Although matrix-assisted laser desorption/ionization (MALDI) was developed more than a decade ago and broad applications have been successfully demonstrated, detailed mechanism of MALDI is still not ...well understood. Two major models; namely photochemical ionization (PI) and cluster ionization (CI) mechanisms have been proposed to explain many of experimental results. With the photochemical ionization model, analyte ions are considered to be produced from a protonation or deprotonation process involving an analyte molecule colliding with a matrix ion in the gas phase. With the cluster ionization model, charged particles are desorbed with a strong photoabsorption by matrix molecules. Analyte ions are subsequently produced by desolvation of matrix from cluster ions. Nevertheless, many observations still cannot be explained by these two models. In this work, we consider a pseudo proton transfer process during crystallization as a primary mechanism for producing analyte ions in MALDI. We propose an energy transfer induced disproportionation (ETID) model to explain the observation of an equal amount of positive and negative ions produced in MALDI for large biomolecules. Some experimental results are used for comparisons of various models.
Hepatocellular carcinoma (HCC) has become one of most common malignancies and a leading cause of cancer mortality worldwide. Previous study has shown that 4-acetylantroquinonol B (4AAQB) isolated ...from Antrodia cinnamomea (or niu-chang-chih) was observed to inhibit HepG2 cell proliferation via affecting cell cycle. However, the in vivo effects and antimetastatic activity of 4AAQB have not yet been addressed. This study found that 4AAQB inhibited HepG2 and HuH-7 hepatoma cell growth in both in vitro and in vivo models and exhibited pronounced inhibitory effects on HuH-7 tumor growth in xenograft and orthotopic models. 4AAQB efficiently inhibited the phosphorylation of mTOR and its upstream kinases and the downstream effectors and decreased the production of VEGF and activity of Rho GTPases in HuH-7 cells. Furthermore, 4AAQB inhibited in vitro HuH-7 cell migration and in vivo pulmonary metastasis. The results suggested that 4AAQB is a potential candidate for HCC therapy.
Abstract Treatment and prevention of pediatric infectious diseases of three commercial probiotic products were evaluated by a double-blind, randomized, controlled trial. Test subjects under age 5, ...1062 in total, were distributed randomly into four groups. This investigation showed that L. casei rhamnosus can control bacterial, viral and respiratory infections; a multi-species probiotic reduced gastrointestinal disease significantly. Long-term consumption of L. rhamnosus T cell-1 decreased the incidence of bacterial infection.
Vehicle speeds are often measured by intelligent transportation systems (ITSs) by utilizing sensors or software solutions. Our previous work proposed the Lin-Chang-Huangfu (LCH) scheme to compute the ...cell residence times by the standard counter values in mobile telecommunications switches. In this paper, we use mathematical and statistical developments to investigate the accuracy of the LCH scheme by deriving the bias of the cell residence times computed in this scheme. Then, we extend the LCH scheme with some filtering and compensation techniques for vehicle speed estimation and validate our approach with vehicle detector (VD) measurements at National Highway 3, Longtan Township, Taoyuan County, Taiwan. Our study indicates that the LCH scheme is an effective approach to vehicle speed estimation.
Background: Coronary artery perforation (CAP) during percutaneous coronary intervention (PCI) is associated with increased mortality. Polytetrafluoroethylene covered stents (CS) are an effective ...approach to treat CAP, but data regarding elderly patients requiring CS implantation for CAP are limited. The aim of this study is to report clinical data for elderly CAP patients undergoing CS implantation during PCI. Methods: Nineteen consecutive elderly patients (≥ 65 years) undergoing CS implantation due to PCI-induced CAP in a tertiary referral center from July 2003 to April 2016 were retrospectively examined. Results: There were 13 men and six women, with a mean age of 75.3 ± 5.6 years (range: 65-86 years). Perforation grade was Ellis type II in five patients (26.3%), and Ellis type III in 14 patients (73.7%). Cardiac tamponade developed in six patients (31.6%), and intra-aortic balloon pumping was needed in four patients (21.1%). The overall success rate for CS implantation rate was 94.7%. The overall in-hospital mortality rate was 15.8%; the in-hospital myocardial infarction rate was 63.2%. Among 16 survival-to-discharge cases, dual antiplatelet therapy (DAPT) was prescribed in 14 cases (87.5%) for a mean duration of 14 months. Overall, there were five angiogram-proven CS failures among 18 patients receiving successful CS implantation. The 1, 2 and 4 years of actuarial freedom from the CS failure were 78%, 65%, and 43% in the angiogram follow-up patients. Conclusions: CS implantation for CAP is feasible and effective in elderly patients, while CS failure remains a major concern that encourages regular angiographic follow-up in these case.
Serotonin transporters (SERTs) have been implicated in various neuropsychiatric disorders. We aim to validate 4-18F-ADAM (N,N-dimethyl-2-(2-amino-4-18Ffluorophenylthio)benzylamine) as a SERT imaging ...agent in rats using micro-positron emission tomography (micro-PET) and autoradiography. Sixty to ninety min after injecting 4-18F-ADAM, specific uptake ratios (SURs) were determined by micro-PET measurements in various brain regions of normal control rats. For n=3, the SUR in the midbrain was 4.94±0.16, for the hypothalamus it was 4.39±0.031 and for the caudate it was 4.18±0.53. The retention of 4-18F-ADAM in the hypothalamus and midbrain regions increased rapidly between 5 to 10 min after injection and declined thereafter. The SURs determined by autoradiography were: 9.31±1.41 for the midbrain, 7.15±1.45 for the hypothalamus and 5.22±1.14 for the caudate putamen. Both micro-PET and autoradiography studies revealed a dose-dependent progressive inhibition of radioligand uptake in the frontal cortex, caudate putamen and hypothalamus in rats treated with 0.01 to 0.25 mg/kg paroxetine. A decrease in 4-18F-ADAM uptake of approximately 84% was observed in the midbrain of rats pretreated with 0.25 mg/kg paroxetine as compared to controls (4.94±0.16 versus 0.80±0.17, n=3). Both 5,7-dihydroxytryptamine and p-chloroamphetamine-treated rats showed pronounced reduction in 4-18F-ADAM binding when compared to normal controls. Rats pretreated with p-chloroamphetamine exhibited significant inhibition of 4-18F-ADAM uptake in brain regions rich in SERT over a period of four weeks. Thus, 4-18F-ADAM is a SERT-specific radioligand that may be useful for evaluating neuropsychiatric conditions involving serotonergic dysfunction.
The development of restenosis involves migration and hyperproliferation of vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) is one of the major factors. Butein modulates ...inflammatory pathways and affects the proliferation and invasion of the tumor. We investigated the hypothesis that butein might prevent the restenosis process via a similar pathway. Our results demonstrated that butein inhibited PDGF-induced VSMC proliferation and migration as determined by BrdU proliferation and two-dimensional migration scratch assay. Butein also concentration-dependently repressed PDGF-induced phosphorylation of PDGF-receptor β, mitogen-activated protein kinases, phosphoinositide 3-kinase/Akt, and phopholipase Cγ/c-Src in VSMCs. In addition, in vivo results showed that butein attenuated neointima formation in balloon-injured rat carotid arteries. These results indicate that butein may inhibit PDGF-induced VSMC proliferation and migration, resulting in attenuation of neointima formation after percutaneous transluminal coronary angioplasty. Our study demonstrates for the first time that systemic administration of butein is able to reduce neointima formation after vascular injury.
A series of 6-ureido-substituted 3-pyrrolemethylidene-2-oxindole derivatives were synthesized and identified as potent inhibitors of the vascular endothelial growth factor receptor and ...platelet-derived growth factor receptor families of receptor tyrosine kinases.
A series of new ureidoindolin-2-one derivatives were synthesized and evaluated as inhibitors of receptor tyrosine kinases. Investigation of structure–activity relationships at positions 5, 6, and 7 of the oxindole skeleton led to the identification of 6-ureido-substituted 3-pyrrolemethylidene-2-oxindole derivatives that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) families of receptor tyrosine kinases. Several derivatives showed potency against the PDGFR inhibiting both its enzymatic and cellular functions in the single-digit nanomolar range. Among them, compound
35 was a potent inhibitor against tyrosine kinases, including VEGFR and PDGFR families, as well as Aurora kinases. Inhibitor
36 (non-substituted on the pyrrole or phenyl ring) had a moderate pharmacokinetic profile and completely inhibited tumor growth initiated with the myeloid leukemia cell line, MV4-11, in a subcutaneous xenograft model in BALB/c nude mice.
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![Validation of 4-[18F]-ADAM ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1053-8119/small "Validation of 4-[18F]-ADAM as a SERT imaging agent using micro-PET and autoradiography")
