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Restenosis frequently occurs after balloon angioplasty. Percutaneous coronary intervention (PCI)‐induced artery damage is a significant part of triggering restenosis of the vascular smooth muscles (VSMC). This study aimed to study how ethanol extract of Phellinus merrillii (EPM) affected balloon injury‐induced overgrowth of VSMC, indicating neointima formation. Firstly, our results demonstrated that EPM notably decreased VSMC viability. A fragmentation assay and Annexin V/Propidium Iodide apoptosis assay showed that higher doses of EPM significantly induced the apoptosis of VSMC after 24 h of exposure. Total protein extracted from VSMC treated with EPM in various time and concentration periods was then conducted in Western blotting analysis. Our data demonstrated that EPM substantially elevated the p53, p21, Fas, Bax, p‐p38, and active caspase‐3 protein expressions. The results indicated that EPM induces VSMC apoptosis via intrinsic and extrinsic pathways. Also, our results demonstrated that EPM effectively attenuated the balloon injury‐induced neointima formation. In conclusion, the information offers a mechanism of EPM in inducing the VSMC apoptosis, thus as a potential interference for restenosis. [ABSTRACT FROM AUTHOR]

This study investigated the effects of methanol extract Magnolia officinalis (MEMO) on baroreceptor reflex sensitivity (BRS) in the hypercholesterolemic rabbits and the involved molecular mechanisms. Male New Zealand white rabbits were randomly divided into Control (normal diet), Cholesterol (0.5% w/w cholesterol diet), and Magnolia groups (0.5% w/w cholesterol diet plus 1% w/w MEMO). The animals were treated with the designated diet for 4 or 8 weeks. BRS in the control of heart rate was assessed by linear regression method. After 8 weeks of treatments, plasma total cholesterol (TC) was significantly elevated in the Cholesterol/Magnolia groups. The arterial blood pressure (aBP) was increased in the Cholesterol and Magnolia groups. The depression of BRS observed in the Cholesterol group was significantly ameliorated in the Magnolia group. After L‐NAME (Nω‐nitro‐Larginine methyl ester, 20 mg/kg, iv), the BRS of the Cholesterol group was significantly improved. Results from our in vitro study further indicated that honokiol, the principle component of MEMO, would protect human umbilical vein endothelial cells (HUVECs) from H2O2‐induced damages and inhibit H2O2‐induced vascular smooth muscles cells (VSMCs) proliferation, which was evident by the decreased expression of pFAK, and p‐Erk1/2. The results of the present study suggested that the improvement of BRS by MEMO in the hypercholesterolemic rabbits might be mediated by the antioxidant property of MEMO as indicated by the results from the L‐NAME and in vitro honokiol studies. [ABSTRACT FROM AUTHOR]

Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell-cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry. Cell migration was examined using a wound-healing analysis and a transwell assay. Protein expressions and gelatinase activities were, respectively, measured using Western blot and gelatin zymography. Balloon angioplasty-induced neointimal formation was induced in a rat carotid artery model and then examined using immunohistochemical staining. Ugonin J induced cell-cycle arrest at the G0 /G1 phase and apoptosis to inhibit VSMC growth. Ugonin J also exhibited marked suppressive activity on VSMC migration. Ugonin J significantly reduced activations of focal adhesion kinase, phosphoinositide 3-kinase, v-akt murine thymoma viral oncogene homolog 1, and extracellular signal-regulated kinase 1/2 proteins. Moreover, ugonin J obviously reduced expressions and activity levels of matrix metalloproteinase-2 and matrix metalloproteinase-9. In vivo data indicated that ugonin J prevented balloon angioplasty-induced neointimal hyperplasia. Our study suggested that ugonin J has the potential for application in the prevention of balloon injury-induced neointimal formation. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess a possible correlation between zolpidem use and acute pyelonephritis (APN) in women in Taiwan. Therefore, we performed a case-control study involving the Taiwan's National Health Insurance Research Database between 2000 and 2011. This study included 3151 female participants aged 20 to 84 years who experienced the first bout of APN (case group) and 6015 randomly selected female participants without APN (control group). Zolpidem use was defined as 'current,' 'early,' or 'late,' if the last remaining 1 tablet for zolpidem was detected within 7 days, between 8 and 14 days, or ≥15 days before the date of APN diagnosis, respectively. The multivariable unconditional logistic regression model was used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the correlation between zolpidem use and APN. After adjusting for confounders, the multivariable analysis yielded an adjusted APN OR of 2.2 for participants with current zolpidem use (95%CI 1.7-2.8) compared with participants who never used zolpidem. The adjusted ORs gradually decreased to 1.4 for participants with early zolpidem use (95%CI 0.8-2.5) and 1.1 for participants with late zolpidem use (95%CI 0.9-1.2), but without statistical significance. Only patients with current zolpidem use had a significantly increased relative risk of APN. Additional large confirmatory studies are needed to illustrate a causal relationship. Meanwhile, physicians and pharmacists should be more cautious about the risk of APN when prescribing and dispensing zolpidem in women. [ABSTRACT FROM AUTHOR]

Background Nanoparticle processing is implicated in enhancing bioactive or nutritional compound release from raw foods. The aim of the present study was to evaluate whether different particle processing might affect the lipid-lowering activity of Dioscorea pseudojaponica ( DP ) and to investigate whether DP could be a potential functional food for prevention of atherogenesis. Its possible molecular mechanisms were also evaluated. Results The results indicated that 50 mesh-size DP (50 mesh DP ) particles exhibited stronger effects than nanoscale DP (nano DP ) particles in terms of lowering the level of serum cholesterol as well as reducing the extent of fatty liver and aortic fatty streak. Moreover, both DP particle types, particularly 50 mesh DP, significantly activated AMPK (5′-adenosine monophosphate-activated protein kinase) and deactivated ACC (acetyl- CoA carboxylase), as demonstrated by the increased levels of both enzymes in their phosphorylated form. Coincidently, high-performance liquid chromatography ( HPLC ) analysis showed a higher content ( P < 0.01) of dioscin, a known lipid-lowering compound, in 50 mesh DP than in nano DP. Conclusion These results suggest that improper processing conditions will lead to the decomposition of bioactive components in yam. They also demonstrate for the first time that the lipid-lowering mechanisms of DP may occur through the AMPK-ACC pathway. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

1. The aim of the present study was to investigate the molecular mechanisms by which pipoxolan exerts its inhibitory effects and apoptotic activity in human leukaemia HL-60 cells. 2. The effects of pipoxolan on the proliferation of HL-60 cells and on the distribution of cells within different phases of the cell cycle were investigated indirectly using a Trypan blue assay and a flow cytometer, respectively. The effects of pipoxolan on the apoptosis of HL-60 cells was investigated using DNA fragmentation and flow cytometer. The expression of factors affecting the cell cycle and apoptosis, including p53, p21, Bax, Bcl2, cytochrome c, caspase 3 and caspase 9, was examined by western blotting. 3. At 6.25 μg/mL, pipoxolan significantly induced apoptosis in human leukaemia HL-60 cells after 24 h exposure. In addition, HL-60 cells were arrested in the G0/G1 phase via the induction of p53/p21 by pipoxolan. Apoptosis was associated with an increased Bax/Bcl-2 ratio, cytochrome c release, cleavage of procaspases-9 and -3 and hydrolysis of poly(ADP-ribose) polymerase. Intracellular reactive oxygen species (ROS) seem to play a key role in the pipoxolan-induced apoptosis, because high levels of ROS were produced early in the drug treatment. Apoptosis was significantly abrogated by the free radical scavenger N-acetylcysteine (NAC). [ABSTRACT FROM AUTHOR]