, commonly known as bitter gourd, is used as a vegetable by the Asian community in Africa. It is frequently used as an anti-diabetic herb for the management of disease in the Ayurvedic system of Medicine. This present study was aimed at evaluating possible cardio-protective properties of M. charantia by determining its effect on blood cholesterol levels in albino rats. The study involved 25 rats and they were divided into 5 groups each comprising of 5 rats. The aqueous extract of M. Charantia was administered orally with syringes and cannula to 4 groups at different doses (80mg/kg, 100mg/kg, 120mg/kg and 140mg/kg body weights per day, respectively) and the last group served as the control and were given drug vehicle (normal saline) only. After two weeks of administration, the 25 rats were sacrificed and blood samples were collected and assayed for total blood cholesterol, triglyceride, highdensity lipoprotein and low-density lipoprotein levels. Results indicated that M. charantia plant extract increased significantly (P<0.05) the low density lipoprotein levels in the experimental group B (100mg/kg), and significantly reduced low density lipoprotein levels (P<0.05) in the experimental group A (80mg/kg), when compared to the control group. This study showed that M. charantia plant extract has cardio-protective properties by its dose-dependent effects on blood cholesterol.

Use of Monte Carlo simulation to estimate and optimize treatment regimens for antibiotic administration in general surgery / 中国药学杂志

OBJECTIVE: To estimate and optimize the dosing regimens of antibiotics in general surgery with the utilization of Monte Carlo simulation (MCS) based on PK/PD. METHODS: The mean treatment duration(MTD) of different dosing regimens were gathered from clinical cases. MCS model was used to simulate the regimens against Escherichia coli, Klebsiella pneumonius, Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. RESULTS: The CFRs of 500 mg TID, 500 mg QID, 1.0 g BID and 1.0 g TID imipenem against Escherichia coli and Klebsiella pneumonius were greater than that of 500 mg BID (100%; 99%). Correspondingly, MTD of those regimens achieved CFR 100% were shorter than that of 500 mg BID. The CFRs of imipenem against Acinetobacter baumannii and Pseudomonas aeruginosa were all less than 90%, the CFRs of 200 mg BID, 400 mg QD levofloxacin and 200 mg QD, 200 mg BID, 400 mg QD amikacin were all below 90%. CONCLUSION: The 5 dosing regimens of imipenem were all effective against Escherichia coli and Klebsiella pneumonius. In consideration of pharmaceutical economics, 500 mg TID was the most rational choice. It suggested drug resistance and promoted combined medication that the CFRs of imipenem against Acinetobacter baumannii and Pseudomonas aeruginosa failed to achieve 90%. Drug resistance was also demonstrated by low CFR values of levofloxacin and amikacin treatments. Nevertheless, results of MCS showed inversely proportional between MTD and CFRs, and displayed obvious dose-dependent characteristics of levofloxacin and amikacin. On the purpose of achieving effective concentration, sufficient dose once a day of levofloxacin and amikacin medication were recommend.

Research on Influence of Cervus and Cucumis Polypeptide on the Bone Biomechanical Properties of Ovariectomized Rats / 浙江中医药大学学报

[Objective]To study whether Cervus and Cucumis Polypeptide(CCP ,Lugua polypeptide) can treat osteoporosis or not. [Methods]Forty 4-month-old female SD rats were randomized into four groups(10 in each group) ,including SHAM,0VX, OVX+CCP1 and OVX+CCP2 groups. Male rats in OVX groups take the ovariectomized surgery. Since the 13th week, rats in groups A and B got 0.9% physiological saline injection once in a day, group C was treated with CCP 0.4mL/(kg·d)injection and group D treated with CCP0.8mL/(kg·d) injection once one day. Twelve weeks later, al rats were sacrificed for obtaining specimen. Took right femurs, measured the bone biomechanical properties. [Results ]After 12 weeks since injection, the biomechanical property of right femurs in group OVX was significantly lower than that of the SHAM group( P<0.01); parameters such as maximum load and elastic load in group OVX+CCP1 and OVX+CCP2 were higher than that of group OVX(P<0.05), but lower than that of group SHAM(P<0.05). The distinction of the above parameters was significant( P<0.05)between group OVX+CCP1 and OVX+CCP2. [Conclusion]1.CCP can significantly im-prove the bone internal biomechanical properties in ovariectomized(OVX) rats, so it has function to treat osteoporosis caused by drop in estrogen level. There are differences of bone biomechanical properties aspects when treated with different dosage of CCP, which shows the tendency of dose-dependent effect. So we can conclude that CCP may have dose-dependent effect.

Saireito Induced Prolonged Survival of Fully Mismatched Cardiac Allografts in Mice / 日本東洋医学雑誌

Saireito, a 12-component Japanese herbal medicine, is used to treat immune-related diseases. We investigated the effects of oral administration of Saireito extract in a murine model of cardiac transplantation with fully mismatched allografts. Untreated recipients and those given water rejected their cardiac allografts acutely (median survival time [MST], 7 and 8 days, respectively), as did those treated with either 0.02 or 0.002 g/kg/day of Saireito extract (MST, 7 days in both groups). Recipients given 0.2 g/kg/day of Saireito extract had only moderate prolongation of allograft survival (MST, 41 days). However, all transplant recipients given 2 g/kg/day of Saireito extract had significant prolongation of allograft survival (MST>100 days). None of the single crude drug extracts of Saireito prolonged allograft survival, suggesting that its effects require administration of the combination agent. In mixed leukocyte cultures, proliferation of splenocytes from Saireito-treated CBA recipients was markedly suppressed compared with that of splenocytes from untreated mice, and interferon-γ production was significantly reduced. In flow cytometry experiment, the population of CD 4+CD 25+FOXP 3+cells was increased in the spleens of Saireito-treated CBA recipients compared with the spleens of naïve CBA mice or untreated CBA recipients. Thus, in our model, Saireito treatment induced hyporesponsiveness to cardiac allografts in a dose-dependent manner, and the combination of the components is essential for this effect.