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https://www.readbyqxmd.com/read/28730957/design-preparation-and-characterization-of-modular-squalene-based-nanosystems-for-controlled-drug-release
#1
Jiao Feng, Sinda Lepetre-Mouelhi, Patrick Couvreur
This article reviews the innovative and original concept the "squalenoylation", a technology allowing the formulation of a wide range of drug molecules (both hydrophilic and lipophilic) as nanoparticles. The "squalenoylation" approach is based on the covalent linkage between the squalene, a natural and biocompatible lipid belonging to the terpenoid family, and a drug, in order to increase its pharmacological efficacy. Fundamentally, the dynamically folded conformation of squalene triggers the resulting squalene-drug bioconjugates to self-assemble as nanoparticles of 100-300 nm...
July 19, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28728107/developing-potential-agents-against-atherosclerosis-design-synthesis-and-pharmacological-evaluation-of-novel-dual-inhibitors-of-oxidative-stress-and-squalene-synthase-activity
#2
Maria G Katselou, Alexios N Matralis, Angeliki P Kourounakis
For the treatment of multifactorial and complex diseases, it has become increasingly apparent that compounds acting at multiple targets often deliver superior efficacy compared to compounds with high specificity for only a single target. Based on previous studies demonstrating the important antioxidant and anti-hyperlipidemic effect of morpholine and 1,4-benzo(x/thi)azine derivatives (A-E), we hereby present the design, synthesis and pharmacological evaluation of novel dual-acting molecules as a therapeutic approach for atherosclerosis...
June 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28722810/impact-of-crude-oil-quality-on-the-refining-conditions-and-composition-of-nutraceuticals-in-refined-palm-oil
#3
Klicia A Sampaio, Jose Vila Ayala, Vera Van Hoed, Simone Monteiro, Roberta Ceriani, Roland Verhé, Antonio J A Meirelles
Palm oil is the major vegetable oil used worldwide due to its unique properties. The effect of crude palm oil acidity on the final free fatty acids (FFA) content, neutral oil loss (NOL), and nutraceutical compounds, such as carotenes, total tocols (tocopherols and tocotrienols), squalene, and phytosterols was investigated. A central composite design was employed to study the influence of the refining conditions: temperature (200 to 260 °C), steam percentage (0.5% to 3.5%), and initial FFA content (2.2% to 6...
July 19, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28720281/evaluation-of-a-primary-course-of-h9n2-vaccine-with-or-without-as03-adjuvant-in-adults-a-phase-i-ii-randomized-trial
#4
Anuradha Madan, Harry Collins, Eric Sheldon, Louise Frenette, Laurence Chu, Damien Friel, Mamadou Drame, David W Vaughn, Bruce L Innis, Anne Schuind
BACKGROUND: Avian influenza A H9N2 strains have pandemic potential. METHODS: In this randomized, observer-blind study (ClinicalTrials.gov: NCT01659086), 420 healthy adults, 18-64years of age, received 1 of 10 H9N2 inactivated split-virus vaccination regimens (30 participants per group), or saline placebo (120 participants). H9N2 groups received 2 doses (days 0, 21) of 15µg hemagglutinin (HA) without adjuvant, or 1.9µgHA+AS03A, 1.9µgHA+AS03B, 3.75µgHA+AS03A, or 3...
July 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28714761/gamma-irradiation-of-medicinally-important-plants-and-the-enhancement-of-secondary-metabolite-production
#5
P Vivek Vardhan, Lata I Shukla
PURPOSE: The profitable production of some important plant-based secondary metabolites (ginsenosides, saponins, camptothecin, shikonins etc.) in vitro by gamma irradiation is a current area of interest. We reviewed different types of secondary metabolites, their mode of synthesis and effect of γ-radiation on their yield for different plants, organs and in vitro cultures (callus, suspension, hairy root). Special effort has been made to review the biochemical mechanisms underlying the increase in secondary metabolites...
July 17, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28710558/pathway-engineering-for-the-production-of-%C3%AE-amyrin-and-cycloartenol-in-escherichia-coli-a-method-to-biosynthesize-plant-derived-triterpene-skeletons-in-e-coli
#6
Miho Takemura, Rie Tanaka, Norihiko Misawa
Cycloartenol is biosynthetically the first sterol skeleton, which is metabolized to phytosterols such as β-sitosterol and stigmasterol. β-Amyrin is the most commonly occurring aglycone skeleton for oleanane-type saponins such as glycyrrhizin and saikosaponins. It has been regarded that these cyclic triterpenes are unable to be produced in Escherichia coli, while no reports are available on their production with E. coli. Here, we describe a method to synthesize triterpene skeletons from higher plants, including cycloartenol and β-amyrin...
July 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28706236/metabolomic-differential-analysis-of-interspecific-interactions-among-white-rot-fungi-trametes-versicolor-dichomitus-squalens-and-pleurotus-ostreatus
#7
Feng Luo, Zixuan Zhong, Li Liu, Yasuo Igarashi, Deti Xie, Nannan Li
Interspecific fungal antagonism occurred commonly in the interaction zone of different white rot fungi. This competitive interaction could markedly influence the metabolic pathway of intracellular metabolites, which was associated with the fungal morphology change and growth restriction. So far, it remains unknown on intracellular metabolite regulation during fungal competitive interaction. Herein, we performed the metabolomic analysis of the in vivo metabolite changes during competitive interaction between each two of the three white rot fungi Trametes versicolor, Pleurotus ostreatus and Dichomitus squalens and identified differential metabolites in the interaction zone compared to each two isolates...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28688419/soft-x-ray-spectroscopy-of-nanoparticles-by-velocity-map-imaging
#8
O Kostko, B Xu, M I Jacobs, M Ahmed
Velocity map imaging (VMI), a technique traditionally used to study chemical dynamics in the gas phase, is applied here to study X-ray photoemission from aerosol nanoparticles. Soft X-rays from the Advanced Light Source synchrotron, probe a beam of nanoparticles, and the resulting photoelectrons are velocity mapped to obtain their kinetic energy distributions. A new design of the VMI spectrometer is described. The spectrometer is benchmarked by measuring vacuum ultraviolet photoemission from gas phase xenon and squalene nanoparticles followed by measurements using soft X-rays...
July 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28686302/plasmalogen-homeostasis-regulation-of-plasmalogen-biosynthesis-and-its-physiological-consequence-in-mammals
#9
REVIEW
Masanori Honsho, Yukio Fujiki
Plasmalogens, mostly ethanolamine-containing alkenyl ether phospholipids, are a major sub-class of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes and completed in endoplasmic reticulum. The absence of plasmalogens in several organs of peroxisome biogenesis-defective patients suggests that the de novo synthesis of plasmalogens plays a pivotal role in its homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the stability of fatty acyl-CoA reductase 1 on peroxisomal membranes, a rate-limiting enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of plasma membranes...
July 7, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28674547/integrated-transcriptomic-and-metabolomic-analysis-of-five-panax-ginseng-cultivars-reveals-the-dynamics-of-ginsenoside-biosynthesis
#10
Yun Sun Lee, Hyun-Seung Park, Dong-Kyu Lee, Murukarthick Jayakodi, Nam-Hoon Kim, Hyun Jo Koo, Sang-Choon Lee, Yeon Jeong Kim, Sung Won Kwon, Tae-Jin Yang
Panax ginseng C.A. Meyer is a traditional medicinal herb that produces bioactive compounds such as ginsenosides. Here, we investigated the diversity of ginsenosides and related genes among five genetically fixed inbred ginseng cultivars (Chunpoong [CP], Cheongsun [CS], Gopoong [GO], Sunhyang [SH], and Sunun [SU]). To focus on the genetic diversity related to ginsenoside biosynthesis, we utilized in vitro cultured adventitious roots from the five cultivars grown under controlled environmental conditions. PCA loading plots based on secondary metabolite composition classified the five cultivars into three groups...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28667762/enhanced-isoprenoid-production-from-xylose-by-engineered-saccharomyces-cerevisiae
#11
Suryang Kwak, Soo Rin Kim, Haiqing Xu, Guo-Chang Zhang, Stephan Lane, Heejin Kim, Yong-Su Jin
Saccharomyces cerevisiae has limited capabilities for producing fuels and chemicals derived from acetyl-CoA, such as isoprenoids, due to a rigid flux partition toward ethanol during glucose metabolism. Despite numerous efforts, xylose fermentation by engineered yeast harboring heterologous xylose metabolic pathways was not as efficient as glucose fermentation for producing ethanol. Therefore, we hypothesized that xylose metabolism by engineered yeast might be a better fit for producing non-ethanol metabolites...
July 1, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28667115/cgmed3-changes-membrane-sterol-composition-to-help-candida-glabrata-tolerate-low-ph-stress
#12
Xiaobao Lin, Yanli Qi, Dongni Yan, Hui Liu, Xiulai Chen, Liming Liu
Candida glabrata is a promising microorganism for organic acid production. The present study aimed to investigate the role of Mediator complex subunit 3 (CgMed3p) in protecting C. glabrata at low pH conditions. To this end, the genes CgMED3A and CgMED3B were deleted, resulting in the double deletion Cgmed3ABΔ strain. Final biomass and cell viability of Cgmed3ABΔ decreased by 64.5% and 35.8%, respectively, compared to the wild-type at pH 2.0. In addition, lack of CgMed3ABp resulted in selective repression of a subset of genes in the lipid biosynthesis and metabolism pathways...
June 30, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28662951/cd11a-and-cd49d-enhance-the-detection-of-antigen-specific-t-cells-following-human-vaccination
#13
Allison F Christiaansen, Upasna Gaur Dixit, Rhea N Coler, Anna Marie Beckmann, Steven G Reed, Patricia L Winokur, M Bridget Zimmerman, Steven M Varga, Mary E Wilson
BACKGROUND: Determining the efficacy of human vaccines that induce antigen-specific protective CD4 T cell responses against pathogens can be particularly challenging to evaluate. Surface expression of CD11a and CD49d has been shown to identify antigen-specific CD4 T cells against viral pathogens in mice. We hypothesized that CD11a and CD49d would also serve as markers of human antigen-specific T cells responding to vaccination. METHODS: A phase I vaccine trial enabled us to evaluate a novel gating strategy based on surface expression of CD11a and CD49d as a means of detecting antigen-specific, cytokine producing CD4 and CD8 T cells induced after vaccination of naïve individuals against leishmaniasis...
June 26, 2017: Vaccine
https://www.readbyqxmd.com/read/28649699/a-wrky-transcription-factor-from-withania-somnifera-regulates-triterpenoid-withanolide-accumulation-and-biotic-stress-tolerance-through-modulation-of-phytosterol-and-defense-pathways
#14
Anup Kumar Singh, Sarma Rajeev Kumar, Varun Dwivedi, Avanish Rai, Shaifali Pal, Ajit K Shasany, Dinesh A Nagegowda
Withania somnifera produces pharmacologically important triterpenoid withanolides that are derived via phytosterol pathway; however, their biosynthesis and regulation remain to be elucidated. A jasmonate- and salicin-inducible WRKY transcription factor from W. somnifera (WsWRKY1) exhibiting correlation with withaferin A accumulation was functionally characterized employing virus-induced gene silencing and overexpression studies combined with transcript and metabolite analyses, and chromatin immunoprecipitation assay...
June 26, 2017: New Phytologist
https://www.readbyqxmd.com/read/28646583/sebum-lipids-influence-macrophage-polarization-and-activation
#15
M Lovászi, M Mattii, K Eyerich, Attila Gácsi, Erzsébet Csányi, D Kovács, R Rühl, A Szegedi, L Kemény, M Ståhle, C C Zouboulis, S Eyerich, D Törőcsik
BACKGROUND: As lipids are known to regulate macrophage functions it is reasonable to suppose that a sebocyte - macrophage axis mediated by sebum lipids may exist. OBJECTIVE: To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids. METHODS: Oil-red-O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets...
June 24, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28642737/pheno-and-genotyping-of-hopanoid-production-in-acidobacteria
#16
Jaap S Sinninghe Damsté, W Irene C Rijpstra, Svetlana N Dedysh, Bärbel U Foesel, Laura Villanueva
Hopanoids are pentacyclic triterpenoid lipids synthesized by different bacterial groups. Methylated hopanoids were believed to be exclusively synthesized by cyanobacteria and aerobic methanotrophs until the genes encoding for the methylation at the C-2 and C-3 position (hpnP and hpnR) were found to be widespread in the bacterial domain, invalidating their use as specific biomarkers. These genes have been detected in the genome of the Acidobacterium "Ca. Koribacter versatilis," but our knowledge of the synthesis of hopanoids and the presence of genes of their biosynthetic pathway in other member of the Acidobacteria is limited...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28640347/psychotria-viridis-chemical-constituents-from-leaves-and-biological-properties
#17
Débora B S Soares, Lucienir P Duarte, André D Cavalcanti, Fernando C Silva, Ariadne D Braga, Miriam T P Lopes, Jacqueline A Takahashi, Sidney A Vieira-Filho
The phytochemical study of hexane, chloroform and methanol extracts from leaves of Psychotria viridis resulted in the identification of: the pentacyclic triterpenes, ursolic and oleanolic acid; the steroids, 24-methylene-cycloartanol, stigmasterol and β-sitosterol; the glycosylated steroids 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol; a polyunsaturated triterpene, squalene; the esters of glycerol, 1-palmitoylglycerol and triacylglycerol; a mixture of long chain hydrocarbons; the aldehyde nonacosanal; the long chain fat acids hentriacontanoic, hexadecanoic and heptadenoic acid; the ester methyl heptadecanoate; the 4-methyl-epi-quinate and two indole alkaloids, N,N-dimethyltryptamine (DMT) and N-methyltryptamine...
April 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28606375/circulating-lipoproteins-a-trojan-horse-guiding-squalenoylated-drugs-to-ldl-accumulating-cancer-cells
#18
Dunja Sobot, Simona Mura, Marie Rouquette, Branko Vukosavljevic, Fanny Cayre, Eric Buchy, Grégory Pieters, Sébastien Garcia-Argote, Maike Windbergs, Didier Desmaële, Patrick Couvreur
Selective delivery of anticancer drugs to rapidly growing cancer cells can be achieved by taking advantage of their high receptor-mediated uptake of low-density lipoproteins (LDLs). Indeed, we have recently discovered that nanoparticles made of the squalene derivative of the anticancer agent gemcitabine (SQGem) strongly interacted with the LDLs in the human blood. In the present study, we showed both in vitro and in vivo that such interaction led to the preferential accumulation of SQGem in cancer cells (MDA-MB-231) with high LDL receptor expression...
July 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28595267/cholesterol-uptake-and-regulation-in-high-grade-and-lethal-prostate-cancers
#19
Konrad H Stopsack, Travis A Gerke, Ove Andrén, Swen-Olof Andersson, Edward L Giovannucci, Lorelei A Mucci, Jennifer R Rider
Lethal prostate cancers have higher expression of squalene monooxygenase (SQLE), the second rate-limiting enzyme of cholesterol synthesis. Preclinical studies suggested that aberrant cholesterol regulators, receptors, and transporters contribute to cholesterol accumulation uniformly. We assessed their association with features of aggressive cancers. In the prospective prostate cancer cohorts within the Health Professional Follow-up Study, the Physicians' Health Study, and the Swedish Watchful Waiting Study, tumor mRNA expression profiling was performed...
June 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28555624/conjugation-of-squalene-to-gemcitabine-as-unique-approach-exploiting-endogenous-lipoproteins-for-drug-delivery
#20
Dunja Sobot, Simona Mura, Semen O Yesylevskyy, Laura Dalbin, Fanny Cayre, Guillaume Bort, Julie Mougin, Didier Desmaële, Sinda Lepetre-Mouelhi, Grégory Pieters, Bohdan Andreiuk, Andrey S Klymchenko, Jean-Louis Paul, Christophe Ramseyer, Patrick Couvreur
Once introduced in the organism, the interaction of nanoparticles with various biomolecules strongly impacts their fate. Here we show that nanoparticles made of the squalene derivative of gemcitabine (SQGem) interact with lipoproteins (LPs), indirectly enabling the targeting of cancer cells with high LP receptors expression. In vitro and in vivo experiments reveal preeminent affinity of the squalene-gemcitabine bioconjugates towards LP particles with the highest cholesterol content and in silico simulations further display their incorporation into the hydrophobic core of LPs...
May 30, 2017: Nature Communications
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