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https://www.readbyqxmd.com/read/29150931/microrna-497-accelerates-apoptosis-while-inhibiting-proliferation-migration-and-invasion-through-negative-regulation-of-the-mapk-erk-signaling-pathway-via-raf-1
#1
Ling Tao, Xia Li, Na-Na Han, Qi Zhou, Zhi-Le Liu
The aim of this study is to explore the various modes of action miR-497 has on human cervical cancer (CC) cell behavior. We also speculate that miR-497 achieves its anti-tumor role by governing RAF-1 via MAPK/ERK signaling pathway. CC tissues with corresponding adjacent normal tissues were collected from 168 CC patients. RAF-1-positive cells were identified by means of immunohistochemistry in tissues. A series of inhibitors, mimics and siRNA against RAF-1 were introduced to validate regulatory mechanisms for miR-497 and RAF-1...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150734/the-sirtuin-1-2-inhibitor-tenovin-1-induces-a-nonlinear-apoptosis-inducing-factor-dependent-cell-death-in-a-p53-null-ewing-s-sarcoma-cell-line
#2
Christian Marx, Lisa Marx-Blümel, Nora Lindig, René Thierbach, Doerte Hoelzer, Sabine Becker, Susan Wittig, Roland Lehmann, Hortense Slevogt, Thorsten Heinzel, Zhao-Qi Wang, James F Beck, Jürgen Sonnemann
The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting...
November 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29149821/statins-therapy-for-connective-tissue-diseases-new-therapeutic-opportunities
#3
Przemyslaw J Kotyla, Eugene J Kucharz
Background and Objective Statins, 3-hydroxyl-3-methyl-glutharyl Coenzyme A reductase inhibitors showed their therapeutic potential in the treatment of atherosclerosis-related diseases. Recently, the properties of statins, separate from their lipid lowering activity have attracted much attention. These properties that cover a wide area of physiopathological activities including cell maturation, immune response regulation, tissue fibrosis, endothelial activity and are called pleiotropic activity. Many in vitro studies demonstrated significant, statins-dependent regulation of immune system reactivity, reduction of pro-inflammatory and pro-fibrotic cytokines as well as suppression of endothelial activity and damage...
November 15, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29149093/evolutionarily-distant-streptophyta-respond-differently-to-genotoxic-stress
#4
Radka Vágnerová, Alena Lukešová, Martin Lukeš, Petra Rožnovská, Marcela Holá, Jana Fulnečková, Jiří Fajkus, Karel J Angelis
Research in algae usually focuses on the description and characterization of morpho-and phenotype as a result of adaptation to a particular habitat and its conditions. To better understand the evolution of lineages we characterized responses of filamentous streptophyte green algae of the genera Klebsormidium and Zygnema, and of a land plant-the moss Physcomitrellapatens-to genotoxic stress that might be relevant to their environment. We studied the induction and repair of DNA double strand breaks (DSBs) elicited by the radiomimetic drug bleomycin, DNA single strand breaks (SSB) as consequence of base modification by the alkylation agent methyl methanesulfonate (MMS) and of ultra violet (UV)-induced photo-dimers, because the mode of action of these three genotoxic agents is well understood...
November 17, 2017: Genes
https://www.readbyqxmd.com/read/29148981/walnut-leaf-extract-acts-as-a-fertility-agent-in-male-wistar-albino-rats-a-search-for-herbal-male-fertility-enhancer
#5
Seun F Akomolafe, Ganiyu Oboh
Background Walnut leaf is one of the many medicinal plants used in folklore as male fertility enhancers. The present work was therefore undertaken with an aim to scientifically validate this claim. As such, we evaluated the effect of the aqueous extract from walnut leaves on biomolecules related to fertility in adult male rats and its mode of action as fertility-enhancing agent. Methods Twenty-five rats were randomly divided into five groups of five animals each; Group 1 served as control and received normal (0...
November 17, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/29147511/cytotoxic-salen-ruthenium-iii-anticancer-complexes-exhibit-different-modes-of-cell-death-directed-by-axial-ligands
#6
Cai Li, Kwok-Wa Ip, Wai-Lun Man, Dan Song, Ming-Liang He, Shek-Man Yiu, Tai-Chu Lau, Guangyu Zhu
Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tests demonstrate that these complexes are cytotoxic against various cancer cell lines and the leading complexes have remarkable cancer-cell selectivity. A detailed study of the guanidine complex 7 and the amidine complex 13 reveals two distinguished modes of action. Complex 7 weakly binds to DNA and induces DNA damage, cell cycle arrest, and typical apoptosis pathways in MCF-7 cells...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147504/immuno-targeting-of-staphylococcus-aureus-via-surface-remodeling-complexes
#7
Mary J Sabulski, Sean E Pidgeon, Marcos M Pires
Agents with novel mechanisms of action are needed to complement traditional antibiotics. Towards these goals, we have exploited the surface-homing properties of vancomycin to tag the surface of Gram-positive pathogens with immune cell attractants in two unique modes. First, vancomycin was conjugated to the small molecule hapten 2,4-dinitrophenol (DNP) to promote bacterial opsonization. Second, we built on these results by improving the tagging specificity and mechanism of incorporation by coupling it to a sortase A substrate peptide...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147019/identification-and-characterization-of-serine-protease-inhibitors-in-a-parasitic-wasp-pteromalus-puparum
#8
Lei Yang, Yaotian Mei, Qi Fang, Jiale Wang, Zhichao Yan, Qisheng Song, Zhe Lin, Gongyin Ye
Serine protease inhibitors (SPIs) regulate protease-mediated activities by inactivating their cognate proteinases, and are involved in multiple physiological processes. SPIs have been extensively studied in vertebrates and invertebrates; however, little SPI information is available in parasitoids. Herein, we identified 57 SPI genes in total through the genome of a parasitoid wasp, Pteromalus puparum. Gene structure analyses revealed that these SPIs contain 7 SPI domains. Depending on their mode of action, these SPIs can be categorized into serpins, canonical inhibitors and alpha-2-macroglobulins (A2Ms)...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146302/mechanisms-involved-in-bone-resorption-regulated-by-vitamin-d
#9
REVIEW
Yuko Nakamichi, Nobuyuki Udagawa, Tatsuo Suda, Naoyuki Takahashi
Active forms of vitamin D enhance osteoclastogenesis in vitro and in vivo through the vitamin D receptor (VDR) in osteoblast-lineage cells consisting of osteoblasts and osteocytes. This pro-resorptive activity was evident basically with higher concentrations of active vitamin D than those expected in physiological conditions. Nevertheless, vitamin D compounds have been used in Japan for treating osteoporosis to increase bone mineral density (BMD). Of note, the increase in BMD by long-term treatment with pharmacological (=near-physiological) doses of vitamin D compounds was caused by the suppression of bone resorption...
November 13, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29146259/characterization-and-assessment-of-two-biocontrol-bacteria-against-pseudomonas-syringae-wilt-in-solanum-lycopersicum-and-its-genetic-responses
#10
Kaliannan Durairaj, Palanivel Velmurugan, Jung-Hee Park, Woo-Suk Chang, Yool-Jin Park, Palaninaicker Senthilkumar, Kyung-Min Choi, Jeong-Ho Lee, Byung-Taek Oh
Pseudomonas and Bacillus species are attractive due to their potential bio-control application against plant bacterial pathogens. Pseudomonas aeruginosa strain D4 and Bacillus stratosphericus strain FW3 were isolated from mine tailings in South Korea. In these potent bacterial strains, we observed improved antagonistic activity against Pseudomonas syringae DC3000. These strains produced biocatalysts for plant growth promotion, and in vivo examination of Solanum lycopersicum included analysis of disease severity, ion leakage, chlorophyll content, and H2O2 detection...
January 2018: Microbiological Research
https://www.readbyqxmd.com/read/29145599/a-role-for-thiopurine-metabolites-in-the-synergism-between-thiopurines-and-infliximab-in-inflammatory-bowel-disease
#11
Ditte V Mogensen, Jørn Brynskov, Mark A Ainsworth, Jacob Nersting, Kjeld Schmiegelow, Casper Steenholdt
Background: Interactions between principal cytotoxic thiopurine metabolites, 6-thioguanine nucleotides (6-TGN), and infliximab (IFX) and anti-IFX antibodies (Abs) may contribute to higher effectiveness of IFX-thiopurine-combination therapy than monotherapies in inflammatory bowel disease. Methods: To examine if thiopurine metabolites influenced trough IFX and anti-IFX Abs, 89 patients previously assessed for anti-IFX Abs were included. To assess if IFX influenced thiopurine metabolites, 8 patients having responded to 12 weeks of intensified IFX at a constant thiopurine dosing were included...
November 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29145489/expert-cognition-in-the-production-sequence-of-acheulian-cleavers-at-gesher-benot-ya-aqov-israel-a-lithic-and-cognitive-analysis
#12
Gadi Herzlinger, Thomas Wynn, Naama Goren-Inbar
Stone cleavers are one of the most distinctive components of the Acheulian toolkit. These tools were produced as part of a long and complex reduction sequence and they provide indications for planning and remarkable knapping skill. These aspects hold implications regarding the cognitive complexity and abilities of their makers and users. In this study we have analyzed a cleaver assemblage originating from the Acheulian site of Gesher Benot Ya'aqov, Israel, to provide a reconstruction of the chaîne opératoire which structured their production...
2017: PloS One
https://www.readbyqxmd.com/read/29144777/urgoclean-ag-evidence-base-and-mode-of-action
#13
Mark Greener
UrgoClean Ag is indicated for all exuding wounds with signs of increased bioburden and biofilm. This article describes the evidence base supporting its efficacy.
November 8, 2017: British Journal of Nursing: BJN
https://www.readbyqxmd.com/read/29144452/ubiquitination-and-degradation-of-gbps-by-a-shigella-effector-to-suppress-host-defence
#14
Peng Li, Wei Jiang, Qin Yu, Wang Liu, Ping Zhou, Jun Li, Junjie Xu, Bo Xu, Fengchao Wang, Feng Shao
Interferon-inducible guanylate-binding proteins (GBPs) mediate cell-autonomous antimicrobial defences. Shigella flexneri, a Gram-negative cytoplasmic free-living bacterium that causes bacillary dysentery, encodes a repertoire of highly similar type III secretion system effectors called invasion plasmid antigen Hs (IpaHs). IpaHs represent a large family of bacterial ubiquitin-ligases, but their function is poorly understood. Here we show that S. flexneri infection induces rapid proteasomal degradation of human guanylate binding protein-1 (hGBP1)...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29144424/synthesis-characterization-and-biological-activities-of-biopolymeric-schiff-bases-prepared-with-chitosan-and-salicylaldehydes-and-their-pd-ii-and-pt-ii-complexes
#15
Hellen Franciane Gonçalves Barbosa, Maha Attjioui, Ana Paula Garcia Ferreira, Edward Ralph Dockal, Nour Eddine El Gueddari, Bruno M Moerschbacher, Éder Tadeu Gomes Cavalheiro
In an attempt to enhance chitosan biological activities, biopolymeric Schiff bases of chitosan and different salicylaldehydes and their palladium(II) and platinum(II) complexes were synthesized and tested. The chemical structures of these derivatives were characterized using ¹H-NMR, FTIR spectroscopy and XPRD. Thermal analysis was done through TGA/DTG-DTA. Electronic absorption spectra and surface morphologies were analyzed by SEM-EDAX. Chitosan and its derivatives were evaluated for their in vitro antimicrobial activity against two common bacterial and fungal plant pathogens Pseudomonas syringae pv...
November 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29143030/quantitative-chemoproteomic-profiling-reveals-multiple-target-interactions-of-spongiolactone-derivatives-in-leukemia-cells
#16
M H Wright, Y Tao, J Drechsel, J Krysiak, S Chamni, A Weigert-Munoz, N L Harvey, D Romo, S A Sieber
The spongiolactones are marine natural products with an unusual rearranged spongiane skeleton and a fused β-lactone ring. These compounds have potential anticancer properties but their mode of action has yet to be explored. Here we employ activity-based protein profiling to identify the targets of a more potent spongiolactone derivative in live cancer cells, and compare these to the targets of a simpler β-lactone. These hits provide the first insights into the covalent mechanism of action of this natural product class...
November 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29142176/evaluation-of-the-human-relevance-of-the-constitutive-androstane-receptor-mediated-mode-of-action-for-rat-hepatocellular-tumor-formation-by-the-synthetic-pyrethroid-momfluorothrin
#17
Yu Okuda, Masahiko Kushida, Hiroko Kikumoto, Yoshimasa Nakamura, Hashihiro Higuchi, Satoshi Kawamura, Samuel M Cohen, Brian G Lake, Tomoya Yamada
High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic risk of momfluorothrin, the effects of momfluorothrin (1-1,000 µM) and a major metabolite Z-CMCA (5-1,000 µM) on hepatocyte replicative DNA synthesis and CYP2B mRNA expression were examined in cultured rat and human hepatocyte preparations...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29140522/ecodrug-a-database-connecting-drugs-and-conservation-of-their-targets-across-species
#18
Bas Verbruggen, Lina Gunnarsson, Erik Kristiansson, Tobias Österlund, Stewart F Owen, Jason R Snape, Charles R Tyler
Pharmaceuticals are designed to interact with specific molecular targets in humans and these targets generally have orthologs in other species. This provides opportunities for the drug discovery community to use alternative model species for drug development. It also means, however, there is potential for mode of action related effects in non-target wildlife species as many pharmaceuticals reach the environment through patient use and manufacturing wastes. Acquiring insight in drug target ortholog predictions across species and taxonomic groups has proven difficult because of the lack of an optimal strategy and because necessary information is spread across multiple and diverse sources and platforms...
November 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29140465/short-chain-arabinoxylans-prepared-from-enzymatically-treated-wheat-grain-exert-prebiotic-effects-during-the-broiler-starter-period
#19
N Yacoubi, L Saulnier, E Bonnin, E Devillard, V Eeckhaut, L Rhayat, R Ducatelle, F Van Immerseel
Carbohydrate-degrading multi-enzyme preparations (MEP) are used to improve broiler performances. Their mode of action is complex and not fully understood. In this study, we compared the effect of water-soluble fractions isolated at the pilot scale from wheat grain incubated with (WE) and without (WC) MEP. The fractions were incorporated in a wheat-based diet (0.1% w/w) to feed Ross PM3 broilers and compared with a non-supplemented control group (NC). The body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) until d 14 were determined...
November 10, 2017: Poultry Science
https://www.readbyqxmd.com/read/29140163/hsp70s-enhance-a-phytophthora-infestans-effector-induced-cell-death-via-a-mapk-cascade-in-nicotiana-benthamiana
#20
Joohyun Lee, So Eui Lee, SooHyun Oh, Eunyoung Seo, Doil Choi
A destructive pathogen, Phytophthora infestans, secretes hundreds of effectors for successful survival in its host plants. The effectors modulate plant defense system at diverse cellular compartments to take an advantage of pathogen survivals. There were a few researches shown the mode-of-action of each effectors and their interacting proteins in plant cells. Here, we investigated the mode-of-action of a P. infestans effector, Pi23226, which induces cell death in Nicotiana benthamiana. To identify its host factors, we performed co-immunoprecipitation and liquid chromatography-mass spectrometry, and selected members of HSP70 as candidates...
November 15, 2017: Molecular Plant-microbe Interactions: MPMI
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