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Frontiers in Pharmacology

Jinxin Liu, Linchun Shi, Jingyuan Song, Wei Sun, Jianping Han, Xia Liu, Dianyun Hou, Hui Yao, Mingyue Li, Shilin Chen
Herbal drug authentication is an important task in traditional medicine; however, it is challenged by the limitations of traditional authentication methods and the lack of trained experts. DNA barcoding is conspicuous in almost all areas of the biological sciences and has already been added to the British pharmacopeia and Chinese pharmacopeia for routine herbal drug authentication. However, DNA barcoding for the Korean pharmacopeia still requires significant improvements. Here, we present a DNA barcode reference library for herbal drugs in the Korean pharmacopeia and developed a species identification engine named KP-IDE to facilitate the adoption of this DNA reference library for the herbal drug authentication...
2017: Frontiers in Pharmacology
Hermann A M Mucke
No abstract text is available yet for this article.
2017: Frontiers in Pharmacology
Tanja Kastien-Hilka, Bernd Rosenkranz, Matthias Schwenkglenks, Bryan M Bennett, Edina Sinanovic
Background: Health-related quality of life (HRQOL) and adherence to treatment are two often inter-related concepts that have implications for patient management and care. Tuberculosis (TB) and its treatment present a major public health concern in South Africa. The study aimed to evaluate the association between HRQOL and adherence in TB patients in South Africa. Methods: Four self-reported HRQOL and one self-reported adherence measures were used in an observational longitudinal multicentre study during 6-month standard TB treatment...
2017: Frontiers in Pharmacology
Verónica Latapiat, Felipe E Rodríguez, Francisca Godoy, Felipe A Montenegro, Nelson P Barrera, Juan P Huidobro-Toro
Protein allosteric modulation is a pillar of metabolic regulatory mechanisms; this concept has been extended to include ion channel regulation. P2XRs are ligand-gated channels activated by extracellular ATP, sensitive to trace metals and other chemicals. By combining in silico calculations with electrophysiological recordings, we investigated the molecular basis of P2X4R modulation by Zn(II) and ivermectin, an antiparasite drug currently used in veterinary medicine. To this aim, docking studies, molecular dynamics simulations and non-bonded energy calculations for the P2X4R in the apo and holo states or in the presence of ivermectin and/or Zn(II) were accomplished...
2017: Frontiers in Pharmacology
Jonathan H Soslow, Larry W Markham, W Bryan Burnette, Cristi L Galindo, Igor Feoktistov, Frank J Raucci, Bruce M Damon, Douglas B Sawyer, Sergey Ryzhov
Duchenne muscular dystrophy (DMD) is an X-linked disorder that leads to cardiac and skeletal myopathy. The complex immune activation in boys with DMD is incompletely understood. To better understand the contribution of the immune system into the progression of DMD, we performed a systematic characterization of immune cell subpopulations obtained from peripheral blood of DMD subjects and control donors. We found that the number of CD8 cells expressing CD26 (also known as adenosine deaminase complexing protein 2) was increased in DMD subjects compared to control...
2017: Frontiers in Pharmacology
Masahiro Mishina, Yuichi Kimura, Muneyuki Sakata, Kenji Ishii, Keiichi Oda, Jun Toyohara, Kazumi Kimura, Kiichi Ishiwata
Adenosine A1 receptors (A1Rs) are widely distributed throughout the entire human brain, while adenosine A2A receptors (A2ARs) are present in dopamine-rich areas of the brain, such as the basal ganglia. A past study using autoradiography reported a reduced binding ability of A1R in the striatum of old rats. We developed positron emission tomography (PET) ligands for mapping the adenosine receptors and we successfully visualized the A1Rs using 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine (11C-MPDX). We previously reported that the density of A1Rs decreased with age in the human striatum, although we could not observe an age-related change in A2ARs...
2017: Frontiers in Pharmacology
Wen-Tsung Huang, Yu-Hsuan Tsai, Shang-Hung Chen, Ching-Wen Kuo, Yao-Lung Kuo, Kuo-Ting Lee, Wen-Chung Chen, Pei Chih Wu, Chun-Yu Chuang, Siao Muk Cheng, Chun-Hui Lin, Euphemia Yee Leung, Yung-Chieh Chang, Chun Hei Antonio Cheung
Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+) breast cancer patients. Even though dysregulations of histone deacetylases (HDACs) are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells...
2017: Frontiers in Pharmacology
M Iqbal Choudhary, Mahwish Siddiqui, Atia-Tul-Wahab, Sammer Yousuf, Narjis Fatima, Malik S Ahmad, Hani Choudhry
In search of selective and effective anti-cancer agents, eight metabolites of anti-cancer steroid, drostanolone enanthate (1), were synthesized via microbial biotransformation. Enzymes such as reductase, oxidase, dehydrogenase, and hydrolase from Cephalosporium aphidicola, and Fusarium lini were likely involved in the biotransformation of 1 into new metabolites at pH 7.0 and 26°C, yielding five new metabolites, 2α-methyl-3α,14α,17β-trihydroxy-5α-androstane (2), 2α-methyl-7α-hydroxy-5α-androstan-3,17-dione (3), 2-methylandrosta-11α-hydroxy-1, 4-diene-3,17-dione (6), 2-methylandrosta-14α-hydroxy-1,4-diene-3,17-dione (7), and 2-methyl-5α-androsta-7α-hydroxy-1-ene-3,17-dione (8), along with three known metabolites, 2α-methyl-3α,17β-dihydroxy-5α-androstane (4), 2-methylandrosta-1, 4-diene-3,17-dione (5), and 2α-methyl-5α-androsta-17β-hydroxy-3-one (9), on the basis of NMR, and HREI-MS data, and single-crystal X-ray diffraction techniques...
2017: Frontiers in Pharmacology
Mohd M M Hanafi, Adlin Afzan, Harisun Yaakob, Ramlan Aziz, Mohamad R Sarmidi, Jean-Luc Wolfender, Jose M Prieto
This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Ficus deltoidea L. on prostate cancer cells, identify the active compound/s and characterize their mechanism of actions. Two farmed varieties were studied, var. angustifolia (FD1) and var. deltoidea (FD2). Their crude methanolic extracts were partitioned into n-hexane (FD1h, FD2h) chloroform (FD1c, FD2c) and aqueous extracts (FD1a, FD2a). Antiproliferative fractions (IC50 < 30 μg/mL, SRB staining of PC3 cells) were further fractionated...
2017: Frontiers in Pharmacology
Eva-Maria Pferschy-Wenzig, Kaisa Koskinen, Christine Moissl-Eichinger, Rudolf Bauer
Herbal preparations are complex mixtures of natural products, many of which are able to reach the distal gut due to low oral bioavailability. There, they can influence the microbial communities, and can be metabolized into potentially absorbable bioactive compounds by the intestinal bacteria. This aspect has often been disregarded when searching for the active principles of medicinal plants and herbal medicinal products. The aim of this study was to establish an interdisciplinary platform to unravel interactions of herbal medicine and intestinal microbiota, using a combined LC-MS metabolomics and 16S rRNA microbiome sequencing approach...
2017: Frontiers in Pharmacology
Paweł Kawalec, Tomas Tesar, Lenka Vostalova, Pero Draganic, Manoela Manova, Alexandra Savova, Guenka Petrova, Zinta Rugaja, Agnes Männik, Christoph Sowada, Ewa Stawowczyk, Andras Harsanyi, Andras Inotai, Adina Turcu-Stiolica, Jolanta Gulbinovič, Andrzej Pilc
Objectives: The aim of this study was to review reimbursement environment as well as pricing and reimbursement requirements for drugs in selected Central and Eastern Europe (CEE) countries. Methods: A questionnaire-based survey was performed in the period from November 2016 to March 2017 among experts involved in reimbursement matters from CEE countries: Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. A review of requirements for reimbursement and implications of Health Technology Assessment (HTA) was performed to compare the issues in above-mentioned countries...
2017: Frontiers in Pharmacology
Francesco Drago, Marta Lombardi, Ilaria Prada, Martina Gabrielli, Pooja Joshi, Dan Cojoc, Julien Franck, Isabelle Fournier, Jacopo Vizioli, Claudia Verderio
Extracellular ATP is among molecules promoting microglia activation and inducing the release of extracellular vesicles (EVs), which are potent mediators of intercellular communication between microglia and the microenvironment. We previously showed that EVs produced under ATP stimulation (ATP-EVs) propagate a robust inflammatory reaction among astrocytes and microglia in vitro and in mice with subclinical neuroinflammation (Verderio et al., 2012). However, the proteome of EVs released upon ATP stimulation has not yet been elucidated...
2017: Frontiers in Pharmacology
Maria Augusta Arruda, Leigh A Stoddart, Karolina Gherbi, Stephen J Briddon, Barrie Kellam, Stephen J Hill
Recent advances in fluorescent ligand technology have enabled the study of G protein-coupled receptors in their native environment without the need for genetic modification such as addition of N-terminal fluorescent or bioluminescent tags. Here, we have used a non-imaging plate reader (PHERAstar FS) to monitor the binding of fluorescent ligands to the human adenosine-A3 receptor (A3AR; CA200645 and AV039), stably expressed in CHO-K1 cells. To verify that this method was suitable for the study of other GPCRs, assays at the human adenosine-A1 receptor, and β1 and β2 adrenoceptors (β1AR and β2AR; BODIPY-TMR-CGP-12177) were also carried out...
2017: Frontiers in Pharmacology
Meng Qin, Yun Luo, Shan Lu, Jing Sun, Ke Yang, Guibo Sun, Xiaobo Sun
Atherosclerosis (AS) is a chronic inflammatory disease and endothelial cell injury is the initial event. In this study, we investigated the protective effects of ginsenoside F1 (GF1) on AS and the potential molecular mechanisms of ox-LDL induced endothelial injury. ApoE-/- mice were fed a high fat diet and orally treated with GF1 (50 mg/kg/day) for 8 weeks. Atherosclerotic plaque and LOX-1, TLR4, NF-κB expression levels in the aortic root and inflammatory factor MPO in whole body were measured. The treatment with GF1 induced a remarkable reduction in the atherosclerotic lesion area, LOX-1, TLR4 expression and decreased the MPO distribution...
2017: Frontiers in Pharmacology
Bo Zhang, Yu Hu, Zhiqing Pang
Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors...
2017: Frontiers in Pharmacology
Aida Menéndez-Méndez, Juan I Díaz-Hernández, Felipe Ortega, Javier Gualix, Rosa Gómez-Villafuertes, María T Miras-Portugal
Adenosine triphosphate (ATP) is an important extracellular neurotransmitter that participates in several critical processes like cell differentiation, neuroprotection or axon guidance. Prior to its exocytosis, ATP must be stored in secretory vesicles, a process that is mediated by the Vesicular Nucleotide Transporter (VNUT). This transporter has been identified as the product of the SLC17A9 gene and it is prominently expressed in discrete brain areas, including the cerebellum. The main population of cerebellar neurons, the glutamatergic granule neurons, depends on purinergic signaling to trigger neuroprotective responses...
2017: Frontiers in Pharmacology
Zhan-Guo Gao, Kenneth A Jacobson
Mast cells are responsible for the majority of allergic conditions. It was originally thought that almost all allergic events were mediated directly only via the high-affinity immunoglobulin E receptors. However, recent evidence showed that many other receptors, such as G protein-coupled receptors and ligand-gated ion channels, are also directly involved in mast cell degranulation, the release of inflammatory mediators such as histamine, serine proteases, leukotrienes, heparin, and serotonin. These mediators are responsible for the symptoms in allergic conditions such as allergic asthma...
2017: Frontiers in Pharmacology
Tomas Tesar, Laszlo Szilberhorn, Bertalan Nemeth, Balazs Nagy, Martin Wawruch, Zoltan Kalo
Objectives: To explore whether Heberprot-P (an epidermal growth factor) is a cost-effective option for the treatment of advanced diabetic foot ulcer as an add-on therapy to good wound care (GWC) in Slovakia from the perspective of health care payers. Methods: A Markov model was constructed to compare the costs and effects of Heberprot-P plus GWC to those of GWC alone from the perspective of health care payers. The 52-week clinical trial period was extended to 5- and 10-year time horizons. Transition probabilities were calculated based on a previous clinical trial of Heberprot, utility values were derived from the scientific literature, and cost vectors were collected from the General Health Insurance Fund database in Slovakia...
2017: Frontiers in Pharmacology
Xue Liu, Jiawen Shen, Danping Fan, Xuemei Qiu, Qingqing Guo, Kang Zheng, Hui Luo, Jun Shu, Cheng Lu, Ge Zhang, Aiping Lu, Chaoying Ma, Xiaojuan He
Yupingfeng San (YPFS) is a representative Traditional Chinese Medicine (TCM) formula with accepted therapeutic effect on Asthma. However, its action mechanism is still obscure. In this study, we used network pharmacology to explore potential mechanism of YPFS on asthma. Nucleotide-binding oligomerization domain (NOD)-like receptor pathway was shown to be the top one shared signaling pathway associated with both YPFS and asthma. In addition, NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome was treated as target protein in the process of YPFS regulating asthma...
2017: Frontiers in Pharmacology
Xiao Yang, Keyi Geng, Jinfan Zhang, Yanshuang Zhang, Jiaxiang Shao, Weiliang Xia
In response to stroke-induced injury, astrocytes can be activated and form a scar. Inflammation is an essential component for glial scar formation. Previous study has shown that adjudin, a potential Sirt3 activator, could attenuate lipopolysaccharide (LPS)- and stroke-induced neuroinflammation. To investigate the potential inhibitory effect and mechanism of adjudin on astrocyte activation, we used a transient middle cerebral artery occlusion (tMCAO) model with or without adjudin treatment in wild type (WT) and Sirt3 knockout (KO) mice and performed a wound healing experiment in vitro...
2017: Frontiers in Pharmacology
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