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Chemical pathology

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https://www.readbyqxmd.com/read/28100269/a-spleen-tyrosine-kinase-inhibitor-attenuates-the-proliferation-and-migration-of-vascular-smooth-muscle-cells
#1
Hyang-Hee Seo, Sang Woo Kim, Chang Youn Lee, Kyu Hee Lim, Jiyun Lee, Eunhyun Choi, Soyeon Lim, Seahyoung Lee, Ki-Chul Hwang
BACKGROUND: Pathologic vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury promotes the development of occlusive vascular disease. Therefore, an effective chemical agent to suppress aberrant proliferation and migration of VSMCs can be a potential therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. To find an anti-proliferative chemical agent for VSMCs, we screened an in-house small molecule library, and the selected small molecule was further validated for its anti-proliferative effect on VSMCs using multiple approaches, such as cell proliferation assays, wound healing assays, transwell migration assays, and ex vivo aortic ring assay...
January 18, 2017: Biological Research
https://www.readbyqxmd.com/read/28098756/detection-of-the-vascular-endothelial-growth-factor-with-a-novel-bioluminescence-resonance-energy-transfer-pair-using-a-two-component-system
#2
Tobias Wimmer, Eva Schroeter, Birgit Lorenz, Knut Stieger
In this paper we describe a two-component BRET (bioluminescence resonance energy transfer)-based method to detect vascular endothelial growth factor (VEGF) molecules in unknown samples as the basis for subsequent in vivo use. A luminescent VEGF binding molecule, which binds in the receptor binding motif of VEGF, is used as the energy donor, transferred to a fluorophore-coupled VEGF binding molecule (acceptor), which binds to the neuropilin binding motif of VEGF, thus enabling energy transfer from the donor to the acceptor molecule...
January 13, 2017: Sensors
https://www.readbyqxmd.com/read/28096729/advanced-mri-for-pediatric-brain-tumors-with-emphasis-on-clinical-benefits
#3
REVIEW
Hyun Woo Goo, Young-Shin Ra
Conventional anatomic brain MRI is often limited in evaluating pediatric brain tumors, the most common solid tumors and a leading cause of death in children. Advanced brain MRI techniques have great potential to improve diagnostic performance in children with brain tumors and overcome diagnostic pitfalls resulting from diverse tumor pathologies as well as nonspecific or overlapped imaging findings. Advanced MRI techniques used for evaluating pediatric brain tumors include diffusion-weighted imaging, diffusion tensor imaging, functional MRI, perfusion imaging, spectroscopy, susceptibility-weighted imaging, and chemical exchange saturation transfer imaging...
January 2017: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/28096269/differentiation-between-radiation-necrosis-and-tumor-progression-using-chemical-exchange-saturation-transfer
#4
Hatef Mehrabian, Kimberly L Desmond, Hany Soliman, Arjun Sahgal, Gregory J Stanisz
PURPOSE: Stereotactic radiosurgery (SRS) is a common treatment used in patients with brain metastases and is associated with high rates of local control, however, at the risk of radiation necrosis. It is difficult to differentiate radiation necrosis from tumor progression using conventional MRI making it a major diagnostic dilemma for practitioners. This prospective study investigated whether chemical exchange saturation transfer (CEST) was able to differentiate these two conditions. MATERIALS & METHODS: Fifteen patients with brain metastases who had been previously treated with SRS were included...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28094986/improving-internal-cell-colonization-of-porous-scaffolds-with-chemical-gradients-produced-by-plasma-assisted-approaches
#5
Eloisa Sardella, Rania A Salama, Gihan H Waly, A Nour Habib, Pietro Favia, Roberto Gristina
Cell colonization of the surrounding environment is a very significant process in both physiological and pathological events. In order to understand the tissue regeneration process and thereby provide guidance principles for designing new biomaterials, it is of paramount importance to study the cell colonization in the presence of physical, chemical and biological cues. Flat "gradient" materials are generally used with this purpose. Three dimensional (3D) gradient scaffolds mimicking more precisely the situation in vivo, are somewhat more complex to fabricate and characterize...
January 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28078379/chitosan-sodium-tetradecyl-sulfate-hydrogel-characterization-and-preclinical-evaluation-of-a-novel-sclerosing-embolizing-agent-for-the-treatment-of-endoleaks
#6
Fatemeh Zehtabi, Vincent Dumont-Mackay, Ahmed Fatimi, Antony Bertrand-Grenier, Hélène Héon, Gilles Soulez, Sophie Lerouge
PURPOSE: To compare the efficacy of an embolization agent with sclerosing properties (made of chitosan and sodium tetradecyl sulfate, CH-STS) with a similar embolization agent but without sclerosing properties (made of chitosan, CH) in treating endoleaks in a canine endovascular aneurysm repair model. METHODS: Two chitosan-based radiopaque hydrogels were prepared, one with STS and one without STS. Their rheological, injectability, and embolizing properties were assessed in vitro; afterwards, their efficacy in occluding endoleaks was compared in a canine bilateral aneurysm model reproducing type I endoleaks (n = 9 each)...
January 11, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28074884/actin-interacting-protein-1-contributes-to-intranuclear-rod-assembly-in-dictyostelium-discoideum
#7
Hellen C Ishikawa-Ankerhold, Wioleta Daszkiewicz, Michael Schleicher, Annette Müller-Taubenberger
Intranuclear rods are aggregates consisting of actin and cofilin that are formed in the nucleus in consequence of chemical or mechanical stress conditions. The formation of rods is implicated in a variety of pathological conditions, such as certain myopathies and some neurological disorders. It is still not well understood what exactly triggers the formation of intranuclear rods, whether other proteins are involved, and what the underlying mechanisms of rod assembly or disassembly are. In this study, Dictyostelium discoideum was used to examine appearance, stages of assembly, composition, stability, and dismantling of rods...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074863/herb-pair-danggui-honghua-mechanisms-underlying-blood-stasis-syndrome-by-system-pharmacology-approach
#8
Shi-Jun Yue, Lan-Ting Xin, Ya-Chu Fan, Shu-Jiao Li, Yu-Ping Tang, Jin-Ao Duan, Hua-Shi Guan, Chang-Yun Wang
Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070107/effects-of-reduced-food-intake-for-4-weeks-on-physiological-parameters-in-toxicity-studies-in-dogs
#9
Junya Morita, Tomoko Izumi, Bunichiro Ogawa, Yoshiki Ban, Hironori Takagi, Minoru Sasaki, Shunsuke Tsutsumi
This study sought to clarify the effects of reduced feeding on physiological parameters in dogs to enable appropriate evaluations of the safety and toxicity of test compounds. We measured alkaline phosphatase isozymes and the circulating blood volume, as well as clinical signs, body weight, hematology, blood chemistry, electrocardiography, organ weight, and histopathology, in male beagle dogs fed a diet consisting of 300 g/day or 150 g/day for 4 weeks. There were no abnormal clinical signs in any of the dogs...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28069662/endoplasmic-reticulum-stress-inhibition-limits-the-progression-of-chronic-kidney-disease-in-the-dahl-salt-sensitive-rat
#10
Victoria Yum, Rachel E Carlisle, Chao Lu, Elise Brimble, Jasmine Chahal, Chandak Upagupta, Kjetil Ask, Jeffrey G Dickhout
Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28068069/re-engineering-extracellular-vesicles-as-smart-nanoscale-therapeutics
#11
James P K Armstrong, Margaret N Holme, Molly M Stevens
In the past decade, extracellular vesicles (EVs) have emerged as a key cell-free strategy for the treatment of a range of pathologies, including cancer, myocardial infarction, and inflammatory diseases. Indeed, the field is rapidly transitioning from promising in vitro reports toward in vivo animal models and early clinical studies. These investigations exploit the high physicochemical stability and biocompatibility of EVs as well as their innate capacity to communicate with cells via signal transduction and membrane fusion...
January 9, 2017: ACS Nano
https://www.readbyqxmd.com/read/28065777/protective-effects-of-petroleum-ether-extracts-of-herpetospermum-caudigerum-against-%C3%AE-naphthylisothiocyanate-induced-acute-cholestasis-of-rats
#12
Wen-Rui Cao, Jing-Qiu Ge, Xin Xie, Meng-Lin Fan, Xu-Dong Fan, Hong Wang, Zhao-Yue Dong, Zhi-Hua Liao, Xiao-Zhong Lan, Min Chen
ETHNOPHARMACOLOGICAL RELEVANCE: The ripe seeds of Herpetospermum caudigerum have been used in Tibetan folk medicine for treatment of bile or liver diseases including jaundice, hepatitis, intumescences or inflammation. Previously reports suggested that the seed oil and some lignans from H. caudigerum exhibited protective effects against carbon tetrachloride (CCl4)-induced hepatic damage in rats, which may be related to their free radical scavenging effect. However, the protective effect of H...
January 5, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28063905/trichloroethylene-induced-formic-aciduria-in-the-male-c57-bl-6-mouse
#13
Edward A Lock, Paul Keane, Philip H Rowe, John R Foster, Daniel Antoine, Christopher M Morris
1, 1, 2-Trichloroethylene (TCE) is of environmental concern, due to evaporation while handling, chemical processing and leakage from chemical waste sites, leading to its contamination of ground water and air. For several decades there has been issues about possible long term health effects of TCE but recently the International Agency for Research on Cancer (IARC) and the US Environmental Protection Agency classified TCE as a human carcinogen. Links having been established between occupational exposures and kidney cancer and possible links to non-Hodgkin lymphoma and liver cancer, but there is more still more to learn...
January 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28063877/myeloid-differentiation-protein-2-dependent-mechanisms-in-retinal-ischemia-reperfusion-injury
#14
Luqing Ren, Jianjian Tao, Huaicheng Chen, Yang Bian, Xi Yang, Gaozhi Chen, Xin Zhang, Guang Liang, Wencan Wu, Zongming Song, Yi Wang
Retinal ischemia-reperfusion (I/R) injury is a common pathological process in many eye disorders. Oxidative stress and inflammation play a role in retinal I/R injury. Recent studies show that toll-like receptor 4 (TLR4) is involved in initiating sterile inflammatory response in retinal I/R. However, the molecular mechanism by which TLR4 is activated is not known. In this study, we show that retinal I/R injury involves a co-receptor of TLR4, myeloid differentiation 2 (MD2). Inhibition of MD2 prevented cell death and preserved retinal function following retinal I/R injury...
January 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28063381/brd4-inhibition-attenuates-unilateral-ureteral-obstruction-induced-fibrosis-by-blocking-tgf-%C3%AE-mediated-nox4-expression
#15
Baoshang Zhou, Jiao Mu, Yi Gong, Caibao Lu, Youguang Zhao, Ting He, Zhexue Qin
Uncovering new therapeutic targets for renal fibrosis holds promise for the treatment of chronic kidney diseases. Bromodomain and extra-terminal (BET) protein inhibitors have been shown to effectively ameliorate pathological fibrotic responses. However, the pharmacological effects and underlying mechanisms of these inhibitors in renal fibrosis remain elusive. In this study, we determined that the inhibition of Brd4, a BET family member, with a selective potent chemical inhibitor, JQ1, could prevent the development of renal fibrosis and block the progression of fibrosis in rats that have undergone unilateral ureteral obstruction (UUO)...
December 30, 2016: Redox Biology
https://www.readbyqxmd.com/read/28063348/the-in-silico-identification-of-small-molecules-for-protein-protein-interaction-inhibition-in-akap-lbc-rhoa-signaling-complex
#16
Asifullah Khan, Mehwish Munir, Sara Aiman, Abdul Wadood, Arif-Ullah Khan
The rational design of small molecules that mimic key residues at the interface of interacting proteins can be a successful approach to target certain biological signaling cascades causing pathophysiological outcome. The A-Kinase Anchoring Protein, i.e. AKAP-Lbc, catalyses nucleotide exchange on RhoA and is involved in cardiac repolarization. The oncogenic AKAP-Lbc induces the RhoA GTPase hyperactivity and aberrantly amplifies the signaling pathway leading to hypertrophic cardiomyocytes. We took advantage of the AKAP-Lbc-RhoA complex crystal structure to design in silico small molecules predicted to inhibit the associated pathological signaling cascade...
December 31, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28060254/quantitative-magnetic-resonance-imaging-of-skeletal-muscle-disease
#17
Bruce M Damon, Ke Li, Richard D Dortch, E Brian Welch, Jane H Park, Amanda K W Buck, Theodore F Towse, Mark D Does, Daniel F Gochberg, Nathan D Bryant
Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization...
December 18, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28059499/inactivation-of-the-nuclear-orphan-receptor-coup-tfii-by-small-chemicals
#18
Rémy Le Guével, Frédérik Oger, Celia P Martinez-Jimenez, Maud Bizot, Céline Gheeraert, François Firmin, Maheul Ploton, Miroslava Kretova, Gaëlle Palierne, Bart Staels, Peter Barath, Iannis Talianidis, Philippe Lefebvre, Jérôme Eeckhoute, Gilles Salbert
Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII/NR2F2) is an orphan member of the nuclear receptor family of transcription factors whose activities are modulated upon binding of small molecules into an hydrophobic ligand-binding pocket (LBP). Although the LBP of COUP-TFII is filled with aromatic amino-acid side chains, alternative modes of ligand binding could potentially lead to regulation of the orphan receptor. Here, we screened a synthetic and natural compound library in a yeast one-hybrid assay and identified 4-methoxynaphthol as an inhibitor of COUP-TFII...
January 13, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28057793/protein-interactions-at-endothelial-junctions-and-signaling-mechanisms-regulating-endothelial-permeability
#19
REVIEW
Yulia A Komarova, Kevin Kruse, Dolly Mehta, Asrar B Malik
The monolayer of endothelial cells lining the vessel wall forms a semipermeable barrier (in all tissue except the relatively impermeable blood-brain and inner retinal barriers) that regulates tissue-fluid homeostasis, transport of nutrients, and migration of blood cells across the barrier. Permeability of the endothelial barrier is primarily regulated by a protein complex called adherens junctions. Adherens junctions are not static structures; they are continuously remodeled in response to mechanical and chemical cues in both physiological and pathological settings...
January 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28057719/structure-and-inhibitor-specificity-of-the-pctaire-family-kinase-cdk16
#20
Sarah E Dixon-Clarke, Saifeldin N Shehata, Tobias Krojer, Timothy D Sharpe, Frank von Delft, Kei Sakamoto, Alex N Bullock
CDK16 (also known as PCTAIRE1 or PCTK1) is an atypical member of the cyclin-dependent protein kinase (CDK) family that has emerged as a key regulator of neurite outgrowth, vesicle trafficking and cancer cell proliferation. CDK16 is activated through binding to cyclin Y via a phosphorylation-dependent 14-3-3 interaction and has an unique consensus substrate phosphorylation motif compared to conventional CDKs. To elucidate the structure and inhibitor binding properties of this atypical CDK we screened the CDK16 kinase domain against different inhibitor libraries and determined the co-structures of identified hits...
January 5, 2017: Biochemical Journal
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