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https://www.readbyqxmd.com/read/30342424/tau-tubulin-kinase-1-ttbk1-a-new-player-in-the-fight-against-neurodegenerative-diseases
#1
Vanesa Nozal, Ana Martinez
Tau-tubuline kinases (TTBK) are a family of serine/threonine and tyrosine kinases recently discovered and implicated in the phosphorylation of important substrates such as tau, tubuline or TDP-43. Its two homologs, TTBK1 and TTBK2, show different expression patterns and different involvements in physiological mechanisms of great importance such as mitosis, ciliogenesis and neurotransmission. Their phosphorylation activity has also linked them to the development of neurodegenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis or spinocerebellar ataxia type 11...
October 15, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30342387/synthesis-of-novel-n-1-3-thiazol-2-yl-benzamide-clubbed-oxadiazole-scaffolds-urease-inhibition-lipinski-rule-and-molecular-docking-analyses
#2
Muhammad Athar Abbasi, Hussain Raza, Aziz-Ur-Rehman, Sabahat Zahra Siddiqui, Syed Adnan Ali Shah, Mubashir Hassan, Sung-Yum Seo
Present work aimed to synthesize some unique bi-heterocyclic benzamides as lead compounds for the in vitro inhibition of urease enzyme, followed by in silico studies. These targeted benzamides were synthesized in good yields through a multi-step protocol and their structures were confirmed by IR, 1 H NMR, 13 C NMR, EI-MS and elemental analysis. The in vitro screening results showed that most of the ligands exhibited good inhibitory potentials against the urease. Chemo-informatics analysis envisaged that all these compounds obeyed the Lipinski's rule...
October 12, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/30342308/synthesis-characterization-and-unravelling-the-molecular-interaction-of-new-bioactive-4-hydroxycoumarin-derivative-with-biopolymer-insights-from-spectroscopic-and-theoretical-aspect
#3
Abhijit Mukherjee, Suvranil Ghosh, Rudraditya Sarkar, Satyajit Samanta, Sudipta Ghosh, Mahadeb Pal, Adinath Majee, Sukanta Kumar Sen, Bula Singh
In the progress of small molecule as drug candidates, 4-hydroxycoumarin based compounds bearing a crucial place as potent antibiotic agents with appreciable safety in drug invention. Being synthetically and easily obtainable, 4-hydroxycoumarin related compounds with planar structure have been promoted predominantly as DNA targeting agent. Nevertheless, here we elucidate the synthesis, characterization and theoretical study of bio-active small molecule 4-hydroxy-3,4'-bichromenyl-2,2'-dione (4HBD). Then we have illuminated the binding interactions of 4HBD with calf thymus DNA (ctDNA), which is particularly designed for biological application...
October 13, 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/30342278/association-of-platelet-response-to-cilostazol-with-clinical-outcome-and-cyp-genotype-in-patients-with-cerebral-infarction
#4
Y Ikeda, J Yamanouchi, Y Kumon, M Yasukawa, T Hato
INTRODUCTION: Cilostazol, an anti-platelet drug that inhibits phosphodiesterase 3, is beneficial for patients with atherothrombosis. In contrast to other anti-platelet drugs such as aspirin and thienopyridines, little information is available on the relationship between platelet responses to cilostazol and clinical outcomes. MATERIALS AND METHODS: We conducted a prospective study on patients with cerebral infarction who were treated with cilostazol. The platelet response to cilostazol was assessed with our new assay for the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) subsequent to the pharmacological action of cilostazol...
October 10, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/30342258/ribociclib-in-hormone-receptor-positive-advanced-breast-cancer-establishing-a-value-based-cost-in-china
#5
XiaoMin Wan, YuCong Zhang, JinAn Ma, Chongqing Tan, XiaoHui Zeng, LiuBao Peng
BACKGROUND: The addition of ribociclib (RIB) to letrozole (LET) significantly increases progression free survival for patients with hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). We identified the range of drug costs for which RIB could be considered cost effective from a Chinese perspective. METHODS: A discrete event simulation model was developed to model the treatment sequences among patients with ABC...
October 16, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/30342240/rv3272-encodes-a-novel-family-iii-coa-transferase-that-alters-the-cell-wall-lipid-profile-and-protects-mycobacteria-from-acidic-and-oxidative-stress
#6
Karade Sharanbasappa Shrimant, Shilpika Pandey, Ahmadullah Ansari, Swetarka Das, Sarita Tripathi, Ashish Arora, Sidharth Chopra, J Venkatesh Pratap, Arunava Dasgupta
The availability of complete genome sequence of Mycobacterium tuberculosis has provided an important tool to understand the mycobacterial biology with respect to host-pathogen interaction, which is an unmet need of the hour owing to continuous increasing drug resistance. Hypothetical proteins are often an overlooked pool though half the genome encodes for such proteins of unknown function that could potentially play vital roles in mycobacterial biology. In this context, we report the structural and functional characterization of the hypothetical protein Rv3272...
October 17, 2018: Biochimica et biophysica acta. Proteins and proteomics
https://www.readbyqxmd.com/read/30342232/label-free-independent-quantitation-of-viable-and-non-viable-cells-using-a-multivariable-multi-resonant-sensor
#7
Radislav A Potyrailo, Jon Dieringer, Victoria Cotero, Yongjae Lee, Steve Go, Matthew Schulmerich, Gunnar Malmquist, Andreas Castan, Klaus Gebauer, Vincent Pizzi
Biological cells are utilized for diverse biotechnological and bioengineering purposes ranging from the production of biopharmaceuticals, to cell therapy, "human-on-a-chip" drug and toxicology assays, and drug-resistance tests. In these and other applications, it is critical to quantify the levels of not only viable but also non-viable cells. While traditional off-line cell-staining methods are available for counting of non-viable cells, many applications cannot periodically remove cells for their off-line analysis because of the risk of contamination or workflow logistics...
October 10, 2018: Bioelectrochemistry
https://www.readbyqxmd.com/read/30342195/reversing-effects-of-ginsenosides-on-lps-induced-hepatic-cyp3a11-3a4-dysfunction-through-the-pregnane-x-receptor
#8
Hai-Yan Sun, Yi-Jing Yan, Yan-Hui Li, Le Lv
ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer), a traditional Chinese medicine, is widely used in the adjunctive therapy of the liver diseases. AIM OF THE STUDY: Ginsenosides are one kind of the main active ingredients in ginseng. Although hepatoprotective mechanisms of ginsenosides, such as anti-oxidation, anti-inflammation and anti-apoptosis, have been well studies, little is known about the effect of ginsenosides on drug metabolism in liver...
October 17, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/30342174/comparison-of-the-in-vitro-cytotoxicity-among-phospholipid-based-parenteral-drug-delivery-systems-emulsions-liposomes-and-aqueous-lecithin-dispersions-wlds
#9
Marcin Płaczek, Dorota Wątróbska-Świetlikowska, Justyna Stefanowicz-Hajduk, Markus Drechsler, Jadwiga Renata Ochocka, Małgorzata Sznitowska
Lecithin and isolated phospholipids (mainly phosphatidylcholine) have been used for years as pharmaceutical excipients in parenteral formulations: submicron emulsions, liposomes and mixed micelles. Under development are also other lecithin-based drug delivery systems, e.g. aqueous lecithin dispersions (WLDs). The aim of the study was to investigate the properties and potential cytotoxicity of 7 different phospholipid-based dispersions intended for parenteral administration: emulsions, liposomes and WLDs. Each formulation contained egg phosphatidylcholine (PC) in the concentration range of 0...
October 17, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/30342006/determination-of-the-plasma-protein-binding-of-liraglutide-using-the-escalate-equilibrium-shift-assay
#10
Jan Ungewiss, Seike Gericke, Hinnerk Boriss
The plasma protein binding capability of drug substances represents an important assay parameter in drug discovery and development. For very strong plasma protein binding molecules, however, the free fraction in plasma fu is very small and therefore difficult to determine with standard methods. To solve this problem the EScalate equilibrium shift in-vitro assay was developed. Escalating concentrations of plasma were found to shift the binding equilibrium in solution between the test item and immobilized human serum albumin...
October 17, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/30341983/cisplatin-versus-cetuximab-with-definitive-concurrent-radiotherapy-for-head-and-neck-squamous-cell-carcinoma-an-analysis-of-veterans-health-affairs-data
#11
Joshua M Bauml, Ravi Vinnakota, Yeun-Hee Anna Park, Susan E Bates, Tito Fojo, Charu Aggarwal, Jessica Di Stefano, Christina Knepley, Sewanti Limaye, Ronac Mamtani, Juan Wisnivesky, Nevena Damjanov, Corey J Langer, Roger B Cohen, Keith Sigel
BACKGROUND: The addition of cisplatin or cetuximab to radiation therapy (RT) improves outcomes in comparison with RT alone in the nonoperative management of head and neck squamous cell carcinoma (HNSCC), but limited data exist for comparing these approaches. Using Veterans Health Affairs data, this study compared the outcomes of patients treated with RT plus cisplatin or cetuximab. METHODS: Patients with stage III to IVb HNSCC who had been treated nonsurgically with RT and cisplatin or cetuximab from 2000 to 2016 within the Veterans Health Affairs system were identified...
October 20, 2018: Cancer
https://www.readbyqxmd.com/read/30341895/migraine-in-america-symptoms-and-treatment-mast-study-baseline-study-methods-treatment-patterns-and-gender-differences
#12
Richard B Lipton, Sagar Munjal, Aftab Alam, Dawn C Buse, Kristina M Fanning, Michael L Reed, Todd J Schwedt, David W Dodick
OBJECTIVES: To summarize the baseline methods for the Migraine in America Symptoms and Treatment (MAST) Study and evaluate gender differences in sociodemographics and headache features; consultation and diagnosis patterns; and patterns of acute and preventive treatment use for migraine among study participants. BACKGROUND: The MAST Study is a longitudinal, internet-based panel study of symptoms, approaches to management, and unmet treatment needs among US adults with migraine...
October 20, 2018: Headache
https://www.readbyqxmd.com/read/30341871/metformin-in-prevention-of-type-2-diabetes
#13
Chamukuttan Snehalatha, Susairaj Priscilla, Arun Nanditha, Raghavan Arun, Krishnamoorthy Satheesh, Ambady Ramachandran
Identification and treatment of individuals with prediabetes is crucial. Effective interventional strategies are key to reducing the diabetes risk at the population level. Lifestyle intervention is found to be more effective but more expensive. Evidence of potential benefits from pharmacotherapy is accumulating. The choice of a pharmacologic intervention to reduce the progression of type 2 diabetes (T2DM) in high risk individuals must consider the balance between the benefit to risk ratio. A meta-analysis of the results of the three important studies has shown that metformin used for up to three years decrease the likelihood of progression to diabetes...
March 2018: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/30341804/comparative-proteomic-analysis-of-four-biotechnological-strains-lactococcus-lactis-through-label-free-quantitative-proteomics
#14
Wanderson M Silva, Cassiana S Sousa, Leticia C Oliveira, Siomar C Soares, Gustavo F M H Souza, Guilherme C Tavares, Cristiana P Resende, Edson L Folador, Felipe L Pereira, Henrique Figueiredo, Vasco Azevedo
Lactococcus lactis is a bacteria with high biotechnological potential, where is frequently used in the amino acid production and production of fermented dairy products, as well as drug delivery systems and mucosal vaccine vector. The knowledge of a functional core proteome is important extremely for both fundamental understanding of cell functions and for synthetic biology applications. In this study, we characterized the L. lacits proteome from proteomic analysis of four biotechnological strains L. lactis: L...
October 19, 2018: Microbial Biotechnology
https://www.readbyqxmd.com/read/30341615/thermal-shift-and-stability-assays-of-disease-related-misfolded-proteins-using-differential-scanning-fluorimetry
#15
Tânia G Lucas, Cláudio M Gomes, Bárbara J Henriques
Systematic identification of buffer formulations and small molecule chaperones that improve the expression, stability, and storage of proteins with therapeutic interest has gained enormous importance in biochemical research as well as in biotechnology and biomedical applications. In particular, the biochemical characterization of disease-related proteins and their genetic variants that result in misfolding requires systematic determination of protein stability, screening of optimal buffer conditions for biophysical and structural studies, and in some cases, the identification of small molecule chaperones with the potential to ameliorate folding defects...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30341504/treatment-patterns-by-egfr-mutation-status-in-non-small-cell-lung-cancer-patients-in-the-usa-a-retrospective-database-analysis
#16
Kathleen M Aguilar, Katherine B Winfree, Catherine E Muehlenbein, Yajun Emily Zhu, Thomas Wilson, Stewart Wetmore, Eric S Nadler
INTRODUCTION: Targeted therapies, including tyrosine kinase inhibitors (TKIs) that target the sensitizing epidermal growth factor receptor (EGFR) gene are recommended for patients with non-small cell lung cancer (NSCLC). Most patients with NSCLC who test positive for the EGFR mutation and receive TKIs develop resistance to these drugs. Questions remain regarding which treatment sequence is optimal for patients with EGFR-mutant NSCLC, and few studies have evaluated patterns of TKI treatment use in NSCLC, irrespective of EGFR mutation status, in a real-world setting...
October 19, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/30341453/on-drug-and-drug-free-remission-by-baseline-symptom-duration-abatacept-with-methotrexate-in-patients-with-early-rheumatoid-arthritis
#17
Vivian P Bykerk, Gerd R Burmester, Bernard G Combe, Daniel E Furst, Tom W J Huizinga, Harris A Ahmad, Paul Emery
Clinical outcomes in patients with early rheumatoid arthritis (RA) were assessed by baseline symptom duration in the Assessing Very Early Rheumatoid arthritis Treatment trial (ClinicalTrials.gov; NCT01142726). Patients with early, active RA were randomized to subcutaneous (SC) abatacept 125 mg/week plus methotrexate (MTX), SC abatacept alone, or MTX monotherapy for 12 months. All RA treatments were withdrawn after 12 months in patients with Disease Activity Score in 28 joints (C-reactive protein; DAS28-CRP) < 3...
October 20, 2018: Rheumatology International
https://www.readbyqxmd.com/read/30341414/impaired-antimicrobial-response-and-mucosal-protection-induced-by-ibuprofen-in-the-immature-human-intestine
#18
Emanuela Ferretti, Eric Tremblay, Marie-Pierre Thibault, Sepideh Fallah, David Grynspan, Karolina M Burghardt, Marcos Bettolli, Corentin Babakissa, Emile Levy, Jean-François Beaulieu
BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (INDO) and ibuprofen (IBU) has been shown to be an effective therapy for the closure of patent ductus arteriosus (PDA). However, this treatment has been associated with an increased risk of developing enteropathies in neonates. Whether the use of IBU is safer than INDO for the immature intestine remains to be elucidated. METHODS: The direct impact of IBU on the human immature intestinal transcriptome was investigated using serum-free organ culture...
October 16, 2018: Pediatric Research
https://www.readbyqxmd.com/read/30341378/predicting-tumor-sensitivity-to-chemotherapeutic-drugs-in-oral-squamous-cell-carcinoma-patients
#19
Beaulah Mary Robert, Muralidharan Dakshinamoorthy, Brindha Ganapathyagraharam Ramamoorthy, Muthu Dhandapani, Radhiga Thangaiyan, Ganesan Muthusamy, R Madhavan Nirmal, Nagarajan Rajendra Prasad
Oral Squamous Cell Carcinoma (OSCC) patients respond poorly to chemotherapy. We analyzed the expression of 11 drug response-related genes in 31 OSCC biopsies, collected prior to any treatment, using custom-designed PCR array. Further, we investigated the drug response pattern of selected anticancer drugs by BH3 (Bcl2 Homology-3) profiling in the primary cells isolated from OSCC tissues. Then, we correlated the results of drug-response gene expression pattern with apoptotic priming to predict tumor response to chemotherapy...
October 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30341300/mutational-interactions-define-novel-cancer-subgroups
#20
Jack Kuipers, Thomas Thurnherr, Giusi Moffa, Polina Suter, Jonas Behr, Ryan Goosen, Gerhard Christofori, Niko Beerenwinkel
Large-scale genomic data highlight the complexity and diversity of the molecular changes that drive cancer progression. Statistical analysis of cancer data from different tissues can guide drug repositioning as well as the design of targeted treatments. Here, we develop an improved Bayesian network model for tumour mutational profiles and apply it to 8198 patient samples across 22 cancer types from TCGA. For each cancer type, we identify the interactions between mutated genes, capturing signatures beyond mere mutational frequencies...
October 19, 2018: Nature Communications
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