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Begoña Miras-Moreno, Lorena Almagro, María Angeles Pedreño, Ana Belén Sabater-Jara
Terbinafine induced a significant increase of squalene production. Terbinafine increased the expression levels of squalene synthase. Cyclodextrins did not work as elicitors due to the gene expression levels obtained. Plant sterols are essential components of membrane lipids, which contributing to their fluidity and permeability. Besides their cholesterol-lowering properties, they also have anti-inflammatory, antidiabetic and anticancer activities. Squalene, which is phytosterol precursor, is widely used in medicine, foods and cosmetics due to its anti-tumor, antioxidant and anti-aging activities...
April 21, 2018: Plant Cell Reports
Francisco Cen-Pacheco, Claudia Pérez Manríquez, María Luisa Souto, Manuel Norte, José Javier Fernández, Antonio Hernández Daranas
The red seaweed Laurencia viridis is a rich source of oxygenated secondary metabolites that were derived from squalene. We report here the structures of three novel compounds, (+)-longilene peroxide ( 1 ), longilene ( 2 ), and (+)-prelongilene ( 3 ) that were isolated from this alga, in addition to other substances, 4 and 5 , resulting from their acid-mediated degradation. The effect of compounds 1 and 3 against Ser-Thr protein phosphatase type 2A (PP2A) was evaluated, showing that (+)-longilene peroxide ( 1 ) inhibited PP2A (IC50 11...
April 17, 2018: Marine Drugs
Dabin Liu, Chi Chun Wong, Li Fu, Huarong Chen, Liuyang Zhao, Chuangen Li, Yunfei Zhou, Yanquan Zhang, Weiqi Xu, Yidong Yang, Bin Wu, Gong Cheng, Paul Bo-San Lai, Nathalie Wong, Joseph J Y Sung, Jun Yu
Nonalcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma (HCC) is an emerging malignancy in the developed world; however, mechanisms that contribute to its formation are largely unknown, and targeted therapy is currently not available. Our RNA sequencing analysis of NAFLD-HCC samples revealed squalene epoxidase ( SQLE ) as the top outlier metabolic gene overexpressed in NAFLD-HCC patients. Hepatocyte-specific Sqle transgenic expression in mice accelerated the development of high-fat, high-cholesterol diet-induced HCC...
April 18, 2018: Science Translational Medicine
Daniela Dorado A, Andrés Hurtado B, Hugo A Martínez-Correa
In the present investigation, the extraction of tamarillo seed oil was conducted using supercritical carbon dioxide (SC-CO2), under different conditions of pressure (20-38.1 MPa) and temperature (40-64°C). In order to determine the effect that these extraction parameters have over the yield and composition of the oil, a central composite design was used. The optimum yield was 21.07 % obtained at 38.1 MPa and 64°C. The fatty acids of the tamarillo seed oil obtained with SC-CO2 were identified: linoleic (70...
April 16, 2018: Electrophoresis
Xiao-Yu Hu, Fu-Ying Qin, Xi-Feng Lu, Lan-Sheng Zhang, Yong-Xian Cheng
Three new polyynes, named choushenpilosulynes A-C ( 1 - 3 ), were isolated from an 85% aqueous EtOH extract of the roots of Codonopsis pilosula cultivated in Xundian County of Yunnan province, China. Their structures, including the absolute configuration of the glucose residue in 1 and 2 , were determined by spectroscopic analysis and gas chromatography (GC). In addition, biological evaluation shows that all the compounds can inhibit the expression of the squalene monooxygenase (SQLE) gene in HepG2 cells, suggesting that these compounds may be involved in lipid metabolism...
April 12, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hiroaki Iwasaka, Ryo Koyanagi, Ryota Satoh, Akiko Nagano, Kenshi Watanabe, Kanako Hisata, Noriyuki Satoh, Tsunehiro Aki
Labyrinthulomycetes have been regarded as a promising industrial source of xanthophylls, including astaxanthin and canthaxanthin, polyunsaturated fatty acids such as docosahexaenoic acid and docosapentaenoic acid, ω-3 oils, and terpenic hydrocarbons, such as sterols and squalene. A Thraustochytrid, Aurantiochytrium sp. KH105 produces carotenoids, including astaxanthin, with strong antioxidant activity. To gain genomic insights into this capacity, we decoded its 97-Mbp genome and characterized genes for enzymes involved in carotenoid biosynthesis...
April 9, 2018: Genes
Kenshi Watanabe, Kim Hazel V Arafiles, Risa Higashi, Yoshiko Okamura, Takahisa Tajima, Yukihiko Matsumura, Yutaka Nakashimada, Keisuke Matsuyama, Tsunehiro Aki
The marine eukaryotic microheterotroph thraustochytrid genus Aurantiochytrium is a known producer of polyunsaturated fatty acids, carotenoids, and squalene. We previously constructed a lipid fermentation system for Aurantiochytrium sp. strains using underutilized biomass, such as canned syrup and brown macroalgae. To improve the productivity, in this study, Aurantiochytrium sp. RH-7A and RH-7A-7 that produced high levels of carotenoids, such as astaxanthin and canthaxanthin, were isolated through chemical mutagenesis...
April 9, 2018: Journal of Oleo Science
Thaís Larré Oliveira, Rodrigo Andrade Schuch, Guilherme Roig Inda, Bárbara Couto Roloff, Amilton Clair Pinto Seixas Neto, Marta Amaral, Odir Antonio Dellagostin, Daiane Drawanz Hartwig
BACKGROUND: Recombinant subunit vaccines have been extensively evaluated as promising alternatives against leptospirosis. Here, we evaluated two proteins in formulations containing the adjuvant AddaVax™ as vaccine candidates for prevention and control of leptospirosis. METHODS: Recombinant proteins rErp Y-like and rLemA were characterized by ELISA to assess their ability to bind extracellular matrix (ECM) components and fibrinogen. Groups of eight hamsters were immunized intramuscularly with rErp Y-like or rLemA mixed with a squalene-based adjuvant (AddaVax), and then vaccine efficacy was determined in terms of protection against a lethal challenge...
April 3, 2018: Vaccine
Gabriella Cirmena, Paola Franceschelli, Edoardo Isnaldi, Lorenzo Ferrando, Marilena De Mariano, Alberto Ballestrero, Gabriele Zoppoli
Oncogenic alteration of the cholesterol synthesis pathway is a recognized mechanism of metabolic adaptation. In the present review, we focus on squalene epoxidase (SE), one of the two rate-limiting enzymes in cholesterol synthesis, retracing its history since its discovery as an antimycotic target to its description as an emerging metabolic oncogene by amplification with clinical relevance in cancer. We review the published literature assessing the association between SE over-expression and poor prognosis in this disease...
March 26, 2018: Cancer Letters
Bin-Xiang Ma, Xia Ke, Xiao-Ling Tang, Ren-Chao Zheng, Yu-Guo Zheng
Ergosterol is the predominant nature sterol constituent of plasma membrane in Saccharomyces cerevisiae. Herein, the biosynthetic pathway of ergosterol was proposed to be metabolically engineered for the efficient production of ergosta-5,7-dien-3β-ol, which is the precursor of vitamin D4. By target disruption of erg5, involved in the end-steps of post-squalene formation, predominantly accumulated ergosta-5,7-dien-3β-ol (4.12 mg/g dry cell weight). Moreover, the rate-limiting enzymes of ergosta-5,7-dien-3β-ol biosynthesis were characterized...
March 28, 2018: World Journal of Microbiology & Biotechnology
Annalisa Ciabattini, Elena Pettini, Fabio Fiorino, Simone Lucchesi, Gabiria Pastore, Jlenia Brunetti, Francesco Santoro, Peter Andersen, Luisa Bracci, Gianni Pozzi, Donata Medaglini
The induction and modulation of the immune response to vaccination can be rationally designed by combining different vaccine formulations for priming and boosting. Here, we investigated the impact of heterologous prime-boost approaches on the vaccine-specific cellular and humoral responses specific for a mycobacterial vaccine antigen. C57BL/6 mice were primed with the chimeric vaccine antigen H56 administered alone or with the CAF01 adjuvant, and boosted with H56 alone, or combined with CAF01 or with the squalene-based oil-in-water emulsion adjuvant (o/w squalene)...
2018: Frontiers in Immunology
Ashutosh Singh, Aradhana Masih, Ananta Khurana, Pradeep Kumar Singh, Meenakshi Gupta, Ferry Hagen, Jacques F Meis, Anuradha Chowdhary
In the last few years infections caused by dermatophytes along with a concomitant increase in the number of difficult to treat cases has increasingly been recognized indicating that dermatophytosis remains a challenging public health problem. The majority of infections are caused by Trichophyton rubrum and T. mentagrophytes complex. Terbinafine, an allylamine antifungal used orally and topically is considered to be a first-line drug in the therapy of dermatophyte infections. Terbinafine resistance has been predominately attributed to point mutations in the squalene epoxidase (SQLE) target gene a key enzyme in the ergosterol biosynthetic pathway leading to single amino acid substitutions...
March 25, 2018: Mycoses
Liu-Jing Wei, Suryang Kwak, Jing-Jing Liu, Stephan Lane, Qiang Hua, Dae-Hyuk Kweon, Yong-Su Jin
Squalene, a valuable acyclic triterpene, can be used as a chemical commodity for pharmacology, flavor, and biofuel industries. Microbial production of squalene has been of great interest due to its limited availability, and increasing prices extracted from animal and plant tissues. Here we report genetic perturbations that synergistically improve squalene production in Saccharomyces cerevisiae. As reported previously, overexpression of a truncated HMG-CoA reductase 1 (tHMG1) led to the accumulation 20-fold higher squalene than a parental strain...
March 24, 2018: Biotechnology and Bioengineering
Sara Casado López, Mao Peng, Tedros Yonatan Issak, Paul Daly, Ronald P de Vries, Miia R Mäkelä
Fungi can decompose plant biomass to small oligo- and monosaccharides to be used as carbon sources. Some of these small molecules may induce metabolic pathways and production of extracellular enzymes targeted for degradation of plant cell wall polymers. Despite extensive studies in ascomycete fungi, little is known about the nature of inducers for the lignocellulolytic systems of basidiomycetes. In this study, we analyzed six sugars, known to induce expression of lignocellulolytic genes in ascomycetes, for their role as inducer in the basidiomycete white-rot fungus Dichomitus squalens using a transcriptomic approach...
March 23, 2018: Applied and Environmental Microbiology
Mariquit M De Los Reyes, Glenn G Oyong, Vincent Antonio S Ng, Chien-Chang Shen, Consolacion Y Ragasa
Background: Mixtures of ursolic acid ( 1 ) and oleanolic acid ( 2 ) (1:1 and 1:2), oleanolic acid ( 2 ), squalene ( 3 ), chlorophyll a ( 4 ), wrightiadione ( 5 ), and α-amyrin acetate ( 6 ) were isolated from the dichloromethane (CH2 Cl2 ) extracts of the leaves and twigs of Wrightia pubescens (R.Br.). Objectives: To test for the cytotoxicity potentials of 1-6 . Materials and Methods: The antiproliferative activities of 1-6 against three human cancer cell lines, breast (MCF-7) and colon (HT-29 and HCT-116), and a normal cell line, human dermal fibroblast neonatal (HDFn), were evaluated using the PrestoBlue® cell viability assay...
January 2018: Pharmacognosy Research
Johannes J Stelzner, Martina Behrens, Sven-Erik Behrens, Karsten Mäder
Potent adjuvant systems are required for subunit and single antigen based vaccines to provide sufficient immunogenicity. Furthermore, adjuvants can reduce the required number of immunisations and the antigen amount. Squalene nanoemulsions, like MF59® and AddaVax™, are potent, safe and well characterised adjuvant systems and approved for use in humans. Here, we developed squalene containing solid lipid nanoparticles, which can be sterilised by steam sterilisation and stored as freeze-dried power together with a yeast-based vaccine...
March 19, 2018: Vaccine
Kanchana Rueksomtawin Kildegaard, Belén Adiego-Pérez, David Doménech Belda, Jaspreet Kaur Khangura, Carina Holkenbrink, Irina Borodina
Astaxanthin is a red-colored carotenoid, used as food and feed additive. Astaxanthin is mainly produced by chemical synthesis, however, the process is expensive and synthetic astaxanthin is not approved for human consumption. In this study, we engineered the oleaginous yeast Yarrowia lipolytica for de novo production of astaxanthin by fermentation. First, we screened 12 different Y. lipolytica isolates for β-carotene production by introducing two genes for β-carotene biosynthesis: bi-functional phytoene synthase/lycopene cyclase ( crtYB ) and phytoene desaturase ( crtI ) from the red yeast Xanthophyllomyces dendrorhous ...
December 2017: Synthetic and Systems Biotechnology
Maria Vono, Christiane Sigrid Eberhardt, Elodie Mohr, Floriane Auderset, Dennis Christensen, Mirco Schmolke, Rhea Coler, Andreas Meinke, Peter Andersen, Paul-Henri Lambert, Beatris Mastelic-Gavillet, Claire-Anne Siegrist
Neonates and infants are more vulnerable to infections and show reduced responses to vaccination. Consequently, repeated immunizations are required to induce protection and early life vaccines against major pathogens such as influenza are yet unavailable. Formulating antigens with potent adjuvants, including immunostimulators and delivery systems, is a demonstrated approach to enhance vaccine efficacy. Yet, adjuvants effective in adults may not meet the specific requirements for activating the early life immune system...
2018: Frontiers in Immunology
Lorenzo León, Raúl de la Rosa, Leonardo Velasco, Angjelina Belaj
A wide genetic diversity has been reported for wild olives, which could be particularly interesting for the introgression of some agronomic traits and resistance to biotic and abiotic stresses in breeding programs. However, the introgression of some beneficial wild traits may be paralleled by negative effects on some other important agronomic and quality traits. From the quality point of view, virgin olive oil (VOO) from olive cultivars is highly appreciated for its fatty acid composition (high monounsaturated oleic acid content) and the presence of several minor components...
2018: Frontiers in Plant Science
Shivaprakash M Rudramurthy, Shamanth A Shankarnarayan, Sunil Dogra, Dipika Shaw, Khurram Mushtaq, Raees A Paul, Tarun Narang, Arunaloke Chakrabarti
Dermatophytosis, the commonest superficial fungal infection, has gained recent attention due to its change of epidemiology and treatment failures. Despite availability of several effective antifungal agents against dermatophytes, the incidence of chronic infection, re-infection and treatment failures are on the rise. Trichophyton rubrum and Trichophyton interdigitale are the two frequent clinical isolates in India. Consecutive patients (n=195) with suspected dermatophytosis during second half of 2014 were included in this study...
March 12, 2018: Antimicrobial Agents and Chemotherapy
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