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https://www.readbyqxmd.com/read/29786964/a-thorough-qt-qtc-study-with-laquinimod-a-novel-immunomodulator-in-development-for-multiple-sclerosis-and-huntington-disease
#1
Ofer Spiegelstein, Dorit Mimrod, Laura Rabinovich, Eli Eyal, Craig Sprenger, Anna Elgart, Emil Samara, Joel Morganroth
In this randomized double-blind study, 4 groups of healthy subjects (50 per arm) participated to evaluate the effect of laquinimod, an oral treatment in development for multiple sclerosis and Huntington disease, on the QTc interval. Subjects received a dose of either 0.6 or 1.2 mg/day laquinimod for 14 days, placebo for 14 days, or 13 days of placebo followed by a dose of 400 mg moxifloxacin on day 14. Continuous 12-lead electrocardiograms were recorded on day -1 (baseline) and days 14 to 17,  and quadruplicate electrocardiograms were extracted at predefined time points...
May 22, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29786944/design-synthesis-and-evaluation-of-a-novel-series-of-inhibitors-reversing-p-glycoprotein-mediated-multidrug-resistance
#2
Hesham Ghaleb, Huilan Li, Mutta Kairuki, Qianqian Qiu, Xinzhou Bi, Chunxia Liu, Chen Liao, Jieming Li, Kamal Hezam, Wenlong Huang, Hai Qian
Multidrug resistance (MDR) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo-reversal agents is needed to overcome MDR. Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR-reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil (VRP) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells...
May 22, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29786934/origin-of-photoluminescence-enhancement-of-gold-doped-silver-nanoclusters-importance-of-relativistic-effects-and-heterogeneous-gold-silver-interaction
#3
Xiao-Ying Xie, Pin Xiao, Xiaoyan Cao, Wei-Hai Fang, Ganglong Cui, Michael Franz Dolg
The weak photoluminescence of silver nanoclusters suppresses their broad applications as luminescent nanomaterials. Recent experiments however showed that Au-doping can significantly enhance the photoluminescence intensity of Ag_29 nanoclusters, whereas molecular and physical origins of this effect remain unknown. Therefore we have computationally explored geometric and electronic structures of Ag_29 and its Au-doped Ag_29-xAu_x (x=1-5) nanoclusters in the S_0 and S_1 states. We found that (1) relativistic effects mainly originating from the Au atoms play an important role in enhancing the fluorescence intensity, especially for highly doped Ag_26Au_3, Ag_25Au_4, and Ag_24Au_5; (2) heteronuclear Au-Ag bonds can increase stabilities and regulate fluorescence intensities of isomers of these Au-doped nanoclusters...
May 22, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29786932/bandgap-tunable-preparation-of-smooth-and-large-two-dimensional-antimonene
#4
Xin Wang, Junjie He, Benqing Zhou, Youming Zhang, Jiatao Wu, Rui Hu, Liwei Liu, Jun Song, Junle Qu
As a highly stable bandgap semiconductor, antimonene is an intriguing two-dimensional (2D) material in optoelectronics. However, its short layer distance and strong binding energy make it challenging to prepare high-quality large 2D antimonene; therefore, its predicted tunable bandgap has not been experimentally confirmed. In this work, we used a novel and simple approach to prepare smooth and large 2D antimonene with uniform layers through a pregrinding and subsequent sonication-assisted liquid-phase exfoliation process...
May 22, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29786918/novel-genes-and-insights-in-complete-asthma-remission
#5
Judith M Vonk, Maartje A E Nieuwenhuis, F Nicole Dijk, Anne Boudier, Valerie Siroux, Emmanuelle Bouzigon, Nicole Probst-Hensch, Medea Imboden, Dirk Keidel, Don Sin, Yohan Bossé, Ke Hao, Maarten van den Berge, Alen Faiz, Gerard H Koppelman, Dirkje S Postma
BACKGROUND: Asthma is a chronic respiratory disease without a cure, though there exists spontaneous remission. Genome wide association(GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. OBJECTIVES: We performed a GWA study to develop insights in asthma remission. METHODS: Clinical remission (ClinR) was defined by absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years, and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR)...
May 22, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29786902/engineered-metalloenzymes-with-non-canonical-coordination-environments
#6
Takahiro Hayashi, Donald Hilvert, Anthony P Green
Nature employs a limited number of genetically encoded, metal coordinating residues to create metalloenzymes with diverse structures and functions. Engineered components of the cellular translation machinery can now be exploited to genetically encode non-canonical ligands with user-defined electronic and structural properties. This ability to efficiently install 'chemically programmed' ligands into proteins can provide powerful chemical probes of metalloenzyme mechanisms and presents excellent opportunities to create metalloprotein catalysts with augmented properties and novel activities...
May 22, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29786900/avian-demographic-responses-to-drought-and-fire-a-community-level-perspective
#7
James F Saracco, Stephen M Fettig, George L San Miguel, David W Mehlman, Steven K Albert
Drought stress is an important consideration for wildlife in arid and semi-arid regions under climate change. Drought can impact plant and animal populations directly, through effects on their physiology, as well as indirectly through effects on vegetation productivity and resource availability, and by creating conditions conducive to secondary disturbance, such as wildfire. We implemented a novel approach to understanding community-level demographic responses of birds and their habitats to these stressors in the context of climate change at 14 study sites in the Four Corners region of the southwestern United States...
May 22, 2018: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/29786897/targeted-next-generation-sequencing-for-the-diagnosis-of-patients-with-rare-congenital-anemias
#8
Noa Shefer Averbuch, Orna Steinberg-Shemer, Orly Dgany, Tanya Krasnov, Sharon Noy-Lotan, Joanne Yacobovich, Amir A Kuperman, Antonis Kattamis, Ayelet Ben Barak, Batia Roth-Jelinek, Evgeni Chubar, Evelyn Shabad, Gustavo Dufort, Martin Ellis, Ofir Wolach, Idit Pazgal, Abed Abu Quider, Hagit Miskin, Hannah Tamary
BACKGROUND: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes. OBJECTIVE: We aimed to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing...
May 22, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29786889/a-novel-conductive-mesoporous-layer-with-a-dynamic-two-step-deposition-strategy-boosts-efficiency-of-perovskite-solar-cells-to-20
#9
Haoxuan Sun, Kaimo Deng, Yayun Zhu, Min Liao, Jie Xiong, Yanrong Li, Liang Li
Lead halide perovskite solar cells (PSCs) with the high power conversion efficiency (PCE) typically use mesoporous metal oxide nanoparticles as the scaffold and electron-transport layers. However, the traditional mesoporous layer suffers from low electron conductivity and severe carrier recombination. Here, antimony-doped tin oxide nanorod arrays are proposed as novel transparent conductive mesoporous layers in PSCs. Such a mesoporous layer improves the electron transport as well as light utilization. To resolve the common problem of uneven growth of perovskite on rough surface, the dynamic two-step spin coating strategy is proposed to prepare highly smooth, dense, and crystallized perovskite films with micrometer-scale grains, largely reducing the carrier recombination ratio...
May 22, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29786861/temporally-feathered-intensity-modulated-radiation-therapy-a-planning-technique-to-reduce-normal-tissue-toxicity
#10
Juan Carlos López Alfonso, Shireen Parsai, Nikhil Joshi, Andrew Godley, Chirag Shah, Shlomo A Koyfman, Jimmy J Caudell, Clifton D Fuller, Heiko Enderling, Jacob G Scott
PURPOSE: Intensity modulated radiation therapy (IMRT) has allowed optimization of three-dimensional spatial radiation dose distributions permitting target coverage while reducing normal tissue toxicity. However, radiation-induced normal tissue toxicity is a major contributor to patients' quality of life and often a dose-limiting factor in the definitive treatment of cancer with radiation therapy. We propose the next logical step in the evolution of IMRT using canonical radiobiological principles, optimizing the temporal dimension through which radiation therapy is delivered to further reduce radiation-induced toxicity by increased time for normal tissue recovery...
May 22, 2018: Medical Physics
https://www.readbyqxmd.com/read/29786788/transplantable-animal-studies-and-whole-body-optical-imaging-in-prostate-carcinoma
#11
Geertje van der Horst, Maaike van der Mark, Henry Cheung, Gabri van der Pluijm
Current treatments of advanced prostate cancer only marginally increase overall survival and can be regarded as predominantly palliative. Hence, there is an urgent need for novel therapeutic strategies for the treatment of primary tumors and, more importantly perhaps, for the prevention of tumor progression and metastasis formation. Clinically relevant preclinical models are therefore urgently needed. An ideal, clinically relevant preclinical model would mimic the genetic and phenotypic changes that occur at the different stages of human prostate cancer progression and subsequent metastasis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786784/generation-of-prostate-cancer-patient-derived-xenografts-to-investigate-mechanisms-of-novel-treatments-and-treatment-resistance
#12
Hung-Ming Lam, Holly M Nguyen, Eva Corey
Treatment advances lead to survival benefits of patients with advanced prostate cancer. These treatments are highly efficacious in a subset of patients; however, similarly to other cancers, after initial responses the tumors develop resistance (acquired resistance) and the patients succumb to the disease. Furthermore, there is a subset of patients who do not respond to the treatment at all (de novo resistance). Preclinical testing using patient-derived xenografts (PDXs) has led to successful drug development, and PDXs will continue to provide valuable resources to generate clinically relevant data with translational potential...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786776/a-framework-for-image-based-modeling-of-acute-myocardial-ischemia-using-intramurally-recorded-extracellular-potentials
#13
Brett M Burton, Kedar K Aras, Wilson W Good, Jess D Tate, Brian Zenger, Rob S MacLeod
The biophysical basis for electrocardiographic evaluation of myocardial ischemia stems from the notion that ischemic tissues develop, with relative uniformity, along the endocardial aspects of the heart. These injured regions of subendocardial tissue give rise to intramural currents that lead to ST segment deflections within electrocardiogram (ECG) recordings. The concept of subendocardial ischemic regions is often used in clinical practice, providing a simple and intuitive description of ischemic injury; however, such a model grossly oversimplifies the presentation of ischemic disease-inadvertently leading to errors in ECG-based diagnoses...
May 21, 2018: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29786775/stormram-4-an-mr-safe-robotic-system-for-breast-biopsy
#14
Vincent Groenhuis, Françoise J Siepel, Jeroen Veltman, Jordy K van Zandwijk, Stefano Stramigioli
Suspicious lesions in the breast that are only visible on magnetic resonance imaging (MRI) need to be biopsied under MR guidance with high accuracy and efficiency for accurate diagnosis. The aim of this study is to present a novel robotic system, the Stormram 4, and to perform preclinical tests in an MRI environment. Excluding racks and needle, its dimensions are 72 × 51 × 40 mm. The Stormram 4 is driven by two linear and two curved pneumatic stepper motors. The linear motor is capable of exerting 63 N of force at a pressure of 0...
May 21, 2018: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29786755/cardiac-progenitor-cell%C3%A2-derived-exosomes-promote-h9c2-cell-growth-via-akt-mtor-activation
#15
Shentang Li, Jie Jiang, Zuocheng Yang, Zhuoying Li, Xing Ma, Xin Li
Exosomes are cell‑derived vesicles released from a variety of mammalian cells that are involved in cell‑to‑cell signalling. It has been reported that cardiac progenitor cells (CPCs) derived from an adult heart are one of the most promising stem cell types for cardioprotection and repair. The mammalian target of rapamycin (mTOR) signalling pathway is a pivotal regulator in CPCs, therefore, CPC‑derived exosomes were used in the present study to investigate whether it can promote H9C2 cell growth through the protein kinase B (PKB, or Akt)/mTOR signalling pathway...
May 21, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786745/histone-modifications-in-fatty-acid-synthase-modulated-by-carbohydrate-responsive-element-binding-protein-are-associated-with-non%C3%A2-alcoholic-fatty-liver-disease
#16
Can Cai, Huihong Yu, Guangming Huang, Xuan Du, Xiaoqing Yu, Youping Zhou, Wei Shen
Non‑alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and is closely associated with diabetes; however, its pathogenesis remains to be elucidated. Carbohydrate responsive element binding protein (ChREBP), the hub of glucolipid metabolism, regulates the induction of fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, by directly binding to carbohydrate response element (ChoRE) in its promoter. Investigations of histone modifications on NAFLD remain in their infancy...
May 22, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786743/role-of-tgf%C3%A2-%C3%AE-1-expressed-in-bone-marrow%C3%A2-derived-mesenchymal-stem-cells-in-promoting-bone-formation-in-a-rabbit-femoral-defect-model
#17
Bing-Yin Sun, Bao-Xiang Zhao, Jie-Ying Zhu, Zheng-Ping Sun, Yong-An Shi, Feng Huang
Bone defects represent a major clinical and socioeconomic problem without suitable treatment options. Previous studies have shown that transforming growth factor β1 (TGF‑β1) is important in the development of various diseases. The present study aimed to investigate the therapeutic potential of rabbit bone marrow‑derived mesenchymal stem cells (BMSCs) expressing TGF‑β1 in the treatment of rabbit femoral defects. First, rabbit BMSCs were identified and cultured. TGF‑β1 was then stably overexpressed in the rabbit BMSCs by lentivirus transfection, which was expressed at a high level in the femoral defects treated with TGF‑β1‑overexpressing BMSCs, compared with PBS‑treated controls...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786742/a-novel-alendronate-functionalized-nanoprobe-for-simple-colorimetric-detection-of-cancer-associated-hypercalcemia
#18
Abhishek Sahu, Youngmin Hwang, Cristian Vilos, Jong-Min Lim, Sunghyun Kim, Won Il Choi, Giyoong Tae
The calcium (Ca2+) ion concentration in the blood serum is tightly regulated, and any abnormalities in the level of serum calcium ions are associated with many potentially dangerous diseases. Thus, monitoring of the Ca2+ ion concentration in the blood serum is of fundamental importance. Gold nanoparticle (GNP)-based colorimetric biosensors have enormous potential in clinical diagnostic applications due to their simplicity, versatility, and unique optical properties. In this study, we have developed an alendronate functionalized gold nanoparticle (GNP-ALD) system for the measurement of Ca2+ ion concentration in biological samples...
May 22, 2018: Nanoscale
https://www.readbyqxmd.com/read/29786738/design-and-mechanistic-study-of-a-novel-gold-nanocluster-based-drug-delivery-system
#19
Qinzhen Li, Yiting Pan, Tiankai Chen, Yuanxin Du, Honghua Ge, Buchang Zhang, Jianping Xie, Haizhu Yu, Manzhou Zhu
Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self-regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide...
May 22, 2018: Nanoscale
https://www.readbyqxmd.com/read/29786736/phase-behaviour-and-applications-of-a-binary-liquid-mixture-of-methanol-and-a-thermotropic-liquid-crystal
#20
Luis A Serrano, Maximiliano J Fornerod, Ye Yang, Simon Gaisford, Francesco Stellacci, Stefan Guldin
Herein, we report on the phase behaviour of a binary liquid mixture composed of methanol (MeOH) and the thermotropic liquid crystal 4-cyano-4'-pentylbiphenyl (5CB). The corresponding phase diagram combines features of a conventional liquid-liquid mixture with characteristics that are particular to the nematic liquid crystal. We observe four arrangements as a function of composition and temperature, namely monophasic isotropic, monophasic nematic, biphasic isotropic-isotropic and biphasic isotropic-nematic, with an upper critical solution temperature of 24...
May 22, 2018: Soft Matter
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