Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.
Lee, Gyoung-Eun;Kim, Ji-Young;Kim, Jae Hyung;Jeong, Myeong Ja;Kim, Soung Hee;Kim, Soo Hyun;Kang, Mi-Jin;Lee, Ji Hae;Bae, Kyung-Eun;Kim, Tae Gyu
Journal of the Korean Society of Radiology
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v.79
no.5
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pp.259-263
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2018
A 52-year-old male complained of a painless, firm, and slow-growing mass in his right breast outer portion. The chest CT revealed a 3.3 cm-sized oval shaped, microlobulated, mild enhancing mass. Ultrasound showed a microlobulated marginated heterogeneous hypoechoic mass with internal vascularity and calcifications in the mass. On the ultrasound-guided core needle biopsy, the mass was confirmed as a benign granular cell tumor (GCT). The patient transferred to another hospital and underwent surgical removal of the lesion. GCT of the breast is uncommon and mostly benign neoplasm to originate from Schwann cell. Clinical and radiologic features of GCTs, including CT and ultrasound images, mimic malignancy and make diagnosis of GCT more difficult. The CT images of GCTs are much rarely reported. Physicians and radiologists must be aware of radiologic characteristics of this rare benign tumor for male breast, to avoid misdiagnosis this tumor for breast malignancy and overtreat.
Background: Diabetic nephropathy (DN) is one of the major complications of chronic hyperglycaemia affecting normal kidney functioning. The ayurvedic medicine curcumin (CUR) is pharmaceutically accepted for its vast biological effects. Objectives: The Curcuma-derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2. Methods: Upon in silico molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method. The NCUR were characterized for shape, size and other physico-chemical properties by Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared (FTIR) Spectroscopy studies. For in vivo validation of nephro-protective effects, Mus musculus were pre-treated with CUR at a dose of 50 mg/kg b.w. and NCUR at a dose of 25 mg/kg b.w. (dose 1), 12.5 mg/kg b.w (dose 2) followed by alloxan administration (100 mg/kg b.w) and serum glucose levels, histopathology and immunofluorescence study were conducted. Results: The in silico study revealed a strong affinity of CUR towards Bcl2 (dock score -10.94 Kcal/mol). The synthesized NCUR were of even shape, devoid of cracks and holes with mean size of ~80 nm having -7.53 mV zeta potential. Dose 1 efficiently improved serum glucose levels, tissue-specific expression of Bcl2 and reduced glomerular space and glomerular sclerosis in comparison to hyperglycaemic group. Conclusion: This study essentially validates the potential of NCUR to inhibit DN by reducing blood glucose level and mitigating glomerular apoptosis by selectively promoting Bcl2 protein expression in kidney tissue.
Kim, Sae-Ro-Mi;Park, Sang-Min;Lee, Kyu-Jun;Lee, Yong-Jin;Bae, Eun-Hye;Park, Sung-Han;Lim, Ji-Hyun;Jung, Yong-Tae
Korean Journal of Microbiology
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v.46
no.1
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pp.15-20
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2010
Xenotransplantation of pig organs is complicated by the existence of polytropic replication-competent porcine endogenous retroviruses (PERV) capable of infecting human cells. Two classes of infectious human-tropic replication-competent PERVs (PERV-A and PERV-B) and one class of ecotropic PERV-C are known. The potential for recombination between ecotropic PERV-C and human-tropic PERVs adds another level of infectious risk. A recombinant PERV-A/C (PERV-A14/220) virus is 500-fold more infectious than PERV-A. Two determinants of this high infectivity was identified; one was isoleucine-to-valine substitution at position 140 in RBD (receptor binding domain), and the other lies within the PRR (proline rich region) of the envelope protein. To examine whether the effects of the cytoplasmic tail of the PERV-C Env on fusogenesity also influences infectivity, we constructed a pseudotype retroviral vectors containing MoMLV core protein and PERV envelopes. Pseudotyping experiments with the PERV envelope glycoproteins indicated that recombinant PERV-A/C virus is 10-fold more infectious than PERV-A by lacZ staining. This result supports the suggestion that viral transduction of PERV-A/C is enhanced by a membrane-proximal cytoplasmic amphiphilic ${\alpha}$-helix in PERV-C Env tail.
Journal of the Korean Society of Food Science and Nutrition
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v.41
no.12
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pp.1663-1670
/
2012
The inhibitory effects of rose hip (Rosa canina L.) water extracts from two different manufactures on osteoarthritis was comparatively investigated in primary cultures of rat cartilage cells. To identify the effects of rose hip extracts against $H_2O_2$ (300 ${\mu}M$, 2 hr) treatment, cell survival was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell survival increased by rose hip extracts in the range of 100 to 600 ${\mu}g/mL$ of $H_2O_2$ treatment. To determine the anti-inflammatory effects of rose hip extracts, tumor necrosis factor alpha (TNF-${\alpha}$), nitric oxide (NO), and Cox-2 expression were measured after lipopolysaccharide (LPS) activation. TNF-${\alpha}$ level with rose hip extract treatment was decreased by 27.4% and 31.9% at 600 ${\mu}g/mL$ of $H_2O_2$ treatment. Nitric oxide was inhibited by rose hip extract at 100~600 ${\mu}g/mL$ of $H_2O_2$ treatment in a dose-dependent manner. In addition, Cox-2 protein expression was dose-dependently decreased while Cox-1 had no change in expression level. The severity of osteoarthritis is controlled by a balance between anabolic and catobolic factors in an articulation, therefore the expression of these factors plays a critical role in preventing osteoarthritis. In measuring anabolic factors, the genetic expression of collagen type I increased with rose hip treatment, while the genetic expression of collagen II did not change. In addition, the genetic expression of aggrecan (proteoglycan core protein) was significantly increased. while the genetic expression of matrix metalloproteinase (MMP) 3, 7 and 13, known catabolic factors, was significantly inhibited by treatment with rose hip extract. The expression of MMP13 was especially highly influenced. In conclusion, rose hip water extracts show inhibitory effects on cell death by $H_2O_2$ mediated oxidative stress, which is related to inhibitory effects on inflammation due to TNF-${\alpha}$, NO, and Cox-2. The ability of rose hip extracts to ameliorate inflammation in primary cultures of cartilage cells seems to associate with an increased genetic expression of specific anabolic factors, collagen type I and aggrecan, and a decreased expression of catabolic factors, MMPs (3, 7, and 13). However, there were no significant differences between rose hip extracts from the two manufacturers.
Choi, Hyo Jin;Hwang, Sang Youn;Jang, Dae Ho;Cho, Hyung Min;Kang, Jung Hye;Seong, Gi Hun;Choo, Jae Bum;Lee, Eun Kyu
Korean Chemical Engineering Research
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v.44
no.1
/
pp.65-72
/
2006
Recent technical advances in the biorecognition engineering and the microparticle fabrication may enable us to develop the single step purification using magnetic particle, because of its simplicity, efficacy, ease of automation, and process economics. In this study, we used commercial magnetic particles from Seradyn, Inc. (Indianapolis, USA). It was ca. 2.8 micron in diameter, consisted of polystyrene core and magnetite coating, and its surface had carboxyl groups. The model, capture protein was IgG and anti-IgG was used as the ligand molecule. We studied the different surfaces ('nude', ester-activated, and anti-IgG coated) for their biorecognition of IgG. At a high pH condition, we could reduce non-specific binding. Also anti-IgG immobilized magnetic particle could capture IgG more selectively. We attempted 'oriented immobilization' of anti-IgG, in which the polysaccharides moiety near the C-terminus was selectively oxidized and linked to the hydrazine-coated MP, to improve the efficacy of biorecognitive binding. Using this method, the IgG capturing ability was improved by ca. 2 fold. From the binary mixture of the IgG-insulin, IgG could be more selectively captured. In summary, the oriented immobilization of oxidized anti-IgG proved to be as effective as the streptavidin-biotin system and yet simpler and cost-effective. This immobilization method can find its applications in protein biochips and biotargeting.
From August 1989 to January 1996, a total of 105 cases of bidirectional Glean operations have been done as the interim stage for the patien s with some risk of univentricular correction at Sejong General Hospital. From December 1992, we started the conversion to Fontal operations for them, and 42 cases underwent Fontal-stage operation till February 1996. Their diagnoses were univentricular heart in 19(right ventricular type : 14), tricuspid atresia 11, double outlet of right ventricle 9, and others in 3 cases. The median age of bidirectional Glerln-stage operation was 12.5 months(range 2 months to 8 years) and Fontan-stage operation was at 59.6 months of median age(range 1 year 5 months to ,9 year 7 months). The mean waiting interval between the two operations was 33.88 $\pm$ 17.85 months with a range of 10 months to 6 years 3 months. During the waiting periods, 18 patients developed significant systemic-pulmonary collaterals andfor systemic verso-veno collateral channels. There were 5 hospital deaths after operations due to low cardiac output in 4 and sepsis in one. Most of the Fontal-stage operations were done by the late al tunneling with Core-Tex tube graft patch and fenestrated with the size of 2.5 ~6 mm. All the patients were followed-up(7 months to 4 years 2 months, mean 21.97$\pm$10.82 months) and there were 5 late deaths(postoperatively 6 months to 2 years) due to thromboembolism in 1, after heart transplantation 1, plastic bronchitis 1, protein loosing enteropathy 1, and pneumonia in 1. Dividing the patients by the waiting interval of 2 years, the early correction to Fontal group (N=16) showed the better results(hospital mortality 1116, late mortality 1116, significant collateral development 2/16) compared to the other group(N=26) (4/26, 4/26, 16/26). In conclusion, after the bidirectional Glean-stage operation successfully got rid of the previous risk factors, we recommand to do the Fontan-stage operation no later than 2 years of interval.
Necrosis is characterized by the cell membrane rupture and release of the cellular contents, including high-mobility group box 1 protein (HMGB1), into the extracellular microenvironment. HMGB1 acts as a transcriptional regulator in nuclei, but exerts a pro-inflammatory and tumor-promoting cytokine activity when released into the extracellular space. Its overexpression is associated with tumor progression and chemoresistance. Thus, HMGB1 acts as a clinically important molecule in tumor biology. In this study, we examined whether HMGB1 affects cell death induced by anti-cancer drugs. Here we show that HMGB1 prevented cisplatin (alkylating agent)-induced apoptosis and switched the cell fate to necrosis in MCF-7, MDA-MB231, and MDA-MB361 cells. Similar apoptosis-to-necrosis switch effects of HMGB1 were observed in cells treated with 4-HC, another alkylating agent. In contrast, HMGB1 did not exert any significant effects on docetaxel (DOC)-induced apoptosis in MCF-7 cells. We also show that cisplatin-induced apoptosis was switched to necrosis in MCF-7 multicellular tumor spheroids (MTS) that were cultured for 8 days and had necrotic cores, but DOC-induced apoptosis was prevented without the apoptosis-to-necrosis switch. Finally, the levels of RAGE, a receptor of HMGB1, were increased with extended culture of MTS. These findings demonstrate that HMGB1 switches alkylating agent-induced apoptosis to necrosis, suggesting that the strategy to prevent necrosis occurring as an undesirable action of alkylating agent-based chemotherapy should be delineated to improve the efficacy of chemotherapy for cancer.
Yoon, Hye-Ran;Cho, Kyung-Hee;Yoo, Han-Wook;Choi, Jin-Ho;Lee, Dong-Hwan;Zhang, Kate;Keutzer, Joan
Journal of Genetic Medicine
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v.4
no.1
/
pp.45-52
/
2007
Purpose : A simple, rapid, and highly sensitive analytical method for Gb3 in plasma was developed without labor-ex tensive pre-treatment by electrospray ionization MS/ MS (ESI-MS/MS). Measurement of globotriaosy lceramide (Gb3, ceramide trihex oside) in plasma has clinical importance for monitoring after enzyme replacement therapy in Fabry disease patients. The disease is an X-linked lipid storage disorder that results from a deficiency of the enzyme ${\alpha}$-galactosidase A (${\alpha}$-Gal A). The lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly Gb3. Methods : Only simple 50-fold dilution of plasma is necessary for the extraction and isolation of Gb3 in plasma. Gb3 in diluted plasma was dissolved in dioxane containing C17:0 Gb3 as an internal standard. After centrifugation it was directly injected and analyzed through guard column by in combination with multiple reaction monitoring mode of ESI-MS/MS. Results : Eight isoforms of Gb3 were completely resolved from plasma matrix. C16:0 Gb3 occupied 50% of total Gb3 as a major component in plasma. Linear relationship for Gb3 isoforms w as found in the range of 0.001-1.0 ${\mu}g$/mL. The limit of detection (S/N=3) was 0.001 ${\mu}g$/mL and limit of quantification was 0.01 ${\mu}g$/mL for C16:0 Gb3 with acceptable precision and accuracy. Correlation coefficient of calibration curves for 8 Gb3 isoforms ranged from 0.9678 to 0.9982. Conclusion : This quantitative method developed could be useful for rapid and sensitive 1st line Fabry disease screening, monitoring and/or diagnostic tool for Fabry disease.
Kim, Kwang-Ho;Koh, Hee-Jong;Lee, Jang-Hoon;Park, Sun-Zik;Heu, Mun-Hue
KOREAN JOURNAL OF CROP SCIENCE
/
v.38
no.3
/
pp.264-274
/
1993
This study was carried out to assess the agronomic characters and physicochemical properties of floury and chalky-endosperm mutant lines induced by chemical mutagen treatment to rice varieties, Hwacheongbyeo and IR24. Linkage analysis of a floury-endosperm gene was carried out using linkage testers. The grain size of brown rice of the mutants was smaller than that of the original varieties. The l, 000-grain and 1$\ell$ weight were lighter in the mutants compared with those in the original varieties. The compound starch granules in the endosperm cell of the mutants showed a loosely-packed crystalline structure. Amylose contents in mutants ranged from 16.9 to 28.5%. Crude protein contents of the mutants were not significantly different from the original rice variety, Hwacheongbyeo, but white core mutant(line 47106) derived from IR24 showed higher protein(l1.32%) compared with IR24(8.30%). The mutants showed slightly harder gel characteristics, and much lower viscosity in Amylograph than original varieties. Steamed rice-cakes from mutant lines showed greater volume than those from original varieties. During the process of alcohol fermentation, Brix in the mutants(especially floury mutants) decreased faster and the alcohol production after 10-day fermentation was much greater in the mutants than in the original varieties. Three different gene loci for floury endosperm characteristics were identified from the allelism test among mutant lines, and the genes were tentatively symbolized as flo-a, flo-b and flo-c, respectively. A floury gene, flo-a, was linked with lg(liguleless) gene in the linkage group N, with R.V. 5.76$\pm$1.72%.
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