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https://www.readbyqxmd.com/read/28529817/coordinated-and-iterative-enzyme-catalysis-in-fungal-polyketide-biosynthesis
#1
Leibniz Hang, Nicholas Liu, Yi Tang
Fungal polyketides are natural products with great chemical diversity that exhibit a wide range of biological activity. This chemical diversity stems from specialized enzymes encoded in the biosynthetic gene cluster responsible for the natural product biosynthesis. Fungal polyketide synthases (PKS) are the megasynthases that produce the carbon scaffolds for the molecules. Subsequent downstream tailoring enzymes such as oxygenases will then further modify the organic framework. In fungi, many of these enzymes have been found to work iteratively-catalyzing multiple reactions on different sites of the substrate...
September 2, 2016: ACS Catalysis
https://www.readbyqxmd.com/read/28511903/novel-role-of-the-nutraceutical-bioactive-compound-berberine-in-lectin-like-oxldl-receptor-1-mediated-endothelial-dysfunction-in-comparison-to-lovastatin
#2
C Caliceti, P Rizzo, R Ferrari, F Fortini, G Aquila, E Leoncini, L Zambonin, B Rizzo, D Calabria, P Simoni, M Mirasoli, M Guardigli, S Hrelia, A Roda, A F G Cicero
BACKGROUND AND AIMS: Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to increased oxidative stress linked to endothelial dysfunction and atherosclerosis. The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering statins inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from plants of gender Berberis, has lipid-lowering and anti-inflammatory activity. However, its role in regulating LOX1-mediated signaling is still unknown. The aim of this study was to investigate the effect of BBR on oxLDL- and TNFα-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and to compare it with that of lovastatin (LOVA)...
April 19, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28490066/the-physico-chemical-alteration-of-lovastatin-and-enhanced-antioxidant-effect-of-bacillus-subtilis-fermented-red-yeast-rice-product
#3
Sang Il Gum, Phuc Anh Nguyen, Jong Rok Lee, Yeong Hwan Han, Min Kyung Cho
Red yeast rice product (RYP) has been used as a food supplement because of its lipid lowering, and in food additives as a natural colorant. Lovastatin of RYP is a hypolipidemic commercial drug. To enhance the beneficial effects of RYP, we performed a bioconversion with Bacillus subtilis. This B. subtilis-fermentation process of RYP increased the ratio of the active open-hydroxyl acid form and the prodrug lactone form of lovastatin, which is a potent cholesterol synthesis inhibitor. 3(2H)-benzofuranone was newly produced in the fermented red yeast rice product (FRYP) as analyzed by GC-MS...
October 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28481927/correction-combined-treatment-with-troglitazone-and-lovastatin-inhibited-epidermal-growth-factor-induced-migration-through-the-downregulation-of-cysteine-rich-protein-61-in-human-anaplastic-thyroid-cancer-cells
#4
https://www.readbyqxmd.com/read/28455524/mechanisms-underlying-cognitive-deficits-in-a-mouse-model-for-costello-syndrome-are-distinct-from-other-rasopathy-mouse-models
#5
Jadwiga Schreiber, Laura-Anne Grimbergen, Iris Overwater, Thijs van der Vaart, Jeffrey Stedehouder, Alberto J Schuhmacher, Carmen Guerra, Steven A Kushner, Dick Jaarsma, Ype Elgersma
RASopathies, characterized by germline mutations in genes encoding proteins of the RAS-ERK signaling pathway, show overlapping phenotypes, which manifest themselves with a varying severity of intellectual disability. However, it is unclear to what extent they share the same downstream pathophysiology that underlies the cognitive deficits. Costello syndrome (CS) is a rare RASopathy caused by activating mutations in the HRAS gene. Here we investigated the mechanisms underlying the cognitive deficits of HRas (G12V/G12V) mice...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428922/the-cost-benefit-balance-of-statins-in-hawai-i-a-moving-target
#6
Corey J Lum, Kazuma Nakagawa, Ralph V Shohet, Todd B Seto, Deborah A Taira
Statins are lipid-lowering medications used for primary and secondary prevention of atherosclerotic disease and represent a substantial portion of drug costs in the United States. A better understanding of prescribing patterns and drug costs should lead to more rational utilization and help constrain health care expenditures in the United States. The 2013 Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use File for the State of Hawai'i was analyzed. The number of prescriptions for statins, total annual cost, and daily cost were calculated by prescriber specialty and drug...
April 2017: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/28413614/the-pathlinker-app-connect-the-dots-in-protein-interaction-networks
#7
Daniel P Gil, Jeffrey N Law, T M Murali
PathLinker is a graph-theoretic algorithm for reconstructing the interactions in a signaling pathway of interest. It efficiently computes multiple short paths within a background protein interaction network from the receptors to transcription factors (TFs) in a pathway. We originally developed PathLinker to complement manual curation of signaling pathways, which is slow and painstaking. The method can be used in general to connect any set of sources to any set of targets in an interaction network. The app presented here makes the PathLinker functionality available to Cytoscape users...
2017: F1000Research
https://www.readbyqxmd.com/read/28410522/development-of-matrix-effect-free-mispe-uhplc-ms-ms-method-for-determination-of-lovastatin-in-pu-erh-tea-oyster-mushroom-and-red-yeast-rice
#8
Pavel Svoboda, Daniel Sander, Kateřina Plachká, Lucie Nováková
Matrix effect-free UHPLC-MS/MS method was developed and validated for the determination of cholesterol-lowering lovastatin in food samples represented by Pu-erh tea, oyster mushroom, and red yeast rice. The resulting method was fully validated in terms of intra-day and inter-day precision, accuracy, linearity, range, LOD, LOQ, and matrix effects. The matrix effect phenomenon evaluated by comparison of slopes of calibration curves was completely eliminated by solid-phase extraction based on the technique of molecularly imprinted polymers (MIPs)...
June 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28389711/genome-editing-approaches-manipulating-of-lovastatin-and-taxol-synthesis-of-filamentous-fungi-by-crispr-cas9-system
#9
REVIEW
Ashraf S A El-Sayed, Salah E Abdel-Ghany, Gul Shad Ali
Filamentous fungi are prolific repertoire of structurally diverse secondary metabolites of remarkable biological activities such as lovastatin and paclitaxel that have been approved by FDA as drugs for hypercholesterolemia and cancer treatment. The clusters of genes encoding lovastatin and paclitaxel are cryptic at standard laboratory cultural conditions (Kennedy et al. Science 284:1368-1372, 1999; Bergmann et al. Nature Chem Biol 3:213-217, 2007). The expression of these genes might be triggered in response to nutritional and physical conditions; nevertheless, the overall yield of these metabolites does not match the global need...
April 7, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28387380/a-staged-screening-of-registered-drugs-highlights-remyelinating-drug-candidates-for-clinical-trials
#10
C Eleuteri, S Olla, C Veroni, R Umeton, R Mechelli, S Romano, M C Buscarinu, F Ferrari, G Calò, G Ristori, M Salvetti, C Agresti
There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28384260/denv-up-regulates-the-hmg-coa-reductase-activity-through-the-impairment-of-ampk-phosphorylation-a-potential-antiviral-target
#11
Rubén Soto-Acosta, Patricia Bautista-Carbajal, Margot Cervantes-Salazar, Antonio H Angel-Ambrocio, Rosa M Del Angel
Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28367417/lovastatin-reduces-stemness-via-epigenetic-reprograming-of-bmp2-and-gata2-in-human-endometrium-and-endometriosis
#12
Mahdieh Taghizadeh, Mehrdad Noruzinia
OBJECTIVE: The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells (eMSCs) such as BMP2, GATA2 and RUNX2 as well as eMSCs markers...
April 2017: Cell Journal
https://www.readbyqxmd.com/read/28353656/volatiles-emitted-at-different-flowering-stages-of-jasminum-sambac-and-expression-of-genes-related-to-%C3%AE-farnesene-biosynthesis
#13
Ying Yu, Shiheng Lyu, Dan Chen, Yi Lin, Jianjun Chen, Guixin Chen, Naixing Ye
Fresh jasmine flowers have been used to make jasmine teas in China, but there has been no complete information about volatile organic compound emissions in relation to flower developmental stages and no science-based knowledge about which floral stage should be used for the infusion. This study monitored volatile organic compounds emitted from living flowers of Jasminum sambac (L.) Ait. 'Bifoliatum' at five developmental stages and also from excised flowers. Among the compounds identified, α-farnesene, linalool, and benzyl acetate were most abundant...
March 29, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28335447/transcriptomic-complexity-of-aspergillus-terreus-velvet-gene-family-under-the-influence-of-butyrolactone-i
#14
Elina K Palonen, Sheetal Raina, Annika Brandt, Jussi Meriluoto, Tajalli Keshavarz, Juhani T Soini
Filamentous fungi of the Ascomycota phylum are known to contain a family of conserved conidiation regulating proteins with distinctive velvet domains. In Aspergilli, this velvet family includes four proteins, VeA, VelB, VelC and VosA, and is involved in conidiation and secondary metabolism along with a global regulator LaeA. In A. terreus, the overexpression of LaeA has been observed to increase the biogenesis of the pharmaceutically-important secondary metabolite, lovastatin, while the role of the velvet family has not been studied...
March 14, 2017: Microorganisms
https://www.readbyqxmd.com/read/28282493/molecular-and-vibrational-dynamics-in-the-cholesterol-lowering-agent-lovastatin-solid-state-nmr-inelastic-neutron-scattering-and-periodic-dft-study
#15
Paweł Bilski, Kacper Drużbicki, Jacek Jenczyk, Jadwiga Mielcarek, Jan Wąsicki
Molecular and vibrational dynamics of a widely used cholesterol-lowering agent, lovastatin, have been studied by combining nuclear magnetic resonance relaxation experiments ((1)H NMR) with inelastic neutron scattering (INS) and periodic density functional theory modeling (plane-wave DFT). According to a complementary experimental study, lovastatin shows no phase transitions down to cryogenic conditions, while a progressive, stepwise activation of several molecular motions is observed below room temperature...
March 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28277227/-red-yeast-rice-induced-muscular-injuries-analysis-of-french-pharmacovigilance-database-and-literature-review
#16
Christelle Philibert, Virginie Bres, Marie-Josèphe Jean-Pastor, Claire Guy, Bénédicte Lebrun-Vignes, Perrine Robin, Véronique Pinzani, Dominique Hillaire-Buys
Red yeast rice (RYR) is a dietary supplement containing monacolins obtained by fermentation of Monascus purpureus strains. Because of its structural homology with lovastatin, monacolin K inhibits HMG-CoA reductase and shows hypocholesterolemic properties comparable to synthetic statins. We studied all cases of myopathy involving RYR reported in the French national pharmacovigilance database (6 cases) and in scientific literature (9 cases). Among these cases, 9 showed elevated creatine kinase, 3 rhabdomyolysis and 2 myalgia...
October 27, 2016: Thérapie
https://www.readbyqxmd.com/read/28276528/variability-in-statin-induced-changes-in-gene-expression-profiles-of-pancreatic-cancer
#17
Helena Gbelcová, Silvie Rimpelová, Tomáš Ruml, Marie Fenclová, Vítek Kosek, Jana Hajšlová, Hynek Strnad, Michal Kolář, Libor Vítek
Statins, besides being powerful cholesterol-lowering drugs, also exert potent anti-proliferative activities. However, their anti-cancer efficacy differs among the individual statins. Thus, the aim of this study was to identify the biological pathways affected by individual statins in an in vitro model of human pancreatic cancer. The study was performed on a human pancreatic cancer cell line MiaPaCa-2, exposed to all commercially available statins (12 μM, 24 h exposure). DNA microarray analysis was used to determine changes in the gene expression of treated cells...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257063/red-yeast-rice
#18
Thu Nguyen, Mitchell Karl, Antonello Santini
Red yeast rice (RYR), produced by the fermentation of the Monascus purpureus mold, has been used for a long time in Asian cuisine and traditional medicine. It consists of multiple bioactive substances, including monacolins, which potentially can be used as a nutraceutical. Monacolin K, which is chemically identical to lovastatin, has been recognized as responsible for the cholesterolreducing effect of this compound. While the European Food Safety Authority maintains that the use of monacolin K from RYR preparations of at least 10 mg can produce a normal blood cholesterol level, the United States Food and Drug Administration considers monacolin K, due to its similarity with lovastatin, an unapproved drug, and therefore marketing of products that label the monacolin content is prohibited...
March 1, 2017: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28247468/discovery-and-quantitative-structure-activity-relationship-study-of-lepidopteran-hmg-coa-reductase-inhibitors-as-selective-insecticides
#19
Yang-Yang Zang, Yuan-Mei Li, Yue Yin, Shan-Shan Chen, Zhen-Peng Kai
BACKGROUND: In a previous study we have demonstrated that insect 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) can be a potential selective insecticide target. Three series of inhibitors were designed on the basis of the difference in HMGR structures from Homo sapiens and Manduca sexta, with the aim of discovering potent selective insecticide candidates. RESULTS: An in vitro bioassay showed that gem-difluoromethylenated statin analogues have potent effects on JH biosynthesis of M...
March 1, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28246253/association-between-statin-use-and-ischemic-stroke-or-major-hemorrhage-in-patients-taking-dabigatran-for-atrial-fibrillation
#20
Tony Antoniou, Erin M Macdonald, Zhan Yao, Simon Hollands, Tara Gomes, Mina Tadrous, Muhammad M Mamdani, David N Juurlink
BACKGROUND: Dabigatran etexilate is a prodrug whose absorption is opposed by intestinal P-glycoprotein and which is converted by carboxylesterase to its active form, dabigatran. Unlike other statins, simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase, and might either increase the risk of hemorrhage with dabigatran etexilate or decrease its effectiveness. METHODS: We conducted 2 population-based, nested case-control studies involving Ontario residents 66 years of age and older who started dabigatran etexilate between May 1, 2012, and Mar...
January 9, 2017: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
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