Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ovx) old rats as a model of menopause.
In the pilot test, a total of 24 seven-week-old female Sprague-Dawley (SD) rats were fed one of three diets for a period of four weeks: casein, unfermented soybean product, or fermented soybean product by R. oligosporus. In the ovx rat model, 20-week-old SD rats weighing 260-290 g underwent either sham-operation (n = 10) or bilateral ovariectomy (n = 30) and were then fed the AIN-93M diet for one week. Thereafter, rats were fed sham-casein, ovx-casein, ovx-soybean, or ovx-fermented soybean diet for five weeks. After decapitation, femoral bones were isolated and preserved in 9% formalin for assessment of bone mineral density (BMD), bone mineral content (BMC), and bone-breaking strength (BBS).
Ovx rats showed significantly increased weight gain and decreased uterine wet weight. Of particular interest, ovx rats fed fermented soybeans showed increased uterine wet weights compared to control rats. Fermented soybean diet caused a significant increase in plasma 17-β estradiol concentrations in young rats, and 17-β estradiol levels were enhanced in ovx rats to match those of sham-operated ones. Significantly lower femoral BMD and BMC were observed in ovx rats compared to sham-operated controls, whereas bone areas did not differ statistically among the groups. In addition, BBS tended to be increased in ovx rats fed soybeans and fermented soybeans.
Supplementation of fermented soybeans could have preventive and therapeutic effects against osteoporosis in postmenopausal women.
Fermented soybean; 17-β estradiol; bone mineral density (BMD); bone-breaking strength
Recently, data with complex characteristics such as epilepsy electroencephalography (EEG) time series has emerged. Epilepsy EEG data has special characteristics including nonlinearity, nonnormality, and nonperiodicity. Therefore, it is important to find a suitable forecasting method that covers these special characteristics. In this paper, we propose a coercively adjusted autoregression (CA-AR) method that forecasts future values from a multivariable epilepsy EEG time series. We use the technique of random coefficients, which forcefully adjusts the coefficients with −1
and 1. The fractal dimension is used to determine the order of the CA-AR model. We applied the CA-AR method reflecting special characteristics of data to forecast the future value of epilepsy EEG data. Experimental results show that when compared to previous methods, the proposed method can forecast faster and accurately.
The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937.
Icariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-xL and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells.
Our results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.
Takju is a Korean alcoholic beverage made from rice, and is brewed with the yeast Saccharomyces cerevisiae. This study was conducted to evaluate the effects of exercise training and moderate Takju consumption on learning ability in 6-week old Sprague-Dawley male rats. The rats were treated with exercise and alcohol for 4 weeks in six separate groups as follows: non-exercised control (CC), exercised control (EC), non-exercised consuming ethanol (CA), exercised consuming ethanol (EA), non-exercised consuming Takju (CT), and exercised consuming Takju (ET). An AIN-93M diet was provided ad libitum. Exercise training was performed at a speed of 10 m/min for 15 minutes per day. Ethanol and Takju were administered daily for 6-7 hours to achieve an intake of about 10 ml after 12 hours of deprivation, and, thereafter, the animals were allowed free access to deionized water. A Y-shaped water maze was used from the third week to understand the effects of exercise and alcohol consumption on learning and memory. After sacrifice, brain acetylcholinesterase (AChE) activity was analyzed. Total caloric intake and body weight changes during the experiment were not significantly different among the groups. AChE activity was not significantly different among the groups. The number of errors for position reversal training in the maze was significantly smaller in the EA group than that in the CA and ET groups, and latency times were shorter in the EA group than those in the CC, EC, CT, and ET groups. The latency difference from the first to the fifth day was shortest in the ET group. The exercised groups showed more errors and latency than those of the non-exercised groups on the first day, but the data became equivalent from the second day. The results indicate that moderate exercise can increase memory and learning and that the combination of exercise and Takju ingestion may enhance learning ability.
Takju intake; exercise training; water maze; AChE; learning ability
Poly-gamma-glutamic acid (γ-PGA) is a mucilaginous and biodegradable compound produced by Bacillus subtilis from fermented soybeans, and is found in the traditional Korean soy product, cheongkukjang. This study was carried out to evaluate the effects of γ-PGA from a food source on the concentration of the neurotransmitter GABA and its metabolic precursor glutamate in diet-induced obese rats. Eight-week old male Sprague-Dawley rats (n=60) were used. The rats were divided into two groups and obesity was induced by providing either a 10% control fat or 45% high fat diet for 5 weeks. The rats were then blocked into 6 groups and supplemented with a 0.1% γ-PGA diet for 4 weeks. After sacrifice, brain and serum GABA and glutamate concentrations were analyzed by high performance liquid chromatography with fluorometric detection. The rats fed the high fat diet had significantly increased body weights. γ-PGA supplementation significantly increased serum concentrations of glutamate and GABA in the control fat diet groups while this effect was not found in the high fat groups. In the brain, glutamate concentrations were significantly higher in the γ-PGA supplemented groups both in rats fed the normal and high fat diets than in the no γ-PGA controls. GABA concentrations showed the same tendency. The results indicated that γ-PGA intake increased GABA concentrations in the serum and brain. However, the effects were not shown in obese rats.
Poly-gamma-glutamic acid (γ-PGA); glutamate; γ-aminobutyric acid (GABA)
Rearrangements of the subtelomeric regions of chromosomes account for a significant proportion of the underlying genetic defects in both idiopathic mental retardation (MR) and multiple congenital anomalies. To detect the rearrangements, a set of subtelomeric fluorescence in situ hybridization (FISH) probes has been developed. The aim of this study was to reveal the frequency of subtelomeric rearrangements in Korean patients with MR or multiple anomalies. We performed a FISH study using a commercially available subtelomeric FISH probes on a series of unrelated Korean pediatric patients with MR or multiple anomalies without identifiable causes. We used a checklist to evaluate the developmental delay and/or MR. Patients who were shown to have chromosome abnormalities, metabolic disorders, or recognizable dysmorphic syndromes by clinical and laboratory findings were excluded. As a result, 100 patients were eligible for the Subtelomeric FISH study, and a total of 29 patients (29%) were suspected to have subtelomeric rearrangements on initial screening by the multiprobe FISH kit. Among theses, confirmatory FISH studies by using single locus-specific FISH probes were performed in 24 patients. One patient (a 10-yr-old girl) was confirmed to have rearrangement, deletion of the telomeric portion of the short arm of chromosome 4 (4p). Her clinical manifestation was compatible with Wolf-Hirschhorn syndrome, which is known to be caused by 4p deletion. The frequency of subtelomeric rearrangements in this study was 1.1% (1/95), lower than those previously reported (0.5-16.3%). We suggest that subtelomeric FISH test is a useful screening tool for patients with idiopathic MR and/or dysmorphism regardless of its false positive value.
Chromosomal Rearrangement; Idiopathic Mental Retardation; Subtelomeric FISH
Using the Korean public health insurance database, we analyzed patients diagnosed as benign prostatic hyperplasia (BPH) from 2004 to 2008. Age and year-specific amount and seasonal variation of hospital visits (HV), duration of treatment (DT), the total and per capita amount of insurance payment (TAIP, PCIP) were evaluated. A total of 12,088,995 HV were studied. Total HV increased 1.7 times and DT almost doubled in 2008 compared to those in 2004. HV, DT, and TAIP showed linearly increasing patterns year by year. In a time series analysis, HV increased in winter and demonstrated seasonality in a 12-month cycle. In a Poisson regression analysis, the annual variations of HV, DT, TAIP, and PCIP were different by age groups. In patients older than 40 yr, HV significantly increased 1.10-1.16 times compared to that of the previous year. DT markedly increased in their 60s and 80s patients. The rate of increase in PCIP was steeper in patients 50 yr and older than in the others.Health care utilization due to BPH was rapidly increasing in Korea and it was remarkable in the elderly population. Seasonal variation of HV demonstrated that health care utilization increased in winter.
Prostatic Hyperplasia; Epidemiology; Insurance Claim Review
The aims of this study were to estimate the incidences of BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions in childhood acute lymphoblastic leukemia (ALL), to identify new abnormalities, and to demonstrate the usefulness of interphase fluorescence in situ hybridization (FISH). We performed G-banding analysis and FISH using probes for BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions on 65 childhood ALL patients diagnosed and uniformly treated at a single hospital. Gene rearrangements were identified in 73.8% of the patients using the combination of G-banding and FISH, while the chromosomal abnormalities were identified in 49.2% using G-banding alone. Gene rearrangements were disclosed by FISH in 24 (72.7%) of 33 patients with normal karyotype or no mitotic cell in G-banding. Among the gene rearrangements detected by FISH, the most common gene rearrangement was p16 deletion (20.3%) and the incidences of others were 14.1% for TEL/AML1, 11.3% for MLL, and 1.8% for BCR/ABL translocations. Infrequent or new aberrations such as AML1 amplification, MLL deletion, ABL deletion, and TEL/AML1 fusion with AML1 deletion were also observed. We established the rough incidences of gene rearrangements in childhood ALL, found new abnormalities and demonstrated the diagnostic capability of interphase FISH to identify cryptic chromosome aberrations.
In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Acute; Childhood; Gene Rearrangements
In CD5 positive (CD5+) mature B-cell lymphomas, newly recognized CD5+ diffuse large B-cell lymphoma (DLBCL) has been characterized by aggressive features. We studied twenty-five cases with CD5+ lymphomas involving bone marrow. Eleven cases were diagnosed as chronic lymphocytic leukemia, six cases were diagnosed as mantle cell lymphoma (MCL), and three cases with morphologic characteristics of MCL and without both the cyclin D1 expression and IGH/CCND1 rearrangement were unclassifiable. The remaining five cases, showing large to medium-sized lym-phoid cells with prominent nucleoli and a moderate amount of cytoplasm, were diagnosed as DLBCL. Five DLBCL cases were positive for CD5, CD20, surface immuno-globulin, but negative for CD23. Patients with CD5+ DLBCL showed a high age of onset (median, 68 yr) and two patients expired one month after the diagnosis. Since CD5+ DLBCL forms a distinct subgroup of DLBCL, a study of CD5 expression in DLBCL would be helpful to predict prognosis and to determine future therapeutic strategy. To the best of our knowledge, this is the first report on de novo CD5+ DLBCL in Koreans.
Antigens, CD5; Leukemia, Lymphocytic, Chronic; Lymphoma, Mantle-Cell; Lymphoma, Large-Cell, Diffuse
HIG2 (hypoxia-inducible gene 2) is a biomarker of hypoxia and elevated in several cancers. Here, we show that HIG2 also upregulated HIF-1α expression under hypoxic conditions and enhanced AP-1 expression under normoxic conditions, which affects colorectal cancer cell survival. Importantly, over-expression of HIG2 promoted tumor growth by suppressing apoptosis in a mouse orthotopic model. These results are likely relevant to human disease since we found that the expression of HIG2 is gradually elevated as tumors progress. Collectively, these findings suggest that HIG2 plays an important role in promoting colorectal cancer growth in hypoxia-dependent and independent manners.
hypoxia; normoxia; HIG2; HIF-1α; colorectal cancer; survival
The introduction of new rotavirus vaccines into the public sphere makes it necessary to maintain constant surveillance and to heighten public awareness of the appearance of new rotavirus strains. We describe the molecular epidemiology of circulating rotavirus strains after vaccine introduction.
We collected a total of 1070 stool samples from children with gastroenteritis from January 2013 to June 2013. The antigenic prevalence of rotavirus group A was distinguished using enzyme immunoassay. The G and P genotypes of enzyme immunoassay-positive samples were determined with reverse transcription-polymerase chain reaction and nucleotide sequencing analysis.
Of the 1070 samples collected, 277 (25.9%) tested positive for rotaviruses by enzyme-linked immunoabsorbent assay. The most prevalent circulating genotype G was G1 (51.3%), followed by G2 (34.7%) and G9 (10.8%). The predominant type of genotype P was P (66.1%), followed by P (31.4%). In this study, nine genotypes were found. G1P was the most prevalent (51.8%), followed by G2P (30.5%), G9P (9.9%), and G2P (4.0%). Several unusual combinations (G1P, G3P, G3P, G4P, and G9P) were also identified.
Molecular epidemiological knowledge of rotaviruses is critical for the development of effective preventive measures, including vaccines. These data will help us monitor the effectiveness of current rotavirus vaccines.
genotype G; genotype P; rotavirus; rotavirus vaccine
The Survey of Autonomic Symptom (SAS) scale was reported as an easy instrument to assess the autonomic symptoms in patients with early diabetic neuropathy. In this study, we investigated the relationship between the SAS scale and the parameters of cardiac autonomic neuropathy (CAN) in Korean patients with diabetic peripheral neuropathy (DPN).
The SAS scale was tested in 30 healthy controls and 73 patients with DPN at Chonbuk National University Hospital, in Korea. The SAS score was compared to the parameters of the CAN test and the total symptom score (TSS) for DPN in patients with DPN.
The SAS symptom score and total impact score were increased in patients with DPN compared to the control group (P=0.01), particularly in sudomotor dysfunction (P=0.01), and vasomotor dysfunction (P=0.01). The SAS score was increased in patients with CAN compared to patients without CAN (P<0.05). Among the diverse CAN parameters, the valsalva ratio and postural hypotension were associated with the SAS score (P<0.05). However, there was no association between the SAS scale and TSS for DPN, and TSS for DPN did not differ between patients with and without CAN.
SAS is a simple instrument that can be used to assess autonomic symptoms in patients with diabetes and can be used as a screening tool for autonomic neuropathy, particularly for CAN.
Autonomic neuropathy; Diabetes; Survey of autonomic symptom scale
The overexpression of histone deacetylase (HDAC) and a subsequent decrease in the acetylation levels of nuclear histones are frequently observed in cancer cells. Generally it was accepted that the deacetylation of histones suppressed expression of the attached genes. Therefore, it has been suggested that HDAC might contribute to the survival of cancer cells by altering the NKG2D ligands transcripts. By the way, the translational regulation of NKG2D ligands remaines unclear in cancer cells. It appears the modulation of this unclear mechanism could enhance NKG2D ligand expressions and the susceptibility of cancer cells to NK cells. Previously, it was reported that irradiation can increase the surface expressions of NKG2D ligands on several cancer cell types without increasing the levels of NKG2D ligand transcripts via ataxia telangiectasia mutated and ataxia telangiectasia and Rad3 related (ATM-ATR) pathway, and suggested that radiation therapy might be used to increase the translation of NKG2D ligands.
Two NSCLC cell lines, that is, A549 and NCI-H23 cells, were used to investigate the combined effects of ionizing radiation and HDAC inhibitors on the expressions of five NKG2D ligands. The mRNA expressions of the NKG2D ligands were quantitated by multiplex reverse transcription-PCR. Surface protein expressions were measured by flow cytometry, and the susceptibilities of cancer cells to NK cells were assayed by time-resolved fluorometry using the DELFIA® EuTDA cytotoxicity kit and by flow cytometry.
The expressions of NKG2D ligands were found to be regulated at the transcription and translation levels. Ionizing radiation and HDAC inhibitors in combination synergistically increased the expressions of NKG2D ligands. Furthermore, treatment with ATM-ATR inhibitors efficiently blocked the increased translations of NKG2D ligands induced by ionizing radiation but did not block the increased ligand translations induced by HDAC inhibitors. The study confirms that increased NKG2D ligand levels by ionizing radiation and HDAC inhibitors could synergistically enhance the susceptibilities of cancer cells to NK-92 cells.
This study suggests that the expressions of NKG2D ligands are regulated in a complex manner at the multilevel of gene expression, and that their expressions can be induced by combinatorial treatments in lung cancer cells.
NKG2D ligands; HDAC inhibitors; Ionizing radiation; Radioresistance
Diabetes; Nerve block; Neuropathy
Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondary form (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disorder that occurs because of constitutional defects in cell-mediated cytotoxicity. Here, we report a fatal neonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation. Clinically, the newborn presented with severe sepsis-like features and required mechanical ventilation and continuous venovenous hemodiafiltration. Flow cytometry analysis showed marked HLH and complete absence of intracytoplasmic perforin expression in cytotoxic cells; therefore, we performed molecular genetic analyses for PRF1 mutations, which showed that the patient had a compound heterozygous mutation in PRF1, that is, c.65delC (p.Pro22Argfs*2) and c.1090_1091delCT (p.Leu364Glufs*93). Clinical and genetic assessments for FHL are required for neonates with refractory fever and progressive multiple organ failure, particularly when there is no evidence of microbiological or metabolic cause.
FHL2; PRF1; Mutation; Neonate
Background and Objective
Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder of the central nervous system with a relapsing and remitting course. We aimed to identify factors associated with the time to next attack, including the effect of the natural disease course and the diverse treatment regimens, by applying a longitudinal statistical analysis to the individual attacks of each patient.
In total, 184 acute attacks among 58 patients with either NMO or NMO spectrum disorder with anti-aquaporin-4 antibody were assessed retrospectively. Patient demographics, clinical characteristics at each attack, and type of treatment during inter-attack periods were assessed. The dependent variable was defined as the time from each attack to the next attack (inter-attack interval). An exponential accelerated failure time model with shared gamma frailty was adapted for statistical analysis.
A multivariable analysis revealed that the time from each attack to the next attack in NMO increased independently by 1.31 times (95% confidence interval (CI), 1.02–1.67; p = 0.035) with each additional cumulative attack experienced, by 5.34 times (95% CI, 1.57–18.13; p = 0.007) with combined azathioprine treatment and continued oral prednisolone, and by 4.26 times (95% CI, 1.09–16.61; p = 0.037) with rituximab treatment.
The time to next attack in NMO can increase naturally in the later stages of the disease as the number of cumulative attacks increases. Nevertheless, both combined azathioprine treatment with continued oral prednisolone and rituximab treatment were also associated with a longer time to next attack, independently of the natural disease course of NMO.
The F8 and F9 genes encode for coagulation factor VIII (FVIII) and FIX, respectively, and mutations in these genes are the genetic basis of hemophilia A/B. To determine whether a sequence variation in F8/F9 is a disease-causing mutation, frequency data from a control population is needed. This study aimed to obtain data on sequence variation in F8/F9 in a set of functionally validated control chromosomes of Korean descent.
We re-sequenced F8 and F9 from DNA samples of 100 Korean male control individuals with normal PT, aPTT, and FVIII activity. PCR and direct sequencing analyses were performed using primer pairs to cover all coding regions and the flanking intronic sequences.
Thirteen individuals (13%) were hemizygous for sequence variations in the coding region of F8. Six (6%) had c.3780C>G (p.Asp1260Glu), five (5%) had c.3864A>C (p.Ser1288=). One each individual (1%) had c.4794G>T (p.Glu1598Asp) and c.5069 A>G (p.Glu1690Gly). Asp1260Glu and Ser1288= were known SNPs (rs1800291 and rs1800292, respectively). Glu1598Asp was assigned as a missense mutation in public databases (HGMD and HAMSTeRS), and Glu1690Gly was a novel variation. Based on the normal FVIII activities in control individuals carrying these variations (109% and 148%, respectively), they were considered to be rare SNPs. No variation was observed in F9 of control individuals.
A significant proportion of control individuals carried sequence variations in F8, but not in F9. These results can be used as a reference dataset for molecular diagnosis of hemophilia A and B, particularly in Korea.
Hemophilia; F8; F9; Sequence variation; Control population; Korea