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      • A Derivative of Chrysin Suppresses Two-Stage Skin Carcinogenesis by Inhibiting Mitogen- and Stress-Activated Kinase 1

        Liu, Haidan,Hwang, Joonsung,Li, Wei,Choi, Tae Woong,Liu, Kangdong,Huang, Zunnan,Jang, Jae-Hyuk,Thimmegowda, N.R.,Lee, Ki Won,Ryoo, In-Ja,Ahn, Jong-Seog,Bode, Ann M.,Zhou, Xinmin,Yang, Yifeng,Erikson, American Association for Cancer Research 2014 CANCER PREVENTION RESEARCH Vol.7 No.1

        <P>Mitogen- and stress-activated kinase 1 (MSK1) is a nuclear serine/threonine protein kinase that acts downstream of both extracellular signal-regulated kinases and p38 mitogen-activated protein kinase in response to stress or mitogenic extracellular stimuli. Increasing evidence has shown that MSK1 is closely associated with malignant transformation and cancer development. MSK1 should be an effective target for cancer chemoprevention and chemotherapy. However, very few MSK1 inhibitors, especially natural compounds, have been reported. We used virtual screening of a natural products database and the active conformation of the C-terminal kinase domain of MSK1 (PDB id 3KN) as the receptor structure to identify chrysin and its derivative, compound 69407, as inhibitors of MSK1. Compared with chrysin, compound 69407 more strongly inhibited proliferation and 12-<I>O</I>-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells with lower cytotoxicity. Western blot data demonstrated that compound 69407 suppressed phosphorylation of the MSK1 downstream effector histone H3 in intact cells. Knocking down the expression of MSK1 effectively reduced the sensitivity of JB6 P+ cells to compound 69407. Moreover, topical treatment with compound 69407 before TPA application significantly reduced papilloma development in terms of number and size in a two-stage mouse skin carcinogenesis model. The reduction in papilloma development was accompanied by the inhibition of histone H3 phosphorylation at Ser10 in tumors extracted from mouse skin. The results indicated that compound 69407 exerts inhibitory effects on skin tumorigenesis by directly binding with MSK1 and attenuates the MSK1/histone H3 signaling pathway, which makes it an ideal chemopreventive agent against skin cancer. <I>Cancer Prev Res; 7(1); 74–85. ©2013 AACR</I>.</P>

      • KCI등재후보

        Effect of Korean Oriental Medicine Extract on Bone Mass as Compared with Alendronate in Ovariectomized Rats

        강주섭,이주원,지옥화,Haidan Yuan,김태화,김동선,이민호,Ae-Son Om,이보배,박성국 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.3

        A number of alternative medicines (AMs) have often been used as traditional therapies for various diseaseswithout scientific or clinical evidence supporting their use. The present study examined the pharmaceutical effects of an AMextract with a long history of use as a traditional medicine for various bone diseases. To evaluate it as a potential candidatefor use as an anti-osteoporotic drug, we investigated the effects of the AM extract on the progression of bone loss in ovariec-tomized (OVX) rats fed a calcium (Ca)-deficient diet for 4 or 12 weeks. We also compared the AM extract with alendronate,an anti-resorptive drug. The AM extract did not influence bone turnover as indicated by biochemical markers [i.e., de-oxypyridinoline (DPD)]. In contrast, alendronate treatment seemed to reduce bone turnover via inhibition of bone resorptionas evidenced by reduced urinary DPD concentrations accompanied by a tendency for decreased serum tartrate-resistant acidphosphatase. Administration of alendronate or AM extracts did not significantly affect bone density, although both tended toincrease bone mineral density (BMD) and bone strength of the femur. Although both treatments did not affect vertebral BMDand bone strength, histological analysis of vertebrae showed well-developed trabecular networking in OVX rats treated withalendronate or AM extract, in contrast to the thin and disconnected trabecule in OVX rats. In conclusion, the AM extract pro-duced a very weak effect on the prevention of bone loss induced by OVX and Ca deficiency in rats, but was similar to theresults observed with alendronate. Further verification is necessary to justify the use of the AM extract as a treatment for os-teoporosis.

      • KCI등재

        Optimization Design for Dynamic Characters of Electromagnetic Apparatus Based on Niche Sorting Multi-objective Particle Swarm Algorithm

        Le Xu,Jiaxin You,Haidan Yu,Huimin Liang 한국자기학회 2016 Journal of Magnetics Vol.21 No.4

        The electromagnetic apparatus plays an important role in high power electrical systems. It is of great importance to provide an effective approach for the optimization of the high power electromagnetic apparatus. However, premature convergence and few Pareto solution set of the optimization for electromagnetic apparatus always happen. This paper proposed a modified multi-objective particle swarm optimization algorithm based on the niche sorting strategy. Applying to the modified algorithm, this paper guarantee the better Pareto optimal front with an enhanced distribution. Aiming at shortcomings in the closing bounce and slow breaking velocity of electromagnetic apparatus, the multi-objective optimization model was established on the basis of the traditional optimization. Besides, by means of the improved multi-objective particle swarm optimization algorithm, this paper processed the model and obtained a series of optimized parameters (decision variables). Compared with other different classical algorithms, the modified algorithm has a satisfactory performance in the multi-objective optimization problems in the electromagnetic apparatus.

      • SCISCIESCOPUS

        Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2.

        Liu, Kangdong,Park, Chanmi,Li, Shengqing,Lee, Ki Won,Liu, Haidan,He, Long,Soung, Nak Kyun,Ahn, Jong Seog,Bode, Ann M,Dong, Ziming,Kim, Bo Yeon,Dong, Zigang IRL Press] ; Oxford University Press 2012 Carcinogenesis Vol.33 No.7

        <P>Phosphatidylinositol 3-kinase (PI3-K) amplification and phosphatase and tensin homolog (PTEN) deletion-caused Akt activation contribute to the development of prostate cancer. Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/G관L and PRR5 and functions in the phosphorylation of Akt at Ser473. Herein, we report that mTORC2 plays an important role in PC3 androgen refractory prostate cell proliferation and anchorage-independent growth. Aloe-emodin, a natural compound found in aloe, inhibited both proliferation and anchorage-independent growth of PC3 cells. Protein content analysis suggested that activation of the downstream substrates of mTORC2, Akt and PKC관, was inhibited by aloe-emodin treatment. Pull-down assay and in vitro kinase assay results indicated that aloe-emodin could bind with mTORC2 in cells and inhibit its kinase activity. Aloe-emodin also exhibited tumor suppression effects in vivo in an athymic nude mouse model. Collectively, our data suggest that mTORC2 plays an important role in prostate cancer development and aloe-emodin suppresses prostate cancer progression by targeting mTORC2.</P>

      • KCI등재

        Detection of Inhibitors of Phenotypically Drug-tolerant Mycobacterium tuberculosis Using an In Vitro Bactericidal Screen

        Ian M. Bassett,Shichun Lun,William R. Bishai,Haidan Guo,Joanna R. Kirman,Mudassar Altaf,Ronan F. O’Toole 한국미생물학회 2013 The journal of microbiology Vol.51 No.5

        Many whole cell screens of chemical libraries currently in use are based on inhibition of bacterial growth. The goal of this study was to develop a chemical library screening model that enabled detection of compounds that are active against drug-tolerant non-growing cultures of Mycobacterium tuberculosis. An in vitro model of low metabolically active mycobacteria was established with 8 and 30 day old cultures of M. smegmatis and M. tuberculosis, respectively. Reduction of resazurin was used as a measure of viability and the assay was applied in screens of chemical libraries for bactericidal compounds. The model provided cells that were phenotypically-resilient to killing by first and second-line clinical drugs including rifampicin. Screening against chemical libraries identified proteasome inhibitors, NSC310551 and NSC321206, and a structurally-related series of thiosemicarbazones,as having potent killing activity towards aged cultures. The inhibitors were confirmed as active against virulent M. tuberculosis strains including multi- and extensively-drug resistant clinical isolates. Our library screen enabled detection of compounds with a potent level of bactericidal activity towards phenotypically drug-tolerant cultures of M. tuberculosis.

      • KCI등재

        DNA methylation of GDF-9 and GHR genes as epigenetic regulator of milk production in Egyptian Zaraibi goat

        Gamal Layaly,Noshy Magda M.,Aboul-Naga A. M.,Sabit Hussein,El-Shorbagy Haidan M. 한국유전학회 2024 Genes & Genomics Vol.46 No.1

        Background DNA methylation is an epigenetic mechanism that takes place at gene promoters and a potent epigenetic marker to regulate gene expression. Objective The study aimed to improve the milk production of Zaraibi goats by addressing the methylation pattern of two milk production-related genes: the growth hormone receptor (GHR) and the growth differentiation factor-9 (GDF-9). Methods 54 and 46 samples of low and high milk yield groups, respectively, were collected. Detection of methylation was assessed in two CpG islands in the GDF-9 promoter via methylation-specific primer assay (MSP) and in one CpG island across the GHR promoter using combined bisulfite restriction analysis (COBRA). Results A positive correlation between the methylation pattern of GDF-9 and GHR and their expression levels was reported. Breeding season was significantly effective on both peak milk yield (PMY) and total milk yield (TMY), where March reported a higher significant difference in PMY than November. Whereas single birth was highly significant on TMY than multiple births. The 3rd and 4th parities reported the highest significant difference in PMY, while the 4th parity was the most effective one on TMY. Conclusion These results may help improve the farm animals' milk productive efficiency and develop prospective epigenetic markers to improve milk yield by epigenetic marker-assisted selection (eMAS) in goat breeding programs.

      • KCI등재

        Ginsenoside Re Inhibits Osteoclast Differentiation in Mouse Bone Marrow-Derived Macrophages and Zebrafish Scale Model

        Park, Chan-Mi,Kim, Hye-Min,Kim, Dong Hyun,Han, Ho-Jin,Noh, Haneul,Jang, Jae-Hyuk,Park, Soo-Hyun,Chae, Han-Jung,Chae, Soo-Wan,Ryu, Eun Kyoung,Lee, Sangku,Liu, Kangdong,Liu, Haidan,Ahn, Jong-Seog,Kim, Y Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.12

        Ginsenosides, which are the active materials of ginseng, have biological functions that include anti-osteoporotic effects. Aqueous ginseng extract inhibits osteoclast differentiation induced by receptor activator of NF-${\kappa}B$ ligand (RANKL). Aqueous ginseng extract produces chromatography peaks characteristic of ginsenosides. Among these peaks, ginsenoside Re is a major component. However, the preventive effects of ginsenoside Re against osteoclast differentiation are not known. We studied the effect of ginsenoside Re on osteoclast differentiation, RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity, and formation of multinucleated osteoclasts in vitro. Ginsenoside Re hampered osteoclast differentiation in a dose-dependent manner. In an in vivo zebrafish model, aqueous ginseng extract and ginsenoside Re had anti-osteoclastogenesis effects. These findings suggest that both aqueous ginseng extract and ginsenoside Re prevent bone resorption by inhibiting osteoclast differentiation. Ginsenoside Re could be important for promoting bone health.

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