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Frontiers in Pharmacology

Maria Teresa Climent, Juan Pardo, Francisco Javier Muñoz-Almaraz, Maria Dolores Guerrero, Lucrecia Moreno
Purpose: The early detection of Mild Cognitive Impairment (MCI) is essential in aging societies where dementia is becoming a common manifestation among the elderly. Thus our aim is to develop a decision tree to discriminate individuals at risk of MCI among non-institutionalized elderly users of community pharmacy. A more clinically and patient-oriented role of the community pharmacist in primary care makes the dispensation of medication an adequate situation for an effective, rapid, easy, and reproducible screening of MCI...
2018: Frontiers in Pharmacology
Ilaria Dettori, Lisa Gaviano, Alessia Melani, Laura Lucarini, Mariaconcetta Durante, Emanuela Masini, Felicita Pedata
Cerebral ischemia is a multifactorial pathology characterized by different events evolving in time. The acute injury, characterized by excitoxicity, is followed by a secondary brain injury that develops from hours to days after ischemia. Extracellular levels of histamine increase in the ischemic area after focal cerebral ischemia induced by occlusion of the middle cerebral artery (MCAo). The histamine H4 receptor (H4 R) is predominantly expressed in cell types of immune system where is involved in the regulation of immunological and inflammatory responses, and in numerous area of the Central Nervous System (CNS) including cortex and striatum...
2018: Frontiers in Pharmacology
An Huang, Dong Sun
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid via cytochrome P450 (CYP)/epoxygenase and are hydrolyzed by soluble epoxide hydrolase (sEH). Circulating and tissue levels of EETs are controlled by CYP (EET synthesis) and sEH (EET degradation). Therefore, both increases in CYP activity and decreases in sEH expression potentiate EET bioavailability, responses that prevail in the female sex as a function of estrogen. This mini review, based on subtitles listed, briefly summarizes studies focusing specifically on (1) female-specific potentiation of CYP/epoxygenase activity to compensate for the endothelial dysfunction; and (2) estrogen-dependent downregulation of sEH expression, which yields divergent actions in both systemic and pulmonary circulation, respectively...
2018: Frontiers in Pharmacology
Yufeng Yao, Yong Li, Xiaofei Zeng, Zheng Ye, Xia Li, Lu Zhang
The endothelial-to-mesenchymal transition (EMT) of glomerular vascular endothelial cells is considered to be pivotal in diabetic nephropathy (DN). The risk of DN can be decreased by losartan, but the potential molecular mechanism(s) are not fully understood. Extensive data show that the EMT occurs in proximal tubular endothelial cells resulting in an endothelial phenotype switch (fibrotic matrix accumulation), consequently enhancing the development of renal interstitial fibrosis. Here, we found that losartan significantly ameliorated DN-induced renal fibrosis progression via inhibition of the EMT in mice...
2018: Frontiers in Pharmacology
Gina D Kusuma, Mehri Barabadi, Jean L Tan, David A V Morton, Jessica E Frith, Rebecca Lim
Extracellular vesicles (EVs)-based therapeutics are based on the premise that EVs shed by stem cells exert similar therapeutic effects and these have been proposed as an alternative to cell therapies. EV-mediated delivery is an effective and efficient system of cell-to-cell communication which can confer therapeutic benefits to their target cells. EVs have been shown to promote tissue repair and regeneration in various animal models such as, wound healing, cardiac ischemia, diabetes, lung fibrosis, kidney injury, and many others...
2018: Frontiers in Pharmacology
Gabriela Pavarini, Alex McKeown, Ilina Singh
The debate about the desirability of using drugs to enhance human skills encompasses cognitive abilities such as memory and attention, and moral capacities such as emotional empathy and a sense of fairness. These two strands of literature in bioethics have grown relatively independent from each other, and an implicit framing assumption has emerged suggesting that apparently morally neutral cognitive capacities and paradigmatically moral capacities are distinct and vary independently of each other. Here, we identify key distinctions between competing accounts of cognitive enhancement and moral enhancement and argue that, despite the polarized nature of the bioethical debate, cognitive and moral capacities are intertwined...
2018: Frontiers in Pharmacology
Jun Lou, Lei Huang, Aimei Wang, Yueyang Liu, Ruiping Cai, Weihong Li, Ming-Sheng Zhou
Background: Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of obesity, insulin resistance and cardiovascular diseases (CVDs). Impairment of insulin vascular action may represent a mechanism linking insulin resistance and CVDs. The present study tested the hypothesis that adipocyte-derived resistin inhibits insulin-stimulated endothelial NO production through the induction of ER stress. Methods and Results: Human umbilical vein endothelial cells (HUVC) were incubated with tunicamycin (an inducer of ER stress, 1-20 μg/mL) or resistin (10-100 ng/mL) for 1 h...
2018: Frontiers in Pharmacology
Maarten Gees, Sara Musch, Steven Van der Plas, Anne-Sophie Wesse, Ann Vandevelde, Katleen Verdonck, Oscar Mammoliti, Tzyh-Chang Hwang, Kathleen Sonck, Pieter Stouten, Andrew M Swensen, Mia Jans, Jan Van der Schueren, Luc Nelles, Martin Andrews, Katja Conrath
There is still a high unmet need for the treatment of most patients with cystic fibrosis (CF). The identification and development of new Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators is necessary to achieve higher clinical benefit in patients. In this report we describe the characterization of novel potentiators. From a small screening campaign on F508del CFTR, hits were developed leading to the identification of pre-clinical candidates GLPG1837 and GLPG2451, each derived from a distinct chemical series...
2018: Frontiers in Pharmacology
Kenta Murata, Nina Fujita, Ryuji Takahashi, Akio Inui
Ninjinyoeito (NYT), a traditional Chinese medicine consisting of 12 herbs, is designed to improve fatigue, cold limbs, anorexia, night sweats, and anemia. Recently, NYT was reported to improve cognitive outcome and depression in patients with Alzheimer's disease. However, little is known about how NYT alleviates depression and cognitive dysfunction. In this study, we investigated the effects and mechanisms of NYT in a corticosterone (CORT)-induced model of depression. Chronic NYT treatment ameliorated the depressive-like behaviors induced by CORT treatment in three types of behavioral tests...
2018: Frontiers in Pharmacology
Marta Concheiro, Rachel Chesser, Justine Pardi, Gail Cooper
One hundred fifteen Americans die every day from opioid overdose. These overdose fatalities have been augmented by the increased availability of potent synthetic opioids, such as fentanyl and its derivatives. The death rate of synthetic opioids, other than methadone, increased by 72.2% from 2014 to 2015, and doubled from 2015 to 2016, situating the USA in the midst of an opioid overdose epidemic. The analytical identification of these opioids in postmortem samples and the correct toxicological data interpretation is critical to identify and implement preventive strategies...
2018: Frontiers in Pharmacology
Yin Jiang, Peng Bai, Hao Chen, Xiao-Yu Zhang, Xiao-Yi Tang, He-Qing Chen, Ye-Yin Hu, Xiao-Li Wang, Xin-Yi Li, You-Ping Li, Gui-Hua Tian
Background: Acupuncture is frequently used as an efficient method to prevent and treat migraines. However, its effect on the quality of life remains controversial. Methods: Seven databases, such as PubMed and Cochrane Library were searched to retrieve reference lists of eligible trials and related reviews. Randomized controlled trials that were published in Chinese and English were included. Results: Acupuncture resulted in lower Visual Analog Scale scores than the medication group at 1 month after treatment (MD -1...
2018: Frontiers in Pharmacology
Ambra Gianotti, Livia Delpiano, Emanuela Caci
Cystic fibrosis (CF) is a chronic disease caused by mutations in the CF transmembrane conductance regulator ( CFTR ) gene, which encodes for a channel expressed at the apical surface of epithelial tissues. Defective chloride and bicarbonate secretion, arising from CFTR mutations, cause a multi-organ disease. In the airways, impaired ion transport results in a thick mucus, dehydration of the periciliar region and bacterial infections. Over the last years, basic research has sustained a great effort to identify therapies that are able to correct defective CFTR...
2018: Frontiers in Pharmacology
Peng Xu, Hua Zhou, Ya-Zhuo Li, Zhong-Wen Yuan, Chang-Xiao Liu, Liang Liu, Ying Xie
Although hepatoprotective properties of silybin are well documented, the clinical therapeutic efficacy is limited by its low bioavailability due to absorption rates, extensive phase II metabolism, and biliary excretion. As our previous study indicated that metabolic enzymes may have limited effects on the pharmacokinetic (PK) behavior of silymarin, here, we intended to increase the oral bioavailability and bio-efficacy of silybin through the inhibition of active efflux. In Caco-2 and transfected MDCKII cell models, flavone baicalein significantly inhibited the efflux of silybin as a BCRP and MRP2 inhibitor...
2018: Frontiers in Pharmacology
Yu Cao, Xiaowei Xu, Shujing Liu, Linfang Huang, Jian Gu
Ganoderma is a significant source of natural fungal medicines and has been used for the treatment of various diseases for many years. However, the use of Ganoderma in cancer immunotherapy is poorly elucidated. In this study, we have analyzed 2,398 English-language papers and 6,968 Chinese-language papers published between 1987 and 2017 by using bibliometrics. A steady growth in the number of publications was observed before 2004, followed by an exponential increase between 2004 and 2017. The most common category for publications about Ganoderma was "Pharmacology & Pharmacy," in which immunomodulation (25...
2018: Frontiers in Pharmacology
Jingyao Zhang, Yun Chen, Huiqin Luo, Linlin Sun, Mengting Xu, Jin Yu, Qigang Zhou, Guoliang Meng, Shengju Yang
As the most abundant natural flavonoid in rattan tea, dihydromyricetin (DMY) has shown a wide range of pharmacological effects. In addition to the general characteristics of flavonoids, DMY has the effects of cardioprotection, anti-diabetes, hepatoprotection, neuroprotection, anti-tumor, and dermatoprotection. DMY was also applied for the treatment of bacterial infection, osteoporosis, asthma, kidney injury, nephrotoxicity and so on. These effects to some extent enrich the understanding about the role of DMY in disease prevention and therapy...
2018: Frontiers in Pharmacology
Karolina Pytka, Monika Głuch-Lutwin, Elżbieta Żmudzka, Kinga Sałaciak, Agata Siwek, Katarzyna Niemczyk, Maria Walczak, Magdalena Smolik, Adrian Olczyk, Adam Gałuszka, Jarosław Śmieja, Barbara Filipek, Jacek Sapa, Marcin Kołaczkowski, Katarzyna Pańczyk, Anna Waszkielewicz, Henryk Marona
Numerous studies have proven that both stimulation and blockade of 5-HT1A and the blockade of 5-HT7 receptors might cause the anxiolytic-like effects. Biased agonists selectively activate specific signaling pathways. Therefore, they might offer novel treatment strategies. In this study, we investigated the anxiolytic-like activity, as well as the possible mechanism of action of 1-[(2,5-dimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-17). In our previous experiments, HBK-17 showed high affinity for 5-HT1A and 5-HT7 receptors and antidepressant-like properties...
2018: Frontiers in Pharmacology
Li-Qun Ma, You Yu, Hui Chen, Mei Li, Awais Ihsan, Hai-Ying Tong, Xian-Ju Huang, Yue Gao
Aconitine is the main bioactive ingredient of Aconitum plants, which are well-known botanical herbs in China. Aconitine is also notorious for its high cardiotoxicity, as it can induce life-threatening ventricular arrhythmias. Unfortunately, there are few effective antidotes to aconitine toxicity. This study aimed to evaluate the potent protective effects of the ingredients from V. baillonii on aconitine toxicity on H9c2 cell line. Cell viability was assessed by methylthiazoltetrazolium bromide (MTT). Intracellular Ca2+ concentration alteration and reactive oxygen species (ROS) generation were observed by confocal microscopy and flow cytometry, respectively...
2018: Frontiers in Pharmacology
Caixia Yin, Yuanyuan Deng, Yuangui Liu, Jianmei Gao, Lingli Yan, Qihai Gong
Chronic cerebral hypoperfusion (CCH) is regarded as a high-risk factor for cognitive decline of vascular dementia (VD) as it is conducive to induce beta-amyloid (Aβ) aggregation. Icariside II (ICS II), a plant-derived flavonoid compound, has showed neuroprotective effect on animal models of Alzheimer's disease (AD) by decreasing Aβ levels. Here, we assessed the effect of ICS II on CCH-induced cognitive deficits and Aβ levels in rats, and the possible underlying mechanisms were also explored. It was disclosed that CCH induced by bilateral common carotid artery occlusion (BCCAO) caused cognitive deficits, neuronal injury and increase of Aβ1-40 and Aβ1-42 levels in the rat hippocampus, while oral administration of ICS II for 28 days abolished the above deficits in the hippocampus of BCCAO rats...
2018: Frontiers in Pharmacology
Qian Zhang, Mingyan Shao, Xuefeng Zhang, Qiyan Wang, Dongqing Guo, Xiaomin Yang, Chun Li, Yong Wang
Aim: Danqi Pill (DQP), a Chinese medicine frequently prescribed in China, has been approved to improve cardiac function by regulating cardiac energy metabolism in heart failure (HF) after acute myocardial infarction (AMI) patients. The aim of this study was to explore whether the mechanism of DQP is associated to the lipid and glucose metabolism mediated via PPARγ (peroxisome proliferator-activated receptor gamma) pathway both in vivo and in vitro . Materials and Methods: Model of HF after AMI was established with ligation of left anterior descending artery on Sprague-Dawley (SD) rats...
2018: Frontiers in Pharmacology
Tatiana A Slastnikova, A V Ulasov, A A Rosenkranz, A S Sobolev
A dominant area of antibody research is the extension of the use of this mighty experimental and therapeutic tool for the specific detection of molecules for diagnostics, visualization, and activity blocking. Despite the ability to raise antibodies against different proteins, numerous applications of antibodies in basic research fields, clinical practice, and biotechnology are restricted to permeabilized cells or extracellular antigens, such as membrane or secreted proteins. With the exception of small groups of autoantibodies, natural antibodies to intracellular targets cannot be used within living cells...
2018: Frontiers in Pharmacology
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