• 동의생리병리학회지
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• 제19권3호
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• pp.671-676
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• 2005

In this study, we investigated the antioxidant effect of extract from Monascus pillosus, on the human wild-type p53 and p21 expressing A549 lung epithelial cell line and MCF-7 mammary adenocarcinoma cell line stimulated by NO. $P21^{waf/cip1}$ was identified as a gene induced in senescent cells. It is a cyclin-dependent kinase inhibitor and has been shown to cause cell cycle arrest and apoptosis. While p53-regulated stimulation of p21 appears to be central for the permanent growth-arrest, the role of p21 in p53-triggered cell death is unclear. Low dose of sodium nitroprusside (SNP) induced the development of senescence associated with increased expression of p53 and p21 in A549 cells. Inhibition of p21 transactivating activity requires high level correlates with the amount of p53 necessary to cause cell death. Association of p21 and p53 results in inhibition of p21-stimulated transcription. This requires a higher p53 level than is necessary for transcriptional activation of endogenous p53-responsive gene but correlates well with the level of p53 necessary to cause cell death. Exposure to W-1 inhibited oxidative stresses-induced senescence-like arrest, resulting in a significant reduction in p53 and p21 steady state levels. These results suggest that p53 and p21 play a central role in the onset of senescence. Thus, it is important to emphasize control of oxidative balance in tumor prevention and aging.

• Archives of Pharmacal Research
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• 제28권11호
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• pp.1270-1274
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• 2005

The vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, which is a process where new blood vessels develop from the endothelium of a pre-existing vasculature. VEGF exerts its activity by binding to its receptor tyrosine kinase, KDR/Flk-1, which is expressed on the surface of endothelial cells. A methanol extract and organic solvent (n-hexane, ethyl acetate, n-butanol, aqueous) fractions from Rubus coreanus were examined for their inhibitory effects on VEGF binding to the VEGF receptor. The methanol extract from the crude drug were found to significantly inhibit VEGF binding to the VEGF receptor ($IC_{50}$$\thickapprox$27 $\mu$g/mL). Among the fractions examined, the aqueous fraction from the medicinal plant showed potent inhibitory effects against the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ in a dose­dependent manner ($IC_{50}$$\thickapprox$11 $\mu$g/mL). Sanguiin H-6 was isolated as an active principle from the aqueous fraction, and inhibited the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ in a dose­dependent manner ($IC_{50}$$\thickapprox$0.3 $\mu$g/mL). In addition, sanguiin H-6 efficiently blocked the VEGF­induced HUVEC proliferation in a dose-dependent manner ($IC_{50}$$\thickapprox$7.4 $\mu$g/mL) but had no effect on the growth of HT1080 human fibrosarcoma cells. This suggests that sanguiin H-6 might be a potential anti-angiogenic agent.

• Tuberculosis and Respiratory Diseases
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• 제62권2호
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• pp.125-128
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• 2007

Docetaxel은 비소세포암에서 널리 사용되는 taxoid 계열의 항암제로, 조갑변화의 부작용은 한국에서 드물게 알려져 있다. 저자들은 비소세포암 4기인 62세 남환이 5차례 docetaxel 및 carboplatin 항암치료시행 7일 후 발생한 조갑하 농양 및 조갑 박리의 진단과 치료 1예를 경험하여 문헌 고찰과 함께 보고하는 바이다.

• BMB Reports
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• 제38권3호
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• pp.300-306
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• 2005

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

• 한국균학회소식:학술대회논문집
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• 한국균학회 2016년도 춘계학술대회 및 임시총회
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• pp.39-39
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• 2016

There is a growing consumer preference for self-medication, which has resulted in the growth of the Korean functional food market to \1.5 trillion in 2014. Functional foods that can modulate immune responses and enhance liver health are in the top 2 product-specific health functional food categories. The aim of this project was to develop and commercialize new health functional foods incorporated with Cordyceps militaris. Cordyceps genus includes about 400 species, many of which have been used as traditional medicines for many years in Asian countries. C. militaris belongs to the class Ascomycetes and has been used extensively as a crude drug and tonic food in East Asia. Owing to the various physiological activities of its main active constituent, cordyceptin, C. militaris is currently being used for multiple medicinal purposes. Recently, many studies have tried to elucidate the pharmacological mechanisms underlying the activities of Cordyceps spp., which include immune activation, anti-inflammatory, anticancer, and antiviral effects. After continuous attempts and research toward industrialization, C. militaris cultivated using brown rice was developed into a product by a standardized process and mass-cultivating system. It was successfully introduced into the market and was approved as a functional food ingredient for the first time in Korea. Based on this information, C. militaris containing functional food product for strengthening the immune system was released in August 2014 under the brand name "Dongchoong Ilgi." Dongchoong Ilgi is potentially beneficial for improving immune and liver functions and may enhance both the convenience and effectiveness of health functional foods taken by healthy people and patients with minor illness. In addition, the results of our study may be applicable for the development of health functional foods that could lower the risk of diseases such as the common cold and cancer.

• 대한약침학회지
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• 제22권2호
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• pp.102-108
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• 2019

Objectives: Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30. Methods: Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level. Results: Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05). Conclusion: Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

• Journal of Ginseng Research
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• 제46권3호
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• pp.337-347
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• 2022

Coronavirus disease 2019 (COVID-19) is currently a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 are directly associated with hyper-activation of innate immune response that excessively produce pro-inflammatory cytokines and induce cytokine storm, leading to multi-organ-failure and significant morbidity/mortality. Currently, several antiviral drugs such as Paxlovid (nirmatrelvir and ritonavir) and molnupiravir are authorized to treat mild to moderate COVID-19, however, there are still no drugs that can specifically fight against challenges of SARS-CoV-2 variants. Panax ginseng, a medicinal plant widely used for treating various conditions, might be appropriate for this need due to its anti-inflammatory/cytokine/viral activities, fewer side effects, and cost efficiency. To review Panax ginseng and its pharmacologically active-ingredients as potential phytopharmaceuticals for treating cytokine storm of COVID-19, articles that reporting its positive effects on the cytokine production were searched from academic databases. Experimental/clinical evidences for the effectiveness of Panax ginseng and its active-ingredients in preventing or mitigating cytokine storm, especially for the cascade of cytokine storm, suggest that they might be beneficial as an adjunct treatment for cytokine storm of COVID-19. This review may provide a new approach to discover specific medications using Panax ginseng to control cytokine storm of COVID-19.

• Journal of Microbiology and Biotechnology
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• 제32권10호
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• pp.1262-1274
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• 2022

Cholangiocarcinoma (CCA) is a complex and refractor type of cancer with global prevalence. Several barriers remain in CCA diagnosis, treatment, and prognosis. Therefore, exploring more biomarkers and therapeutic drugs for CCA management is necessary. CCA gene expression data was downloaded from the TCGA and GEO databases. KEGG enrichment, GO analysis, and protein-protein interaction network were used for hub gene identification. miRNA were predicted using Targetscan and validated according to several GEO databases. The relative RNA and miRNA expression levels and prognostic information were obtained from the GEPIA. The candidate drug was screened using pharmacophore-based virtual screening and validated by molecular modeling and through several in vitro studies. 301 differentially expressed genes (DEGs) were screened out. Complement and coagulation cascades-related genes (including AHSG, F2, TTR, and KNG1), and cell cycle-related genes (including CDK1, CCNB1, and KIAA0101) were considered as the hub genes in CCA progression. AHSG, F2, TTR, and KNG1 were found to be significantly decreased and the eight predicted miRNA targeting AHSG, F2, and TTR were increased in CCA patients. CDK1, CCNB1, and KIAA0101 were found to be significantly abundant in CCA patients. In addition, Molport-003-703-800, which is a compound that is derived from pharmacophores-based virtual screening, could directly bind to CDK1 and exhibited anti-tumor activity in cholangiocarcinoma cells. AHSG, F2, TTR, and KNG1 could be novel biomarkers for CCA. Molport-003-703-800 targets CDK1 and work as potential cell cycle inhibitors, thereby having potential for consideration for new chemotherapeutics for CCA.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.465-472
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• 2022

Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl₂ is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl₂-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl₂-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl₂ but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl₂, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

• BMB Reports
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• 제55권10호
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• pp.506-511
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• 2022

Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress.