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Frontiers in Pharmacology

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https://www.readbyqxmd.com/read/28443025/honokiol-induces-apoptosis-g1-arrest-and-autophagy-in-kras-mutant-lung-cancer-cells
#1
Lian-Xiang Luo, Ying Li, Zhong-Qiu Liu, Xing-Xing Fan, Fu-Gang Duan, Run-Ze Li, Xiao-Jun Yao, Elaine Lai-Han Leung, Liang Liu
Aberrant signaling transduction induced by mutant KRAS proteins occurs in 20∼30% of non-small cell lung cancer (NSCLC), however, a direct and effective pharmacological inhibitor targeting KRAS has not yet reached the clinic to date. Honokiol, a small molecular polyphenol natural biophenolic compound derived from the bark of magnolia trees, exerts anticancer activity, however, its mechanism remains unknown. In this study, we sought to investigate the in vitro effects of honokiol on NSCLC cell lines harboring KRAS mutations...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28443024/low-dose-of-bergamot-derived-polyphenolic-fraction-bpf-did-not-improve-metabolic-parameters-in-second-generation-antipsychotics-treated-patients-results-from-a-60-days-open-label-study
#2
Antonio Bruno, Gianluca Pandolfo, Manuela Crucitti, Massimo Cacciola, Vincenza Santoro, Edoardo Spina, Rocco A Zoccali, Maria R A Muscatello
Objectives: The nutraceutical approach to the management of metabolic syndrome (MetS) might be a promising strategy in the prevention of cardio-metabolic risk. Low-dose bergamot-derived polyphenolic fraction (BPF) has been proven effective in patients with MetS, as demonstrated by a concomitant improvement in lipemic and glycemic profiles. The present study was aimed to further explore, in a sample of subjects receiving second generation antipsychotics (SGAs), the effects on body weight and metabolic parameters of a low dose of BPF (500 mg/day) administered for 60 days...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28443023/inhibition-of-vegf-and-angiopoietin-2-to-reduce-brain-metastases-of-breast-cancer-burden
#3
Kaci A Bohn, Chris E Adkins, Mohamed I Nounou, Paul R Lockman
For metastases in the central nervous system, angiogenesis enhances metastatic potential and promotes progression. Primary factors which drive vessel growth are vascular endothelial growth factor (VEGF) and angiopoietin-2. Preclinical models show inhibition of either factor reduces metastases spread and inhibits growth. This work sets out to answer two questions in a preclinical mouse model. First, whether the combined inhibition of VEGF and angiopoietin-2, reduces passive permeability and limits drug uptake into brain metastases; and second, whether this inhibition reduces metastases burden in brain...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28443022/evaluating-quality-of-decision-making-processes-in-medicines-development-regulatory-review-and-health-technology-assessment-a-systematic-review-of-the-literature
#4
REVIEW
Magdalena Bujar, Neil McAuslane, Stuart R Walker, Sam Salek
Introduction: Although pharmaceutical companies, regulatory authorities, and health technology assessment (HTA) agencies have been increasingly using decision-making frameworks, it is not certain whether these enable better quality decision making. This could be addressed by formally evaluating the quality of decision-making process within those organizations. The aim of this literature review was to identify current techniques (tools, questionnaires, surveys, and studies) for measuring the quality of the decision-making process across the three stakeholders...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28443021/functional-and-biochemical-endothelial-profiling-in-vivo-in-a-murine-model-of-endothelial-dysfunction-comparison-of-effects-of-1-methylnicotinamide-and-angiotensin-converting-enzyme-inhibitor
#5
Anna Bar, Mariola Olkowicz, Urszula Tyrankiewicz, Edyta Kus, Krzysztof Jasinski, Ryszard T Smolenski, Tomasz Skorka, Stefan Chlopicki
Although it is known that 1-methylnicotinamide (MNA) displays vasoprotective activity in mice, as yet the effect of MNA on endothelial function has not been demonstrated in vivo. Here, using magnetic resonance imaging (MRI) we profile the effects of MNA on endothelial phenotype in mice with atherosclerosis (ApoE/LDLR(-/-)) in vivo, in comparison to angiotensin (Ang) -converting enzyme (ACE) inhibitor (perindopril), with known vasoprotective activity. On a biochemical level, we analyzed whether MNA- or perindopril-induced improvement in endothelial function results in changes in ACE/Ang II-ACE2/Ang-(1-7) balance, and L-arginine/asymmetric dimethylarginine (ADMA) ratio...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28443020/bgp-15-protects-against-oxaliplatin-induced-skeletal-myopathy-and-mitochondrial-reactive-oxygen-species-production-in-mice
#6
James C Sorensen, Aaron C Petersen, Cara A Timpani, Dean G Campelj, Jordan Cook, Adam J Trewin, Vanesa Stojanovska, Mathew Stewart, Alan Hayes, Emma Rybalka
Chemotherapy is a leading intervention against cancer. Albeit highly effective, chemotherapy has a multitude of deleterious side-effects including skeletal muscle wasting and fatigue, which considerably reduces patient quality of life and survivability. As such, a defense against chemotherapy-induced skeletal muscle dysfunction is required. Here we investigate the effects of oxaliplatin (OXA) treatment in mice on the skeletal muscle and mitochondria, and the capacity for the Poly ADP-ribose polymerase (PARP) inhibitor, BGP-15, to ameliorate any pathological side-effects induced by OXA...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28439239/development-of-automated-patch-clamp-technique-to-investigate-cftr-chloride-channel-function
#7
Arnaud Billet, Lionel Froux, John W Hanrahan, Frederic Becq
The chloride (Cl(-)) channel cystic fibrosis transmembrane conductance regulator (CFTR) is defective in cystic fibrosis (CF), and mutation of its encoding gene leads to various defects such as retention of the misfolded protein in the endoplasmic reticulum, reduced stability at the plasma membrane, abnormal channel gating with low open probability, and thermal instability, which leads to inactivation of the channel at physiological temperature. Pharmacotherapy is one major therapeutic approach in the CF field and needs sensible and fast tools to identify promising compounds...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28439238/rechallenge-to-carboplatin-in-children-with-low-grade-glioma-and-carboplatin-hypersensitivity-reactions
#8
Antonio Ruggiero, Daniela Rizzo, Martina Catalano, Palma Maurizi, Stefano Mastrangelo, Giorgio Attinà, Riccardo Riccardi
Background: Carboplatin based regimens have demonstrated activity in pediatric patients with low grade gliomas (LGG). However, carboplatin hypersensitivity reactions (CHRs) may be a major problem leading to premature cessation of an effective therapy. The objectives of this study were to describe the prevalence, characteristics and management of CHR. Methods: We performed a retrospective review of children with LGG treated between January 1994 and July 2015 with carboplatin and vincristine who had a documented CHR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28439237/biomarkers-of-osteosarcoma-chondrosarcoma-and-ewing-sarcoma
#9
REVIEW
Francesco R Evola, Luciano Costarella, Vito Pavone, Giuseppe Caff, Luca Cannavò, Andrea Sessa, Sergio Avondo, Giuseppe Sessa
Osteosarcoma is the most frequent malignant bone neoplasm, followed by chondrosarcoma and Ewing sarcoma. The diagnosis of bone neoplasms is generally made through histological evaluation of a biopsy. Clinical and radiological features are also important in aiding diagnosis and to complete the staging of bone cancer. In addition to these, there are several non-specific serological or specific molecular markers for bone neoplasms. In bone tumors, molecular markers increase the accuracy of the diagnosis and assist in subtyping bone tumors...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428755/pharmacological-analysis-of-the-anti-epileptic-mechanisms-of-fenfluramine-in-scn1a-mutant-zebrafish
#10
Jo Sourbron, Ilse Smolders, Peter de Witte, Lieven Lagae
Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe seizures and prominent co-morbidities (e.g., physical, intellectual disabilities). More than 85% of the DS patients carry an SCN1A mutation (sodium channel, voltage gated, type I alpha subunit). Although numerous anti-epileptic drugs have entered the market since 1990, these drugs often fail to adequately control seizures in DS patients. Nonetheless, current clinical data shows significant seizure reduction in DS patients treated with the serotonergic (5-hydroxytryptamine, 5-HT) drug fenfluramine (FA)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428754/pu-erh-tea-water-extract-mediates-cell-cycle-arrest-and-apoptosis-in-mda-mb-231-human-breast-cancer-cells
#11
Jing Xie, Haishuang Yu, Shuang Song, Chongye Fang, Xuanjun Wang, Zhongbin Bai, Xiao Ma, Shumei Hao, Hong-Ye Zhao, Jun Sheng
Pu-erh tea is believed to have health benefits, the growth inhibition activity of Pu-erh tea on breast cancer cell has not been investigated. In this study, we examined the activity of Pu-erh tea water extract on apoptosis and cell cycle arrest in the human breast adenocarcinoma cell line MDA-MB-231 and clarified its underlying mechanism of action. We found that Pu-erh tea extract inhibited cell proliferation and induced apoptosis in a dose-dependent manner. We also found that Pu-erh tea extract inhibited tumor cell growth within 24 h via accumulation of cells in S phase...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428753/a-clinical-perspective-of-anti-fibrotic-therapies-for-cardiovascular-disease
#12
REVIEW
Lu Fang, Andrew J Murphy, Anthony M Dart
Cardiac fibrosis are central to various cardiovascular diseases. Research on the mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in recent years. However, while many anti-fibrotic treatments have been studied in animal models and seem promising, translation of experimental findings into human patients has been rather limited. Thus, several potential new treatments which have shown to reduce cardiac fibrosis in animal models have either not been tested in humans or proved to be disappointing in clinical trials...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428752/desensitizing-mitochondrial-permeability-transition-by-erk-cyclophilin-d-axis-contributes-to-the-neuroprotective-effect-of-gallic-acid-against-cerebral-ischemia-reperfusion-injury
#13
Jing Sun, Da-Dui Ren, Jin-Yi Wan, Chen Chen, Dong Chen, Huan Yang, Chun-Lai Feng, Jing Gao
Ischemic stroke is a devastating disease with complex pathophysiology. Much evidence confirms that opening of the mitochondrial permeability transition pore (MPTP) is related with mitochondrial dysfunction to apoptosis in ischemic stroke, thus elucidating its signaling mechanism and screening novel MPTP inhibitor is therefore of paramount importance. Our earlier studies identified that gallic acid (GA), a naturally occurring plant phenol, endows with effect on inhibition of mitochondrial dysfunction, which has significant neuroprotective effect in cerebral ischemia/reperfusion injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428751/identification-of-nf-%C3%AE%C2%BAb-as-determinant-of-posttraumatic-stress-disorder-and-its-inhibition-by-the-chinese-herbal-remedy-free-and-easy-wanderer
#14
Chunlan Hong, Anja Schüffler, Ulrich Kauhl, Jingming Cao, Ching-Fen Wu, Till Opatz, Eckhard Thines, Thomas Efferth
Posttraumatic stress disorder (PTSD) is a mental disorder developing after exposure to traumatic events. Although psychotherapy reveals some therapeutic effectiveness, clinically sustainable cure is still uncertain. Some Chinese herbal formulae are reported to work well clinically against mental diseases in Asian countries, but the safety and their mode of action are still unclear. In this study, we investigated the mechanisms of Chinese remedy free and easy wanderer (FAEW) on PTSD. We used a reverse pharmacology approach combining clinical data to search for mechanisms of PTSD with subsequent in vitro verification and bioinformatics techniques as follows: (1) by analyzing microarray-based transcriptome-wide mRNA expression profiling of PTSD patients; (2) by investigating the effect of FAEW and the antidepressant control drug fluoxetine on the transcription factor NF-κB using reporter cell assays and western blotting; (3) by performing molecular docking and literature data mining based on phytochemical constituents of FAEW...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424624/commentary-a-bk-slo1-channel-journey-from-molecule-to-physiology
#15
COMMENT
Domenico Tricarico, Antonietta Mele
No abstract text is available yet for this article.
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424623/notch-signaling-in-ischemic-damage-and-fibrosis-evidence-and-clues-from-the-heart
#16
REVIEW
Silvia Nistri, Chiara Sassoli, Daniele Bani
Notch signaling is a major intercellular coordination mechanism highly conserved throughout evolution. In vertebrates, Notch signaling is physiologically involved in embryo development, including mesenchymal cell commitment, formation of heart tissues and angiogenesis. In post-natal life, Notch signaling is maintained as a key mechanism of cell-cell communication and its dysregulations have been found in pathological conditions such as ischemic and fibrotic diseases. In the heart, Notch takes part in the protective response to ischemia, being involved in pre- and post-conditioning, reduction of reperfusion-induced oxidative stress and myocardial damage, and cardiomyogenesis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424622/pravastatin-chronic-treatment-sensitizes-hypercholesterolemic-mice-muscle-to-mitochondrial-permeability-transition-protection-by-creatine-or-coenzyme-q10
#17
Estela N B Busanello, Ana C Marques, Noelia Lander, Diogo N de Oliveira, Rodrigo R Catharino, Helena C F Oliveira, Anibal E Vercesi
Statins are efficient cholesterol-lowering medicines utilized worldwide. However, 10% of patients suffer from adverse effects specially related to skeletal muscle function. Pro- or anti-oxidant effects of statins have been reported. Here we hypothesized that statins induce muscle mitochondrial oxidative stress leading to mitochondrial permeability transition (MPT) which may explain statin muscle toxicity. Thus, our aims were to investigate the effects of statin chronic treatment on muscle mitochondrial respiration rates, MPT and redox state indicators in the context of hypercholesterolemia...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424621/activation-of-sirtuin-3-by-silybin-attenuates-mitochondrial-dysfunction-in-cisplatin-induced-acute-kidney-injury
#18
Yin Li, Zengchun Ye, Weiyan Lai, Jialing Rao, Wanbing Huang, Xiaohao Zhang, Ziying Yao, Tanqi Lou
Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle (Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and antitumor properties. Here, we showed that silybin protected against cisplatin-induced acute kidney injury (AKI) by improving mitochondrial function through the regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3 knockout (KO) mice were administered a single intraperitoneal (i.p.) injection of cisplatin with or without treatment with silybin...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424620/relations-between-effects-and-structure-of-small-bicyclic-molecules-on-the-complex-model-system-saccharomyces-cerevisiae
#19
Matteo Brilli, Andrea Trabocchi, Tobias Weil, Duccio Cavalieri, Irene Stefanini
The development of compounds able to modify biological functions largely took advantage of parallel synthesis to generate a broad chemical variance of compounds to be tested for the desired effect(s). The budding yeast Saccharomyces cerevisiae is a model for pharmacological studies since a long time as it represents a relatively simple system to explore the relations among chemical variance and bioactivity. To identify relations between the chemical features of the molecules and their activity, we delved into the effects of a library of small compounds on the viability of a set of S...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424619/retinal-and-circulating-mirnas-in-age-related-macular-degeneration-an-in-vivo-animal-and-human-study
#20
Giovanni L Romano, Chiara B M Platania, Filippo Drago, Salvatore Salomone, Marco Ragusa, Cristina Barbagallo, Cinzia Di Pietro, Michele Purrello, Michele Reibaldi, Teresio Avitabile, Antonio Longo, Claudio Bucolo
Age related macular degeneration (AMD) is the leading cause of blindness among people aged 50 and over. Retinal deposition of amyloid-β (Aβ) aggregates in AMD patients has suggested a potential link between AMD and Alzheimer's disease (AD). We have evaluated the differential retinal expression profile of miRNAs in a rat model of AMD elicited by Aβ. A serum profile of miRNAs in AMD patients has been also assessed using single TaqMan assay. Analysis of retina from rats intravitreally injected with Aβ revealed that miR-27a, miR-146a, and miR-155 were up-regulated in comparison to control rats...
2017: Frontiers in Pharmacology
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