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This study aims to investigate the role of microRNA‐145 (miR‐145) in protection against myocardial ischemia/reperfusion (I/R) injury in mice by regulating expression of granzyme K (GZMK) with the treatment of sevoflurane. The mice model of myocardial I/R injury was established by left coronary artery ligation. The expression of miR‐145 and GZMK in myocardial tissues of mice was detected by Reverse transcription quantitative polymerase chain reaction and western blot analysis. The changes of the cardiac function and hemodynamics, pathological changes of myocardial tissues, the ultrastructure of cardiomyocytes, myocardial infarction area, and cardiomyocyte apoptosis were observed. The expression of the apoptosis‐related protein cleaved‐caspase‐3, Bax, and Bcl‐2 was detected by western blot analysis. The levels of malondialdehyde, myeloperoxidase, superoxide dismutase in myocardial tissues were detected by spectrophotometric colorimetry. The levels of interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α in the serum of mice were detected by the enzyme‐linked immunosorbent assay. The level of oxidative stress and the expression of inflammatory factors increased in mice with myocardial I/R injury. Sevoflurane postconditioning could reduce myocardial I/R injury in mice. Sevoflurane postconditioning may protect myocardial I/R injury through miR‐145‐regulation of GZMK in mice. Inhibition of miR‐145 expression could reduce the protective effect of sevoflurane posttreatment on myocardial I/R injury in mice. Low expression of GZMK could attenuate the inhibitory effect of miR‐145 on myocardial I/R injury after sevoflurane treatment in mice. Our study suggests that sevoflurane postconditioning may protect against myocardial I/R injury by upregulating miR‐145 expression and downregulating GZMK expression. [ABSTRACT FROM AUTHOR]

Background: Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects. In this study, we focus on the effects of BSYSC on promoting nerve repair and the underlying mechanisms in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Methods: The EAE mouse model was induced by injecting subcutaneously with myelin oligodendrocyte glycoprotein (MOG)35-55 supplemented with pertussis toxin. BSYSC was orally administrated at dose of 3. 0 g/kg once a day for 40 days. The levels of protein gene product (PGP) 9.5, p-Tau, growth associated protein (GAP) -43, KI67 and Nestin in the brain or spinal cord on 20 and 40 day post-induction (dpi) were detected via immunofluorescence and Western blot analysis. Furthermore, NogoA/NgR and RhoA/ROCK signaling molecules were studied by qRT-PCR and Western blot analysis. Results: Twenty or 40 days of treatment with BSYSC increased markedly PGP9.5 and GAP-43 levels, reduced p-Tau in the brain or spinal cord of mice with EAE. In addition, BSYSC elevated significantly the expression of KI67 and Nestin in the spinal cord 40 dpi. Further study showed that the activation of NogoA/NgR and RhoA/ROCK were suppressed by the presence of BSYSC. Conclusions: BSYSC could attenuate axonal injury and promote repair of axonal damage in EAE mice in part through the down-regulation of NogoA/NgR and RhoA/ROCK signaling pathways. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop an intravenous clarithromycin lipid emulsion (CLE) with good stability and excellent antibacterial activity. The CLE was prepared by the thinfilm dispersed homogenization method. The interaction between clarithromycin (CLA) and cholesteryl hemisuccinate (CHEMS) was confirmed by DSC, FT-IR and 1H NMR analysis. The interfacial drug loading, thermal sterilization, freeze-thaw stability, and in vitro and in vivo antibacterial activity were investigated systematically. DSC, FT-IR and 1H NMR spectra showed that CHEMS (CLA: CHEMS, M ratio 1:2) could interact with CLA through H-bonding and a hydrogen-bonded ion pair. The CHEMS was found necessary to maintain the stability of CLE. Ultracentrifugation showed that almost 88% CLA could be loaded into the interfacial layer. The optimized CLE formulation could withstand autoclaving at 121 °C for 10 min and remain stable after three freeze-thaw cycles. The in vitro susceptibility test revealed that the CLA- CHEMS ion-pair and CLE have similar activity to the parent drug against many different bacterial strains. The in vivo antibacterial activity showed that the ED50 of intravenous CLE was markedly lower than that of CLA solution administrated orally. CLE exhibited pronounced antibacterial activity and might be a candidate for a new nanocarrier for CLA with potential advantages over the current commercial formulation. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have demonstrated that the NDV-mediated gene therapy is a promising new approach for treatment of cancers. P53 plays a vital role in tumor suppression and surveillance. Therefore, we hypothesize that a recombinant NDV expressing P53 would be an ideal agent for the hepatoma therapy. Results: In the essay, the human P53 gene was incorporated into the genome of a lentogenic strain (named rNDV-P53), which did not affect viral replication kinetics and magnitude in HepG2 cells. Compared to the vehicle virus, rNDV-P53 increased cell growth suppressor ratio and early apoptosis by 2 folds, and decreased the mitochondrial membrane potential in HepG2 cells. In vivo studies, treatment with rNDV-P53 reduced tumor volume of tumor-bearing mice by more than 4 folds, tumor weight by more than 5 folds comparing with rNDV. The 120-day survival rate of rNDV-P53-treated mice was 75%, survival rate of rNDV-treated mice was 12.5%. TUNEL analysis showed a significant increase in the apoptosis rate in the tumor tissues of rNDV-P53-treated mice than that of rNDV-treated mice. Moreover, serum chemistries revealed an insignificant change of blood urea nitrogen (BUN), creatinine levels, alanine aminotransferase (ALT) and aspartate transaminase (AST) in rNDV-P53-treated group compared to normal mice, suggesting treatment with the recombinant virus was not toxic. Conclusion: rNDV-P53 is a potent candidate for carcinoma therapy especially for hepatocarcinoma. [ABSTRACT FROM AUTHOR]

Background Cystic echinococcosis is a serious zoonotic infection worldwide caused by metacestodes of Echinococcus gruanulosus. Mebendazole and albendazole are the only two drugs used in the treatment of this disease with cure rates only about 30% due to the poor oral absorption. Thus an alternative treatment for this disease is needed. Methods A mebendazole oily suspension (MBZ-OS) was prepared and orally administrated to mice infected with echinococcus cysts for 8 months at 12.5 mg/kg and 25 mg/kg for 14 consecutive days. Mebendazole suspended in 1% tragacanth (MBZ-1% tragacanth) served as treated control. In addition, liver and serum samples were collected from these treated mice (25 mg/kg) for histopathology examination and liver function test. For pharmacokinetic analysis, plasma, parasite (cyst wall and cyst fluid) and tissue samples were collected at 0.25, 0.5, 1, 2, 4, 8, 16 and 24 h after orally administrating MBZ-OS and MBZ-1% tragacanth to E. granulosus-infected mice at 25 mg/kg. These samples were then processed and quantitatively analyzed by HPLC. Results The administration of MBZ-OS resulted in a treatment efficacy with the cyst weight reductions higher than 80%, significantly better than the corresponding MBZ-1% tragacanth groups. The better treatment efficacy of MBZ-OS was related to the higher drug concentration in plasma, parasites and tissues. It was also shown that the injury of the liver was not significantly altered by taking MBZ-OS compared to the untreated control. Conclusion These findings demonstrate that MBZ-OS is a promising new formulation of MBZ for treatment of hydatid diseases without showing significantly liver toxicity. [ABSTRACT FROM AUTHOR]

A correction to the article "Pancreatic cancer cell-derived IGFBP-3 contributes to muscle wasting" in the May 10, 2016 issue.

Wedescribe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea(1), which exhibits inhibitory activity but low potencyagainst FLT3 and VEGFR2. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure–activityrelationship analysis using cell- and transgenic-zebrafish-based assaysled to the discovery of a number of compounds that exhibited bothhigh potency against FLT3-driven human acute myeloid leukemia (AML)MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-basedassays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin −4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea(33), which exhibited the highest activity in preliminaryin vivo anti-AML assays, was chosen for further anti-AML studies.The results demonstrated that compound 33is a multikinaseinhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograftmouse model, a once-daily dose of compound 33at 10 mg/kgfor 18 days led to complete tumor regression without obvious toxicity.Western blot and immunohistochemical analyses were performed to determinethe mechanism of action of compound 33. [ABSTRACT FROM AUTHOR]