• Nutrition Research and Practice
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• 제8권1호
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• pp.46-53
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• 2014

Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide ($As_2O_3$) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As ($iAs^{III}$) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by $As_2O_3$ exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, $Na^+-K^+$ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of $As_2O_3$ exposure. AST showed a significant protective effect against $As_2O_3$-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to $iAs^{III}$ from natural sources or cancer therapy.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.311-319
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• 2020

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC₅₀ values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.

• 한국약용작물학회지
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• 제22권5호
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• pp.369-377
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• 2014

In order to find out anticancer activity of Korean pepper (Capsicum annuum L.), the cytotoxicity against 8 cell lines including 293 (normal kidney cells) and A-431 (epidermoid carcinoma cells) of extracts by extraction solvents and plant parts were investigated using MTT assay. Also the correlation between content of capsaicin known as anticancer ingredient and cytotoxicity of extracts from pepper were analyzed. The distilled water extracts from seed and germinated seed showed very high cytotoxicity against 6 cancer cell lines including A549 (lung carcinoma cells), AGS (stomach adenocarcinoma cells), HeLa (cervix adenocarcinoma cells), HepG2 (hepatoblastoma cells), HT-29 (colon adenocarcinoma cells), and MCF-7 (breast adenocarcinoma cells). But 80% ethanol and methanol extracts showed cytotoxicity against 293 and AGS. The $RC_{50}$, that was, the concentration of sample required for 50% reduction of cell viability, of seed and germinated seed extracts against AGS were $33.4{\sim}389.1{\mu}g/m{\ell}$ and $63.9{\sim}1,316.7{\mu}g/m{\ell}$, respectively, so anticancer activity was higher in seed than in germinated seed. In capsaicin contents, seed with high cytotoxicity and pericarp with a little cytotoxicity contained $47.4{\sim}1,260.0{\mu}g/g$ and $58.3{\sim}1,498.0{\mu}g/g$, respectively. As these results, the correlation was not between cytotoxicity and capsaicin content.

• 생약학회지
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• 제35권3호통권138호
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• pp.244-249
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• 2004

The effects of hesperetin and naringenin on $NF-{\kappa}B$ activation were investigated in normal rat kidney cells transformed by temperature sensitive Rous Sarcoma Virus (tsNRK). The flavonoids, naringenin and hesperetin, significantly reduced v-Src-induced $NF-{\kappa}B$ activation as well as phosphorylation of Akt and GSK-3 in tsNRK cells, whereas these compounds did not effect on platelet-derived growth factor (PDGF)-induced $NF-{\kappa}B$ activation in $NIH3T3{\gamma}l$ cells. In addition, the DNA binding activity of SP-I was also reduced but that of AP-1 was not affected by the compounds. Our study suggests that Src-induced $NF-{\kappa}B$ activation could occur via Akt-GSK-3 pathway without $IkB{\alpha}$ degradation and that naringenin and hesperetin could be used in the treatment of cancer through the inhibition of $NF-{\kappa}B$ activation.

• 대한한방내과학회지
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• 제26권1호
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• pp.107-118
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• 2005

Objectives : Peroxynitrite $(ONOO^-)$, fonned from the reaction of $O_2^-$ and NO, is a cytotoxic species that can oxidize several cellular components such as proteins, lipids and DNA. It has been implicated in the aging process and age-related disease such as Alzheimer's disease, rheumatoid arthritis, cancer and atherosclerosis. Due to the lack of endogenous enzymes to thwart $ONOO^-$ activation, developing a specific $ONOO^-$ scavenger is remarkably important. The aim of this study was to investigate scavenging activities of $ONOO^-$ and its precursors, NO and $O_2^-$ and its scavenging mechanism of Ojawhan. Methods : To investigate scavenging activities of $ONOO^-$, NO, $O_2^-$ and its scavenging mechanism using fluorescent probes, DCFDA, DAF-2 and DHR 123. The $ONOO^-$ scavenging activity on Ojawhan was assayed by measuring oxidized dihydrorhodamine 123 (DHR 123) by fluorometry. Oxidative stress was induced by strong oxidants t-butyl hydroperoxide (t-BHP). Endothelial cell (YPEN-1) was used for detection of intracellular oxidative stress. Results : Ojawhan markedly scavenged authentic $ONOO^-$, $O_2^-$ and NO. It also inhibited $ONOO^-$ induced by $O_2^-$ and NO which are derived from SIN-1. Furthennore, ${\underline{Ojawhan}}$ blocked lipopolysaccharide (LPS)-induced $ONOO^-$, $O_2^-$ and NO generation utilizing kidney homogenates of LPS-injected mouse and inhibited t-BHP-induced ROS and $ONOO^-$ in endothelial cell culture system. Conclusions : These results suggest that Ojawhan be developed as an effective $ONOO^-$ scavenger for the prevention of $ONOO^-$ involved diseases and age-related diseases.

• 한국식생활문화학회지
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• 제20권6호
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• pp.721-730
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• 2005

Recently, epidemiological evidence has raised concerns that moderate elevation in body iron stores may increase oxidative stress and the risk of cardiovascular disease and cancer. Onion flesh or peel contains antioxidant such as flavonoids and alk(en)ylcysteine sulphoxides. This study was conducted to examine the effect of onion flesh or peel feeding on antioxidative capacity in aged rats supplemented with high dietary iron. Thirty-two Sprague-Dawley male 16-month-old rats weighing $618{\pm}6g$ were acclimated for 10 days with medium-iron diet (35ppm in diet), and blocked into 4 groups according to their body weights and raised for 3 months on either control diets (adequate iron-35ppm or high iron-350ppm) or experimental diets containing onion flesh/peel (5% w/w in diet) with high iron (350ppm). Rats fed high iron-onion peel diet had significantly high quercetin and isorhamnetin levels in plasma whereas rats fed high iron-onion flesh diet did not show. Plasma TBARS level was lowered by onion flesh or peel diet with high iron supplementation. However, there was no significant difference in cellular DNA damage in brain and kidney tissue among all experimental groups. We concluded that high iron diet (10 times higher than requirement) tend to increase oxidative stress and it is plausible that onion flesh or peel feeding enhances antioxidative capacity in the elderly even with iron supplementation.

• Journal of Ginseng Research
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• 제30권3호
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• pp.100-105
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• 2006

Liver and kidney are specific organs which play an active role in biotransformation and detoxification mechanisms. Ant adverse effect of chemicals or heavy metal can cause the delay or fade in these mechanisms. Present study was designed to find out the protective effect of Panax ginseng extract on renal functions altered by mercuric chloride (heavy metal) in albino rat. Fifty albino rats were divided into 10 groups. Five groups for acute study and five groups for sud-acute study viz. control group (Tween 20 and distilled water), mercuric chloride treated group (0.926 mg/kg body wt. for acute and 0.044 mg/kg body wt. for sub-acute group after calculated $LD_{50}$ (9.26 mg/kg body wt.) by probit analysis (Finney, 1971), Panax ginseng extract treated group (10 mg/kg body wt. for acute and sub-acute sets), mercuric chloride treated followed by Panax ginseng extract and Panax ginseng extract followed by mercuric chloride group. All doses were given orally by gavage tube. The result revealed that the serum urea and creatinine significantly increased in mercuric chloride treated group, while significantly decreased (p<0.01) in Panax ginseng extract group after acute and sub-acute treatment. The biochemical estimation is also confirmed by nephropathological aspect. However, the Panax ginseng extract treated followed by mercuric chloride group is more prominent than the mercuric chloride treated followed by Panax ginseng extract group. It can be concluded that Panax ginseng extract had a protective nature on renal functions against mercuric chloride toxicity in albino rats.

• The Korean Journal of Physiology and Pharmacology
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• 제19권5호
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• pp.441-449
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• 2015

Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus, Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-${\alpha}$ in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-${\kappa}B$-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-${\beta}$ (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-${\kappa}B$ nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-${\kappa}B$ activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-${\kappa}B$ activation.

• Journal of Yeungnam Medical Science
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• 제2권1호
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• pp.259-264
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• 1985

신경아세포종은 소아기에 발생하는 악성종양중 뇌종양 다음으로 흔히 발생하는 것으로 원발 혹은 전이된 부위에 따라 다양한 임상증상이 나타날 수 있으나 실명을 주소로 한 경우는 드물다. 본 증례는 4세된 남아의 복부에서 기원하여 사골동으로 원위전이하여 갑작스런 실명을 주소로 한 신경아세포종으로 cytoxan, vincristine, DTIC, adriamycin 및 VM-26의 병합요법으로 치료하여 실명은 그대로 있으나 복부와 사골동의 종괴는 현저히 감소하였고 환아는 건강이 양호한 상태이다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제40권
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• pp.41.1-41.4
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• 2018

Background: Free fibular flap is one of the most useful methods in the hard tissue reconstruction of the maxillamandible. Free fibular flap presents some advantages in which the reconstruction of both soft and hard tissues can be done at the same time. It also provides a safe and successful bone graft for the reconstruction, along with a low rate of complications. Despite these advantages and the rarity of a postoperative complication, particularly in oral and maxillofacial surgery procedures, a prolonged operation might exhibit some complications related with rhabdomyolysis. We experienced the rare event of rhabdomyolysis after oral cancer surgery. Case presentation: In this article, we report the case of a patient who developed rhabdomyolysis after undergoing free fibular flap surgery. Conclusions: Despite the advantages of the free fibular flap operation, clinicians must be aware of the risk of complications because there are multiple factors that could result in rhabdomyolysis, such as duration of operation, position of the subject, and pre-existing conditions of diabetes and hypertension. Once the diagnosis of rhabdomyolysis is confirmed, a prompt treatment plan should be made and applied as soon as possible. This will increase the chance of a full recovery for the patient who is exhibiting symptoms of rhabdomyolysis.