[Show abstract][Hide abstract] ABSTRACT: Epidemiological data of Bordetella pertussis infection among adolescents and adults are limited in Korea. Patients (≥ 11 yr of age) with a bothersome cough for less than 30 days were enrolled during a 1-yr period at 22 hospitals in Korea. Nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and for bacteriologic culture. In total, 490 patients were finally enrolled, and 34 (6.9%) patients tested positive for B. pertussis; cough duration (14.0 days [7.0-21.0 days]) and age distribution were diverse. The incidence was the highest in secondary referral hospitals, compared to primary care clinics or tertiary referral hospitals (24/226 [10.6%] vs. 3/88 [3.4%] vs. 7/176 [4.0%], P = 0.012), and the peak incidence was observed in February and August (15.8% and 15.9%), with no confirmed cases between March and June. In the multivariate analysis, post-tussive vomiting was significantly associated with pertussis (odds ratio, 2.508; 95% confidence interval, 1.146-5.486) and secondary referral hospital showed a borderline significance. In conclusion, using a PCR-based method, 6.9% of adolescent and adult patients with an acute cough illness had pertussis infection in an outpatient setting. However, hospital levels and seasonal trends must be taken into account to develop a better strategy for controlling pertussis.
Journal of Korean medical science. 09/2014; 29(9):1232-9.
[Show abstract][Hide abstract] ABSTRACT: The xynC gene, which encodes high molecular weight xylanase from Paenibacillus sp. DG-22, was cloned and expressed in Escherichia coli, and its nucleotide sequence was determined. The xynC gene was comprised of a 4,419-bp open reading frame (ORF) encoding 1,472 amino acid residues, including a 27 amino acid signal sequence. Sequence analysis indicated that XynC is a multidomain enzyme composed of two family 4_9 carbohydrate-binding modules (CBMs), a catalytic domain of family 10 glycosyl hydrolases, a family 9 CBM, and three S-layer homologous (SLH) domains. Recombinant XynC was purified to homogeneity by heat treatment, followed by Avicel affinity chromatography. SDS-PAGE and zymogram analysis of the purified enzyme identified three active truncated xylanase species. Protein sequencing of these truncated proteins showed that all had identical N-terminal sequences. In the protein characterization, recombinant XynC exhibited optimal activity at pH 6.5 and 65degrees C and remained stable at neutral to alkaline pH (pH 6.0-10.0). The xylanase activity of recombinant XynC was strongly inhibited by 1 mM Cu2+ and Hg2+, whereas it was noticeably enhanced by 10 mM dithiothreitol. The enzyme exhibited strong activity towards xylans, including beechwood xylan and arabinoxylan, while it showed no cellulase activity. The hydrolyzed product patterns of birchwood xylan and xylooligosaccharides by thin-layer chromatography confirmed XynC as an endoxylanase.
Journal of microbiology and biotechnology. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: N‐doped sites at carbon nanotubes and graphene trigger the spontaneous decoration of bimetal (Pt and Pd) particles by the facile electroless redox reaction. The created hybrid catalyst yields remarkable current density (≈2.44 mA cm−2), lower onset potential (≈0.13 V), higher electron transfer number ≈4), and long‐term stability for oxidation–reduction reactions.
Particle and Particle Systems Characterization 03/2014; · 0.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previously, we reported on the anticancer effect of the diastereoisomeric compound MHY-449, a novel dihydro-benzofuro[4,5-b][1,8] naphthyridin-6-one derivative, in HCT116 human colon cancer cells. In the current study, we investigated whether MHY-449 has anticancer effect in prostate cancer cells, and if so, what the molecular mechanisms are. We examined the growth inhibitory effect of MHY-449 on p53 wild‑type (p53-wt) LNCaP (androgen‑dependent) and p53-null PC3 (androgen-independent) prostate cancer cells. MHY-449 treatment in androgen-independent and p53-null PC3 cells resulted in inhibition of cell growth and induction of apoptosis in a concentration-dependent manner. However, MHY-449 did not show any significant effects on the growth inhibition and apoptotic cell death in androgen-dependent and p53-wt LNCaP cells. Therefore, we used PC3 cells for further studies. The induction of apoptosis in PC3 cells was observed by decreased viability, DNA fragmentation, cleavage of poly (ADP-ribose) polymerase, activations of caspase-3, -8 and -9, and alteration in the ratio of Bax/Bcl-2 protein expression. In addition, MHY-449 induced increase of late apoptosis and sub-G1 DNA which were observed by flow cytometry analysis. Furthermore, MHY-449 reduced the phosphorylation of Akt and FoxO1 and induced the translocation of FoxO1 from cytoplasm to nucleus as shown by western blot analysis. MHY-449 treatment activated extracellular signal-regulated kinase (ERK) signaling in a concentration-dependent manner. MHY-449-induced apoptosis was partially prevented by pretreatment with the ERK inhibitor PD98059 suggesting involvement of ERK in the MHY-449-induced apoptosis. Taken together, these findings suggest that MHY-449 induces apoptosis via downregulation of the Akt/FoxO1 and activation of ERK in androgen-independent, p53-null and PTEN-negative PC3 human prostate cancer cells.
International Journal of Oncology 01/2014; · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 58-year-old woman presenting with atypical chest pain showed a turbulent color Doppler signal at the interatrial septum on a transthoracic echocardiography was found to have a huge coronary arteriovenous fistula originating from the middle right coronary artery and draining into right atrium with a very tortuous course using cardiac multidetector computed tomography (MDCT). A trivial echocardiographic finding should not be overlooked and could be evaluated thoroughly and noninvasively by MDCT.
Journal of Cardiovascular Computed Tomography. 01/2014;
[Show abstract][Hide abstract] ABSTRACT: In this study, we compared cytotoxicity, cell cycle distribution, and apoptosis on MHY336 treatment in three human colorectal carcinoma HCT116 cells: p53+/+ (p53‑wt), p53-/- (p53-null), and p21-/- (p21-null), as well as investigated the roles of p53 and p21 in cell death. Using these three isogenic variants, the roles of p53 and p21 in the cellular response to treatment with MHY336, a novel topoisomerase IIα inhibitor, were investigated. Our results showed that MHY336 treatment increased the expression of p53 over time in cells with wild-type p53 status. This elevated levels of p53 is associated with increased DNA fragmentation, and cleavage of poly(ADP-ribose) polymerase, consistent with increased sensitivity of these cells to apoptotic stimuli. However, p53-null and p21-null cells were more resistant to the antiproliferative and apoptotic effects of MHY336 than p53-wt cells. The same result was achieved by knocking down p53 and p21 with siRNA in p53-wt cells, indicating that p53 and p21 play a crucial role in MHY336-induced cell cycle arrest and apoptosis. Taken together, these results suggest that MHY336 could be a potential candidate to be used in chemoprevention and/or treatment of colon cancer.
International Journal of Oncology 12/2013; · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first committed step in triacylglycerol (TAG) and phospholipid biosynthesis, and has been considered as one of the drug targets for treating hepatic steatosis, insulin resistance, and other metabolic disorders. The aim of this study was to investigate the GPAT inhibitors from natural products and to evaluate their effects. The methanol extract of Aralia cordata roots showed a strong inhibitory effect on the human GPAT1 activity. A further bioactivity-guided approach led to the isolation of ent-pimara-8(14),15-dien-19-oic acid, (PA), one of the major compounds of A. cordata, which suppressed the GPAT1 activity with IC50 value of 60.5 μM. PA markedly reduced de novo lysophosphatidic acid synthesis through inhibition of GPAT activity and therefore significantly decreased synthesis of TAG in the HepG2 cells. These results suggest that PA as well as A. cordata root extract could be beneficial in controlling lipid metabolism.
Journal of medicinal food 11/2013; · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The gene encoding α-L-arabinofuranosidase (AFase) from Paenibacillus sp. DG-22 was cloned, sequenced, and expressed in Escherichia coli. The AFase gene (abfA) comprises a 1,509 bp open reading frame (ORF) encoding 502 amino acids with a molecular weight of 56,520 daltons. The deduced amino acid sequence of the gene shows that AbfA is an enzyme consisting of only a catalytic domain, and that the enzyme has significant similarity to AFases classified into family 51 of the glycosyl hydrolases. abfA was subcloned into the pQE60 expression vector to fuse it with a six-histidine tag and the recombinant AFase (rAbfA) was purified to homogeneity. The specific activity of the recombinant enzyme is 96.7 U/mg protein. Determination of apparent molecular mass by gel-filtration chromatography indicated that AbfA has a tetrameric structure. The optimal pH and temperature of the enzyme are 6.0 and 60°C, respectively. The enzyme activity is completely inhibited by 1 mM HgCl2. rAbfA is active only towards p-nitrophephenyl α-L-arabinofuranoside (pNPA) and exhibits Km and Vmax values of 3.5 mM and 306.1 U/mg, respectively. rAbfA shows a synergistic effect in combination with endoxylanase on the degradation of oat spelt xylan and wheat arabinoxylan.
Journal of Microbiology and Biotechnology 11/2013; · 1.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) is one of the most common malignant diseases and frequent cause of cancer deaths in the world. In spite of the significant advances in conventional therapeutic approaches to CRC, most patients ultimately die of their disease. There is a need to develop novel preventive approaches for this malignancy. This study was carried out to investigate the anticancer effect of MHY218, a hydroxamic acid derivative, in HCT116 human colon cancer cells. Treatment of cells with MHY218 resulted in growth inhibition and induction of apoptosis in a concentration-dependent manner. MHY218 induced G2/M phase arrest in the cell cycle progression which was observed by flow cytometry analysis, and a decrease in the protein expression of cyclin B1 and its activating partners Cdc25C and Cdc2. MHY218 also caused an increase in the expression levels of p21WAF1/CIP1, a G2/M phase inhibitor, in a p53-independent pathway. The induction of apoptosis was observed by decreased viability, DNA fragmentation, cleavage of poly(ADP-ribose) polymerase, alteration in the ratio of Bax/Bcl-2 protein expression, and activation of caspase-3, -8 and -9. In addition, MHY218 treatment showed downregulation of the expression levels of the transcription factor nuclear factor-kappa B (NF-κB) in the nucleus, which has been reported to be implicated in the apoptotic cell death of several types of cancer cells, suppression of TNF-α-induced NF-κB activation, inhibition of cyclooxygenase-2 expression, repression of matrix metalloproteinase-9 activation and decrease of 5-lipoxygenase in a concentration-dependent manner. These results suggest that MHY218 may be a useful candidate to be used in the chemoprevention and/or treatment of colon cancer.
International Journal of Oncology 11/2013; · 2.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stress-induced cardiomyopathy (SCM) is characterized by apical ballooning on echocardiography, but some of SCM patients show non-apical involvement and their characteristics are not well defined.
We investigated 56 patients that were diagnosed as SCM and divided them into 2 groups: apical ballooning syndrome (ABS, n = 49, 87.5%) and non-apical ballooning syndrome (N-ABS, n = 7, 12.5%) groups. Patients with N-ABS were significantly younger than those of the ABS group (52 ± 11 vs. 73 ± 10 years, p < 0.001).
Types of preceding stressors and clinical presentation including chest pain, pulmonary edema, cardiogenic shock and in-hospital mortality were comparable between the two groups. In the N-ABS group, wall motion score index was significantly lower than in the ABS group (1.61 ± 0.35 vs. 1.93 ± 0.31, p = 0.016). On electrocardiogram (ECG), T-wave inversion (57.1% vs. 95.8%, p < 0.001) were less frequent in the N-ABS than in the ABS group. Furthermore, maximum QT and corrected QT (QTc) intervals in the N-ABS patients were significantly shorter than the ABS patients (QT, 419.9 ± 66.1 vs. 487.3 ± 79.6 ms, p = 0.038; QTc, 479.0 ± 61.9 vs. 568.0 ± 50.5 ms, p < 0.001).
Patients with the N-ABS showed not only atypical echocardiographic findings, but also atypical clinical and ECG manifestations. Integrated consideration is needed to reach a diagnosis of the non-apical subtype of SCM.
Journal of cardiovascular ultrasound 09/2013; 21(3):116-22.
[Show abstract][Hide abstract] ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from a progressive loss of motor neurons. Familial ALS (fALS) is caused by missense mutations in Cu, Zn-superoxide dismutase 1 (SOD1) that frequently result in the accumulation of mutant-protein aggregates that are associated with impairments in the ubiquitin-proteasome system (UPS). UPS impairment has been implicated in many neurological disorders. Bee venom (BV) extracted from honey bees has been used as a traditional medicine for treating inflammatory diseases and has been shown to attenuate the neuroinflammatory events that occur in a symptomatic ALS animal model.
NSC34 cells were transiently transfected with a WT or G85R hSOD1-GFP construct for 24 hrs and then stimulated with 2.5 mug/ml BV for 24 hrs. To determine whether a SOD1 mutation affects UPS function in NSC34 cells, we examined proteasome activity and performed western blotting and immunofluorescence using specific antibodies, such as anti-misfolded SOD1, anti-ubiquitin, anti-GRP78, anti-LC3, and anti-ISG15 antibodies.
We found that GFP-hSOD1G85R overexpression induced SOD1 inclusions and reduced proteasome activity compared with the overexpression of GFP alone in NSC34 motor neuronal cells. In addition, we also observed that BV treatment restored proteasome activity and reduced the accumulation of ubiquitinated and misfolded SOD1 in GFP-hSOD1G85R-overexpressing NSC34 motor neuronal cells. However, BV treatment did not activate the autophagic pathway in these cells.
Our findings suggest that BV may rescue the impairment of the UPS in ALS models.
BMC Complementary and Alternative Medicine 07/2013; 13(1):179. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antithrombotic activity and bleeding complication of a new potent, selective, and direct thrombin inhibitor, LB30870, were evaluated in comparison with other anticoagulants. In order to improve oral absorption of LB30870, pharmacokinetics of LB30889, which is a double prodrug with blocking groups in both amidine and carboxyl groups, was studied in rats and dogs. LB30870 was more potent than melagatran or argatroban with thrombin inhibition constants of 0.02, 1.3 and 4.5nM, respectively. All three direct thrombin inhibitors were selective towards other serine proteases with selectivity ratio greater than 1000, except for trypsin. Thrombin binding kinetics of LB30870 showed rapid association and slow dissociation rate constants, demonstrating its potential as anticoagulant. LB30870 was more effective than melagatran or argatroban in plasma clot-bound thrombin inhibition. In the rat venous stasis model of the caval vein, LB30870 reduced wet clot weights in a dose dependent manner after the intravenous bolus with infusion administration. The ED50 of LB30870, melagatran and enoxaparin were 50μg/kg+2μg/kg/min, 35μg/kg+1.4μg/kg/min and 200μg/kg+8.3μg/kg/min, respectively. No significant bleeding problem was observed with LB30870 at the dose up to two times ED80 in rats. LB30889, a double prodrug of LB30870, showed species difference in pharmacokinetics. Its oral bioavailability in rats or dogs was not better than that of LB30870. In conclusion, LB30870 has the potential to be useful as an effective oral anticoagulant for the prevention and treatment of thromboembolic diseases.
[Show abstract][Hide abstract] ABSTRACT: We evaluated the performance of the VITEK MS for identification of Gram-positive cocci routinely isolated in clinical microbiology laboratories. With a total of 424 well-characterized isolates, the results of the VITEK MS were compared to those of conventional methods and 16S rRNA gene sequencing. The VITEK MS correctly identified 97.9% of the isolates tested to species level. The VITEK MS correctly identified the species of 97.2% of the staphylococci (95.9% of coagulase-negative staphylococci), 97.8% of the streptococci, and 100% of the enterococci. For the identification of Gram-positive cocci isolates, the overall concordance rate between conventional identification and the VITEK MS was 94.5%. The VITEK MS MALDI-TOF system can be a reliable and rapid method for the identification of most relevant Gram-positive cocci. In addition, expanding the database of the VITEK MS, especially for coagulase-negative staphylococci, is needed to enhance the performance of the VITEK MS.
Journal of Medical Microbiology 06/2013; · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective: We investigated the effects of fetal undernutrition during pregnancy/lactation on visceral fat, lipid profiles, leptin, and adiponectin and examined the gender differences between males and females. Study Design: From 10 days to term gestation and through lactation, control pregnant rats were fed ad libitum (AdLib) food, whereas study rats were 50% food restricted (FR). Cross-fostering techniques were used to examine the effects of food restriction during pregnancy and lactation periods. Lipid profiles, leptin, and adiponectin were determined in offspring at ages 3 weeks and 6 months. We also measured the amount of visceral fat in the offspring. Results: The amount of visceral fat in the 6 month old FR/AdLib offspring was higher than that in control (p<0.05). Among the 6 month old offspring, triglyceride and leptin levels were higher in FR/AdLib offspring than those in controls (p<0.05). The female offspring had higher levels of triglyceride, HDL-cholesterol, and adiponectin and the male offspring had higher levels of LDL cholesterol and leptin. Conclusion: Fetal undernutrition only during pregnancy resulted in obese offspring, higher levels of plasma triglyceride and leptin with gender differences.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 01/2013; · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was to examine the pharmacokinetics of LB30870, a thrombin inhibitor, after IV and oral administration to rats, dogs, and monkeys. In rats and dogs, LB30870 showed linear pharmacokinetics after IV and oral administration. The oral bioavailability (BA) in rats was about 30 % with high inter-subject variability in the time to reach peak plasma concentration (Tmax). Oral absorption of a solution and prototype tablet formulations of LB30870 were tested in dogs. Tmax was 30 min and the BA values were 40.8–43.1 % with solution formulation. BA values after oral administration of the two tablet formulations at the dose of 100 mg/dog were 27.0 and 30.8 %. Tmax were 60 min in the tablet formulation, indicating that the disintegration and dissolution of tablets caused delay in Tmax compared to solution formulation. After IV administration of LB30870 to monkeys, the plasma concentrations decreased bi-exponentially and BA was 15.0 % after oral (20 mg/kg) dosing. In summary, linear pharmacokinetics of LB30870 were observed in both rats and dogs. The differences in BA among species could be due to difference in absorbed fraction and/or the first pass extraction (pre-systemic elimination) of LB30870.
Journal of Pharmaceutical Investigation. 01/2013; 43(3).
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) is the second most frequent cancer in men and the third most common cancer in women in Korea. In spite of the significant advances in conventional therapeutic approaches to CRC, most patients ultimately die of their disease. There is a need to develop novel preventive approaches for this malignancy. This study was carried out to investigate the anticancer effect of the diastereoisomeric compounds, MHY-449 and MHY-450, novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivatives, on HCT116 human colon cancer cells. MHY-449 exhibited more potent cytotoxicity than MHY-450, against HCT116 cells. Treatment of cells with MHY-449 resulted in growth inhibition and induction of apoptosis in a concentration-dependent manner, and inhibition of proliferation in a time-dependent manner. The induction of apoptosis was observed by decreased cell viability, DNA fragmentation, activation of protein levels involved in death receptors. Moreover, activation of caspase-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase and alteration in the ratio of Bax/Bcl-2 protein expression was observed. MHY-449 induced G2/M phase arrest in the cell cycle progression which was observed by flow cytometry analysis, and a decrease in the protein expression of cyclin B1 and its activating partners Cdc25c and Cdc2. MHY-449 also caused increase in the expression levels of p53, a tumor suppressor gene, and p21WAF1/CIP and p27KIP, G2/M phase inhibitors. These results suggest that MHY-449 may be a useful candidate for chemo-prevention and/or treatment of colon cancer.
International Journal of Oncology 10/2012; · 2.66 Impact Factor