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https://www.readbyqxmd.com/read/27933735/danazol-has-potential-to-cause-pkc-translocation-cell-cycle-dysregulation-and-apoptosis-in-breast-cancer-cells
#1
Suman Jyoti Deka, Ashalata Roy, Vibin Ramakrishnan, Debasis Manna, Vishal Trivedi
Danazol, the established clinical drug has given promising therapeutic results in a series of clinical trials with breast cancer patients. Danazol shares structural similarities with several known PKC agonists and fits well into the C1 domain. Danazol binds to the C1b domain of PKC with Kd of 5.64±1.27 μM. MD simulation studies further support that the PKC-Danazol molecular model is stable and showing minimum distortion to the structure during the simulation period. Immunofluorescence and western-blotting studies indicate that MDAMB-231 cells stimulated with danazol exhibit translocation of PKCα to the plasma membrane...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27933725/cellular-engineering-for-therapeutic-protein-production-product-quality-host-modification-and-process-improvement
#2
REVIEW
Evan Wells, Anne Skaja Robinson
Recombinant proteins offer many therapeutic advantages unavailable in traditional small molecule drugs, but the need for cellular versus chemical synthesis complicates production. Avenues for producing therapeutic biologics are continuously expanding, and developments in biochemistry, cell biology, and bioengineering fuel new discoveries that promise safer, more efficient, and cheaper drugs for consumers. Numerous approaches to express recombinant proteins exist, but Escherichia coli, Saccharomyces cerevisiae, and mammalian systems (e...
December 9, 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/27933721/shared-molecular-networks-in-orofacial-and-neural-tube-development
#3
Youssef A Kousa, Tamer A Mansour, Haitham Seada, Samaneh Matoo, Brian C Schutte
BACKGROUND: Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality...
December 9, 2016: Birth Defects Research. Part A, Clinical and Molecular Teratology
https://www.readbyqxmd.com/read/27933669/characterization-of-nitrated-sugar-alcohols-by-atmospheric-pressure-chemical-ionization-mass-spectrometry
#4
Alla Ostrinskaya, Jude A Kelley, Roderick R Kunz
RATIONALE: The nitrated sugar alcohols mannitol hexanitrate (MHN), sorbitol hexanitrate (SHN) and xylitol pentanitrate (XPN) are in the same class of compounds as the powerful military grade explosive pentaerythritol tetranitrate (PETN) and the homemade explosive erythritol tetranitrate (ETN) but, unlike for PETN and ETN, ways to detect MHN, SHN and XPN by mass spectrometry (MS) have not been fully investigated. METHODS: Atmospheric-pressure chemical-ionization mass spectrometry (APCI-MS) was used to detect ions characteristic of nitrated sugar alcohols...
December 9, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/27933650/up-regulation-of-microrna-133a-inhibits-the-mek-erk-signaling-pathway-to-promote-cell-apoptosis-and-enhance-radio-sensitivity-by-targeting-egfr-in-esophageal-cancer-in-vivo-and-in-vitro
#5
Qing-Shan Yang, Li-Peng Jiang, Chun-Yan He, Yu-Na Tong, Yuan-Yuan Liu
This study aims to explore how microRNA-133a (miR-133a) affects cell apoptosis and radio-sensitivity by targeting EGFR via regulating MEK/ERK pathway in esophageal cancer (EC). A total of 358 EC patients were selected and assigned into the resistant and sensitive groups. Human EC KYSE 150 cell line was assigned into the blank, negative control (NC), miR-133a mimic, miR-133a inhibitors, si-EGFR, miR-133a inhibitors + si-EGFR groups after transfection. MiR-133a and EGFR mRNA expressions were detected by qRT-PCR and EGFR, MEK/ERK pathway-related protein expressions were detected by Western blotting...
December 8, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27933604/chemoresistant-lung-cancer-stem-cells-display-high-dna-repair-capability-to-remove-cisplatin-dna-damage
#6
Wai-Kin Yu, Zhigang Wang, Chi-Chun Fong, Dandan Liu, Tak-Chun Yip, Siu-Kie Au, Guangyu Zhu, Mengsu Yang
BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor of lung cancer recurrence due to their high resistance to conventional chemotherapy. The underlying mechanisms, however, have not been fully addressed. EXPERIMENTAL APPROACH: In this study, we examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27933584/matrine-treatment-blocks-nogoa-induced-neural-inhibitory-signaling-pathway-in-ongoing-experimental-autoimmune-encephalomyelitis
#7
Quan-Cheng Kan, Hui-Jun Zhang, Yuan Zhang, Xing Li, Yu-Ming Xu, Rodolfo Thome, Ming-Liang Zhang, Nan Liu, Yao-Juan Chu, Guang-Xian Zhang, Li Zhu
Myelin-associated inhibitors, such as NogoA, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), play a pivotal role in the lack of neuroregeneration in multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). Matrine (MAT), a monomer that is used in traditional Chinese medicine as an anti-inflammatory agent, has shown beneficial effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, the underlying mechanisms of MAT-induced EAE amelioration are not fully understood...
December 9, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27933580/headache-service-quality-evaluation-of-quality-indicators-in-14-specialist-care-centres
#8
Sara Schramm, Derya Uluduz, Raquel Gil Gouveia, Rigmor Jensen, Aksel Siva, Ugur Uygunoglu, Giorgadze Gvantsa, Maka Mania, Mark Braschinsky, Elena Filatova, Nina Latysheva, Vera Osipova, Kirill Skorobogatykh, Julia Azimova, Andreas Straube, Ozan Emre Eren, Paolo Martelletti, Valerio De Angelis, Andrea Negro, Mattias Linde, Knut Hagen, Aleksandra Radojicic, Jasna Zidverc-Trajkovic, Ana Podgorac, Koen Paemeleire, Annelien De Pue, Christian Lampl, Timothy J Steiner, Zaza Katsarava
BACKGROUND: The study was a collaboration between Lifting The Burden (LTB) and the European Headache Federation (EHF). Its aim was to evaluate the implementation of quality indicators for headache care Europe-wide in specialist headache centres (level-3 according to the EHF/LTB standard). METHODS: Employing previously-developed instruments in 14 such centres, we made enquiries, in each, of health-care providers (doctors, nurses, psychologists, physiotherapists) and 50 patients, and analysed the medical records of 50 other patients...
December 2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27933565/kshv-strategies-for-host-dsdna-sensing-machinery
#9
REVIEW
Hang Gao, Yanyan Song, Chengrong Liu, Qiming Liang
The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling...
December 5, 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27933551/pentoxifylline-alleviates-early-brain-injury-after-experimental-subarachnoid-hemorrhage-in-rats-possibly-via-inhibiting-tlr-4-nf-%C3%AE%C2%BAb-signaling-pathway
#10
Da-Yong Xia, Hua-Sheng Zhang, Ling-Yun Wu, Xiang-Sheng Zhang, Meng-Liang Zhou, Chun-Hua Hang
Early brain injury (EBI) after subarachnoid hemorrhage (SAH) generally causes significant and lasting damage. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, has shown anti-inflammatory and neuroprotective properties in several brain injury models, but the role of PTX with respect to EBI following SAH remains uncertain. The purpose of this study was to investigate the effects of PTX on EBI after SAH in rats. Adult male Sprauge-Dawley rats were randomly assigned to the sham and SAH groups. PTX (30 or 60 mg/kg) or an equal volume of the administration vehicle (normal saline) was administrated at 30 min intervals following SAH...
December 8, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27933548/metabolic-characterization-of-acutely-isolated-hippocampal-and-cerebral-cortical-slices-using-u-13-c-glucose-and-1-2-13-c-acetate-as-substrates
#11
Laura F McNair, Rasmus Kornfelt, Anne B Walls, Jens V Andersen, Blanca I Aldana, Jakob D Nissen, Arne Schousboe, Helle S Waagepetersen
Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few comparative characterization studies exist for acute hippocampal and cerebral cortical slices, hence, the aim of the current study was to characterize and compare glucose and acetate metabolism in these slice preparations in a newly established incubation design...
December 8, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27933547/anti-neuroinflammatory-effects-of-fucoxanthin-via-inhibition-of-akt-nf-%C3%AE%C2%BAb-and-mapks-ap-1-pathways-and-activation-of-pka-creb-pathway-in-lipopolysaccharide-activated-bv-2-microglial-cells
#12
Dong Zhao, Seung-Hwan Kwon, Yoon Sun Chun, Ming-Yao Gu, Hyun Ok Yang
Microglia play a critical role in controlling the homeostasis of the brain, but over-activated microglia secrete pro-inflammatory mediators and cytokines, which induce neuronal cell death. Fucoxanthin (Fx), a marine carotenoid, has demonstrated a variety of beneficial health effects. Despite accumulating evidence supporting the immune-modulating effects of Fx in vitro, the underlying signaling pathways remain unknown. In the present study, Fx dose-dependently inhibited the secretion of lipopolysaccharide (LPS)-induced pro-inflammatory mediators including interleukin (IL)-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), prostaglandin (PG) E2, and nitric oxide (NO) productions, and also suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 enzymes...
December 8, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27933546/using-systems-genetics-to-understanding-the-etiology-of-complex-disease
#13
Ramesh Ram, Grant Morahan
Here, we discuss Systems Genetics applications for systematic evaluation of candidate causal genes together with follow-up bioinformatics pathway analysis. The aim of this chapter is to illustrate analytic procedures and we provide examples in the context of Type 1 diabetes (T1day), the risk of which is conferred by over 60 loci. We also describe the Type 1 Diabetes Systems Genetics website and provide a guide for its use and application to other diseases.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933533/systems-genetics-as-a-tool-to-identify-master-genetic-regulators-in-complex-disease
#14
Aida Moreno-Moral, Francesco Pesce, Jacques Behmoaras, Enrico Petretto
Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933531/using-baseline-transcriptional-connectomes-in-rat-to-identify-genetic-pathways-associated-with-predisposition-to-complex-traits
#15
Laura Saba, Paula Hoffman, Boris Tabakoff
Although rat is a critical model organism in preclinical medications development, its use in systems genetics studies remains sparse. The PhenoGen database and website contain detailed information on the qualitative and quantitative aspects of the rat brain, liver, heart, and brown adipose transcriptome. This database has been generated using the HXB/BXH recombinant inbred panel and is being expanded to a hybrid rat diversity panel that includes many common inbred strains as well. By using such a panel, the PhenoGen project has created a renewable and cumulative resource for the rat genomics community...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933523/integrative-functional-genomics-for-systems-genetics-in-geneweaver-org
#16
Jason A Bubier, Michael A Langston, Erich J Baker, Elissa J Chesler
The abundance of existing functional genomics studies permits an integrative approach to interpreting and resolving the results of diverse systems genetics studies. However, a major challenge lies in assembling and harmonizing heterogeneous data sets across species for facile comparison to the positional candidate genes and coexpression networks that come from systems genetic studies. GeneWeaver is an online database and suite of tools at www.geneweaver.org that allows for fast aggregation and analysis of gene set-centric data...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933504/mental-health-support-provided-throughout-the-bariatric-surgery-clinical-pathway-in-french-specialized-care-centers-for-obesity
#17
Kristopher Lamore, Sandra S Kaci, Sébastien Czernichow, Marion Bretault, Jean-Luc Bouillot, Anne-Jeanne Naudé, Sandra Gribe-Ouaknine, Claire Carette, Cécile Flahault
OBJECTIVE: Pre-operative psychological assessment is recommended by international guidelines for bariatric surgery candidates. Thereby, service teams caring for bariatric patients should include at least one mental health provider (e.g., a psychologist or psychiatrist). The objective of this study was to evaluate the psychology and psychiatry resources and practices in the 37 specialized obesity centers (CSOs) created by the French Ministry of Health. MATERIALS AND METHODS: CSO coordinators were contacted by e-mail to collect general information on the centers (e...
December 8, 2016: Obesity Surgery
https://www.readbyqxmd.com/read/27933456/penicillin-v-acylases-from-gram-negative-bacteria-degrade-n-acylhomoserine-lactones-and-attenuate-virulence-in-pseudomonas-aeruginosa
#18
Avinash Vellore Sunder, Putri Dwi Utari, Sureshkumar Ramasamy, Ronald van Merkerk, Wim Quax, Archana Pundle
Virulence pathways in gram-negative pathogenic bacteria are regulated by quorum sensing mechanisms, through the production and sensing of N-acylhomoserine lactone (AHL) signal molecules. Enzymatic degradation of AHLs leading to attenuation of virulence (quorum quenching) could pave the way for the development of new antibacterials. Penicillin V acylases (PVAs) belong to the Ntn hydrolase superfamily, together with AHL acylases. PVAs are exploited widely in the pharmaceutical industry, but their role in the natural physiology of their native microbes is not clearly understood...
December 8, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27933454/improved-production-of-adipate-with-escherichia-coli-by-reversal-of-%C3%AE-oxidation
#19
Nicolai Kallscheuer, Jochem Gätgens, Marvin Lübcke, Jörg Pietruszka, Michael Bott, Tino Polen
The linear C6 dicarboxylic acid adipic acid is an important bulk chemical in the petrochemical industry as precursor of the polymer nylon-6,6-polyamide. In recent years, efforts were made towards the biotechnological production of adipate from renewable carbon sources using microbial cells. One strategy is to produce adipate via a reversed β-oxidation pathway. Hitherto, the adipate titers were very low due to limiting enzyme activities for this pathway. In most cases, the CoA intermediates are non-natural substrates for the tested enzymes and were therefore barely converted...
December 8, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27933453/engineering-of-escherichia-coli-to-facilitate-efficient-utilization-of-isomaltose-and-panose-in-industrial-glucose-feedstock
#20
Kenji Abe, Akio Kuroda, Ryo Takeshita
Industrial glucose feedstock prepared by enzymatic digestion of starch typically contains significant amounts of disaccharides such as maltose and isomaltose and trisaccharides such as maltotriose and panose. Maltose and maltosaccharides can be utilized in Escherichia coli fermentation using industrial glucose feedstock because there is an intrinsic assimilation pathway for these sugars. However, saccharides that contain α-1,6 bonds, such as isomaltose and panose, are still present after fermentation because there is no metabolic pathway for these sugars...
December 8, 2016: Applied Microbiology and Biotechnology
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