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https://www.readbyqxmd.com/read/29036797/effects-of-venotonic-drugs-on-the%C3%A2-microcirculation-comparison-between-ruscus-extract-and-micronized-diosmine1
#1
Fatima Zely Garcia de Almeida Cyrino, Daniela Signorelli Balthazar, Fernando Lencastre Sicuro, Eliete Bouskela
BACKGROUND: Chronic venous disease of the lower limbs is a common public health problem worldwide with negative impact on quality of life and results with drugs used to treat it are sparse, probably due to lack of good experimental models. OBJECTIVE: In this investigation we have tested the effects of two commonly used venotonic substances, Ruscus extract and micronized diosmine, on the microcirculation in vivo. METHODS: These substances were given orally, by gavage, during two weeks, twice daily and observations were made using the hamster cheek pouch preparation...
October 7, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29036683/cr2cancer-a-database-for-chromatin-regulators-in-human-cancer
#2
Beibei Ru, Jianlong Sun, Yin Tong, Ching Ngar Wong, Aditi Chandra, Acacia Tsz So Tang, Larry Ka Yue Chow, Wai Lam Wun, Zarina Levitskaya, Jiangwen Zhang
Chromatin regulators (CRs) can dynamically modulate chromatin architecture to epigenetically regulate gene expression in response to intrinsic and extrinsic signalling cues. Somatic alterations or misexpression of CRs might reprogram the epigenomic landscape of chromatin, which in turn lead to a wide range of common diseases, notably cancer. Here, we present CR2Cancer, a comprehensive annotation and visualization database for CRs in human cancer constructed by high throughput data analysis and literature mining...
October 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29036218/crystallographic-and-thermodynamic-characterization-of-phenylaminopyridine-bisphosphonates-binding-to-human-farnesyl-pyrophosphate-synthase
#3
Jaeok Park, Dmitry Rodionov, Joris W De Schutter, Yih-Shyan Lin, Youla S Tsantrizos, Albert M Berghuis
Human farnesyl pyrophosphate synthase (hFPPS) catalyzes the production of the 15-carbon isoprenoid farnesyl pyrophosphate. The enzyme is a key regulator of the mevalonate pathway and a well-established drug target. Notably, it was elucidated as the molecular target of nitrogen-containing bisphosphonates, a class of drugs that have been widely successful against bone resorption disorders. More recently, research has focused on the anticancer effects of these inhibitors. In order to achieve increased non-skeletal tissue exposure, we created phenylaminopyridine bisphosphonates (PNP-BPs) that have bulky hydrophobic side chains through a structure-based approach...
2017: PloS One
https://www.readbyqxmd.com/read/29035939/predictors-for-the-development-of-microalbuminuria-and-interaction-with-renal-function
#4
Christos Chatzikyrkou, Jan Menne, Joseph Izzo, Giancarlo Viberti, Ton Rabelink, Luis M Ruilope, Christian Rump, Peter R Mertens, Hermann Haller
AIM: It is important to know which factors predict the development of microalbuminuria in patients with diabetes mellitus type II. MATERIAL: Data from the Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study were used to identify predictors for the new onset of microalbuminuria. Furthermore, the interaction of baseline albuminuria and baseline estimated glomerular filtration rate (eGFR) and the effects of treatment with olmesartan were investigated...
October 13, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29035747/studies-on-the-adsorption-and-desorption-of-mitoxantrone-to-lauric-acid-albumin-coated-iron-oxide-nanoparticles
#5
Jan Zaloga, Artem Feoktystov, Vasil M Garamus, Weronika Karawacka, Alexander Ioffe, Thomas Brückel, Rainer Tietze, Christoph Alexiou, Stefan Lyer
A rational use of superparamagnetic iron oxide nanoparticles (SPIONs) in drug delivery, diagnostics, and other biomedical applications requires deep understanding of the molecular drug adsorption/desorption mechanisms for proper design of new pharmaceutical formulations. The adsorption and desorption of the cytostatic Mitoxantrone (MTO) to lauric acid-albumin hybrid coated particles SPIONs (SEON(LA-HSA)) was studied by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), surface titration, release experiments and small-angle neutron and X-ray scattering...
September 28, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29035510/crispri-and-crispra-screens-in-mammalian-cells-for-precision-biology-and-medicine
#6
Martin Kampmann
Next-generation DNA sequencing technologies have led to a massive accumulation of genomic and transcriptomic data from patients and healthy individuals. The major challenge ahead is to understand the functional significance of the elements of the human genome and transcriptome, and implications for diagnosis and treatment. Genetic screens in mammalian cells are a powerful approach to systematically elucidate gene function in health and disease states. In particular, recently developed CRISPR/Cas9-based screening approaches have enormous potential to uncover mechanisms and therapeutic strategies for human diseases...
October 16, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29035502/binding-mechanism-of-model-charged-dye-carboxyfluorescein-to-hyaluronan-polylysine-multilayers
#7
Vladimir Z Prokopovic, Anna S Vikulina, David Sustr, Elena M Shchukina, Dmitry G Shchukin, Dmitry V Volodkin
Biopolymer-based multilayers become more and more attractive due to the vast span of biological application they can be used for, e.g. implant coatings, cell culture supports, scaffolds. Multilayers have demonstrated superior capability to store enormous amount of small charged molecules such as drugs and release them in a controlled manner, however, the binding mechanism for drug loading into the multilayers is still poorly understood. Here we focus on this mechanism using model hyaluronan/polylysine (HA/PLL) multilayers and a model charged dye carboxyfluorescein (CF)...
October 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29035389/-mcc-protein-interacts-with-e-cadherin-and-%C3%AE-catenin-strengthening-cell-cell-adhesion-of-hct116-colon-cancer-cells
#8
F A Benthani, D Herrmann, P N Tran, L Pangon, M C Lucas, A H Allam, N Currey, S Al-Sohaily, M Giry-Laterriere, J Warusavitarne, P Timpson, M R J Kohonen-Corish
E-cadherin and β-catenin are key proteins that are essential in the formation of the epithelial cell layer in the colon but their regulatory pathways that are disrupted in cancer metastasis are not completely understood. Mutated in colorectal cancer (MCC) is a tumour suppressor gene that is silenced by promoter methylation in colorectal cancer and particularly in patients with increased lymph node metastasis. Here, we show that MCC methylation is found in 45% of colon and 24% of rectal cancers and is associated with proximal colon, poorly differentiated, circumferential and mucinous tumours as well as increasing T stage and larger tumour size...
October 16, 2017: Oncogene
https://www.readbyqxmd.com/read/29035298/molecular-docking-and-3d-pharmacophore-modeling-to-study-the-interactions-of-chalcone-derivatives-with-estrogen-receptor-alpha
#9
Muchtaridi Muchtaridi, Hasna Nur Syahidah, Anas Subarnas, Muhammad Yusuf, Sharon D Bryant, Thierry Langer
Tamoxifen is the most frequently used anti-estrogen adjuvant treatment for estrogen receptor-positive breast cancer. However, it is associated with an increased risk of several serious side-effects, such as uterine cancer, stroke, and pulmonary embolism. The 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone (ChalcEA) from plant leaves of Eugenia aquea, has been found to inhibit the proliferation of MCF-7 human breast cancer cells in a dose-dependent manner, with an IC50 of 74.5 μg/mL (250 μM). The aim of this work was to study the molecular interactions of new ChalcEA derivatives formed with the Estrogen Receptor α (ERα) using computer aided drug design approaches...
October 16, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29035201/anti-diabetic-drug-binding-site-in-a-mammalian-katp-channels-revealed-by-cryo-em
#10
Gregory M Martin, Balamurugan Kandasamy, Frank DiMaio, Craig Yoshioka, Show-Ling Shyng
Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic KATP channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP at 3.63Å resolution, which reveals unprecedented details of the ATP and glibenclamide binding sites...
October 16, 2017: ELife
https://www.readbyqxmd.com/read/29034942/guanidinium-based-molecular-glues-for-modulation-of-biomolecular-functions
#11
Rina Mogaki, P K Hashim, Kou Okuro, Takuzo Aida
Molecular adhesion based on multivalent interactions plays essential roles in various biological processes. Hence, "molecular glues" that can adhere to biomolecules may modulate biomolecular functions and therefore can be applied to therapeutics. This tutorial review describes design strategies for developing adhesive motifs for biomolecules based on multivalent interactions. We highlight a guanidinium ion-based salt-bridge as a key interaction for adhesion to biomolecules and discuss the application of molecular glues for manipulation of biomolecular assemblies, drug delivery systems, and modulation of biomolecular functions...
October 16, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/29034890/derivation-of-a-disease-specific-human-induced-pluripotent-stem-cell-line-from-a-biliary-atresia-patient
#12
Lipeng Tian, Lindsey Eldridge, Pooja Chaudhari, Linyi Zhang, Robert A Anders, Kathleen B Schwarz, Zhaohui Ye, Yoon-Young Jang
Biliary atresia (BA) is a common cause of pediatric end-stage liver disease. While its etiology is not yet clear, evidence has suggested that BA results from interactions between genetic susceptibility and environmental factors. Disease relevant human cellular models of BA will facilitate identification of both genetic and environmental factors that are important for disease prevention and treatment. Here we report the generation of a human induced pluripotent stem cell line from a BA patient using episomal vectors...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29034773/substrate-dependent-effects-of-molecular-targeted-anticancer-agents-on-activity-of-organic-anion-transporting-polypeptide-1b1
#13
Hiroyoshi Koide, Masayuki Tsujimoto, Ai Takeuchi, Miyu Tanaka, Yoko Ikegami, Mayu Tagami, Syoko Abe, Miki Hashimoto, Tetsuya Minegaki, Kohshi Nishiguchi
1. Organic anion-transporting polypeptide 1B1 (OATP1B1) plays an important role in the hepatic uptake of a broad range of substrate drugs. In vitro experiments show that molecular-targeted agents do not always have similar effects on OATP1B1 activity. 2. The purpose of this study was to clarify whether the effects of molecular-targeted agents on OATP1B1 are substrate-dependent. We used OATP1B1-transfected cells to compare the effects of molecular-targeted agents on OATP1B1-mediated uptake of fluorescein (FL), 2',7'-dichlorofluorescein (DCF), atorvastatin, SN-38, and valsartan...
October 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29034772/opa-interacting-protein-5-modulates-docetaxel-induced-cell-death-via-regulation-of-mitophagy-in-gastric-cancer
#14
Tae Woo Kim, Seon-Jin Lee, Young-Jun Park, Sang Yoon Park, Byung Moo Oh, Yun Sun Park, Bo-Yeon Kim, Young-Ha Lee, Hee Jun Cho, Suk Ran Yoon, Yong-Kyung Choe, Hee Gu Lee
Damage to mitochondria induces mitophagy, a cellular process that is gaining interest for its therapeutic relevance to a variety of human diseases. However, the mechanism underlying mitochondrial depolarization and clearance in mitophagy remains poorly understood. We previously reported that mitochondria-induced cell death was caused by knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 in gastric cancer. In this study, we show that Neisseria gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for gastric cancer...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29034683/a-budding-defective-m2-mutant-exhibits-reduced-membrane-interaction-insensitivity-to-cholesterol-and-perturbed-interdomain-coupling
#15
Alice Lydia Herneisen, Indra Dev Sahu, Robert M McCarrick, Jimmy B Feix, Gary A Lorigan, Kathleen P Howard
Influenza A M2 is a membrane-associated protein with a C-terminal amphipathic helix that plays a cholesterol-dependent role in viral budding. An M2 mutant with alanine substitutions in the C-terminal amphipathic helix is deficient in viral scission. With the goal of providing atomic-level understanding of how the wild-type protein functions, we used a multi-pronged site-directed spin labeling electron paramagnetic spectroscopy (SDSL-EPR) approach to characterize the conformational properties of the alanine mutant...
October 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/29034375/extracting-drug-drug-interactions-with-word-and-character-level-recurrent-neural-networks
#16
Ramakanth Kavuluru, Anthony Rios, Tung Tran
Drug-drug interactions (DDIs) are known to be responsible for nearly a third of all adverse drug reactions. Hence several current efforts focus on extracting signal from EMRs to prioritize DDIs that need further exploration. To this end, being able to extract explicit mentions of DDIs in free text narratives is an important task. In this paper, we explore recurrent neural network (RNN) architectures to detect and classify DDIs from unstructured text using the DDIExtraction dataset from the SemEval 2013 (task 9) shared task...
August 2017: IEEE International Conference on Healthcare Informatics IEEE International Conference on Healthcare Informatics
https://www.readbyqxmd.com/read/29034137/valproic-induced-hyperammonemic-encephalopathy-in-a-known-case-of-epilepsy
#17
Syed F Imam, Omair Ul Haq Lodhi, Rizwan Zafar, Saneeya Nasim, Waseem T Malik
Valproic acid, a broad-spectrum anticonvulsant drug, commonly causes elevated ammonia levels, which is usually asymptomatic in most cases. On rare occasions, potentially fatal hyperammonemia-induced encephalopathy can occur. We present a case of a 24-year-old female who presented to the emergency department with status epilepticus that was being managed with valproic acid. Further workup was done because of prolonged postictal state, which revealed increased ammonia levels; she was eventually diagnosed with valproic-induced hyperammonemic encephalopathy...
August 10, 2017: Curēus
https://www.readbyqxmd.com/read/29033850/designing-dietary-recommendations-using-system-level-interactomics-analysis-and-network-based-inference
#18
Tingting Zheng, Yueqiong Ni, Jun Li, Billy K C Chow, Gianni Panagiotou
Background: A range of computational methods that rely on the analysis of genome-wide expression datasets have been developed and successfully used for drug repositioning. The success of these methods is based on the hypothesis that introducing a factor (in this case, a drug molecule) that could reverse the disease gene expression signature will lead to a therapeutic effect. However, it has also been shown that globally reversing the disease expression signature is not a prerequisite for drug activity. On the other hand, the basic idea of significant anti-correlation in expression profiles could have great value for establishing diet-disease associations and could provide new insights into the role of dietary interventions in disease...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29033832/cyclotides-isolated-from-an-ipecac-root-extract-antagonize-the-corticotropin-releasing-factor-type-1-receptor
#19
Mohsen Fahradpour, Peter Keov, Carlotta Tognola, Estela Perez-Santamarina, Peter J McCormick, Alireza Ghassempour, Christian W Gruber
Cyclotides are plant derived, cystine-knot stabilized peptides characterized by their natural abundance, sequence variability and structural plasticity. They are abundantly expressed in Rubiaceae, Psychotrieae in particular. Previously the cyclotide kalata B7 was identified to modulate the human oxytocin and vasopressin G protein-coupled receptors (GPCRs), providing molecular validation of the plants' uterotonic properties and further establishing cyclotides as valuable source for GPCR ligand design. In this study we screened a cyclotide extract derived from the root powder of the South American medicinal plant ipecac (Carapichea ipecacuanha) for its GPCR modulating activity of the corticotropin-releasing factor type 1 receptor (CRF1R)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29033825/acute-stress-affects-the-expression-of-hippocampal-mu-oscillations-in-an-age-dependent-manner
#20
Samir Takillah, Jérémie Naudé, Steve Didienne, Claude Sebban, Brigitte Decros, Esther Schenker, Michael Spedding, Alexandre Mourot, Jean Mariani, Philippe Faure
Anxiolytic drugs are widely used in the elderly, a population particularly sensitive to stress. Stress, aging and anxiolytics all affect low-frequency oscillations in the hippocampus and prefrontal cortex (PFC) independently, but the interactions between these factors remain unclear. Here, we compared the effects of stress (elevated platform, EP) and anxiolytics (diazepam, DZP) on extracellular field potentials (EFP) in the PFC, parietal cortex and hippocampus (dorsal and ventral parts) of adult (8 months) and aged (18 months) Wistar rats...
2017: Frontiers in Aging Neuroscience
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