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Natural product

Hilal Ahmad Parray, Jameel Lone, Jong Pil Park, Jang Won Choi, Jong Won Yun
OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively...
February 5, 2018: Nutrition
Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
Christopher Ryan Shugrue, Aaron L Featherston, Rachel M Lackner, Angela Lin, Scott J Miller
Phosphothreonine (pThr)-embedded peptide catalysts are found to mediate the reductive amination of 3-amidocyclohexanones with divergent selectivity. Choice of peptide sequence can be used to alter the diastereoselectivity to favor either cis-product or trans-product, which are obtained in up to 93:7 er. NMR studies and DFT calculations are reported and indicate that both pathways rely on secondary interactions between substrate and catalyst to achieve selectivity. Furthermore, catalysts appear to accomplish a parallel kinetic resolution of the substrates...
March 16, 2018: Journal of Organic Chemistry
Hai-Jun Zhang, Alexander W Schuppe, Shi-Tao Pan, Jin-Xiang Chen, Bo-Ran Wang, Timothy R Newhouse, Liang Yin
A mild and operationally simple copper-catalyzed vinylogous aerobic oxidation of ,- and ,-unsaturated esters is described. This method features good yields, broad substrate scope, excellent chemo- and regioselectivity and good functional group tolerance. This method is additionally capable of oxidizing ,- and ,-unsaturated aldehydes, ketones, amides, nitriles and sulfones. Furthermore, the present catalytic system is suitable for bisvinylogous and trisvinylogous oxidation. TMG was found to be crucial in its role as a base, but we also speculate it serves as a ligand to copper(II) triflate to produce the active copper(II) catalyst...
March 16, 2018: Journal of the American Chemical Society
Alhanouf Zakaria Aljahdali, Kathryn Ann Foster, George Augustine O'Doherty
The recent total syntheses of cryptocaryols A and B are reviewed. These efforts include the correction of the initially assigned absolute and relative stereochemistry of this class of natural products. In addition to enabling the initial structure activity relationships for this class of natural products, these syntheses demonstrated the practical utility of several novel synthetic approaches.
March 16, 2018: Chemical Communications: Chem Comm
Vsevolod A Peshkov, Olga P Pereshivko, Anton A Nechaev, Anatoly A Peshkov, Erik V Van der Eycken
This focused review aims to summarize recent developments in the processes involving additions of secondary propargylamines to various heteroallenes and subsequent transition metal-catalyzed or electrophile-mediated cyclizations. The utility of this convenient and tunable strategy spans from the carbon dioxide fixation and target-oriented synthesis of complex natural and biologically active products to the generation of extended synthetic libraries of diverse oxygen-, nitrogen- and sulfur-containing heterocycles...
March 16, 2018: Chemical Society Reviews
Hengyao You, Srinivas Rao Vegi, Chandraiah Lagishetti, Shuo Chen, Rekula Santhosh Reddy, Xiaohong Yang, Jian Guo, Chenhui Wang, Yun He
A convenient synthesis of 3,4-dihydro-2H-naphtho [2,3-b] [1,4] oxazine-5,10-diones and 2,3,4,5-tetrahydro-1H-naphtho [2,3-b] azepine-6,11-diones via copper catalysed intramolecular C-O/C-C coupling reaction is described. This method showed good tolerance for functional groups and was applied to the synthesis of natural product core strcutures. Some coupling products exhibited moderate activities against lung cancer A549 cells.
March 16, 2018: Journal of Organic Chemistry
Mаhmoud Youns, Abeer ElKhoely, Rehab Kamel
Pancreatic cancer, the fourth most common cause of cancer-related deaths, is one of the most aggressive and devastating human malignancies with increasing incidence worldwide. To date, surgical resection is the only potentially curative therapy available for pancreatic cancer patients. Early diagnosis of pancreatic tumors is difficult, and hence, nearly 80% of patients cannot receive surgical resection. Natural products have always been a vital source for novel compounds for cancer treatment. The naturally occurring prenylated xanthone, gambogic acid, has been previously shown to exert potent anticancer, anti-inflammatory, apoptotic, antiangiogenic, and antioxidant activities...
March 15, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Patrícia Branco, Helena Albergaria, Nils Arneborg, Catarina Prista
Saccharomyces cerevisiae secretes antimicrobial peptides (AMPs) derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which induce death of several non-Saccharomyces yeasts. Previously, we demonstrated that the naturally-secreted GAPDH-derived AMPs (i.e. saccharomycin) caused a loss of culturability and decreased the intracellular pH (pHi) of Hanseniaspora guilliermondii cells. In this study, we show that chemically-synthesized analogues of saccharomycin also induce a pHi drop and loss of culturability in H...
March 13, 2018: FEMS Yeast Research
Alhanouf Zakaria Aljahdali, Kathryn Ann Foster, George Augustine O'Doherty
The recent total syntheses of cryptocaryols A and B are reviewed. These efforts include the correction of the initially assigned absolute and relative stereochemistry of this class of natural products. In addition to enabling the initial structure activity relationships for this class of natural products, these syntheses demonstrated the practical utility of several novel synthetic approaches.
March 16, 2018: Chemical Communications: Chem Comm
Raúl Cassia, Macarena Nocioni, Natalia Correa-Aragunde, Lorenzo Lamattina
Here, we review information on how plants face redox imbalance caused by climate change, and focus on the role of nitric oxide (NO) in this response. Life on Earth is possible thanks to greenhouse effect. Without it, temperature on Earth's surface would be around -19°C, instead of the current average of 14°C. Greenhouse effect is produced by greenhouse gasses (GHG) like water vapor, carbon dioxide (CO2 ), methane (CH4 ), nitrous oxides (Nx O) and ozone (O3 ). GHG have natural and anthropogenic origin. However, increasing GHG provokes extreme climate changes such as floods, droughts and heat, which induce reactive oxygen species (ROS) and oxidative stress in plants...
2018: Frontiers in Plant Science
Peter L Cummins, Babu Kannappan, Jill E Gready
The ubiquitous enzyme Ribulose 1,5-bisphosphate carboxylase-oxygenase (RuBisCO) fixes atmospheric carbon dioxide within the Calvin-Benson cycle that is utilized by most photosynthetic organisms. Despite this central role, RuBisCO's efficiency surprisingly struggles, with both a very slow turnover rate to products and also impaired substrate specificity, features that have long been an enigma as it would be assumed that its efficiency was under strong evolutionary pressure. RuBisCO's substrate specificity is compromised as it catalyzes a side-fixation reaction with atmospheric oxygen; empirical kinetic results show a trend to tradeoff between relative specificity and low catalytic turnover rate...
2018: Frontiers in Plant Science
Camila Carlos, Huan Fan, Cameron R Currie
Deconstructing the intricate matrix of cellulose, hemicellulose, and lignin poses a major challenge in biofuel production. In diverse environments in nature, some microbial communities, are able to overcome plant biomass recalcitrance. Identifying key degraders of each component of plant cell wall can help improve biological degradation of plant feedstock. Here, we sequenced the metagenome of lignocellulose-adapted microbial consortia sub-cultured on xylan and alkali lignin media. We observed a drastic shift on community composition after sub-culturing, independently of the original consortia...
2018: Frontiers in Microbiology
Godwin U Ebiloma, Evangelos Katsoulis, John O Igoli, Alexander I Gray, Harry P De Koning
Natural products have made remarkable contributions to drug discovery and therapy. In this work we exploited various biochemical approaches to investigate the mode of action of 16-α-hydroxy-cleroda-3,13 (14)-Z-dien-15,16-olide (HDK-20), which we recently isolated from Polyalthia longifolia, on Trypanosoma brucei bloodstream trypomastigotes. HDK20 at concentrations ≥ EC50 (0.4 μg/ml) was trypanocidal, with its effect irreversible after only a brief exposure time (<1 h). Fluorescence microscopic assessment of DNA configuration revealed severe cell cycle defects after 8 h of incubation with the compound, the equivalent of a single generation time...
March 15, 2018: Scientific Reports
Michael D Oberst, Catherine Auge, Chad Morris, Stacy Kentner, Kathy Mulgrew, Kelly McGlinchey, James Hair, Shino Hanabuchi, Qun Du, Melissa Damschroder, Hui Feng, Steven Eck, Nicholas Buss, Lolke de Haan, Andrew J Pierce, Haesun Park, Andrew Sylwester, Michael K Axthelm, Louis Picker, Nicholas P Morris, Andrew Weinberg, Scott A Hammond
Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells...
March 15, 2018: Molecular Cancer Therapeutics
Peggy Stolt-Bergner, Christian Benda, Tim Bergbrede, Hüseyin Besir, Patrick H N Celie, Cindy Chang, David Drechsel, Ariane Fischer, Arie Geerlof, Barbara Giabbai, Joop van den Heuvel, Georg Huber, Wolfgang Knecht, Anita Lehner, Regis Lemaitre, Kristina Nordén, Gwynn Pardee, Ines Racke, Kim Remans, Astrid Sander, Judith Scholz, Magda Stadnik, Paola Storici, Daniel Weinbruch, Isabel Zaror, Linda H L Lua, Sabine Suppmann
Baculovirus-insect cell expression system has become one of the most widely used eukaryotic expression systems for heterologous protein production in many laboratories. The availability of robust insect cell lines, serum-free media, a range of vectors and commercially-packaged kits have supported the demand for maximizing the exploitation of the baculovirus-insect cell expression system. Naturally, this resulted in varied strategies adopted by different laboratories to optimize protein production. Most laboratories have preference in using either the E...
March 12, 2018: Journal of Structural Biology
Gustavo F Paz, Jeronimo M N Rugani, Andreza P Marcelino, Célia M F Gontijo
The aim of this study was to evaluate the relationship between naturally occurring Leishmania spp. infections in dogs (Canis familiaris) and the practical implications of the use of serological and molecular methods to confirm diagnoses. The study population consisted of 96 domestic dogs in southeastern Brazil. Serum samples were tested for the presence of anti-Leishmania immunoglobulin G (IgG) antibodies using four commercial canine visceral leishmaniasis kits. Dogs confirmed positive by immunofluorescence antibody test (IFAT) were culled and samples from mesenteric lymph nodes, spleen border, bone marrow and ear skin were taken and submitted to DNA extraction...
March 12, 2018: Acta Tropica
Yufei Chen, Yannick L Traore, Sidi Yang, Julie Lajoie, Keith R Fowke, Daniel W Rickey, Emmanuel A Ho
Evidence suggests that women who are naturally resistant to HIV infection exhibit low baseline immune activation at the female genital tract (FGT). This "immune quiescent" state is associated with lower expression of T-cell activation markers, reduced levels of gene transcription and pro-inflammatory cytokine or chemokine production involved in HIV infection while maintaining an intact immune response against pathogens. Therefore, if this unique immune quiescent state can be pharmacologically induced locally, it will provide an excellent women-oriented strategy against HIV infection To our knowledge, this is the first research article evaluating in vivo, an innovative trackable implant that can provide controlled delivery of hydroxychloroquine (HCQ) to successfully attenuate vaginal T lymphocyte activation and inflammation in a rabbit model as a potential strategy to induce an "immune quiescent" state within the FGT for the prevention of HIV infection...
March 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Hemachander Subramanian, Robert A Gatenby
Due to the asymmetric nature of the nucleotides, the extant informational biomolecule, DNA, is constrained to replicate unidirectionally on a template. As a product of molecular evolution that sought to maximize replicative potential, DNA's unidirectional replication poses a mystery since symmetric bidirectional self-replicators obviously would replicate faster than unidirectional self-replicators and hence would have been evolutionarily more successful. Here we carefully examine the physico-chemical requirements for evolutionarily successful primordial self-replicators and theoretically show that at low monomer concentrations that possibly prevailed in the primordial oceans, asymmetric unidirectional self-replicators would have an evolutionary advantage over bidirectional self-replicators...
March 12, 2018: Journal of Theoretical Biology
Andrew Best, Jason M Kamilar
Sweating is an unusual thermoregulatory strategy for most mammals, yet is critical for humans. This trait is commonly hypothesized to result from human ancestors moving from a forest to a warmer and drier open environment. As soft tissue traits do not typically fossilize, this idea has been difficult to test. Therefore, we used a comparative approach to examine 15 eccrine gland traits from 35 primate species. For each trait we measured phylogenetic signal, tested three evolutionary models to explain trait variation, and used phylogenetic models to examine how traits varied in response to climate variables...
April 2018: Journal of Human Evolution
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