The cytogenetic and molecular data is recognized as the most valuable prognostic factor in acute myeloid leukemia (AML). Our aim was to systemically analyze the cytogenetics of Korean AML patients ...and to compare the cytogenetic profiles of various races to identify possible geographic heterogeneity. We retrospectively reviewed medical records of 2806 AML patients diagnosed at 11 tertiary teaching hospitals in Korea between January 2007 and December 2011. The most common recurrent chromosomal abnormality was t(8;21) (8.8 %, 238/2717), but t(15;17) showed an almost same number (8.6 %,235/2717). Among de novo AML, the most frequent aberrations were t(15;17), observed in 229 (10.7 %). The most common French-American-British (FAB) classification type was M2 (32.2 %), and recurrent cytogenetic abnormalities correlated with the FAB subtypes. Among 283 secondary AML cases, myelodysplastic syndrome was the most common predisposing factor. About 67.1 % of the secondary AML cases were associated with chromosomal aberrations, and chromosome 7 abnormalities (
n
= 45, 15.9 %) were most common. The incidence of FLT3 internal tandem duplication mutation was relatively low at 15 %. Our study reports certain similarities and differences in comparison to previous reports. Such discrepancies call for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.
One of the primary goals of epidemiology is to quantify various aspects of a population's health, illness, and death status and the determinants (or risk factors) thereof by calculating health ...indicators that measure the magnitudes of various conditions. There has been some confusion regarding health indicators, with discrepancies in usage among organizations such as the World Health Organization the, Centers for Disease Control and Prevention (CDC), and the CDC of other countries, and the usage of the relevant terminology may vary across papers. Therefore, in this review, we would like to propose appropriate terminological definitions for health indicators based on the most commonly used meanings and/or the terms used by official agencies, in order to bring clarity to this area of confusion. We have used appropriate examples to make each health indicator easy for the reader to understand. We have included practical exercises for some health indicators to help readers understand the underlying concepts.
In previous studies we have demonstrated that the γ-aminobutryic acid-A (GABA-A) receptor antagonist oroxylin A has an awakening effect and it also represses ADHD-like behaviors (hyperactivity, ...impulsivity and inattention) in the spontaneously hypertensive rat (SHR) model of attention-deficit hyperactivity disorder (ADHD). We hypothesized that the effects of oroxylin A were exerted via the GABA-A receptor given the important role of the GABAergic system in ADHD. However, it is possible that aside from the GABAergic system, oroxylin A may influence other systems especially those implicated in ADHD (e.g. DAergic, etc.). To test this hypothesis, we evaluated the effects of GABA agonist, or dopamine (DA) antagonist in oroxylin A-induced alleviation of ADHD-like behaviors in SHR. SHR showed inattention and impulsivity as measured by the Y-maze and the electro-foot shock aversive water drinking tests, respectively. Oroxylin A significantly improved these behaviors, furthermore, its effect on SHR impulsivity was attenuated by haloperidol, a DA antagonist, but not by baicalein, an agonist of the GABA-A receptor. In vitro studies showed that oroxylin A inhibited DA uptake similar to methylphenidate, a dopamine transporter blocker, but did not influence norepinephrine uptake unlike atomoxetine, a selective NE reuptake inhibitor. Collectively, the present findings suggest that oroxylin A improves ADHD-like behaviors in SHR via enhancement of DA neurotransmission and not modulation of GABA pathway as previously reported. Importantly, the present study indicates the potential therapeutic value of oroxylin A in the treatment of ADHD.
Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer’s disease. However, little information is ...available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptor-benzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with IC
50
of 1.19, 0.84 μg/kg, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.
This study aimed to develop a new risk prediction model for operative mortality in a Korean cohort undergoing heart valve surgery using the Korea Heart Valve Surgery Registry (KHVSR) database.
We ...analyzed data from 4,742 patients registered in the KHVSR who underwent heart valve surgery at 9 institutions between 2017 and 2018. A risk prediction model was developed for operative mortality, defined as death within 30 days after surgery or during the same hospitalization. A statistical model was generated with a scoring system by multiple logistic regression analyses. The performance of the model was evaluated by its discrimination and calibration abilities.
Operative mortality occurred in 142 patients. The final regression models identified 13 risk variables. The risk prediction model showed good discrimination, with a c-statistic of 0.805 and calibration with Hosmer-Lemeshow goodness-of-fit p-value of 0.630. The risk scores ranged from -1 to 15, and were associated with an increase in predicted mortality. The predicted mortality across the risk scores ranged from 0.3% to 80.6%.
This risk prediction model using a scoring system specific to heart valve surgery was developed from the KHVSR database. The risk prediction model showed that operative mortality could be predicted well in a Korean cohort.
Oroxylin A is a flavonoid compound that is found in the root of
Scutellaria baicalensis Georgi. The aim of this study was to determine the effects of oroxylin A on memory impairment induced by ...transient bilateral common carotid artery occlusion (2VO) in mice. The ameliorating effect of oroxylin A on memory impairment was investigated using a passive avoidance task, the Y-maze task, and the Morris water maze task in mice. Oroxylin A was found to significantly reverse 2VO-induced cognitive impairments in the passive avoidance and Y-maze tasks in a dose dependant manner (
P
<
0.05). Moreover, oroxylin A (5 mg/kg, p.o.) shortened the escape-latency and prolonged swimming times in the target quadrant during the probe trial in the Morris water maze task (
P
<
0.05). Histochemical and immunohistochemical studies showed that the number of Nissl bodies and OX-42 positive cells in the hippocampal CA1 and dentate gyrus regions were attenuated by oroxylin A. Moreover, phosphorylated cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) positive cell numbers were markedly increased in animals treated with oroxylin A than in untreated 2VO controls. These results suggest that oroxylin A dramatically attenuates the memory impairment induced by 2VO, and that this effect may be mediated by the neuroprotective effects of oroxylin A as supported oroxylin A induced reductions in activated microglia and increases in BDNF expression and CREB phosphorylation.
Chitooligosaccharides decreases plasma lipid levels in healthy men Choi, Cheong-Rak; Kim, Eun-Kyung; Kim, Yon-Suk ...
International journal of food sciences and nutrition,
2012-February, 2/1/2012, 2012-Feb, 2012-02-00, 20120201, Letnik:
63, Številka:
1
Journal Article
Recenzirano
Chitosan, which is derived from chitin, has drawn much attention due to its low toxicity and potential use in medical and pharmaceutical applications. The biological activities of chitosan have been ...shown to depend on its molecular weight (MW) and degree of deacetylation. In this study, we investigated whether oral chitooligosaccharides, which are easily absorbed into the body, can reduce the plasma level of lipid in smokers and non-smokers because smoking is a high-risk factor for cardiovascular diseases. All healthy men (11 smokers and 8 non-smokers) consumed 500 mg of chitooligosaccharides in water twice daily before a meal (breakfast and dinner) over a 6-week period. Total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased in both the smoker group and non-smoker group when compared with baseline. These results suggest that low MW chitooligosaccharides would be an effective dietary supplement for lowering cholesterol level.
Tanshinones are a group of diterpenoids found in the roots of
Salvia miltiorrhiza Bunge which has been used to treat cardiac disease. In the present study, we investigated the effect of the ...tanshinone congeners, tanshinone I, tanshinone IIA, cryptotanshinone, and 15, 16-dihydrotanshinone I, on learning and memory impairments induced by scopolamine (1 mg/kg, i.p.), a muscarinic antagonist, using passive avoidance tasks in mice. Tacrine was used as a positive control. Tanshinone I (2 or 4 mg/kg, p.o.), tanshinone IIA (10 or 20 mg/kg, p.o.), cryptotanshinone (10 mg/kg, p.o.), and 15, 16-dihydrotanshinone I (2 or 4 mg/kg, p.o.) significantly reversed scopolamine-induced cognitive impairments (
P
<
0.05). Tanshinone I (2 mg/kg, p.o.) and tanshinone IIA (10 or 20 mg/kg, p.o.) were also reversed diazepam-induced cognitive dysfunctions (
P
<
0.05). In addition, cryptotanshinone and 15, 16-dihydrotanshinone I were found to have an inhibitory effect on acetylcholinesterase in vitro with IC
50 values 82 and 25 μM, respectively. Furthermore, cryptotanshinone inhibited acetylcholinesterase activity for 3 h and 15, 16-dihydrotanshinone I for 6 h in an ex-vivo study. These results suggest that tanshinone congeners may be useful for the treatment of cognitive impairment and that their beneficial effects are mediated, in part, by cholinergic signaling enhancement.
Purpose
It has been reported that the abnormal activation of receptor tyrosine kinases is associated with the development of many human carcinomas and the high activation of EGFR and Met mediates the ...tumorigenicity of laryngeal carcinoma. In this study, we have done the therapeutic efficacy of ME22S (a novel EGFR/Met bispecific antibody) in laryngeal carcinoma in vitro and in vivo was thoroughly evaluated.
Methods
The effects of ME22S on cell viability was assessed through MTT assays, and then Western blotting and immunocytochemistry were used to determine the expression of EGFR and Met. Also, wound healing and invasion assays were performed to observe the inhibitory effects of ME22S.
Results
We found the ability of ME22S reducing the expression of both EGFR and Met and significantly inhibiting the cell migration, invasion, and proliferation of SNU899 and HN3 in vitro. Also, the notably reduced levels of p-Met, p-ERK, and p-AKT were found when the cells were treated with only ME22S alone or with HGF together. Meanwhile, ME22S, interestingly enough, caused caspase-3-dependent apoptotic cell death when HN3 cells were treated with ME22S for 72 h, decreased the HGF-induced Slug expression, and also inhibited the tumor growth of HN3 cells in a xenograft model in vivo.
Conclusions
Taken together, our findings suggest that the dual inhibition of EGFR and Met through ME22S largely suppresses the invasion and growth of laryngeal carcinoma both in vitro and in vivo, hence, can be a practical approach as a novel therapeutic strategy for the treatment of laryngeal carcinoma.
Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is associated with various diseases. We evaluated the diagnostic and prognostic significance of serum ITIH4 levels in healthy controls and ...patients with chronic hepatitis B (CHB), hepatitis B virus (HBV)-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC).
The study enrolled 300 individuals (50 healthy controls, 50 with CHB, 100 with HBV-associated cirrhosis, and 100 with HBV-associated HCC). Serum ITIH4 levels were determined by western blot analysis and expressed in densitometry units (DU).
ITIH4 levels were higher in CHB (mean: 252.96 DU) and liver cirrhosis (mean: 206.43 DU) patients than in healthy controls (mean: 75.92 DU) and HCC patients (mean: 92.86 DU) (P<0.001). The area under the receiver operating characteristic curve was 0.71 for the diagnosis of HCC in patients with HBV-related liver disease. Multivariate Cox regression analysis showed that large tumor size (≥5cm) was independently associated with overall survival (hazard ratio 5.894, 95% confidence interval 1.373–25.300, P=0.017). A Kaplan–Meier survival analysis showed significantly worse survival among HCC patients with both low ITIH4 (<80 DU) and a large tumor size compared to that among other HCC patients (P<0.001), and among patients with high AFP (>200ng/mL) and low ITIH4 compared to that among other HCC patients (P=0.041).
Serum ITIH4 levels are reduced in HCC patients compared to that in CHB and cirrhosis patients, and low serum ITIH4 levels are associated with shorter survival in HBV-associated HCC patients.
•Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is associated with HCC development.•Serum ITIH4 levels are reduced in HCC compared to that in CHB and cirrhosis.•Low serum ITIH4 levels are associated with shorter survival in HCC patients.