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Frontiers in Pharmacology

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https://www.readbyqxmd.com/read/28529486/the-role-of-statins-in-prevention-of-preeclampsia-a-promise-for-the-future
#1
REVIEW
Vasiliki Katsi, Georgios Georgountzos, Manolis S Kallistratos, Ioannis Zerdes, Thomas Makris, Athanasios J Manolis, Petros Nihoyannopoulos, Dimitris Tousoulis
Preeclampsia has been linked to high morbidity and mortality during pregnancy. However, no efficient pharmacological options for the prevention of this condition are currently available. Preeclampsia is thought to share several pathophysiologic mechanisms with cardiovascular disease, which has led to investigations for the potential role of statins (HMG CoA reductase inhibitors) in its prevention and early management. Pravastatin seems to have a safer pharmacokinetic profile compared to other statins, however, the existing preclinical evidence for its effectiveness in preeclampsia treatment has been mostly restricted to animal models...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529485/hydrostatin-sn1-a-sea-snake-derived-bioactive-peptide-reduces-inflammation-in-a-mouse-model-of-acute-lung-injury
#2
Guosheng Wu, Junjie Wang, Pengfei Luo, An Li, Song Tian, Hailong Jiang, Yongjun Zheng, Feng Zhu, Yiming Lu, Zhaofan Xia
Snake venom has been used for centuries as a traditional Chinese medicine. Hydrostatin-SN1 (H-SN1), a bioactive peptide extracted from the Hydrophis cyanocinctus venom gland T7 phage display library, was reported to have the ability to reduce inflammation in a dextran sulfate sodium-induced murine colitis model. In this study, we sought to investigate the inhibitory potential of H-SN1 on inflammation in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI), and elucidate the anti-inflammatory mechanism in LPS-stimulated RAW 264...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529484/targeting-adenosine-receptors-for-the-treatment-of-cardiac-fibrosis
#3
REVIEW
Elizabeth A Vecchio, Paul J White, Lauren T May
Adenosine is a ubiquitous molecule with key regulatory and cytoprotective mechanisms at times of metabolic imbalance in the body. Among a plethora of physiological actions, adenosine has an important role in attenuating ischaemia-reperfusion injury and modulating the ensuing fibrosis and tissue remodeling following myocardial damage. Adenosine exerts these actions through interaction with four adenosine G protein-coupled receptors expressed in the heart. The adenosine A2B receptor (A2BAR) is the most abundant adenosine receptor (AR) in cardiac fibroblasts and is largely responsible for the influence of adenosine on cardiac fibrosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529483/identification-of-a-novel-allosteric-inhibitory-site-on-tryptophan-hydroxylase-1-enabling-unprecedented-selectivity-over-all-related-hydroxylases
#4
Mike Petrassi, Rob Barber, Celine Be, Sarah Beach, Brian Cox, Anne-Marie D'Souza, Nick Duggan, Martin Hussey, Roy Fox, Peter Hunt, Gabor Jarai, Takatoshi Kosaka, Paul Oakley, Viral Patel, Neil Press, David Rowlands, Clemens Scheufler, Oliver Schmidt, Honnappa Srinivas, Mary Turner, Rob Turner, John Westwick, Alison Wolfreys, Nuzhat Pathan, Simon Watson, Matthew Thomas
Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529482/mode-of-action-analyses-of-neferine-a-bisbenzylisoquinoline-alkaloid-of-lotus-nelumbo-nucifera-against-multidrug-resistant-tumor-cells
#5
Onat Kadioglu, Betty Y K Law, Simon W F Mok, Su-Wei Xu, Thomas Efferth, Vincent K W Wong
Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28529481/topical-ophthalmic-formulation-of-trichostatin-a-and-surr9-c84a-for-quick-recovery-post-alkali-burn-of-corneal-haze
#6
Kislay Roy, Chun Hei Antonio Cheung, Rupinder K Kanwar, Rajat Sandhir, Jagat R Kanwar
Alkali burn injury is a true ocular emergency of the conjunctiva and cornea that requires immediate precision. Lack of an immediate therapy can lead to a substantial damage in the ocular surface and anterior segment further causing visual impairment and disfigurement. We explored the regenerative capability of dominant negative survivin protein (SurR9-C84A) and histone deacetylase inhibitor trichostatin-A (TSA) in vivo, in a rat alkali burn model. A topical insult in rat eyes with NaOH led to degradation of the conjunctival and corneal epithelium...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28522974/low-dose-paclitaxel-inhibits-tumor-cell-growth-by-regulating-glutaminolysis-in-colorectal-carcinoma-cells
#7
Chaoxiang Lv, Hao Qu, Wanyun Zhu, Kaixiang Xu, Anyong Xu, Baoyu Jia, Yubo Qing, Honghui Li, Hong-Jiang Wei, Hong-Ye Zhao
Paclitaxel (PTX) is a natural alkaloid isolated from the bark of a tree, Taxus brevifolia, and is currently used to treat a variety of tumors. Recently, it has been found that low-dose PTX is a promising treatment for some cancers, presenting few side effects. However, antitumor mechanisms of low-dose PTX (<1 nM) have rarely been illuminated. Here we report a new antitumor mechanism of low-dose PTX in colorectal carcinoma cells. We treated colorectal carcinoma HCT116 cells with PTX at 0.1 and 0.3 nM for 0, 1, 2, or 3 days, and found that low-dose PTX inhibits cell growth without altering cell morphology and cell cycle...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28522973/profiling-and-distribution-of-metabolites-of-procyanidin-b2-in-mice-by-uplc-dad-esi-it-tof-ms-n-technique
#8
Ying Xiao, Zhongzhi Hu, Zhiting Yin, Yiming Zhou, Taiyi Liu, Xiaoli Zhou, Dawei Chang
The metabolite profiles and distributions of procyanidin B2 were qualitatively described using UPLC-DAD-ESI-IT-TOF-MS(n) without help of reference standards, and a possible metabolic pathway was proposed in the present study. Summarily, 53 metabolites (24 new metabolites) were detected as metabolites of procyanidin B2, and 45 of them were tentatively identified. Twenty seven metabolites were assigned as similar metabolites of (-)-epicatechin by scission of the flavanol interflavanic bond C4-C8, including 16 aromatic metabolites, 5 conjugated metabolites, 3 ring-cleavage metabolites, and 2 phenylvalerolactone metabolites...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28515693/rolipram-improves-outcome-in-a-rat-model-of-infant-sepsis-induced-cardiorenal-syndrome
#9
Clark R Sims, Sharda P Singh, Shengyu Mu, Neriman Gokden, Dala Zakaria, Trung C Nguyen, Philip R Mayeux
While the mortality rate associated with sepsis in children has fallen over the years, it still remains unacceptably high. The development of both acute cardiac dysfunction and acute kidney injury during severe sepsis is categorized as type 5 cardiorenal syndrome (CRS) and is poorly understood in infants. To address this lack of understanding and the need for an appropriate animal model in which to conduct relevant preclinical studies, we developed a model of infant sepsis-induced CRS in rat pups then evaluated the therapeutic potential of the phosphodiesterase (PDE) 4 inhibitor, rolipram...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28515692/wu-tou-decoction-in-rheumatoid-arthritis-integrating-network-pharmacology-and-in-vivo-pharmacological-evaluation
#10
Qingqing Guo, Kang Zheng, Danping Fan, Yukun Zhao, Li Li, Yanqin Bian, Xuemei Qiu, Xue Liu, Ge Zhang, Chaoying Ma, Xiaojuan He, Aiping Lu
Purpose: This study aimed to explore underlying action mechanism of Wu-Tou decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology prediction and experimental verification. Methods: Chemical compounds and human target proteins of WTD as well as RA-related human genes were obtained from TCM Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular networks and canonical pathways presumably involved in the treatment of WTD on RA were generated by ingenuity pathway analysis (IPA) software...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28512430/cyp2d6-phenotyping-using-urine-plasma-and-saliva-metabolic-ratios-to-assess-the-impact-of-cyp2d6-%C3%A2-10-on-interindividual-variation-in-a-chinese-population
#11
Rui Chen, Xin Zheng, Pei Hu
Purpose: Asian populations have around 40-60% frequency of reduced function allele CYP2D6(∗)10 compared to 1-2% in Caucasian populations. The wide range of CYP2D6 enzyme activities in subjects with the CYP2D6(∗)10 variant is a big concern for clinical practice. The quantitative analysis measuring the impact of CYP2D6 enzyme activity as a result of one CYP2D6(∗)10 allele or two CYP2D6(∗)10 alleles has not been reported in large Asian populations. Methods: A total of 421 healthy Chinese subjects were genotyped for CYP2D6 by polymerase chain reaction and direct DNA sequencing...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28507520/in-vitro-and-in-silico-antidiabetic-and-antimicrobial-evaluation-of-constituents-from-kickxia-ramosissima-nanorrhinum-ramosissimum
#12
Adnan Amin, Emmy Tuenter, Kenn Foubert, Jamhsed Iqbal, Paul Cos, Louis Maes, Vassiliki Exarchou, Sandra Apers, Luc Pieters
Background and Aims:Kickxia ramosissima (Wall.) Janch (or Nanorrhinum ramosissimum (Wall.) Betsche is a well-known medicinal plant in Pakistan that is traditionally used in diabetic and inflammatory conditions. Because little information is available on its phytochemical composition, a range of constituents were isolated and evaluated in vitro in assays related to the traditional use. Methods: Dried whole plant material was extracted and chromatographically fractionated. Isolated constituents were evaluated in silico and in vitro in assays related to the traditional use against diabetes (inhibition of α-glucosidase activity; inhibition of advanced glycation endproducts) and in inflammatory conditions (inhibition of AAPH induced linoleic acid peroxidation, inhibition of 15-LOX, antimicrobial activity)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28507519/vasorelaxing-action-of-the-kynurenine-metabolite-xanthurenic-acid-the-missing-link-in-endotoxin-induced-hypotension
#13
Francesco Fazio, Albino Carrizzo, Luana Lionetto, Antonio Damato, Luca Capocci, Mariateresa Ambrosio, Giuseppe Battaglia, Valeria Bruno, Michele Madonna, Maurizio Simmaco, Ferdinando Nicoletti, Carmine Vecchione
The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28503148/management-of-benign-prostatic-hyperplasia-could-dietary-polyphenols-be-an-alternative-to-existing-therapies
#14
REVIEW
Chinedum Eleazu, Kate Eleazu, Winner Kalu
The incidence of benign prostatic hyperplasia (BPH) is gradually on the increase. While conventional drugs such as the α1-adrenergic receptor antagonists and 5α-reductase inhibitors have been found to be useful in the treatment of BPH, the adverse side effects associated with their usage, have led to increased search for alternative means of managing this disease. Furthermore, although surgery has also been suggested to be a sure method, the cost and risks associated with it excludes it as a routine treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28503147/an-ethanolic-extract-of-ampelopsis-radix-exerts-anti-colorectal-cancer-effects-and-potently-inhibits-stat3-signaling-in-vitro
#15
Tao Su, Jing-Xuan Bai, Ying-Jie Chen, Xin-Ning Wang, Xiu-Qiong Fu, Ting Li, Hui Guo, Pei-Li Zhu, Yue Wang, Zhi-Ling Yu
Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in CRC, and has been proposed as a pathogenic factor and a therapeutic target of CRC. Ampelopsis Radix (AR), a traditional Chinese medicinal herb, possesses low toxicity and has long been used clinically for the treatment of cancers including CRC. Some constituents of AR have been reported to exert anti-cancer properties by targeting STAT3...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28503146/statin-therapy-is-associated-with-reduced-risk-of-peptic-ulcer-disease-in-the-taiwanese-population
#16
Chun-Jung Lin, Wei-Chih Liao, Yu-An Chen, Hwai-Jeng Lin, Chun-Lung Feng, Cheng-Li Lin, Ying-Ju Lin, Min-Chuan Kao, Mei-Zi Huang, Chih-Ho Lai, Chia-Hung Kao
Although statin use may affect the severity of chronic gastritis and gastric cancer, no data exists about the relationship between statin therapy and risk of peptic ulcer disease (PUD) in patients. We investigated the effect of statin use and the incidence of PUD from the Taiwan National Health Insurance Research Database (NHIRD). A total of 35,194 patients records for medical claims were enrolled. We performed a population-based case-control analysis to compare the incidence of PUD in patients who were prescribed statins and that in patients who were not...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28496409/rapid-screening-for-%C3%AE-glucosidase-inhibitors-from-gymnema-sylvestre-by-affinity-ultrafiltration-hplc-ms
#17
Guilin Chen, Mingquan Guo
Gymnema sylvestre R. Br. (Asclepiadaceae) has been known to posses potential anti-diabetic activity, and the gymnemic acids were reported as the main bioactive components in this plant species. However, the specific components responsible for the hypoglycemic effect still remain unknown. In the present study, the in vitro study revealed that the extract of G. sylvestre exhibited significant inhibitory activity against α-glucosidase with IC50 at 68.70 ± 1.22 μg/mL compared to acarbose (positive control) at 59...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28491038/yokukansan-and-yokukansankachimpihange-ameliorate-aggressive-behaviors-in-rats-with-cholinergic-degeneration-in-the-nucleus-basalis-of-meynert
#18
Masahiro Tabuchi, Keita Mizuno, Kazushige Mizoguchi, Tomohisa Hattori, Yoshio Kase
Yokukansan (YKS) and yokukansankachimpihange (YKSCH) are traditional Japanese Kampo medicines. The latter comprises YKS along with the medicinal herbs Citrus unshiu peel and Pinellia tuber. Both of these Kampo medicines are indicated for the treatment of night crying and irritability in children and for neurosis and insomnia in adults. In recent clinical trials, YKS exhibited ameliorative effects on the behavioral and psychological symptoms of dementia, such as aggressiveness, excitement, and irritability. In the present study, we aimed to clarify the involvement of cholinergic degeneration in the nucleus basalis of Meynert (NBM) in the development of aggressiveness in rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28491037/sodium-4-carboxymethoxyimino-4-hpr-a-novel-water-soluble-derivative-of-4-oxo-4-hpr-endowed-with-in-vivo-anticancer-activity-on-solid-tumors
#19
Paola Tiberio, Elena Cavadini, Loredana Cleris, Sabrina Dallavalle, Loana Musso, Maria G Daidone, Valentina Appierto
4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR), an active polar metabolite of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR), was shown to exert promising antitumor activity through at least two independent mechanisms of action. Specifically, differently from 4-HPR and other retinoids, 4-oxo-4-HPR targets microtubules and inhibits tubulin polymerization causing mitotic arrest and on the other hand, analogously to the parent drug, it induces apoptosis through the activation of a signaling cascade involving the generation of reactive oxygen species (ROS)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28491036/pharmacological-activity-and-clinical-use-of-pdrn
#20
REVIEW
Francesco Squadrito, Alessandra Bitto, Natasha Irrera, Gabriele Pizzino, Giovanni Pallio, Letteria Minutoli, Domenica Altavilla
PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions...
2017: Frontiers in Pharmacology
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