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Primary hepatic tumors mainly include hepatocellular carcinoma (HCC), which is one of the most frequent causes of cancer‐related deaths worldwide. Thus far, HCC prognosis has remained extremely poor given the lack of effective treatments. Numerous studies have described the roles played by microRNAs (miRNAs) in cancer progression and the potential of these small noncoding RNAs for diagnostic or therapeutic applications. The current consensus supports the idea that direct repression of a wide range of oncogenes by a single key miRNA could critically affect the malignant properties of cancer cells in a synergistic manner. In this study, we aimed to investigate the oncogenes controlled by miR‐493‐5p, a major tumor suppressor miRNA that inactivates miR‐483‐3p oncomir in hepatic cancer cells. Using global gene expression analysis, we highlighted a set of candidate genes potentially regulated by miR‐493‐5p. In particular, the canonical MYCN protooncogene (MYCN) appeared to be an attractive target of miR‐493‐5p given its significant inhibition through 3′‐UTR targeting in miR‐493‐5p‐rescued HCC cells. We showed that MYCN was overexpressed in liver cancer cell lines and clinical samples from HCC patients. Notably, MYCN expression levels were inversely correlated with miR‐493‐5p in tumor tissues. We confirmed that MYCN knockdown mimicked the anticancer effect of miR‐493‐5p by inhibiting HCC cell growth and invasion, whereas MYCN rescue hindered miR‐493‐5p activity. In summary, miR‐493‐5p is a pivotal miRNA that modulates various oncogenes after its reexpression in liver cancer cells, suggesting that tumor suppressor miRNAs with a large spectrum of action could provide valuable tools for miRNA replacement therapies., Our study highlighted the MYCN protooncogene as a critical target of microRNA (miR)‐493‐5p tumor suppressor. We found that MYCN was overexpressed in hepatic cancer cells and that miR‐493‐5p negatively repressed MYCN at the posttranscriptional level. We confirmed that MYCN silencing mimicked the anticancer activity of miR‐493‐5p by inhibiting hepatic tumor cell growth and invasion.

The aqueous extract of Peltophorum pterocarpum (Fabaceae) wood exhibited potent inhibitory effects against EpsteinBarr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and against melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 melanoma cells, as well as potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging activity. Two phenolic acid derivatives, bergenin (1) and gallic acid (2), were isolated from the ethyl acetate (AcOEt)-soluble fraction obtained from the extract. Compound 1 exhibited potent inhibitory effect against EBV-EA activation and against skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. Both compounds 1 and 2 exhibited melanogenesis-inhibitory activities in α-MSH-stimulated B16 melanoma cells, and, in addition, compound 2 showed strong DPPH radical-scavenging activity.

A new phloroglucinol derivative, 5-deprenyllupulonol C (1), along with four other phloroglucinol derivatives, 2-5, five chalcones, 6-10, four flavanones, 11-14, two flavonol glycosides, 15 and 16, and five triterpenoids, 17-21, were isolated from the female inflorescence pellet extracts of hop (Humulus lupulus L.). Upon evaluation of these compounds against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, twelve compounds, i.e., 1-4, 11-14, 17-19, and 21, showed potent inhibitory effects on EBV-EA induction, with IC₅₀ values in the range of 215-393 mol ratio/32 pmol TPA. In addition, eleven compounds, i.e., 1-4, 6, 11, 12, 14, 17, 18, and 20, were found to inhibit TPA-induced inflammation (1 μg/ear) in mice, with ID₅₀ values in the range of 0.13-1.06 μmol per ear. Further, lupulone C (2) and 6-prenylnaringenin (14) exhibited inhibitory effects on skin-tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and with TPA as promoter.

A novel dimeric diarylheptanoid, (5R,5′R)-7,7′-(6,6′-dihydroxy-5,5′-dimethoxy[1,1′-biphenyl]-3,3′-diyl)bis[5-methoxy-1-phenylheptan-3-one] (1), and two new diarylheptanoids, (4E,6R)-6-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (2) and (4E,6R)-6-hydroxy-1,7-diphenylhept-4-en-3-one (3), together with seven known diarylheptanoids, were isolated from the rhizomes of Alpinia officinarum. Their structures were elucidated by application of extensive spectroscopic analyses and the modified Mosher method.

550.Over the past three decades, the red-winged blackbird Agelaius phoeniceus has servedas a model species for studies of sexual selection and the evolution of ornamental traits.Particular attention has been paid to the role of the colorful red-and-yellow epauletsthat are striking in males but reduced in females and juveniles. It has been assumed thatcarotenoid pigments bestow the brilliant red and yellow colors on epaulet feathers, butthis has never been tested biochemically. Here, we use high-performance liquidchromatography (HPLC) to describe the pigments present in these colorful feathers.Two red ketocarotenoids (astaxanthin and canthaxanthin) are responsible for thebright red hue of epaulets. Two yellow dietary precursors pigments (lutein andzeaxanthin) are also present in moderately high concentrations in red feathers. Afterextracting carotenoids, however, red feathers remained deep brown in color. HPLCtests show that melanin pigments (primarily eumelanin) are also found in the red-pigmented barbules of epaulet feathers, at an ‘approximately equal concentration tocarotenoids. This appears to be an uncommon feature of carotenoid-based ornamentalplumage in birds, as was shown by comparable analyses of melanin in the yellowfeathers of male American goldfinches Carduelis tristis and the red feathers of northerncardinals Cardinalis cardinalis, in which we detected virtually no melanins.Furthermore, the yellow bordering feathers of male epaulets are devoid ofcarotenoids (except when tinged with a carotenoid-derived pink coloration onoccasion) and instead are comprised of a high concentration of primarilyphaeomelanin pigments. The dual pigment composition of red epaulet feathers andthe melanin-only basis for yellow coloration may have important implications for thehonesty-reinforcing mechanisms underlying ornamental epaulets in red-wingedblackbirds, and shed light on the difficulties researchers have had to date incharacterizing the signaling function of this trait. As in several other birds, themelanic nature of feathers may explain why epaulets are used largely to settle aggressivecontests rather than to attract mates.K. J. McGraw (correspondence), Department of Neurobiology and Behavior, CornellUniversity, Ithaca, NY 14853 USA. K. Wakamatsu, Fujita Health University, School ofHealth Sciences, Toyoake, Aichi, 470-1192 Japan. A. B. Clark, Department of BiologicalSciences, Binghamton University, Binghamton, NY 13902 USA. K. Yasukawa,Department of Biology, Beloit College, Beloit, WI 53511 USA. Present address ofK. J. McGraw: School of Life Sciences, Arizona State University, Tempe, AZ 85287-4501USA. E-mail: Kevin.McGraw@asu.edu

The methanol extract of the florets of Tagetes patula (MEFTP) inhibited acute and chronic inflammation in mice and rats. MEFTP significantly suppressed hind-paw oedema induced by gamma-carrageenin in mice. Furthermore, MEFTP not only inhibited the hind-paw oedema induced by various acute phlogogens, such as histamine, serotonin, bradykinin and prostaglandin E1, but also suppressed the increase of vascular permeability by acetic acid, indicating that it primarily acts at the exudative stage of inflammation. In the chronic inflammation, MEFTP did not inhibit the proliferation of granulation tissue when tested by the cotton pellet method, however, it was effective on the development of adjuvant arthritis in rats. Oral MEFTP inhibited acute and chronic inflammation in mice and rats.

We report that the extracts of Compositae plants inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear oedema in mice. Seventy five methanol extracts obtained from 53 species in 11 tribes of Compositae plants were assayed and their inhibitory ratios calculated. In general, medicinal and edible plant extracts were more effective inhibitors than those from other materials, and the flower extracts were more effective inhibitors than those from other parts. The methanol extracts of the flowers of Cirsium arvense, Taraxacum officinale and T. platycarpum (dandelion), Chrysanthemum morifolium var. sinensis forma esculentum (edible chrysanthemum), C. nipponicum, Matricaria matricarioides and Helianthus annuus (sunflower) markedly inhibited the inflammation induced by TPA in mice. Copyright © 1998 John Wiley & Sons, Ltd.

The methanol extract of Pruni Cortex inhibited tumour promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mice. The active component was isolated from the methanol extract of Pruni Cortex. The active compound was characterized as octacosyl ferulate by physical and chemical analysis. Octacosyl ferulate markedly inhibited the inflammatory activity induced by TPA in mice. The 50% inhibitory dose of octacosyl ferulate is 0.7 mg/ear on TPA-induced inflammation. Furthermore, octacosyl ferulate suppressed markedly the tumour-promoting effect of TPA on skin tumour formation following initiation with DMBA. Since protein kinase C (PK-C) was shown to be an intracellular target of TPA, effects of octacosyl ferulate on the activity of this enzyme were investigated. Octacosyl ferulate also inhibited the phosphorylation of histon III-S by PK-C in a concentration dependent manner. © 1998 John Wiley & Sons, Ltd.

An antitumour-promoting activity in two-stage carcinogenesis, is found in the methanol extract of the Carthami Flos (Carthamus tinctorius L.; Compositae), which is a traditional Chinese medicine and natural pigment of rouge additivies in certain Asian countries. From these active fractions, Δ 5 - and Δ 7 -sterol fractions were separated. The separation was examined for inhibitory activity against TPA-induced inflammatory ear oedema in mice. Stigmasterol (71% in the mixture) was the most abundant of 14 sterols identified in the Δ 7 -sterol fraction. Schottenol (70% in the mixture) constituted the dominant sterol of the Δ 7 -sterol fraction. Furthermore, stigmasterol markedly inhibited tumour promotion in two-stage carcinogenesis experiments

An antitumour-promoting activity in two-stage carcinogenesis, was found in the methanol and ethyl acetate extracts of the Japanese edible mushroom ‘Buna-shimeji’, Hypsizigus marmoreus (Tricholomataceae). From the active fractions of the extracts, two sterols, ergosterol and ergosterol peroxide, were isolated. The isolates showed inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate induced ear inflammation in mice, and ergosterol markedly inhibited tumour promotion in a two-stage carcinogenesis experiment. These sterols may be useful in developing an effective method of cancer prevention.

We report that spice, vegetable and fruit extracts inhibit 12–O-tetradecanoylphorbol–13-acetate (TPA)-induced ear oedema in mice. About 100 methanol extracts obtained from spices, vegetables and fruits were assayed and their inhibition ratios calculated. In general, the spice extracts were more effective inhibitors than vegetable and fruit extracts. The methanol extracts of hop, stevia, cinnamon, turmeric, mate, mint, New Zealand spinach, watercress, tomato and seedling of radish markedly inhibited the inflammatory activity induced by TPA in mice. Two active compounds, humulone and lupeol 3-palmitate were separated from hop and stevia, respectively.

Five triterpenes with a D:C-friedo-oleanane skeleton, D:C-friedo-oleana-7,9(11)-diene-3 beta,29-diol (3-epikarounidiol), 7-oxo-D:C-friedo-olean-8-en-3 beta-ol (7-oxoisomultiflorenol), 7-oxo-8 beta-D:C-friedo-olean-9(11)-ene-3 alpha,29-diol, D:C-friedo-olean-8-ene-3 alpha,29-diol (3-epibryonolol), and D:C-friedo-olean-8-ene-3 beta,29-diol (bryonolol), the first four of which are new naturally occurring compounds, were isolated from the seeds of Trichosanthes kirilowii Maxim. The structures were determined by spectral and chemical methods. 3-Epikarounidiol, 7-oxoisomultiflorenol, and 3-epibryonolol showed marked inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation in mice. The 50% inhibitory dose of these triterpenes for TPA-induced inflammation (1 microgram) was 0.2-0.6 mg/ear.

Five hydroxylated sterols, stigmastane-3β, 6α-diol, poriferastane-3β, 6α-diol, stigmast-5-ene-3β, 4β-diol, poriferast-5-ene-3β, 4β-diol, and poriferasta-5, 25-diene-3β, 4β-diol, the latter four of which are new naturally occurring compounds, were isolated from the unsaponifiable lipid of the seed extract of Trichosanthes kirilowii MAXIM. The structures were determined by spectral and chemical methods.

A novel 3, 4-seco-triterpene alcohol with a migrated euphane-type skeleton, called helianol, was isolated together with seven known triterpene alcohols from the nonsaponifiable lipid of the tabular flower extract of Helianthus annus L. The structure was determined by extensive spectroscopic analyses.

Four novel triterpene alcohols with a Δ5-unsaturated tirucallane-type skeleton, i.e. tirucall-5-en-3β-ol, tirucalla-5,24-dien-3β-ol, 24-methyltirucalla-5,24(241)-dien-3β-ol and (24S)-24-methyltirucalla-5,25-dien-3β-ol, have been isolated from the roots of Bryonia dioica Jacq. (Cucurbitaceae). The structures have been determined by spectroscopic and chromatographic methods. These compounds are the first examples of naturally occurring C-10 methylated triterpenes with a Δ5-monounsaturated skeleton.

Two novel cycloartane-type triterpene alcohols possessing a monohydroxy-tetrahydrofuran ring in the side chain, cyclokirilodiol and isocyclokirilodiol, were isolated from the nonsaponifiable lipid fraction obtained from the methanolic extract of Trichosanthes kirilowii seeds. Their structures were determined as (22S, 24S)-22, 25-epoxy-24-hydroxy-5α-cycloartan-3β-ol and (22R, 24S)-22, 25-epoxy-24-hydroxy-5α-cycloartan-3β-ol, respectively, by detailed spectroscopic analyses.

The structure of astertarone A isolated from the root extract of Aster tataricus L. (Compositae) was established to be D : A-friedoeuph-21-en-3-one (1) based on spectroscopic methods. This is the first example of a naturally occurring triterpenoid with a D : A-friedoeuphane skeleton. Isolation and identification of epishinol (2), shionone (3), friedelin, epifriedelinol, and Ψ-taraxasterol are also described.

Four new polyketide derivatives, Trichodermatides A−D (1−4) were isolated from the marine-derived fungus Trichoderma reesei. Trichodermatide A (1) is an unprecedented example of a polyketide with a ketal-containing pentacyclic skeleton. The chemical structures and absolute configurations of compounds 1−4 were elucidated by extensive spectroscopic methods, especially 2D NMR and CD spectral analysis, and supported by their proposed biosynthesis pathway. The cytotoxicity of 1−4 was evaluated against A375-S2 human melanoma cell line.

Edible mushroom extracts inhibited 12.O.tetradecanoylphorbol-13-acetate (TPA)-induced ear oedema in mice. Twenty seven methanol extracts obtained from mushrooms were assayed and their inhibition ratios calculated. The methanol extracts of Russula delica, Mycoleptodonoides aitchisonii, Lactarius deliciosus, Naematoloma sublateritium, Lyophyllum decastes and Lyophyllum connatum markedly inhibited the inflammatory activity induced by TPA in mice. The methanol extract from Mycoleptodonoides aitchisoni was found to inhibit tumour promotion in two-stage carcinogenesis in mouse skin.

The asymmetric synthesis of (6S,8R)-, (6S,8S)-, (6R,8S)- and (6R,8R)-heptacosane-6,8-diols from (2S)-, (2R)-1-[(R)-p-tolylsulfinyl]-2-heptanols and 1-icosanal is described.

The Deltadelta (deltaS-deltaR) values for the C-1 methyl 1H signals in the 1H-NMR spectroscopy of the bis-MTPA esters of four synthetic stereoisomers of alkane-6,8-diols, viz., bis-MTPA esters of (6S,8R)-C27- (1a) and C29- (3a) (Deltadelta = -0.05 ppm), (6R,8S)-C27- (2a) and C29- (4a) (Deltadelta = +0.05 ppm), (6S,8S)-C27- (5a) (Deltadelta = -0.01 ppm), and (6R,8R)-C27- (6a) (Deltadelta = +0.01 ppm) alkane-6,8-diols, made it possible to differentiate unequivocally among the four stereoisomers. This allowed the determination of the (6S,8R)-stereochemistry (Deltadelta = -0.05 ppm for the bis-MTPA esters) for the natural C27- and C29-alkane-6,8-diols isolated from the flowers of three Compositae plants, Carthamus tinctorius, Cynara cardanclus, and Taraxacum platycarpum.

Male Red-winged Blackbird pairing success was studied to determine the role of male quality in female choice of territory and mate. Data on date of first nest, harem size, and proportion of territorial males surviving to subsequent breeding seasons did not support the hypothesis that territory quality alone determines female choice of mate. Male reproductive experience and body size were significantly positively correlated with harem size, but correlations between male age and harem size, and male courtship intensity and harem size, appeared to occur because females preferred territories defended by experienced males. There was no evidence that male aggressive tendencies influenced female choice of mate. Although these data indicate that females were influenced by male characteristics, it is suggested that a complex interaction of male and territory quality determines female choice of mate in the Red-winged Blackbird.