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https://www.readbyqxmd.com/read/28329443/analyzing-the-potential-root-causes-of-variability-of-pharmacokinetics-in-preclinical-species
#1
Pierre Daublain, Kung-I Feng, Michael D Altman, Iain Martin, Suman Mukherjee, Rebecca Nofsinger, Alan B Northrup, Richard Tschirret-Guth, Mark Cartwright, Caroline McGregor
The purpose of this research was to assess variability in pharmacokinetic profiles (PK variability) in preclinical species and identify the risk factors associated with the properties of a drug molecule that contribute to the variability. Exposure data in mouse, rat, dog and monkey for a total of 16,592 research compounds studied between 1999 and 2013 were included in the analysis. Both in vivo study parameters and in silico/experimental physicochemical properties of the molecules were analyzed. Areas under the plasma concentration vs...
March 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28327179/pterostilbene-prevents-akt-erk-axis-mediated-polymerization-of-surface-fibronectin-on-suspended-lung-cancer-cells-independently-of-apoptosis-and-suppresses-metastasis
#2
Ying-Jan Wang, Jing-Fang Lin, Li-Hsin Cheng, Wen-Tsan Chang, Ying-Hsien Kao, Ming-Min Chang, Bour-Jr Wang, Hung-Chi Cheng
BACKGROUND: Polymeric fibronectin (polyFN) assembled on suspended breast cancer cells is required for metastasis. Conceivably, drugs that target such polyFN may fight against cancer metastasis. While stilbene analogs trigger pro-apoptotic effect on attached cancer cells, whether they prevent polyFN assembly and metastasis of suspended cancer cells via an apoptosis-independent manner remains unexplored. METHODS: We depleted suspended Lewis lung carcinoma (LLC) cells of polyFN by silencing the endogenous FN expression or pterostilbene (PS) to examine whether metastasis of lung cancer cells could thus be suppressed...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28324784/an-in%C3%A2-vivo-active-1-2-5-oxadiazole-pt-ii-complex-a-promising-anticancer-agent-endowed-with-stat3-inhibitory-properties
#3
Federica Porta, Giorgio Facchetti, Nicola Ferri, Arianna Gelain, Fiorella Meneghetti, Stefania Villa, Daniela Barlocco, Daniela Masciocchi, Akira Asai, Nao Miyoshi, Silvia Marchianò, Byoung-Mog Kwon, Yena Jin, Valentina Gandin, Cristina Marzano, Isabella Rimoldi
New Pt(II) complexes (Pt-1-3) bearing 1,2,5-oxadiazole ligands (1-3) were synthesized, characterized and evaluated for their ability to disrupt STAT3 dimerization. Ligand 3·HCl showed cytotoxic effects on HCT-116 cells (IC50 = 95.2 μM) and a selective ability to interact with STAT3 (IC50 = 8.2 μM) versus STAT1 (IC50 > 30 μM). Its corresponding platinum complex Pt-3 exhibited an increased cytotoxicity (IC50 = 18.4 μM) and a stronger interaction with STAT3 (IC50 = 1.4 μM), leading to inhibition of its signaling pathway...
March 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28301620/anti-pruritic-efficacy-of-itch-relief-lotion-and-cream-in-patients-with-atopic-history-comparison-with-hydrocortisone-cream
#4
Matthew J Zirwas, Sylvia Barkovic
<p>Objective: To evaluate the speed of onset and duration of relief of two ceramide-containing formulations with 1% pramoxine hydroxide (CeraVe® Itch Relief Lotion and Cream,Valeant Pharmaceuticals North America LLC, Irvine, CA) in patients with atopic history, including those with active flare and the comparative efficacy of CeraVe Itch Relief Cream to hydrocortisone 1% cream and night-time itch relief with continued use. METHODS: Two double-blind, split-body, randomized studies in 66 male and female subjects, ages 11+ years, with history of atopic dermatitis (AD)...
March 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28301605/ocf-can-repress-tumor-metastasis-by-inhibiting-epithelial-mesenchymal-transition-involved-in-pten-pi3k-akt-pathway-in-lung-cancer-cells
#5
Ye Yang, Shuang Qiu, Lei Qian, Yuan Tian, Yingna Chen, Lei Bi, Weiping Chen
A component formula with definite compositions provides a new approach to treat various diseases. Salvia miltiorrhiza and Panax ginseng are widely used in China because of their antitumor properties. In the previous study, the optimizing component formula (OCF), prepared with salvianolic acids, ginsenosides, and ginseng polysaccharides (5, 10, and 5 mg·L-1, respectively) extracted from S. miltiorrhiza and P. ginseng on the basis of IC50 in lung cancer A549 cells and damage minimization on human bronchial epithelial cells in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28301505/the-impact-and-determinants-of-the-energy-paradigm-on-economic-growth-in-european-union
#6
Jean Vasile Andrei, Mihai Mieila, Mirela Panait
Contemporary economies are strongly reliant on energy and analyzing the determining factors that trigger the changes in energy paradigm and their impact upon economic growth is a topical research subject. Our contention is that energy paradigm plays a major role in achieving the sustainable development of contemporary economies. In order to prove this the panel data methodology of research was employed, namely four panel unit root tests (LLC, IPS, F-ADF and F-PP) aiming to reveal the connections and relevance among 17 variables denoting energy influence on economic development...
2017: PloS One
https://www.readbyqxmd.com/read/28299958/a-model-of-self-monitoring-blood-glucose-measurement-error
#7
Martina Vettoretti, Andrea Facchinetti, Giovanni Sparacino, Claudio Cobelli
BACKGROUND: A reliable model of the probability density function (PDF) of self-monitoring of blood glucose (SMBG) measurement error would be important for several applications in diabetes, like testing in silico insulin therapies. In the literature, the PDF of SMBG error is usually described by a Gaussian function, whose symmetry and simplicity are unable to properly describe the variability of experimental data. Here, we propose a new methodology to derive more realistic models of SMBG error PDF...
March 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28296945/longitudinal-associations-between-body-mass-index-physical-activity-and-healthy-dietary-behaviors-in-adults-a-parallel-latent-growth-curve-modeling-approach
#8
Youngdeok Kim, Jung-Min Lee, Jungyoon Kim, Emily Dhurandhar, Ghada Soliman, Nizar K Wehbi, James Canedy
BACKGROUND: Physical activity (PA) and healthy dietary behaviors (HDB) are two well-documented lifestyle factors influencing body mass index (BMI). This study examined 7-year longitudinal associations between changes in PA, HDB, and BMI among adults using a parallel latent growth curve modeling (LGCM). METHODS: We used prospective cohort data collected by a private company (SimplyWell LLC, Omaha, NE, USA) implementing a workplace health screening program. Data from a total of 2,579 adults who provided valid BMI, PA, and HDB information for at least 5 out of 7 follow-up years from the time they entered the program were analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28285311/postural-transitions-during-activities-of-daily-living-could-identify-frailty-status-application-of-wearable-technology-to-identify-frailty-during-unsupervised-condition
#9
Saman Parvaneh, Jane Mohler, Nima Toosizadeh, Gurtej Singh Grewal, Bijan Najafi
BACKGROUND: Impairment of physical function is a major indicator of frailty. Functional performance tests have been shown to be useful for identification of frailty in older adults. However, these tests are often not translatable into unsupervised and remote monitoring of frailty status at home and/or community settings. OBJECTIVE: In this study, we explored daily postural transition quantified using a chest-worn wearable technology to identify frailty in community-dwelling older adults...
March 11, 2017: Gerontology
https://www.readbyqxmd.com/read/28282460/induction-of-immunogenic-cell-death-of-tumors-by-newly-synthesized-heterocyclic-quinone-derivative
#10
Keum-Joo Son, Ki Ryung Choi, Chung-Kyu Ryu, Seog Jae Lee, Ho Jeong Kim, Hyunah Lee
Many cancer types are serious diseases causing mortality, and new therapeutics with improved efficacy and safety are required. Immuno-(cell)-therapy is considered as one of the promising therapeutic strategies for curing intractable cancer. In this study, we tested R2016, a newly developed heterocyclic quinone derivative, for induction of immunogenic tumor cell death and as a possible novel immunochemotherapeutic. We studied the anti-cancer effects of R2016 against LLC, a lung cancer cell line and B16F10, a melanoma cell line...
2017: PloS One
https://www.readbyqxmd.com/read/28272757/aldosterone-activates-the-oncogenic-signals-erk1-2-and-stat3-via-redox-regulated-mechanisms
#11
Nina Queisser, Nicole Schupp, Eva Schwarz, Christina Hartmann, Gerardo G Mackenzie, Patricia I Oteiza
Epidemiological studies found an increased risk for kidney cancer in hypertensive patients, of which a subgroup has high aldosterone (Ald) levels. We recently showed that Ald is genotoxic both in kidney tubular cells and in rats with mineralocorticoid-mediated hypertension. The present work investigated in vitro and in vivo, if the oxidative stress-mediated activation of the ERK1/2 pathway, and its downstream target STAT3, could be one mechanism involved in the potential oncogenic potential of excess Ald exposure...
March 8, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28272377/spotlight-on-biomimetic-systems-based-on-lyotropic-liquid-crystal
#12
REVIEW
Juliana F de Souza, Katiusca da S Pontes, Thais F R Alves, Venâncio A Amaral, Márcia de A Rebelo, Moema A Hausen, Marco V Chaud
The behavior of lyotropic biomimetic systems in drug delivery was reviewed. These behaviors are influenced by drug properties, the initial water content, type of lyotropic liquid crystals (LLC), swell ability, drug loading rate, the presence of ions with higher or less kosmotropic or chaotropic force, and the electrostatic interaction between the drug and the lipid bilayers. The in vivo interaction between LCC-drugs, and the impact on the bioavailability of drugs, was reviewed. The LLC with a different architecture can be formed by the self-assembly of lipids in aqueous medium, and can be tuned by the structures and physical properties of the emulsion...
March 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28266094/controlled-growth-of-gold-nanostars-effect-of-spike-length-on-sers-signal-enhancement
#13
Ganesh Venkatachalam, S V Sheen Mers, Shivakumar Umadevi
In this work, two different types of gold nanostars (Au NS) namely short-spiked nanostars (SSNS) and long-spiked nanostars (LSNS) are prepared by using hexagonal lyotropic liquid crystalline (LLC) phase as a template. Basically the formation, size and length of spikes or arms of the resultant Au NS are controlled by preparation either in a hexagonal LLC phase or in an isotropic phase. These NS are anchored onto ITO electrodes through self-assembled monolayer (SAM) of 3-mercaptopropyltrimethoxysilane (MPTMS) acting as a linker molecule...
March 7, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28251952/-influence-of-doxorubicin-inclusion-into-phospholipid-nanoparticles-on-tumor-accumulation-and-specific-activity
#14
N V Medvedeva, T I Torkhovskaya, L V Kostryukova, T S Zakharova, V A Kudinov, E O Kasatkina, V N Prozorovskiy, O M Ipatova
The specific activity of drug formulation of doxorubicin embedded into phospholipid nanoparticles with diameter less than 30 nm ("Doxolip") was studied in mice LLC carcinoma. Doxolip was prepared according to technology that was elaborated in Institute earlier. Doxorubicin tumor accumulation after intraperitoneal administration (at 4 h) was 4.5 times higher for Doxolip, than for free doxorubicin. The study of doxorubicin antitumor activity in developing tumor after single intravenous administration, 48 h after inoculation, showed, that: 1) tumor growth inhibition of Doxolip was observed at 6th day, while it was only at 11th day for free doxorubicin and revealed in less extent; 2) there was no antitumor effect of free doxorubicin at 8 days after administration of doses 2 and 4 mg/kg, but it was observed for Doxolip in dose-dependent manner, 10% and 30% correspondently...
January 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28243062/oral-and-transdermal-drug-delivery-systems-role-of-lipid-based-lyotropic-liquid-crystals
#15
REVIEW
Rajan Rajabalaya, Muhammad Nuh Musa, Nurolaini Kifli, Sheba R David
Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28230759/analysis-of-the-total-biflavonoids-extract-from-selaginella-doederleinii-by-hplc-qtof-ms-and-its-in-vitro-and-in-vivo-anticancer-effects
#16
Hong Yao, Bing Chen, Yanyan Zhang, Huigen Ou, Yuxiang Li, Shaoguang Li, Peiying Shi, Xinhua Lin
Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS...
February 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28229902/impact-of-high-glucose-and-ages-on-cultured-kidney-derived-cells-effects-on-cell-viability-lysosomal-enzymes-and-effectors-of-cell-signaling-pathways
#17
Giovani B Peres, Nestor Schor, Yara M Michelacci
We have previously reported decreased expression and activities of lysosomal cathepsins B and L in diabetic kidney. Relevant morphological changes were observed in proximal tubules, suggesting that these cells are implicated in the early stages of the disease. The aim of the present study was to investigate the mechanisms that lead to these changes. The effects of high glucose (HG) and advanced glycation end products (AGEs) on cell viability, lysosomal enzymes and other effectors of cell signaling of cultured kidney cells were studied...
April 2017: Biochimie
https://www.readbyqxmd.com/read/28224391/development-and-evaluation-of-a-nanoemulsion-containing-ursolic-acid-a-promising-trypanocidal-agent-nanoemulsion-with-ursolic-acid-against-t-cruzi
#18
Erika Cristina Vargas de Oliveira, Zumira Aparecida Carneiro, Sérgio de Albuquerque, Juliana Maldonado Marchetti
Over a hundred years after the discovery of Chagas disease, this ailment continues to affect thousands of people. For more than 40 years, only two drugs have been available to treat it. Ursolic acid is a naturally occurring terpene that has shown a good trypanocidal action. However, the hydrophobicity of this compound presents a challenge for the development of proper delivery systems. Nanostructured systems are a prominent in delivering lipophilic drugs. Thus, a nanoemulsion containing ursolic acid was developed and had its trypanocidal activity and cytotoxicity evaluated...
February 21, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28223926/frontal-functional-connectivity-of-electrocorticographic-delta-and-theta-rhythms-during-action-execution-versus-action-observation-in-humans
#19
Claudio Babiloni, Claudio Del Percio, Susanna Lopez, Giancarlo Di Gennaro, Pier P Quarato, Luigi Pavone, Roberta Morace, Andrea Soricelli, Giuseppe Noce, Vincenzo Esposito, Vittorio Gallese, Giovanni Mirabella
We have previously shown that in seven drug-resistant epilepsy patients, both reaching-grasping of objects and the mere observation of those actions did desynchronize subdural electrocorticographic (ECoG) alpha (8-13 Hz) and beta (14-30) rhythms as a sign of cortical activation in primary somatosensory-motor, lateral premotor and ventral prefrontal areas (Babiloni et al., 2016a). Furthermore, that desynchronization was greater during action execution than during its observation. In the present exploratory study, we reanalyzed those ECoG data to evaluate the proof-of-concept that lagged linear connectivity (LLC) between primary somatosensory-motor, lateral premotor and ventral prefrontal areas would be enhanced during the action execution compared to the mere observation due to a greater flow of visual and somatomotor information...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28222152/alteration-of-the-exdna-profile-in-blood-serum-of-llc-bearing-mice-under-the-decrease-of-tumour-invasion-potential-by-bovine-pancreatic-dnase-i-treatment
#20
Ludmila A Alekseeva, Nadezhda L Mironova, Evgenyi V Brenner, Alexander M Kurilshikov, Olga A Patutina, Marina A Zenkova
Taking into account recently obtained data indicating the participation of circulating extracellular DNA (exDNA) in tumorigenesis, enzymes with deoxyribonucleic activity have again been considered as potential antitumour and antimetastatic drugs. Previously, using murine Lewis lung carcinoma and hepatocellular carcinoma A1 tumour models, we have shown the antimetastatic activity of bovine DNase I, which correlates with an increase of DNase activity and a decrease of exDNA concentration in the blood serum of tumour-bearing mice...
2017: PloS One
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