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Identification of Novel Functional Variants of SIN3A and SRSF1 among Somatic Variants in Acute Myeloid Leukemia Patients

  • Min, Jae-Woong;Koh, Youngil;Kim, Dae-Yoon;Kim, Hyung-Lae;Han, Jeong A;Jung, Yu-Jin;Yoon, Sung-Soo;Choi, Sun Shim
    • Molecules and Cells
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    • v.41 no.5
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    • pp.465-475
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    • 2018
  • The advent of massively parallel sequencing, also called next-generation sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AML-related genes. Notably, SIN3A expression shows prognostic value in AML. A newly designed method, referred to as "hot-zone" analysis, detected two putative functional noncoding variants that can alter transcription factor binding affinity near PPP1R10 and SRSF1. Moreover, the functional importance of the SRSF1 noncoding variant was further investigated by luciferase assays, which showed that the variant is critical for the regulation of gene expression leading to leukemogenesis. We expect that further functional investigation of these coding and noncoding variants will contribute to a more in-depth understanding of the underlying molecular mechanisms of AML and the development of targeted anti-cancer drugs.

The Anticancer Role of Capsaicin in Experimentally-induced Lung Carcinogenesis

  • Anandakumar, Pandi;Kamaraj, Sattu;Jagan, Sundaram;Ramakrishnan, Gopalakrishnan;Asokkumar, Selvamani;Naveenkumar, Chandrashekar;Raghunandhakumar, Subramanian;Vanitha, Manickam Kalappan;Devaki, Thiruvengadam
    • Journal of Pharmacopuncture
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    • v.18 no.2
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    • pp.19-25
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    • 2015
  • Objectives: Capsaicin (CAP) is the chief pungent principle found in the hot red peppers and the chili peppers that have long been used as spices, food additives and drugs. This study investigated the anticancer potential of CAP through its ability to modify extracellular matrix components and proteases during mice lung carcinogenesis. Methods: Swiss albino mice were treated with benzo(a) pyrene (50 mg/kg body weight dissolved in olive oil) orally twice a week for four successive weeks to induce lung cancer at the end of $14^{th}$ week. CAP was administrated (10 mg/kg body weight dissolved in olive oil) intraperitoneally. Extracellular matrix components were assayed; Masson's trichome staining of lung tissues was performed. Western blot analyses of matrix metalloproteases 2 and 9 were also carried out. Results: In comparison with the control animals, animals in which benzo(a)pyrene had induced lung cancer showed significant increases in extracellular matrix components such as collagen (hydroxy proline), elastin, uronic acid and hexosamine and in glycosaminoglycans such as hyaluronate, chondroitin sulfate, keratan sulfate and dermatan sulfate. The above alterations in extracellular matrix components were effectively counteracted in benzo(a)pyrene along with CAP supplemented animals when compared to benzo(a) pyrene alone supplemented animals. The results of Masson's trichome staining for collagen and of, immunoblotting analyses of matrix metalloproteases 2 and 9 further supported the biochemical findings. Conclusion: The apparent potential of CAP in modulating extracellular matrix components and proteases suggests that CAP plays a chemomodulatory and anti-cancer role working against experimentally induced lung carcinogenesis.

Guideline for Bioequivalence Studies of Generic Products for Topical Use (국소용 후발의약품의 생물학적동등성시험을 위한 가이드라인)

  • Choi, Sun-Ok;Jung, Sung-Hee;Um, So-Young;Jung, Seo-Jeong;Kim, Joo-Il;Chung, Soo-Youn
    • Journal of Pharmaceutical Investigation
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    • v.34 no.4
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    • pp.333-340
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    • 2004
  • A new medical system of separation of dispensary from medical practice was started in 2000 in Korea. To expand bioequivalence-proven drug products and to ensure the credibility of the therapeutic equivalence of generic drug are hot issues in Korea. The KFDA also has a plan to revise the pharmaceutical affairs law that bioequivalence reports of all the generic prescription drugs should be submitted to the KFDA in the application for drug approval. Therefore, it becomes more necessary to develop bioequivalence-demonstrating methods for specific preparations such as topical drug products. There are some differences between US and Japanese guidances of bioequivalence studies of generic drug products for topical use. In this paper, we examined the recently published Japanese guideline, Guideline for Bioequivalence Studies of Generic Products For Topical Uses, and Q&A of the guideline, which will be references to make a guidance on bioequivalence studies of topical drug products in Korea.

Physiological Activities of Extract from Edible Mushrooms (주요 식용버섯 추출물의 생리활성 효과)

  • Choi, Se-Jin;Lee, Yeon-Sil;Kim, Jin-Kyung;Kim, Jin-Kyu;Lim, Soon-Sung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.8
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    • pp.1087-1096
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    • 2010
  • This study was conducted to investigate the physiological activity of extracts of fresh mushrooms. The components were extracted by hot water; subsequently, the hot-water extract was subjected to 60% ethanol precipitation to yield high-molecular-weight (HMW) and low-molecular-weight (LMW) fractions. Total polyphenol contents, $\beta$-glucan contents, electron-donating ability (EDA), superoxide dismutase (SOD)-like activity, nitrite-scavenging activity, fibrinolytic activity, nitric oxide (NO) production, and inhibition of NO production of the mushroom extracts were measured using lipopolysaccharide (LPS)-stimulated murine macrophages, RAW 264.7 cells. The extracts of Lentinus edodes (Berk.) Singer and Pleurotus ostreatus (Fr.) Kummer contained the highest levels of $\beta$-glucan (33.5% and 25.57%, respectively). Further, the LMW fractions of the Phellinus linteus contained the highest levels of polyphenols (233.23 mg/g). The EDA of LMW fractions (10 mg/mL) of the Phellinus linteus and Agaricus bisporus were 80.74% and 51.35%, respectively. Further, SOD-like activities of the LMW fractions were high as compared to those of the HMW fractions. Nitrite-scavenging activities of the LMW fractions (pH 1.2; concentration, 10 mg/mL) of the Phellinus linteus and Pleurotus ostreatus (Fr.) Kummer were 75.95% and 41.05%, respectively. The fibrinolytic activity of the LMW fractions of all mushrooms showed no enzyme activity by fibrin plate assay. The fibrinolytic activity of the extracts of Tricholoma matsutake was the greatest inhibitory activity at 60.4%. Further study revealed that the mushroom extracts exhibited anti-inflammatory effects on RAW 264.7 cells. The LMW fraction ($500\;{\mu}g/mL$) of the Phellinus linteus considerably inhibited NO production (100%).

The Anti-angiogenic Potential of a Phellodendron amurense Hot Water Extract in Vitro and ex Vivo (in Vitro와 ex vivo에서 황백 온수추출물의 신생혈관 억제효과)

  • Kim, Eok-Cheon;Kim, Seo Ho;Bae, Kiho;Kim, Han Sung;Gelinsky, Michael;Kim, Tack-Joong
    • Journal of Life Science
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    • v.25 no.6
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    • pp.693-702
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    • 2015
  • Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

Pharmacological Effects of Proteoglycans Extracted from Fruiting Bodies of Fomitella fraxinea (장수버섯 자실체의 열탕추출액으로부터 분리한 단백다당체의 약리적 효과)

  • Yoon, Sang-Hong;Lim, Jae-Hyeon;Kim, Yang-Seop;Kim, Chang-Han;Jo, Joon-Hyeong;Hwang, Young-Soo
    • The Korean Journal of Mycology
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    • v.26 no.4 s.87
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    • pp.511-518
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    • 1998
  • Anti-complementary assay for immuno-stimulating polysaccharide screening, human tumor colony-forming assay for discovering anti-tumor drugs, and toxic assay against mouse were performed to examine pharmacological activities of polysaccharides extracted from fruiting bodies of Jang-soo mushroom (Fomitella fraxinea). Hot water $(100^{\circ}C,\;FF-I)$, 1% ammonium oxalate solution $(80^{\circ}C,\;FF-II)$, and 5% sodium hydroxide solution $(80^{\circ}C,\;FF-III)$ were used for extraction of three polysaccharides from fruiting bodies of it. Anti-complementary activity of FF-I was more effective than the others. FF-I was further fractionated into three groups of polysaccharide by DEAE-Sephadex A25 column chromatography (FF-NP, FF-AP1, and FF-AP2). FF-AP1 showed not only the highest anti-complementary activity but also the growth-inhibitory activity against Snu-I (human stomach cancer cell) among 9 kinds of human tumor cell lines. But FF-AP2 exhibited its activity against Hep-2(larynx cancer) and KB(mouth epidermal cancer) cell lines at $500\;{\mu}g/ml$ although its anti-complementary activity was lower than it of FF-AP1. When FF-I was orally administrated to mice with dosage of 5000 mg/kg, no remarkable changes were observed in viewpoint of tissue-pathology.

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Structural analysis, anti-inflammatory activity of the main water-soluble acidic polysaccharides (AGBP-A3) from Panax quinquefolius L berry

  • Zhihao Zhang;Huijiao Yan;Hidayat Hussain;Xiangfeng Chen;Jeong Hill Park;Sung Won Kwon;Lei Xie;Bowen Zheng;Xiaohui Xu;Daijie Wang;Jinao Duan
    • Journal of Ginseng Research
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    • v.48 no.5
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    • pp.454-463
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    • 2024
  • Background: Panax quinquefolius L, widely recognized for its valuable contributions to medicine, has aroused considerable attention globally. Different from the extensive research has been dedicated to the root of P. quinquefolius, its berry has received relatively scant focus. Given its promising medicinal properties, this study was focused on the structural characterizations and anti-inflammatory potential of acidic polysaccharides from the P. quinquefolius berry. Materials and methods: P. quinquefolius berry was extracted with hot water, precipitated by alcohol, separated by DEAE-52-cellulose column to give a series of fractions. One of these fractions was further purified via Sephadex G-200 column to give three fractions. Then, the main fraction named as AGBP-A3 was characterized by methylation analysis, NMR spectroscopy, etc. Its anti-inflammatory activity was assessed by RAW 264.7 cell model, zebrafish model and molecular docking. Results: The main chain comprised of α-L-Rhap, α-D-GalAp and β-D-Galp, while the branch consisted mainly of α-L-Araf, β-D-Glcp, α-D-GalAp, β-D-Galp. The RAW264.7 cell assay results showed that the inhibition rates against IL-6 and IL-1β secretion at the concentration of 625 ng/mL were 24.83 %, 11.84 %, while the inhibition rate against IL-10 secretion was 70.17 % at the concentration of 312 ng/mL. In the zebrafish assay, the migrating neutrophils were significantly reduced in number, and their migration to inflammatory tissues was inhibited. Molecular docking predictions correlated well with the results of the anti-inflammatory assay. Conclusion: The present study demonstrated the structure of acidic polysaccharides of P. quinquefolius berry and their effect on inflammation, providing a reference for screening anti-inflammatory drugs.

Investigation of radical scavenging and anti-inflammatory activity of the extract and fractions of Termitomyces albuminosus (계종버섯 추출물과 분획물의 라디칼 소거 활성과 항염증 활성 분석)

  • Kang, Min-Jae;Kim, Young-Jae;Hwang, Hyeon-Jeong;Kim, Moon-Ho;Sin, Jong-Moo;Shin, Pyung-Gyun;Kim, Gun-Do;Kim, Keun Ki
    • Journal of Mushroom
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    • v.18 no.1
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    • pp.45-52
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    • 2020
  • Termitomyces albuminosus has been recognized to have the best mushrooms in China, in terms of taste and aroma. The efficacy of these mushrooms has been recorded in the botanical list. However, research on the development of their artificial culture methods is necessary. In this study, we prepared an organic solvent extract and a hot water extract to understand the development of compounds and functional foods with antioxidant and anti-inflammatory activities. The IC50 value of DPPH radical scavenging activity of the hot water extract (TA4) was 1.5 mg/mL and the IC50 value of the MeOH fraction (TA2) was 1.93 mg/mL. The anti-inflammatory activity was investigated by the inhibition of NO production. EtOAc fraction (TA1) is a crude extract, but 79% of NO production was inhibited at 100 ㎍/mL. NO was not produced at 200 ㎍/mL. TA1-5-6, from TA1 inhibited NO production by 15% as compared to the positive control at 15 ㎍/mL, and completely inhibited NO production at 30 ㎍/mL. No cytotoxicity was observed at 50 ㎍/mL. TA2-1-5 from the MeOH fraction (TA2) inhibited more than 75% of NO production at 30 ㎍/mL; cytotoxicity was very low even at 50 ㎍/mL. In conclusion, by selective solvent selection, it was possible to manufacture an extract with no cytotoxicity and excellent biological activities. Furthermore, the extracts showed potential for developing various functional foods and drugs.