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1.  Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models 
Background
Alzheimer’s disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and behavioral activities of curcuminoids from rhizomes of Curcuma longa (Zingiberaceae), diarylalkyls curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD Drosophila melanogaster models.
Methods
Neuro-protective ability of the curcuminoids was assessed using Drosophila melanogaster model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. Feeding and climbing activity, lifespan, and morphostructural changes in fly eyes also were evaluated.
Results
BDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC50, which was 20 and 13 times lower than those of CCN and DMCCN respectively. Overexpression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Remarkably, supplementing diet with either 1 mM BDMCCN or 1 mM CCN rescued APP/BACE1-expressing flies and kept them from developing both morphological and behavioral defects. Our results suggest that structural characteristics, such as degrees of saturation, types of carbon skeleton and functional group, and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1.
Conclusion
Further studies will warrant possible applications of curcuminoids as therapeutic BACE-1 blockers.
doi:10.1186/1472-6882-14-88
PMCID: PMC3946151  PMID: 24597901
Alzheimer’s disease; Drosophila melanogaster; Curcuma longa; Curcuminoids; BACE-1; Structure–activity relationship
2.  Breast Sparganosis Incidentally Detected by FDG PET/CT 
Sparganosis is a rare, parasitic infection that is caused by the plercercoid tapeworm larvae of the genus Spirometra. Sparganosis is transmitted by ingestion of larvae-containing water or intermediate hosts, such as raw amphibians, and usually presented with a subcutaneous nodule in the abdominal wall, extremities, and genital organs. Among the various involved organs, the breast is a seldom encountered site for sparganosis. However, breast sparganosis has clinical importance, since it is generally presented with an indolent palpable mass that mimics malignancy, even without evidence of inflammation. Herein, we report a case of breast sparganosis that was detected incidentally by FDG PET/CT during staging work ups in a patient with gall bladder cancer.
doi:10.1007/s13139-012-0187-z
PMCID: PMC4041977  PMID: 24900094
Human sparganosis; 18F-FDG; PET/CT; Breast
3.  Antiviral activity and possible mode of action of ellagic acid identified in Lagerstroemia speciosa leaves toward human rhinoviruses 
Background
Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cause billions of USD annually in medical visits and school and work absenteeism. An assessment was made of the cytotoxic and antiviral activities and possible mode of action of the tannin ellagic acid from the leaves of Lagerstroemia speciosa toward HeLa cells and three rhinoviruses, HRV-2, -3, and -4.
Methods
The antiviral property and mechanism of action of ellagic acid were evaluated using a sulforhodamine B assay and real-time reverse transcription-PCR (RT-PCR) with SYBR Green dye. Results were compared with those of the currently used broad-spectrum antiviral agent, ribavirin.
Results
As judged by 50% inhibitory concentration values, natural ellagic acid was 1.8, 2.3, and 2.2 times more toxic toward HRV-2 (38 μg/mL), HRV-3 (31 μg/mL), and HRV-4 (29 μg/mL) than ribavirin, respectively. The inhibition rate of preincubation with 50 μg/mL ellagic acid was 17%, whereas continuous presence of ellagic acid during infection led to a significant increase in the inhibition (70%). Treatment with 50 μg/mL ellagic acid considerably suppressed HRV-4 infection only when added just after the virus inoculation (0 h) (87% inhibition), but not before -1 h or after 1 h or later (<20% inhibition). These findings suggest that ellagic acid does not interact with the HRV-4 particles and may directly interact with the human cells in the early stage of HRV infections to protect the cells from the virus destruction. Furthermore, RT-PCR analysis revealed that 50 μg/mL ellagic acid strongly inhibited the RNA replication of HRV-4 in HeLa cells, suggesting that ellagic acid inhibits virus replication by targeting on cellular molecules, rather than virus molecules.
Conclusions
Global efforts to reduce the level of antibiotics justify further studies on L. speciosa leaf-derived materials containing ellagic acid as potential anti-HRV products or a lead molecule for the prevention or treatment of HRV infection.
doi:10.1186/1472-6882-14-171
PMCID: PMC4052798  PMID: 24885569
Human rhinovirus; Natural antiviral agent; Lagerstroemia speciosa; Ellagic acid; Tannin; Cytotoxicity; Selectivity; RNA replication
4.  Growth Inhibitory, Bactericidal, and Morphostructural Effects of Dehydrocostus Lactone from Magnolia sieboldii Leaves on Antibiotic-Susceptible and -Resistant Strains of Helicobacter pylori 
PLoS ONE  2014;9(4):e95530.
Helicobacter pylori is associated with various diseases of the upper gastrointestinal tract, such as gastric inflammation and duodenal and gastric ulcers. The aim of the study was to assess anti-H. pylori effects of the sesquiterpene lactone dehydrocostus lactone (DCL) from Magnolia sieboldii leaves, compared to commercial pure DCL, two previously known sesquiterpene lactones (costunolide and parthenolide), (–)-epigallocatechin gallate, and four antibiotics. The antibacterial activity of natural DCL toward antibiotic-susceptible H. pylori ATCC 700392 and H. pylori ATCC 700824 strains (MIC, 4.9 and 4.4 mg/L) was similar to that of commercial DCL and was more effective than costunolide, parthenolide, and EGCG. The activity of DCL was slightly lower than that of metronidazole (MIC, 1.10 and 1.07 mg/L). The antibacterial activity of DCL was virtually identical toward susceptible and resistant strains, even though resistance to amoxicillin (MIC, 11.1 mg/L for PED 503G strain), clarithromycin (49.8 mg/L for PED 3582GA strain), metronidazole (21.6 mg/L for H. pylori ATCC 43504 strain; 71.1 mg/L for 221 strain), or tetracycline (14.2 mg/L for B strain) was observed. This finding indicates that DCL and the antibiotics do not share a common mode of action. The bactericidal activity of DCL toward H. pylori ATCC 43504 was not affected by pH values examined (4.0–7.0). DCL caused considerable conversion to coccoid form (94 versus 49% at 8 and 4 mg/L of DCL for 48 h). The Western blot analysis revealed that urease subunits (UreA and UreB) of H. pylori ATCC 43504 were not affected by 10 mM of DCL, whereas UreA monomer band completely disappeared at 0.1 mM of (–)-epigallocatechin gallate. Global efforts to reduce the level of antibiotics justify further studies on M. sieboldii leaf-derived materials containing DCL as potential antibacterial products or a lead molecule for the prevention or eradication of drug-resistant H. pylori.
doi:10.1371/journal.pone.0095530
PMCID: PMC3991664  PMID: 24747984
5.  Novel Histopathological and Molecular Effects of Natural Compound Pellitorine on Larval Midgut Epithelium and Anal Gills of Aedes aegypti 
PLoS ONE  2013;8(11):e80226.
The yellow fever mosquito, Aedes aegypti, is a vector for transmitting dengue fever and yellow fever. In this study, we assessed the histopathological and molecular effects of pellitorine, an isobutylamide alkaloid, on the third instar of Ae. aegypti larvae. At 5 mg/l concentration of pellitorine, the whole body of the treated larvae became dark in color, particularly damaged thorax and abdominal regions. Pellitorine was targeted mainly on midgut epithelium and anal gills, indicating variably dramatic degenerative responses of the midgut through a sequential epithelial disorganization. The anterior and posterior midgut was entirely necrosed, bearing only gut lumen residues inside the peritrophic membranes. Pellitorine caused comprehensive damage of anal gill cells and branches of tracheole and debris was found in hemolymph of the anal gills. RT-PCR analysis indicates that the compound inhibited gene expression encoding V-type H+-ATPase and aquaporine 4 after treatment with 2.21 mg/l pellitorine. These results verify that pellitorine merits further study as a potential larvicide with a specific target site and a lead molecule for the control of mosquito populations.
doi:10.1371/journal.pone.0080226
PMCID: PMC3832413  PMID: 24260359
6.  Neuromodulation of Olfactory Sensitivity in the Peripheral Olfactory Organs of the American Cockroach, Periplaneta americana 
PLoS ONE  2013;8(11):e81361.
Olfactory sensitivity exhibits daily fluctuations. Several studies have suggested that the olfactory system in insects is modulated by both biogenic amines and neuropeptides. However, molecular and neural mechanisms underlying olfactory modulation in the periphery remain unclear since neuronal circuits regulating olfactory sensitivity have not been identified. Here, we investigated the structure and function of these signaling pathways in the peripheral olfactory system of the American cockroach, Periplaneta americana, utilizing in situ hybridization, qRT-PCR, and electrophysiological approaches. We showed that tachykinin was co-localized with the octopamine receptor in antennal neurons located near the antennal nerves. In addition, the tachykinin receptor was found to be expressed in most of the olfactory receptor neurons in antennae. Functionally, the effects of direct injection of tachykinin peptides, dsRNAs of tachykinin, tachykinin receptors, and octopamine receptors provided further support for the view that both octopamine and tachykinin modulate olfactory sensitivity. Taken together, these findings demonstrated that octopamine and tachykinin in antennal neurons are olfactory regulators in the periphery. We propose here the hypothesis that octopamine released from neurons in the brain regulates the release of tachykinin from the octopamine receptor neurons in antennae, which in turn modulates the olfactory sensitivity of olfactory receptor neurons, which house tachykinin receptors.
doi:10.1371/journal.pone.0081361
PMCID: PMC3828268  PMID: 24244739
7.  Growth-Inhibiting and morphostructural effects of constituents identified in Asarum heterotropoides root on human intestinal bacteria 
Background
The growth-inhibiting and morphostructural effects of seven constituents identified in Asarum heterotropoides root on 14 intestinal bacteria were compared with those of the fluoroquinolone antibiotic ciprofloxacin.
Method
A microtiter plate-based bioassay in sterile 96-well plates was used to evaluate the minimal inhibitory concentrations (MICs) of the test materials against the organisms.
Results
δ-3-Carene (5) exhibited the most potent growth inhibition of Gram-positive bacteria (Clostridium difficile ATCC 9689, Clostridium paraputrificum ATCC 25780, Clostridium perfringens ATCC 13124, and Staphylococcus aureus ATCC 12600) and Gram-negative bacteria (Escherichia coli ATCC 11775 and Bacteroides fragilis ATCC 25285) (minimal inhibitory concentrations (MIC), 0.18–0.70 mg/mL) except for Salmonella enterica serovar Typhimurium ATCC 13311 (MIC, 2.94 mg/mL). The MIC of methyleugenol (2), 1,8-cineole (3), α-asarone (4), (−)-asarinin (6), and pellitorine (7) was between 1.47 and 2.94 mg/mL against all test bacteria (except for compound 2 against C. difficile (0.70 mg/mL); compounds 1 (23.50 mg/mL) and 4 (5.80 mg/mL) against C. paraputricum; compounds 2 (5.80 mg/mL), 4 (12.0 mg/mL), and 7 (0.70 mg/mL) against C. perfringens); compound 1 against E. coli (7.20 mg/mL) and S. enterica serovar Typhimurium (12.0 mg/mL). Overall, all of the constituents were less potent at inhibiting microbial growth than ciprofloxacin (MIC, 0.063–0.25 mg/ mL). The lactic acid-producing bacteria (four bifidobacteria and two lactobacilli) and one acidulating bacterium Clostridium butyricum ATCC 25779 were less sensitive and more susceptible than the five harmful bacteria and two nonpathogenic bacteria (B. fragilis and E. coli) to the constituents and to ciprofloxacin, respectively. Beneficial Gram-positive bacteria and harmful and nonpathogenic Gram-negative bacteria were observed to have different degrees of antimicrobial susceptibility to the constituents, although the antimicrobial susceptibility of the harmful Gram-positive bacteria and the harmful and nonpathogenic Gram-negative bacteria was not observed. Scanning electron microscopy observations showed different degrees of physical damage and morphological alteration to both Gram-positive and Gram-negative bacteria treated with α-asarone, δ-3-carene, pellitorine, or ciprofloxacin, indicating that they do not share a common mode of action.
Conclusion
A. heterotropoides root-derived materials described merit further study as potential antibacterial products or lead molecules for the prevention or eradication from humans from diseases caused by harmful intestinal bacteria.
doi:10.1186/1472-6882-13-245
PMCID: PMC3850407  PMID: 24083511
Asarum heterotropoides; Natural growth inhibitor; Gram-positive bacteria; Gram-negative bacteria; Morphological alteration; Minimal inhibitory concentrations
8.  Ethanol and Methanol Can Improve Huperzine A Production from Endophytic Colletotrichum gloeosporioides ES026 
PLoS ONE  2013;8(4):e61777.
Huperzine A (HupA) is a plant alkaloid that is of great interest as a therapeutic candidate for the treatment of Alzheimer's disease. However, the current production of HupA from plants in large quantity is unsustainable because the plant resource is scarce and the content of HupA in plants is extremely low. Surprisingly, this compound was recently found to be produced by various endophytic fungi, which are much more controllable than the plants due to simpler genetics and ease of manipulation. However, it might be due to the innate properties of endophytic symbiosis, that production of this chemical in large quantity from endophytes has not yet been put into practice. Endophytic Colletotrichum gloeosporioides ES026 was previously isolated from a HupA producing plant and the fungi also proved to produce HupA. In this study, various fermentation conditions were tried to optimize the production of HupA from C. gloeosporioides ES026. Optimization of these parameters resulted in a 25.58% increase in HupA yield. Potato extracts supplemented with glucose or sucrose but not maltose facilitated HupA producing from the fungi. A final concentration of 0.5–2% ethanol stimulated the growth of fungi while methanol with the same treatment slightly inhibited the growth. However, both methanol and ethanol greatly increased the HupA production with the highest yield of HupA (51.89% increment) coming from ethanol treatment. Further analysis showed that both ethanol and methanol were strong inducers of HupA production, while ethanol was partially used as a carbon source during fermentation. It was noticed that the color of that ethanol treated mycelia gradually became dark while methanol treated ones stayed grey during fermentation. The present study sheds light on the importance of optimizing the fermentation process, which, combined with effective inducers, maximizes production of chemicals of important economic interest from endophytic fungi.
doi:10.1371/journal.pone.0061777
PMCID: PMC3629160  PMID: 23613930
9.  Insecticide Susceptibility of Field-Collected Populations of Culex tritaeniorhynchus in the Republic of Korea 
The toxicities of 10 insecticides were examined against late third instar Culex tritaeniorhynchus Giles (Diptera: Culicidae) using the direct-contact mortality bioassay. Six geospatially-distant field mosquitoes were collected from Chuncheon-si, Hwaseong, Seosan. Jeonju, Daegu, and Busan in the Republic of Korea. Marked regional variations of insecticide susceptibility were observed. Field populations of Seosan, Jeonju, and Daegu from agricultural areas showed higher to extremely higher insecticide susceptibility to pyrethroids than those of Chuncheon-si, Hwaseong, and Busan strains from non-agricultural areas. Extremely high to low levels of susceptibility were measured: bifenthrin, susceptible ratio (SR) = 2.7–896.3; β-cyfluthrin, SR = 1.8–633.3; α-cypermethrin, SR = 1.2–1,051.9; deltamethrin, SR = 1.3–711.1; permethrin, SR = 1.5–1,053.4; etofenprox, SR = 2.2–29.3; chlorfenapyr, SR = 5.1–103.6; chlorpyrifos, SR = 2.3– 337.0; fenitrothion, SR = 2.0–142.3; and fenthion, SR = 1.4–186.2. Cx. tritaeniorhynchus populations from rice paddies had been under heavy selection pressure due to the agricultural insecticides, and that's why the mosquito species demonstrated high resistance to pyrethroids, which were used for a long time to control agricultural pests in the localities. These results indicate that careful selection and rotational use of these insecticides may result in continued satisfactory control against field populations of Japanese encephalitis vector mosquitoes.
doi:10.1673/031.013.0201
PMCID: PMC3735112  PMID: 23879898
Japanese encephalitis vector; regional variation
10.  Current Status of Laparoscopic Liver Resection in Korea 
Journal of Korean Medical Science  2012;27(7):767-771.
Since laparoscopic liver resection was first introduced in 2001, Korean surgeons have chosen a laparoscopic procedure as one of the treatment options for benign or malignant liver disease. We distributed and analyzed a nationwide questionnaire to members of the Korean Laparoscopic Liver Surgery Study Group (KLLSG) in order to evaluate the current status of laparoscopic liver resection in Korea. Questionnaires were sent to 24 centers of KLLSG. The questionnaire consisted of operative procedure, histological diagnosis of liver lesions, indications for resection, causes of conversion to open surgery, and postoperative outcomes. A laparoscopic liver resection was performed in 416 patients from 2001 to 2008. Of 416 patients, 59.6% had malignant tumors, and 40.4% had benign diseases. A total laparoscopic approach was performed in 88.7%. Anatomical laparoscopic liver resection was more commonly performed than non-anatomical resection (59.9% vs 40.1%). The anatomical laparoscopic liver resection procedures consisted of a left lateral sectionectomy (29.3%), left hemihepatectomy (19.2%), right hemihepatectomy (6%), right posterior sectionectomy (4.3%), central bisectionectomy (0.5%), and caudate lobectomy (0.5%). Laparoscopy-related serious complications occurred in 12 (2.8%) patients. The present study findings provide data in terms of indication, type and method of liver resection, and current status of laparoscopic liver resection in Korea.
doi:10.3346/jkms.2012.27.7.767
PMCID: PMC3390725  PMID: 22787372
Laparoscopic Liver Resection; Laparoscopy; Anatomical Liver Resection; Liver Diseases; HCC
11.  Carcinoembryonic antigen level of draining venous blood as a predictor of recurrence in colorectal cancer patient 
Purpose
We designed this study to evaluate the efficacy of carcinoembryonic antigen in draining venous blood (vCEA) as a predictor of recurrence.
Methods
Draining venous and supplying arterial bloods were collected separately during the operation of 82 colorectal cancer patients without distant metastasis from September 2004 to December 2006. Carcinoembryonic antigen was measured and assessed for the efficacy as a prognostic factor of recurrence using receiver operating characteristic (ROC) and Kaplan-Meier curves.
Results
vCEA is a statistically significant factor that predicts recurrence (P = 0.032) and the optimal cut-off value for vCEA from ROC curve is 8.0 ng/mL. The recurrence-free survival between patients with vCEA levels >8 ng/mL and ≤8 ng/mL significantly differed (P < 0.001). The significance of vCEA as a predictor of recurrence gets higher when limited to patients without lymph node metastasis. The proper cut-off value for vCEA is 4.0 ng/mL if confined to patients without lymph node metastasis. The recurrence-free survival between the patients of vCEA levels >4 ng/mL and ≤4 ng/mL significantly differed (P < 0.001). Multivariate analysis revealed vCEA is an independent prognostic factor in patients without lymph node metastasis.
Conclusion
vCEA is an independent prognostic factor of recurrence in colorectal cancer patients especially in patients without lymph node metastases.
doi:10.4174/jkss.2011.81.6.387
PMCID: PMC3243855  PMID: 22200039
Colorectal neoplasms; Carcinoembryonic antigen; Prognosis; Recurrence
12.  Determination of Malignant and Invasive Predictors in Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Suggested Scoring Formula 
Journal of Korean Medical Science  2011;26(6):740-746.
Prediction of malignancy or invasiveness of branch duct type intraductal papillary mucinous neoplasm (Br-IPMN) is difficult, and proper treatment strategy has not been well established. The authors investigated the characteristics of Br-IPMN and explored its malignancy or invasiveness predicting factors to suggest a scoring formula for predicting pathologic results. From 1994 to 2008, 237 patients who were diagnosed as Br-IPMN at 11 tertiary referral centers in Korea were retrospectively reviewed. The patients' mean age was 63.1 ± 9.2 yr. One hundred ninty-eight (83.5%) patients had nonmalignant IPMN (81 adenoma, 117 borderline atypia), and 39 (16.5%) had malignant IPMN (13 carcinoma in situ, 26 invasive carcinoma). Cyst size and mural nodule were malignancy determining factors by multivariate analysis. Elevated CEA, cyst size and mural nodule were factors determining invasiveness by multivariate analysis. Using the regression coefficient for significant predictors on multivariate analysis, we constructed a malignancy-predicting scoring formula: 22.4 (mural nodule [0 or 1]) + 0.5 (cyst size [mm]). In invasive IPMN, the formula was expressed as invasiveness-predicting score = 36.6 (mural nodule [0 or 1]) + 32.2 (elevated serum CEA [0 or 1]) + 0.6 (cyst size [mm]). Here we present a scoring formula for prediction of malignancy or invasiveness of Br-IPMN which can be used to determine a proper treatment strategy.
doi:10.3346/jkms.2011.26.6.740
PMCID: PMC3102866  PMID: 21655058
Branch Duct Type Intraductal Papillary Mucinous Neoplasm (IPMN); Cyst Size; Mural Nodule; CEA; Malignancy; Invasive Carcinoma
13.  Experience of non-vascular complications following endovascular aneurysm repair for abdominal aortic aneurysm 
Journal of the Korean Surgical Society  2011;80(Suppl 1):S67-S70.
Endovascular aneurysm repair (EVAR) for the treatment of abdominal aortic aneurysm (AAA) is a widely used method, and its decreased invasiveness compared to traditional surgical repair has brought about reduced rates of morbidity and mortality. Several vascular complications related to the procedure have been reported, but non-vascular complications have rarely occurred. We report herein the case of a 78-year-old man who underwent EVAR for AAA and presented with active duodenal ulcer bleeding and acute acalculous cholecystitis as complications after the procedure. We must consider that a wide spectrum of complications may occur following EVAR, and therefore it is important to evaluate the risks of complication and to take the necessary measures to minimize them.
doi:10.4174/jkss.2011.80.Suppl1.S67
PMCID: PMC3205366  PMID: 22066089
Complication; Endovascular aneurysm repair; Abdominal aortic aneurysm
14.  Risk factors for adjacent segment disease after lumbar fusion 
European Spine Journal  2009;18(11):1637-1643.
The incidence of adjacent segment problems after lumbar fusion has been found to vary, and risk factors for these problems have not been precisely verified, especially based on structural changes determined by magnetic resonance imaging. The purpose of this retrospective clinical study was to describe the incidence and clinical features of adjacent segment disease (ASD) after lumbar fusion and to determine its risk factors. We assessed the incidence of ASD in patients who underwent lumbar or lumbosacral fusions for degenerative conditions between August 1995 and March 2006 with at least a 1-year follow-up. Patients less than 35 years of age at the index spinal fusion, patients with uninstrumented fusion, and patients who had not achieved successful union were excluded. Of the 1069 patients who underwent fusions, 28 (2.62%) needed secondary operations because of ASD and were included in this study. In order to identify the risk factors, we matched a disease group and a control group. The disease group consisted of 26 of the 28 patients with ASD, excluding the 2 patients for whom we did not have initial MRI data. Each patient in the disease group was matched by age, sex, fusion level and follow-up period with a control patient. The assumed risk factors included disc and facet degeneration, instability, listhesis, rotational deformity, and disc wedging. The mean age of the 28 patients with ASD requiring surgical treatment was 58.4 years, which did not differ significantly from that of the population in which ASD did not develop (58.2 years, p = 0.894). Of the 21 patients who underwent floating fusion, only 1 developed distal ASD. Facet degeneration was a significant risk factor (p < 0.01) on logistic regression analysis. The incidence of distal ASD was much lower than that of proximal ASD. Pre-existing facet degeneration may be associated with a high risk of adjacent segment problems following lumbar fusion procedures.
doi:10.1007/s00586-009-1060-3
PMCID: PMC2899393  PMID: 19533182
Adjacent segment; Degeneration; Lumbar fusion; Risk factor
15.  Epstein-Barr Virus, Beta-Catenin, and E-cadherin in Gastric Carcinomas 
Journal of Korean Medical Science  2007;22(5):855-861.
Activated beta-catenin is suggested to inhibit NF-kappaB activation, and we previously demonstrated that NF-kappaB nuclear positivity was more frequent in Epstein-Barr virus (EBV)-infected gastric carcinomas. It is controversial that beta-catenin and E-cadherin are prognostic markers in gastric carcinomas. To define a relationship between beta-catenin and EBV, and the prognostic value of beta-catenin and E-cadherin, we analyzed in situ hybridization for EBV-encoded small RNAs, beta-catenin, and E-cadherin immunohistochemistry, and clinicophatological features in 111 gastric carcinomas. EBV infection was detected in seven carcinomas (6.3%); none of seven showed beta-catenin nuclear accumulation, and five out of seven revealed beta-catenin membranous loss or cytoplamic expression. Eighty cases (72.1%) showed beta-catenin alteration; i.e., loss of membrane staining in 65 (58.6%), cytoplasmic expression in 35 (31.5%), and nuclear accumulation in 15 (13.5%). E-cadherin alteration was observed in 34 cases (30.6%) and correlated with beta-catenin alteration. On multivariate analysis, the combined immunoexpression group of beta-catenin nuclear accumulation/ E-cadherin alteration and the advanced TNM cancer stage group showed poor patient's survival (p<0.05). In conclusion, beta-catenin activation through nuclear accumulation hardly occurred in EBV-infected gastric carcinomas. The combined immunoexpression pattern of beta-catenin and E-cadherin can be used as a prognostic marker in gastric carcinomas.
doi:10.3346/jkms.2007.22.5.855
PMCID: PMC2693853  PMID: 17982235
Stomach Neoplasms; Herpesvirus 4, Human; Beta Catenin; Cadherins; Prognosis
16.  Nematicidal and Propagation Activities of Thyme Red and White Oil Compounds toward Bursaphelenchus xylophilus (Nematoda: Parasitaphelenchidae) 
Journal of nematology  2007;39(3):237-242.
The toxic and propagation effects on Bursaphelenchus xylophilus of 28 Thymus vulgaris red oil and white oil compounds were examined using direct contact and cotton ball bioassays. Results were compared with those of the trunk-injection nematicides emmamectin benzoate, levamisol hydrochloride and morantel tartrate. In direct contact bioassays, geraniol (LC50, 0.47 mg/ml) was the most toxic compound, followed by thymol (1.08 mg/ml), carvacrol (1.23 mg/ml) and terpinen-4-ol (2.61 mg/ml). In cotton ball tests with 20 inactive compounds at 2 mg/cotton ball, p-cymene significantly inhibited propagation (propagation ratio [PR] 8), compared with the castor oil-ethanol-treated control (PR 56). Propagation stimulation was observed with (–)-caryophyllene oxide, (+)-ledene, (+)- and (–)-limonene, linalool oxide, β-myrcene, (–)-α-phellandrene, (+)-α-pinene and γ-terpinene (PR 63–100). The other 10 compounds exhibited low to moderate levels of propagation inhibition (PR 36–56). At 0.1 μg/cotton ball, emmamectin benzoate and morantel tartrate exhibited complete suppression of propagation, whereas a very low level of propagation inhibition was obtained from levamisol hydrochloride (PR 6). In conclusion, propagation-stimulating compounds can exist in plants in addition to nematicidal compounds, and careful use of plant preparations containing high quantities of these compounds is mandatory.
PMCID: PMC2586503  PMID: 19259493
Bursaphelenchus xylophilus; pine wood nematode; botanical nematicide; propagation stimulation; propagation inhibition; essential oil; Thymus vulgaris
17.  Nematicidal Activity of Cassia and Cinnamon Oil Compounds and Related Compounds toward Bursaphelenchus xylophilus (Nematoda: Parasitaphelenchidae) 
Journal of nematology  2007;39(1):31-36.
The nematicidal activity of two cassia, Cinnamomum cassia, oils (Especial and true), four cinnamon, Cinnamomum zey-lanicum, oils (technical, #500, bark and green leaf), and their compounds (e.g., trans-cinnamaldehyde and trans-cinnamic acid) toward adult Bursaphelenchus xylophilus was examined by a direct contact bioassay. Results were compared with those of 34 related compounds. As judged by 24-hour LC50 values, two cassia oils (0.084–0.085 mg/ml) and four cinnamon oils (0.064–0.113 mg/ml) were toxic toward adult B. xylophilus. Of 45 test compounds, trans-cinnamaldehyde (0.061 mg/ml) was the most active nematicide, followed by ethyl cinnamate, α-methyl-trans-cinnamaldehyde, methyl cinnamate and allyl cinnamate (0.114–0.195 mg/ml). Potent nematicidal activity was also observed with 4-methoxycinnamonitrile, trans-4-methoxycinnamaldehyde, trans-2-methoxy-cinnamaldehyde, ethyl α-cyanocinnamate, cinnamonitrile and cinnamyl bromide (0.224–0.502 mg/ml). Structure-activity relationships indicate that structural characteristics, such as types of functional groups, saturation and carbon skeleton, appear to play a role in determining the toxicities to adult B. xylophilus. Cassia and cinnamon oils and test compounds described merit further study as potential nematicides or leads for the control of pine wilt disease caused by B. xylophilus.
PMCID: PMC2586484  PMID: 19259472
Bursaphelenchus xylophilus; pine wood nematode; pine wilt disease; botanical nematicide; cassia oil; Cinnamomum cassia; cinnamon oil; Cinnamomum zeylanicum; cinnamaldehyde; structure-activity relationship
18.  Bacterial Growth in Amniotic Fluid Is Dependent on the Iron-Availability and the Activity of Bacterial Iron-Uptake System 
Journal of Korean Medical Science  2004;19(3):333-340.
In the present study, the relationship among iron-availability, antibacterial activity, role of meconium as an iron source and the activity of bacterial iron-uptake system (IUS) for bacterial growth in amniotic fluid (AF) were investigated. Staphylococcus aureus ATCC 6538 and its streptonigrin-resistant (SR) mutant with defective IUS were used as the test strains. The growth of S. aureus in AF was stimulated dosedependently by addition of meconium. Bacterial growth stimulated by meconium was re-inhibited dose-dependently by addition of iron-chelator, dipyridyl and apotransferrin. Iron concentration was correlated with the meconium content in AF (r2=0.989, p=0.001). High-affinity IUS of S. aureus was expressed only in AF but not in AF with meconium. The growth of SR strain was more retarded than that of the parental strain in the iron-deficient brain heart infusion (ID-BHI), clear AF and AF containing apotransferrin. The retarded growth of both strains in the ID-BHI and AF was recovered by addition of holotransferrin, hemoglobin and FeCl3. Taken together, the antibacterial activity of AF is closely related with low iron-availability. Bacterial growth in AF considerably depends on the activity of bacterial IUS. Meconium acts as one of the exogenous iron-sources and thus can stimulate bacterial growth in AF.
doi:10.3346/jkms.2004.19.3.333
PMCID: PMC2816831  PMID: 15201496
Amniotic Fluid; Staphylococcus aureus; Iron; Iron Chelating Agents

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