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1.  Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways 
Nutrients  2016;8(2):100.
Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress.
PMCID: PMC4772062  PMID: 26901224
Allomyrina dichotoma larvae; diet-induced obesity; ER stress; hypothalamus; appetite
2.  Molecular Characterization of Endoplasmic Reticulum Oxidoreductin 1 from Bombyx mori 
We isolated a complementary DNA (cDNA) clone encoding endoplasmic reticulum oxidoreductin 1 (bERO1, a specific oxidant of protein disulfide isomerase (PDI)) from Bombyx mori. This protein has a putative open reading frame (ORF) of 489 amino acids and a predicted size of 57.4 kDa. Although bERO1 protein shares less than 57% amino acid sequence homology with other reported ERO1s, it contains two conserved redox active motifs, a Cys-X-X-X-X-Cys motif of N-terminal and Cys-X-X-Cys-X-X-Cys motif of C-terminal. Both motifs are typically present in ERO1 protein family members. The bEro1 mRNA expression was highest in posterior silk gland on the sixth day of the 5th instar larvae. Expression of bEro1 mRNA also markedly increased during endoplasmic reticulum (ER) stress induced by stimulation with antimycin, calcium ionophore A23187, dithiothreitol, H2O2, monencin, and tunicamycin. In addition, expression levels of bEro1 exactly coincided with that of bPdi. This is the first result suggesting that bERO1 plays an essential role in ER quality control through the combined activities of bERO1 and bPDI as a catalyst of protein folding in the ER and sustaining cellular redox homeostasis.
PMCID: PMC4661836  PMID: 26556347
Bombyx mori; endoplasmic reticulum oxidoreductin 1 (ERO1); protein disulfide isomerase (PDI); disulfide bond
3.  Endovascular Treatment of Ruptured Pericallosal Artery Aneurysms 
Aneurysms arising from the pericallosal artery (PA) are uncommon and challenging to treat. The aim of this study was to report our experiences of the endovascular treatment of ruptured PA aneurysms.
From September 2003 to December 2013, 30 ruptured PA aneurysms in 30 patients were treated at our institution via an endovascular approach. Procedural data, clinical and angiographic results were retrospectively reviewed.
Regarding immediate angiographic control, complete occlusion was achieved in 21 (70.0%) patients and near-complete occlusion in 9 (30.0%). Eight procedure-related complications occurred, including intraprocedural rupture and early rebleeding in three each, and thromboembolic event in two. At last follow-up, 18 patients were independent with a modified Rankin Scale (mRS) score of 0-2, and the other 12 were either dependent or had expired (mRS score, 3-6). Adjacent hematoma was found to be associated with an increased risk of poor clinical outcome. Seventeen of 23 surviving patients underwent follow-up conventional angiography (mean, 16.5 months). Results showed stable occlusion in 14 (82.4%), minor recanalization in two (11.8%), and major recanalization, which required recoiling, in one (5.9%).
Our experiences demonstrate that endovascular treatment for a ruptured PA aneurysms is both feasible and effective. However, periprocedural rebleedings were found to occur far more often (20.0%) than is generally suspected and to be associated with preoperative contrast retention. Analysis showed existing adjacent hematoma is predictive of a poor clinical outcome.
PMCID: PMC4630349  PMID: 26539261
Intracranial aneurysm; Pericallosal artery; Endovascular treatment
4.  Anticancer activity of CopA3 dimer peptide in human gastric cancer cells 
BMB Reports  2015;48(6):324-329.
CopA3 is a homodimeric α-helical peptide derived from coprisin which is a defensin-like antimicrobial peptide that was identified from the dung beetle, Copris tripartitus. CopA3 has been reported to have anticancer activity against leukemia cancer cells. In the present study, we investigated the anticancer activity of CopA3 in human gastric cancer cells. CopA3 reduced cell viability and it was cytotoxic to gastric cancer cells in the MTS and LDH release assay, respectively. CopA3 was shown to induce necrotic cell death of the gastric cancer cells by flow cytometric analysis and acridine orange/ethidium bromide staining. CopA3-induced cell death was mediated by specific interactions with phosphatidylserine, a membrane component of cancer cells. Taken together, these data indicated that CopA3 mainly caused necrosis of gastric cancer cells, probably through interactions with phosphatidylserine, which suggests the potential utility of CopA3 as a cancer therapeutic. [BMB Reports 2015; 48(6): 324-329]
PMCID: PMC4578618  PMID: 25047444
Antimicrobial peptide; Anticancer activity; CopA3; Necrosis; Phosphatidylserine
5.  Anti-aging Effect and Gene Expression Profiling of Aged Rats Treated with G. bimaculatus Extract 
Toxicological Research  2015;31(2):173-180.
Extract from Gryllus bimaculatus crickets inhibits oxidation at the DNA level, with reduced production of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Microarray analyses were performed with a rat 28K cDNA clone set array to identify the gene expression profiles of aged (10 months old) Wistar Kyoto rats treated for one month with 100 mg/kg G. bimaculatus ethanol extract to assess the effects. The extract produced a meaningful anti-edema effect, evident by the inhibition of creatinine phosphokinase activity. The weights of abdominal and ovarian adipose tissues were reduced and the proportion of unsaturated fatty acids in adipose tissues was increased in an extract dose-dependent manner. Compared with untreated control rats, rats treated with the extract displayed the upregulation of 1053 genes including Fas (tumor necrosis factor receptor superfamily, member 6), Amigo3 (adhesion molecule with an immunoglobulin-like domain), Reticulon 4, 3-hydroxy-3-methylglutaryl-coenzyme (Hmgcr; a reductase), related anti-fatigue (enzyme metabolism), and Rtn antioxidant, and the downregulation of 73 genes including Ugt2b (UDP glycosyltransferase 2 family), Early growth response 1, and Glycoprotein m6a. Data suggest that G. bimaculatus extract may have value in lessening the effects of aging, resulting in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes.
PMCID: PMC4505348  PMID: 26191384
Anti-aging effect; G. bimaculatus; Wistar Kyoto rats; Microarray
6.  Efficacy of Systemic Postoperative Pulmonary Rehabilitation After Lung Resection Surgery 
Annals of Rehabilitation Medicine  2015;39(3):366-373.
To investigate the efficacy of systemic pulmonary rehabilitation (PR) after lung resection in patients with lung cancer.
Forty-one patients undergoing lung resection were enrolled and classified into the experimental (n=31) and control groups (n=10). The experimental group underwent post-operative systemic PR which was conducted 30 min/day on every hospitalization day by an expert physical therapist. The control group received the same education about the PR exercises and were encouraged to self-exercise without supervision of the physical therapist. The PR group was taught a self-PR program and feedback was provided regularly until 6 months after surgery. We conducted pulmonary function testing (PFT) and used a visual analog scale (VAS) to evaluate pain, and the modified Borg Dyspnea Scale (mBS) to measure perceived respiratory exertion shortly before and 2 weeks, 1, 3, and 6 months after surgery.
A significant improvement on the VAS was observed in patients who received systemic PR >3 months. Significant improvements in forced vital capacity (FVC) and mBS score were observed in patients who received systemic PR >6 months (p<0.05). Other PFT results were not different compared with those in the control group.
Patients who received lung resection suffered a significant decline in functional reserve and increases in pain and subjective dyspnea deteriorating quality of life (QoL). Systemic PR supervised by a therapist helped improve reduced pulmonary FVC and QoL and minimized discomfort during the postoperative periods in patients who underwent lung resection.
PMCID: PMC4496507  PMID: 26161342
Pulmonary rehabilitation; Lung resection; Quality of life
7.  Retromer Promotes Immune Quiescence by Suppressing Spätzle-Toll pathway in Drosophila 
Journal of cellular physiology  2014;229(4):512-520.
The Toll and Toll-Like Receptor signaling pathways are evolutionarily conserved pathways that regulate innate immunity in insects and mammals. While efforts have been made to clarify the signal transduction events that occur during infection, much less is known about the components that maintain immune quiescence. Here we show that retromer, an intracellular protein complex known for regulating vesicle trafficking, functions in modulating the Toll pathway in Drosophila melanogaster. In mutant animals lacking retromer function, the Toll pathway but not JAK-STAT or IMD pathway is activated, triggering both cellular and humoral responses. Genetic epistasis and clonal analysis suggest that retromer regulates a component that acts upstream of Toll. Our data further show that in the mutant the Toll ligand Spätzle has a processing pattern similar to that of after infection. Together, the results suggest a novel function of retromer in regulating Toll pathway and innate immunity at a step that modulates ligand processing or activity.
PMCID: PMC4346153  PMID: 24343480
Retromer; Vps35; Toll; Spz; Drosophila
8.  Subchronic Oral Dose Toxicity of Freeze-dried Powder of Allomyrina dichotoma Larvae 
Toxicological Research  2015;31(1):69-75.
The objective of this study was to investigate the toxicological information of freeze-dried powder from Allomyrina dichotoma (A. dichotoma) larvae as a food ingredient. The powder, suspended in distilled water, was administered once daily by oral gavage to four groups of Sprague-Dawley (SD) rats at dose levels of 0 (vehicle control), 250, 850, and 2500 mg/kg/day. After 13 wks of repeated administration, the standard toxicological parameters such as mortality, clinical signs, body weight, food consumption, ophthalmologic examination, clinical pathology, organ weights and macro/microscopic examination were applied for assessment of general toxicity. In addition, serum IgE and histamine levels were determined to evaluate allergenicity. The freeze-dried powder from A. dichotoma larvae did not produce treatmentrelated changes or findings in any toxicological parameters in either sex of any dosed groups except for slight increases in serum histamine levels at 2500 mg/kg/day. The changes were considered not to be adverse since the magnitude was minimal. In conclusion, the NOAEL (No Observed Adverse Effect Level) of the freeze-dried powder from A. dichotoma larvae was determined to be 2500 mg/kg/day or more in both sexes of SD rats and it is considered a candidate to be edible material.
PMCID: PMC4395657  PMID: 25874035
Allomyrinal dichotoma larvae; 13 wks oral administration; GLP study; Toxicity/safety; Edible insect
9.  Allomyrina dichotoma (Arthropoda: Insecta) Larvae Confer Resistance to Obesity in Mice Fed a High-Fat Diet 
Nutrients  2015;7(3):1978-1991.
To clarify the anti-obesity effect of Allomyrina dichotoma larvae (ADL), we previously reported that ADL block adipocyte differentiation on 3T3-L1 cell lines through downregulation of transcription factors, such as peroxisome proliferator-activated receptor-γ (PPARG) and CCAAT/enhancer binding protein-α (CEBPA). In this study, we tested whether ADL prevent obesity in mice fed a high-fat diet (HFD) and further investigated the mechanism underlying the effects of ADL. All mice were maintained on a normal-fat diet (NFD) for 1 week and then assigned to one of five treatment groups: (1) NFD; (2) HFD; (3) HFD and 100 mg·kg−1·day−1 ADL; (4) HFD and 3000 mg·kg−1·day−1ADL; or (5) HFD and 3000 mg·kg−1·day−1 yerba mate (Ilex paraguariensis, positive control). ADL and yerba mate were administered orally daily. Mice were fed experimental diets and body weight was monitored weekly for 6 weeks. Our results indicated that ADL reduced body weight gain, organ weight and adipose tissue volume in a dose-dependent manner. Body weight gain was approximately 22.4% lower compared to mice fed only HFD, but the difference did not reach the level of statistical significance. Real-time polymerase chain reaction (PCR) analysis revealed that gene expression levels of PPARG, CEBPA and lipoprotein lipase (LPL) in the epididymal fat tissue of HFD-fed mice receiving 3000 mg·kg−1·day−1 ADL were reduced by 12.4-, 25.7-, and 12.3-fold, respectively, compared to mice fed HFD only. Moreover, mice administered ADL had lower serum levels of triglycerides and leptin than HFD-fed mice that did not receive ADL. Taken together our results suggest that ADL and its constituent bioactive compounds hold potential for the treatment and prevention of obesity.
PMCID: PMC4377894  PMID: 25790040
high-fat diet (HFD); Allomyrina dichotoma; adipogenesis; lipogenesis; obesity
10.  Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm) 
Toxicological Research  2014;30(2):121-130.
The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.
PMCID: PMC4112063  PMID: 25071922
Edible insect; Genotoxicity; Repeated dose toxicity; Tenebrio molitor larvae
11.  Hemorrhage Rates Associated with Two Methods of Ventriculostomy: External Ventricular Drainage vs. Ventriculoperitoneal Shunt Procedure 
Neurologia Medico-Chirurgica  2014;54(7):545-551.
Cerebrospinal fluid (CSF) diversion is an essential component of neurosurgical care, but the rates and significance of hemorrhage associated with external ventricular drainage (EVD) and ventriculoperitoneal (VP) shunt procedures have not been well quantified. In this retrospective study, the authors examined the frequencies of hemorrhagic complications associated with EVD and VP shunt procedures, and attempted to identify associated risk factors. The treatment records of 370 EVDs in 276 patients and 102 VP shunts in 96 patients performed between 2008 and 2010 were retrospectively reviewed. Post-insertion computed tomographic (CT) scans were analyzed for any new hemorrhage related to the ventricular catheter. The effects of diagnosis at admission, endovascular treatment, anti-platelet medication, and a concurrent craniotomy operation were included in the analysis conducted to identify risk factors of ventricular catheter-related hemorrhage. Hemorrhage following EVD was detected on CT scans in 76 (20.5%) of the 370 cases. However, symptomatic hemorrhage occurred in only 5 cases (1.4% of all EVDs). VP shunt was associated with a higher incidence of ventricular catheter-related hemorrhage than EVD (hemorrhage rate: 43.1%) and the rate of detectable neurological change was 2.9%. Multivariate logistic-regression analysis of risk factors of EVD-related hemorrhage identified preoperative anti-platelet medication as the only significant factor (odds ratio, 3.583 [95% confidence interval, 1.353 to 9.486]; p = 0.010). Ventriculostomy-related hemorrhagic complications were more common than anticipated, especially for the VP shunt procedure. However, such hemorrhages are rarely large, rarely the cause of neurological deterioration, and rarely require surgical removal. Preoperative anti-platelet medication appears to affect EVD-related hemorrhage development.
PMCID: PMC4533471  PMID: 24522005
complication; drain; hemorrhage; intracranial; ventriculostomy
12.  Anti-inflammatory Effect of Isaria sinclairii Glycosaminoglycan in an Adjuvant-treated Arthritis Rat Model 
Toxicological Research  2013;29(3):195-201.
The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund’s adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin® as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-κB activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin E2-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-α production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin® (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.
PMCID: PMC3877999  PMID: 24386520
Isaria sinclairii; Glycosaminoglycan; Inflammation
13.  Fatty Acid Composition and Volatile Constituents of Protaetia brevitarsis Larvae 
A total of 48 different volatile oils were identified form P. brevitarsis larvae by gas chromatography/mass spectrometry (GC/MS). Acids (48.67%) were detected as the major group in P. brevitarsis larvae comprising the largest proportion of the volatile compounds, followed by esters (19.84%), hydrocarbons (18.90%), alcohols (8.37%), miscellaneous (1.71%), aldehydes (1.35%) and terpenes (1.16%). The major volatile constituents were 9-hexadecenoic acid (16.75%), 6-octadecenoic acid (14.88%) and n-hexadecanoic acid (11.06%). The composition of fatty acid was also determined by GC analysis and 16 fatty acids were identified. The predominant fatty acids were oleic acid (C18:1, 64.24%) followed by palmitic acid (C16:0, 15.89%), palmitoleic acid (C16:1, 10.43%) and linoleic acid (C18:2, 4.69%) constituting more than 95% of total fatty acids. The distinguished characteristic of the fatty acid profile of P. brevitarsis larvae was the high proportion of unsaturated fatty acid (80.54% of total fatty acids) versus saturated fatty acids (19.46% of total fatty acids). Furthermore, small but significant amounts of linoleic, linolenic and γ-linolenic acids bestow P. brevitarsis larvae with considerable nutritional value. The novel findings of the present study provide a scientific basis for the comprehensive utilization of the insect as a nutritionally promising food source and a possibility for more effective utilization.
PMCID: PMC3892504  PMID: 24471125
Protaetia brevitarsis; fatty acid; volatile oil; simultaneous distillation extraction (SDE); GC; GC/MS
14.  Fatty Acid and Volatile Oil Compositions of Allomyrina dichotoma Larvae 
Thirty-two different volatile oils were identified from Allomyrina dichotoma (A. dichotoma) larvae by gas chromatography/mass spectrometry (GC/MS). The major volatile components were 2,2,4-trimethyl-3-carboxyisopropyl pentanoic acid isobutyl ester (5.83%), phenol,2,6-bis(a,a-dimethyl ethyl)-4-(1-methyl-1-phenylethyl) (5.72%), heptacosane (5.49%) and phenol,2,4-bis(1-methyl-1-phenylethyl) (5.47%). The composition of the fatty acids in A. dichotoma larvae was also determined by gas chromatography (GC) and fourteen constituents were identified. Oleic acid (19.13%) was the most abundant fatty acid followed by palmitic acid (12.52%), palmitoleic acid (3.71%) and linoleic acid (2.08%) in 100 g of A. dichotoma larvae on a dry weight basis. The quantity of unsaturated fatty acids (64.00%) were higher than that of saturated ones (36.00%). The predominant fatty acids in A. dichotoma consist of monounsaturated fatty acid (MUFA, 57.70%) such as oleic acid, myristoleic acid and palmitoleic acid, followed by saturated fatty acids (36.00%) and polyunsaturated fatty acids (PUFA, 6.50%). In particular, the presence of essential fatty acids, such as linoleic (5.30%) and linolenic acid (0.40%) give A. dichotoma larvae considerable nutritional and functional value and it may be a useful source for food and/or industrial utilization.
PMCID: PMC3866728  PMID: 24471102
Allomyrina dichotoma; fatty acids; GC; GC/MS; SDE; volatile oils
15.  Segmental bile duct leakage after hepatic resection managed with percutaneous ablation by N-butyl cyanoacrylate 
A biloma is a rare abnormal accumulation of intrahepatic or extrahepatic bile caused by a traumatic or spontaneous rupture of the biliary tree. The reported incidence of postoperative biloma ranges from 4.8% to 7.6%. Biliary drainage is usually important and necessary for the treatment of biloma, but sometimes bile leakage fails to improve despite prolonged conservative drainage. We report a case of postoperative refractory biliary leakage managed with percutaneous ablation by N-butyl cyanoacrylate.
PMCID: PMC4575005  PMID: 26388919
Biloma; Biliary leakage; N-butyl cyanoacrylate
16.  The Insect Peptide Coprisin Prevents Clostridium difficile-Mediated Acute Inflammation and Mucosal Damage through Selective Antimicrobial Activity▿ 
Antimicrobial Agents and Chemotherapy  2011;55(10):4850-4857.
Clostridium difficile-associated diarrhea and pseudomembranous colitis are typically treated with vancomycin or metronidazole, but recent increases in relapse incidence and the emergence of drug-resistant strains of C. difficile indicate the need for new antibiotics. We previously isolated coprisin, an antibacterial peptide from Copris tripartitus, a Korean dung beetle, and identified a nine-amino-acid peptide in the α-helical region of it (LLCIALRKK) that had antimicrobial activity (J.-S. Hwang et al., Int. J. Pept., 2009, doi:10.1155/2009/136284). Here, we examined whether treatment with a coprisin analogue (a disulfide dimer of the nine peptides) prevented inflammation and mucosal damage in a mouse model of acute gut inflammation established by administration of antibiotics followed by C. difficile infection. In this model, coprisin treatment significantly ameliorated body weight decreases, improved the survival rate, and decreased mucosal damage and proinflammatory cytokine production. In contrast, the coprisin analogue had no apparent antibiotic activity against commensal bacteria, including Lactobacillus and Bifidobacterium, which are known to inhibit the colonization of C. difficile. The exposure of C. difficile to the coprisin analogue caused a marked increase in nuclear propidium iodide (PI) staining, indicating membrane damage; the staining levels were similar to those seen with bacteria treated with a positive control for membrane disruption (EDTA). In contrast, coprisin analogue treatment did not trigger increases in the nuclear PI staining of Bifidobacterium thermophilum. This observation suggests that the antibiotic activity of the coprisin analogue may occur through specific membrane disruption of C. difficile. Thus, these results indicate that the coprisin analogue may prove useful as a therapeutic agent for C. difficile infection-associated inflammatory diarrhea and pseudomembranous colitis.
PMCID: PMC3186999  PMID: 21807975
17.  Thirteen-Week Oral Dose Toxicity Study of G. bimaculatus in Sprague-Dawley Rats 
Toxicological Research  2011;27(4):231-240.
Gryllus bimaculatus (Gb) was orally administered at doses of 0, 0.04, 0.2, 1 and 5 g/kg bw/day for 13 consecutive weeks. There were no observed clinical signs or deaths related to treatment in all the groups tested. Therefore, the approximate lethal oral dose of G. bimaculatus was considered to be higher than 5 g/kg in rats. Throughout the administration period, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis) or gross pathology were detected. Minor changes were found in hematological parameters for the 5 g/kg Gb-treated group (triglyceride reduction of 35.8%), but all changes were within normal physiological ranges. Microscopic examination did not identify any treatment-related histopathologic changes in the organs of Gb-treated rats in the high dose group. From these results, one can conclude that the no-observed adverse effect level (NOAEL) of G. bimaculatus is higher than 5 g/kg bw/day in rats.
PMCID: PMC3834393  PMID: 24278577
G. bimaculatus; 13-Week toxicity
18.  Endobronchial Aspergilloma: Report of 10 Cases and Literature Review 
Yonsei Medical Journal  2011;52(5):787-792.
A retrospective investigation of the clinical and radiologic features as well as the bronchoscopic appearance was carried out in patients with endobronchial aspergilloma.
Materials and Methods
Ten patients with endobronchial aspergilloma diagnosed by bronchoscopy and histological examination were identified at the Gyeongsang University Hospital of Korea, from May 2003 to May 2009.
The patients included 9 men and 1 woman, and the age of the patients ranged from 36 to 76 (median, 58 years). The associated diseases or conditions were: previous pulmonary tuberculosis in 7 patients, lung cancer in 2 patients, pulmonary resection in 1 patient, and foreign body of the bronchus in 1 patient. The chest radiologic finding showed fibrotic changes as a consequence of previous tuberculosis infection in 6 patients and a mass-like lesion in 2 patients. Two patients had a co-existing fungus ball, and an endobronchial lesion was suspected in only 2 patients on the CT scan. The bronchoscopic appearance was a whitish to yellow necrotic mass causing bronchial obstruction in 7 patients, foreign body with adjacent granulation tissue and whitish necrotic tissue in 1 patient, whitish necrotic tissue at an anastomosis site in 1 patient, and a protruding mass with whitish necrotic tissue in 1 patient.
An endobronchial aspergilloma is a rare presentation of pulmonary aspergilosis and is usually incidentally found in immunocompetent patients with underlying lung disease. It usually appears as a necrotic mass causing bronchial obstruction on bronchoscopy and can be confirmed by biopsy.
PMCID: PMC3159936  PMID: 21786444
Endobronchial aspergilloma
19.  Fatty Acid Composition of Adipose Tissues in Obese Mice and SD Rats Fed with Isaria sinclairii Powder 
Toxicological Research  2010;26(3):185-192.
Isaria sinclairii (Cicada Dongchunghacho) was studied as a potential crude natural food in powdered form. The role of tissue fatty acids in relation to the anti-obesity effects of I. sinclairii (IS) was examined by feeding the powder to SD rats ad libitum at 0, 1.25, 2.5, 5 and 10% (calculated about 8 g/kg) of the feed for a period of 3 months and 6 months. The fatty acid composition profile as indicated GC-MS, showed significantly slight dose-dependent increases in the levels of unsaturated fatty acids, particularly, arachidonic acid (C20: 4n6) , oleic acid, linoleic acid, eicosadienoic acid, eicosapentaenoic acid (EPA) (C20: 5) concentration in the the ad libitum IS-fed groups compared to the control group in SD abdominal fat over 6 month period. Over viewing of the SD and Ob mice treated Isaria sinclairii powder; there were increases in the single (mono) unsaturated fatty acids ratio but decreases in polyunsaturated fatty acid. In IS-fed groups in proportion to the treatment period, this Dongchunghacho also induced an increase in the level of same result of unsaturated fatty acid in C57BL/6 obese (ob/ob) mice over a 6-month period treatment compared to those given 10% dry mulberry leaf powder (ML) or silkworm powder mixed with the standard diet.
PMCID: PMC3834485  PMID: 24278523
Anti-diabetic effect; Isaria sinclairii; Obese mice; 6 months treatment
20.  A Case of Anaphylaxis After the Ingestion of Yacon 
Anaphylaxis is a potentially life-threatening systemic allergic reaction, often with an explosive onset; the symptoms range from mild flushing to upper respiratory obstruction, with or without vascular collapse. Foods are common offending allergens and remain the leading cause of outpatient anaphylaxis in most surveys. Yacon (Smallanthus sonchifolius) is a plant native to the Andes region, where its root is cultivated and consumed mainly as food. Unlike most edible roots, yacon contains large amounts of ructooligosaccharides. Traditionally, yacon tubers have been used as a source of natural sweetener and syrup for people suffering from various disorders. We report the case of a 55-year-old woman who developed syncope and generalized urticaria after ingesting yacon roots. The patient had positive skin prick and intradermal tests to yacon extract. An open food challenge test was performed to confirm food anaphylaxis and was positive 10 minutes after the consumption of yacon roots. To our knowledge, this is the first reported case of anaphylaxis after the ingestion of yacon roots.
PMCID: PMC2846740  PMID: 20358031
Yacon; anaphylaxis; syncope; urticaria; hypotension
21.  Isolation and Characterization of a Defensin-Like Peptide (Coprisin) from the Dung Beetle, Copris tripartitus 
The antibacterial activity of immune-related peptides, identified by a differential gene expression analysis, was investigated to suggest novel antibacterial peptides. A cDNA encoding a defensin-like peptide, Coprisin, was isolated from bacteria-immunized dung beetle, Copris tripartitus, by using differential dot blot hybridization. Northern blot analysis showed that Coprisin mRNA was up-regulated from 4 hours after bacteria injection and its expression level was reached a peak at 16 hours. The deduced amino acid sequence of Coprisin was composed of 80 amino acids with a predicted molecular weight of 8.6 kDa and a pI of 8.7. The amino acid sequence of mature Coprisin was found to be 79.1% and 67.4% identical to those of defensin-like peptides of Anomala cuprea and Allomyrina dichotoma, respectively. We also investigated active sequences of Coprisin by using amino acid modification. The result showed that the 9-mer peptide, LLCIALRKK-NH2, exhibited potent antibacterial activities against Escherichia coli and Staphylococcus aureus.
PMCID: PMC2915626  PMID: 20721297
22.  Molecular characterization of a Bombyx mori protein disulfide isomerase (bPDI) 
Cell Stress & Chaperones  2002;7(1):118-125.
We have isolated a complementary deoxyribonucleic acid clone that encodes the protein disulfide isomerase of Bombyx mori (bPDI). This protein has a putative open reading frame of 494 amino acids and a predicted size of 55.6 kDa. In addition, 2 thioredoxin active sites, each with a CGHC sequence, and an endoplasmic reticulum (ER) retention signal site with a KDEL motif were found at the C-terminal. Both sites are typically found in members of the PDI family of proteins. The expression of bPDI messenger ribonucleic acid (mRNA) was markedly increased during ER stress induced by stimulation with calcium ionophore A23187, tunicamycin, and dithiothreitol, all of which are known to cause an accumulation of unfolded proteins in the ER. We also examined the tissue distribution of bPDI mRNA and found pronounced expression in the fat body of insects. Hormonal regulation studies showed that juvenile hormone, insulin, and a combination of juvenile hormone and transferrin (although not transferrin alone) affected bPDI mRNA expression. A challenge with exogenous bacteria also affected expression, and the effect peaked 16 hours after infection. These results suggest that bPDI is a member of the ER-stress protein group, that it may play an important role in exogenous bacterial infection of the fat body, and that its expression is hormone regulated.
PMCID: PMC514797  PMID: 11892983

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