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https://www.readbyqxmd.com/read/28632991/uncovering-the-repertoire-of-fungal-secondary-metabolites-from-fleming-s-lab-to-the-international-space-station
#1
Tomasz Boruta
Fungi produce a variety of secondary metabolites (SMs), low-molecular weight compounds associated with many potentially useful biological activities. The examples of biotechnologically relevant fungal metabolites include penicillin, a beta-lactam antibiotic, and lovastatin, a cholesterol-lowering drug. The discovery of pharmaceutical lead compounds within the microbial metabolic pools relies on the selection and biochemical characterization of promising strains. Not all SMs are produced under standard cultivation conditions, hence the uncovering of chemical potential of investigated strains often requires the use of induction strategies to awake the associated biosynthetic genes...
June 20, 2017: Bioengineered
https://www.readbyqxmd.com/read/28624878/a-combination-of-three-repurposed-drugs-administered-at-reperfusion-as-a-promising-therapy-for-postischemic-brain-injury
#2
I-Chen Yu, Ping-Chang Kuo, Jui-Hung Yen, Hallel C Paraiso, Eric T Curfman, Benecia C Hong-Goka, Robert D Sweazey, Fen-Lei Chang
Cerebral ischemia leads to multifaceted injury to the brain. A polytherapeutic drug that can be administered immediately after reperfusion may increase protection to the brain by simultaneously targeting multiple deleterious cascades. This study evaluated efficacy of the combination of three clinically approved drugs: lamotrigine, minocycline, and lovastatin, using two mouse models: global and focal cerebral ischemia induced by transient occlusion of the common carotid arteries or the middle cerebral artery, respectively...
June 17, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28620871/lipophilic-statins-and-the-risk-of-intracranial-hemorrhage-following-ischemic-stroke-a-population-based-study
#3
Kieran L Quinn, Erin M Macdonald, Muhammad M Mamdani, Christina Diong, David N Juurlink
BACKGROUND: Statins are commonly prescribed for the secondary prevention of ischemic stroke, but there is conflicting evidence as to whether they increase the risk of intracranial hemorrhage. Lipophilic statins cross the blood-brain barrier more freely than hydrophilic statins and may therefore increase the risk of intracranial hemorrhage. OBJECTIVE: To determine whether, in older patients following ischemic stroke, receipt of lipophilic statins was associated with differences in the risk of intracranial hemorrhage...
June 15, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28619444/single-step-production-of-the-simvastatin-precursor-monacolin-j-by-engineering-of-an-industrial-strain-of-aspergillus-terreus
#4
Xuenian Huang, Yajing Liang, Yong Yang, Xuefeng Lu
Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct bioproduction of monacolin J has not yet been achieved...
June 12, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28601545/red-yeast-rice-preparations-are-they-suitable-substitutions-for-statins
#5
REVIEW
Carlos A Dujovne
Red yeast rice, a commercially available food supplement known to reduce serum cholesterol, has been repeatedly advocated as alternative therapy for hypercholesterolemic patients that refuse statins, cannot tolerate statin therapy's side effects, or request a "naturopathic" medicine. Red yeast rice contains a fungus (Monascus purpureus), which was utilized in the original production of lovastatin (Mevacor TM), the first marketed pharmaceutical statin, and is chemically identical to such product. Their identical properties account for the similarity in therapeutic and side effects of red yeast rice and lovastatin...
June 7, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28583899/statins-do-not-inhibit-the-fgfr-signaling-in-chondrocytes
#6
B Fafilek, M Hampl, N Ricankova, I Vesela, L Balek, M Kunova Bosakova, I Gudernova, M Varecha, M Buchtova, P Krejci
OBJECTIVE: Statins are widely used drugs for cholesterol lowering, which were recently found to counteract the effects of aberrant fibroblast growth factor receptor (FGFR3) signaling in cell and animal models of FGFR3-related chondrodysplasia. This opened an intriguing therapeutic possibility for human dwarfing conditions caused by gain-of-function mutations in FGFR3, although the mechanism of statin action on FGFR3 remains unclear. Here, we determine the effect of statins on FGFR signaling in chondrocytes...
June 3, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28570591/statin-and-rottlerin-small-molecule-inhibitors-restrict-colon-cancer-progression-and-metastasis-via-macc1
#7
Manisha Juneja, Dennis Kobelt, Wolfgang Walther, Cynthia Voss, Janice Smith, Edgar Specker, Martin Neuenschwander, Björn-Oliver Gohlke, Mathias Dahlmann, Silke Radetzki, Robert Preissner, Jens Peter von Kries, Peter Michael Schlag, Ulrike Stein
MACC1 (Metastasis Associated in Colon Cancer 1) is a key driver and prognostic biomarker for cancer progression and metastasis in a large variety of solid tumor types, particularly colorectal cancer (CRC). However, no MACC1 inhibitors have been identified yet. Therefore, we aimed to target MACC1 expression using a luciferase reporter-based high-throughput screening with the ChemBioNet library of more than 30,000 compounds. The small molecules lovastatin and rottlerin emerged as the most potent MACC1 transcriptional inhibitors...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28548867/statins-determination-a-review-of-electrochemical-techniques
#8
I Antal, M Koneracka, V Zavisova, M Kubovcikova, Zh Kormosh, P Kopcansky
The use of electroanalytical techniques for the determination of statins (Atorvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin and Simvastatin) is reviewed covering the period from 1997 to 2016. Among all of the published electrochemical methods, voltammetry and polarography are the most popular techniques for determination of statins and both are used for the analysis of pharmaceutical dosage forms and biological samples. Determination of statins by potentiometric method using ion-selective electrodes is reported in only few papers...
May 26, 2017: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/28546815/role-of-statin-drugs-for-polycystic-ovary-syndrome
#9
REVIEW
Lisa Cassidy-Vu, Edwina Joe, Julienne K Kirk
Objective: To review the potential role and specific impact of statin drugs in women with PCOS. The evidence for this use of statins in PCOS is limited and still under further investigation. Materials and methods: A search was conducted using PubMed, DynaMed and PubMedHealth databases through October 16, 2016 using the terms polycystic ovary syndrome, PCOS, hydroxymethylglutaryl-CoA reductase inhibitors, hydroxymethylglutaryl-CoA, statin, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin...
December 2016: Journal of Family & Reproductive Health
https://www.readbyqxmd.com/read/28539592/atorvastatin-promotes-phagocytosis-and-attenuates-pro-inflammatory-response-in-human-retinal-pigment-epithelial-cells
#10
Bo Tian, Ahmad Al-Moujahed, Peggy Bouzika, Yijun Hu, Shoji Notomi, Pavlina Tsoka, Joan W Miller, Haijiang Lin, Demetrios G Vavvas
Phagocytosis of daily shed photoreceptor outer segments is an important function of the retinal pigment epithelium (RPE) and it is essential for retinal homeostasis. RPE dysfunction, especially impairment of its phagocytic ability, plays an essential role in the pathogenesis of age-related macular degeneration (AMD). Statins, or HMG CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, are drugs with multiple properties that have been extensively used to treat hyperlipidemia. However, their effect on RPE cells has not been fully elucidated...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536795/exploration-of-alginates-as-potential-stabilizers-of-nanosuspension
#11
Jian Guan, Yeli Zhang, Qiaoyu Liu, Xin Zhang, Rina Chokshi, Shirui Mao
The objective of this study was to explore the feasibility of using alginate as a potential stabilizer of nanosuspension and elaborate the corresponding stabilization mechanism. Using lovastatin as a Biopharmaceutics Classification System (BCS) II drug model, alginate-stabilized nanosuspension was fabricated by the high-pressure homogenization method. The particle size, zeta potential, short-term stability, and dissolution behavior of the nanosuspension were characterized. Thereafter, the surface morphology, crystallinity, redispersability, and stability of the spray-dried nanosuspension were investigated...
May 23, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28529817/coordinated-and-iterative-enzyme-catalysis-in-fungal-polyketide-biosynthesis
#12
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
#13
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)...
June 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
#14
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
#15
https://www.readbyqxmd.com/read/28455524/mechanisms-underlying-cognitive-deficits-in-a-mouse-model-for-costello-syndrome-are-distinct-from-other-rasopathy-mouse-models
#16
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
#17
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
#18
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
#19
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
#20
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
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