keyword
MENU ▼
Read by QxMD icon Read
search

Systems pharmacology

keyword
https://www.readbyqxmd.com/read/28109168/integrated-omics-analysis-of-specialized-metabolism-in-medicinal-plants
#1
Amit Rai, Kazuki Saito, Mami Yamazaki
Medicinal plants are the rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their approach to explore biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. Recent advancements in the high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. Reduced cost to generate omics datasets, and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several plant origin bio-active metabolites...
January 21, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28108836/smad-dependent-signaling-plays-a-detrimental-role-in-a-fly-model-of-smarcb1-deficiency-and-the-biology-of-atypical-teratoid-rhabdoid-tumors
#2
Astrid Jeibmann, Jacqueline Schulz, Kristin Eikmeier, Pascal D Johann, Katharina Thiel, Isabel Tegeder, Oliver Ambrée, Michael C Frühwald, Stefan M Pfister, Marcel Kool, Werner Paulus, Martin Hasselblatt
Atypical teratoid/rhabdoid tumors (ATRT) are highly malignant brain tumors arising in young children. The majority of ATRT is characterized by inactivation of the chromatin remodeling complex member SMARCB1 (INI1/hSNF5). Little is known, however, on downstream pathways involved in the detrimental effects of SMARCB1 deficiency which might also represent targets for treatment. Using Drosophila melanogaster and the Gal4-UAS system, modifier screens were performed in order to identify the role of SMAD dependent signaling in the lethal phenotype associated with knockdown of snr1, the fly homolog of SMARCB1...
January 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28108814/the-small-neurotoxin-apamin-blocks-not-only-small-conductance-ca-2-activated-k-channels-sk-type-but-also-the-voltage-dependent-kv1-3-channel
#3
Patrick Voos, Mehtap Yazar, René Lautenschläger, Oliver Rauh, Anna Moroni, Gerhard Thiel
Apamin is frequently used as a specific blocker of small-conductance Ca(2+)-activated (SK type) K(+) channels. Here we show that the small neurotoxin is not as specific as anticipated. It is also a high-affinity inhibitor with an IC50 of 13 nM of the Kv1.3 channel; it blocks the latter with potency similar to the Kv1.3 blocker PAP-1. Since SK type channels and Kv1.3 channels are frequently coexpressed in different tissues such as cells of the immune system, apamin must be used with caution as a pharmacological tool...
January 20, 2017: European Biophysics Journal: EBJ
https://www.readbyqxmd.com/read/28108508/two-pore-channel-function-is-crucial-for-migration-of-invasive-cancer-cells
#4
Ong Nam Phuong Nguyen, Christian Grimm, Lina S Schneider, Yu-Kai Chao, Carina Atzberger, Karin Bartel, Anna Watermann, Melanie Ulrich, Doris Mayr, Christian Wahl-Schott, Martin Biel, Angelika M Vollmar
Metastatic invasion is the major cause of cancer-related deaths. In this study, we introduce two-pore channels (TPC), a recently described class of NAADP- and PI(3,5)P2-sensitive Ca2+-permeable cation channels in the endolysosomal system of cells, as candidate targets for the treatment of invasive cancers. Inhibition of the channel abrogated migration of metastatic cancer cells in vitro. Silencing or pharmacological inhibition of the two-pore channel TPC2 reduced lung metastasis of mammary mouse cancer cells...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28108356/lipid-a-structural-modifications-in-extreme-conditions-and-identification-of-unique-modifying-enzymes-to-define-the-toll-like-receptor-4-structure-activity-relationship
#5
REVIEW
Alison J Scott, Benjamin L Oyler, David R Goodlett, Robert K Ernst
Strategies utilizing Toll-like receptor 4 (TLR4) agonists for treatment of cancer, infectious diseases, and other targets report promising results. Potent TLR4 antagonists are also gaining attention as therapeutic leads. Though some principles for TLR4 modulation by lipid A have been described, a thorough understanding of the structure-activity relationship (SAR) is lacking. Only through a complete definition of lipid A-TLR4 SAR is it possible to predict TLR4 signaling effects of discrete lipid A structures, rendering them more pharmacologically relevant...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108129/cardiovascular-impact-in-patients-undergoing-maintenance-hemodialysis-clinical-management-considerations
#6
REVIEW
Srisakul Chirakarnjanakorn, Sankar D Navaneethan, Gary S Francis, W H Wilson Tang
Patients undergoing maintenance hemodialysis develop both structural and functional cardiovascular abnormalities. Despite improvement of dialysis technology, cardiovascular mortality of this population remains high. The pathophysiological mechanisms of these changes are complex and not well understood. It has been postulated that several non-traditional, uremic-related risk factors, especially the long-term uremic state, which may affect the cardiovascular system. There are many cardiovascular changes that occur in chronic kidney disease including left ventricular hypertrophy, myocardial fibrosis, microvascular disease, accelerated atherosclerosis and arteriosclerosis...
January 4, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28107677/sensitization-of-melanoma-cells-to-alkylating-agent-induced-dna-damage-and-cell-death-via-orchestrating-oxidative-stress-and-ikk%C3%AE-inhibition
#7
Anfernee Kai-Wing Tse, Ying-Jie Chen, Xiu-Qiong Fu, Tao Su, Ting Li, Hui Guo, Pei-Li Zhu, Hiu-Yee Kwan, Brian Chi-Yan Cheng, Hui-Hui Cao, Sally Kin-Wah Lee, Wang-Fun Fong, Zhi-Ling Yu
Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS) induction and IKKβ inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKβ inhibitor which enhanced the function of nitrosoureas. Elevated ROS level results in increased DNA crosslink efficiency triggered by nitrosoureas and IKKβ inhibition enhances DNA damage signals and sensitizes nitrosourea-induced cell death...
January 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28107590/endocannabinoid-activation-of-cb1-receptors-contributes-to-long-lasting-reversal-of-neuropathic-pain-by-repetitive-spinal-cord-stimulation
#8
L Sun, L Tai, Q Qiu, R Mitchell, S Fleetwood-Walker, E A Joosten, C W Cheung
BACKGROUND: Spinal cord stimulation (SCS) has been shown to be effective in the management of certain neuropathic pain conditions, however, the underlying mechanisms are incompletely understood. In this study, we investigated repetitive SCS in a rodent neuropathic pain model, revealing long-lasting and incremental attenuation of hyperalgesia and a mechanism of action involving endocannabinoids. METHOD: Animals were implanted with monopolar electrodes at the time of partial sciatic nerve injury...
January 20, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28107514/karyopherin-alpha-proteins-regulate-oligodendrocyte-differentiation
#9
Benjamin M Laitman, John N Mariani, Chi Zhang, Setsu Sawai, Gareth R John
Proper regulation of the coordinated transcriptional program that drives oligodendrocyte (OL) differentiation is essential for central nervous system myelin formation and repair. Nuclear import, mediated in part by a group of karyopherin alpha (Kpna) proteins, regulates transcription factor access to the genome. Understanding how canonical nuclear import functions to control genomic access in OL differentiation may aid in the creation of novel therapeutics to stimulate myelination and remyelination. Here, we show that members of the Kpna family regulate OL differentiation, and may play distinct roles downstream of different pro-myelinating stimuli...
2017: PloS One
https://www.readbyqxmd.com/read/28106092/pharmacological-characterisation-of-the-highly-nav1-7-selective-spider-venom-peptide-pn3a
#10
Jennifer R Deuis, Zoltan Dekan, Joshua S Wingerd, Jennifer J Smith, Nehan R Munasinghe, Rebecca F Bhola, Wendy L Imlach, Volker Herzig, David A Armstrong, K Johan Rosengren, Frank Bosmans, Stephen G Waxman, Sulayman D Dib-Hajj, Pierre Escoubas, Michael S Minett, Macdonald J Christie, Glenn F King, Paul F Alewood, Richard J Lewis, John N Wood, Irina Vetter
Human genetic studies have implicated the voltage-gated sodium channel NaV1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits NaV1.7 (IC50 0.9 nM) with at least 40-1000-fold selectivity over all other NaV subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by NaV1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106018/cardioneuroablation-in-the-treatment-of-neurally-mediated-reflex-syncope-a-review-of-the-current-literature
#11
Tolga Aksu, Tümer Erdem Güler, Serdar Bozyel, Kazım Serhan Özcan, Kıvanç Yalın, Ferit Onur Mutluer
OBJECTIVE: An imbalance between parasympathetic and sympathetic tone is a main cause of neurally mediated reflex syncope (NMRS). These patients may be very symptomatic and the condition may require cardiac pacemaker implantation. Cardioneuroablation (CNA) is a relatively novel technique based on radiofrequency ablation of vagal ganglia that can be used in treatment of NMRS. The aim of this analysis was to compare potential role of CNA in patients with NMRS. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement, literature search was conducted using the keywords "cardioneuroablation," "vagal denervation," "reflex syncope," "vagal ablation," and "ganglionic plexi ablation...
December 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28105946/a-physarum-inspired-prize-collecting-steiner-tree-approach-to-identify-subnetworks-for-drug-repositioning
#12
Yahui Sun, Pathima Nusrath Hameed, Karin Verspoor, Saman Halgamuge
BACKGROUND: Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning...
December 5, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/28105924/molecular-determinants-of-the-adrenal-gland-functioning-related-to-stress-sensitive-hypertension-in-isiah-rats
#13
Larisa A Fedoseeva, Leonid O Klimov, Nikita I Ershov, Yury V Alexandrovich, Vadim M Efimov, Arcady L Markel, Olga E Redina
BACKGROUND: The adrenals are known as an important link in pathogenesis of arterial hypertensive disease. The study was directed to the adrenal transcriptome analysis in ISIAH rats with stress-sensitive arterial hypertension and predominant involvement in pathogenesis of the hypothalamic-pituitary-adrenal and sympathoadrenal systems. RESULTS: The RNA-Seq approach was used to perform the comparative adrenal transcriptome profiling in hypertensive ISIAH and normotensive WAG rats...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28105791/the-future-of-pleiotropic-therapy-in-heart-failure-lessons-from-the-benefits-of-exercise-training-on-endothelial-function
#14
REVIEW
Gilles W De Keulenaer, Vincent F M Segers, Faiez Zannad, Dirk L Brutsaert
A novel generation of drugs is introduced in the treatment of heart failure (HF). These drugs, including phosphodiesterase-5 inhibitors, guanylate cyclase stimulators and activators, share the feature that their action is either endothelial-mediated or substitutes for endothelial pathways, in particular the nitric oxide-cyclic guanosine monophosphate pathway, thereby influencing homeostatic balances in virtually each organ system in a pleiotropic fashion. Unfortunately, recent clinical trials with some of these drugs have shown disappointing results, at least in the setting of HF with a preserved ejection fraction...
January 19, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28104530/long-lasting-alterations-of-hippocampal-gabaergic-neurotransmission-in-adult-rats-following-perinatal-%C3%AE-9-thc-exposure
#15
Sarah Beggiato, Andrea Celeste Borelli, Maria Cristina Tomasini, Lucia Morgano, Tiziana Antonelli, Sergio Tanganelli, Vincenzo Cuomo, Luca Ferraro
The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored...
January 16, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28104499/methylene-blue-increases-the-amount-of-hsf1-through-promotion-of-pka-mediated-increase-in-hsf1-p300-interaction
#16
Chao Huang, Wenfeng Hu, Jili Wang, Lijuan Tong, Xu Lu, Feng Wu, Yong Ling, Bo Jiang, Wei Zhang, Zhuo Chen, Yibin Qin, Rongrong Yang
Heat shock factor 1 (HSF1) critically contributes to the host defense, and its amount determines the mobilization efficiency of HSF1 under stress conditions. To date, how HSF1 amount is regulated remains largely unknown. We found that methylene blue (MB), an anti-oxidative and anti-inflammatory agent, increased the amount of HSF1 in BV-2 microglia, primary microglia, astrocytes, neurons and vital organs. The increased HSF1 contributed to a more increase in nuclear translocation of HSF1, association of HSF1 with heat shock protein 70 (Hsp70) promoters and Hsp70 expression levels, and also induced a synergistic protection against oxidative stress-induced injuries in MB and heat shock-treated cells...
January 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28104434/effects-of-human-opiorphin-on-food-intake-and-water-intake-in-mice-following-central-administration
#17
Yong Chen, Xiao-Zhu Tian, Lu Bai, Ze-Qi Liu, Xing-Peng Xiao, Pu Liu, Xiang-Kai Li
Human opiorphin, plays important pharmacological functions in rats or mice. The present study was performed to investigate effects and underlying mechanism of central injected opiorphin on food intake and water intake in mice. Intracerebroventricularly (i.c.v.) administered opiorphin (5-20μg/kg) dose-dependently suppressed food intake in fasted mice, but had no influence on food intake in freely feeding mice. The cumulative food intake was significantly decreased at 60min after injection of 10 and 20μg/kg opiorphin and the food intake was significantly reduced during the 20-60min period after treatment...
January 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28104294/rodent-models-of-depression-cardiovascular-comorbidity-bridging-the-known-to-the-new
#18
REVIEW
Luca Carnevali, Nicola Montano, Rosario Statello, Andrea Sgoifo
Numerous epidemiological studies have demonstrated a close and bidirectional association between depression and cardiovascular disorders (CVD). This comorbidity places a significant burden on individuals and the healthcare system. Not surprisingly, in the last two decades preclinical research in the field of depression and CVD has rapidly progressed. Multiple studies have demonstrated that aspects of human depression/cardiovascular comorbidity can be modeled in rodents exposed to chronic stress paradigms and that a depressive-like syndrome can be induced in rodent models of CVD...
January 16, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28103740/novel-functionalization-strategies-to-improve-drug-delivery-from-polymers
#19
Emanuele Mauri, Simonetta Papa, Maurizio Masi, Pietro Veglianese, Filippo Rossi
The utility of controlled and sustained release of drugs from polymeric systems, both bulk (hydrogels) and colloids (nanoparticles), is a key point that should be addressed. Unfortunately, classic delivery systems are essentially driven by diffusion, which is very quick due to the high concentration gradient present in the body. Area covered: This review provides an overview of functionalization strategies which have been used to reduce release rates by taking advantage of post-polymerization functionalization of polymers...
January 20, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28103441/enantio-specific-allosteric-modulation-of-cannabinoid-1-receptor
#20
Robert B Laprairie, Pushkar M Kulkarni, Jeffrey R Deschamps, Melanie E M Kelly, David R Janero, Maria G Cascio, Lesley A Stevenson, Roger G Pertwee, Terry Kenakin, Eileen M Denovan-Wright, Ganesh A Thakur
The cannabinoid 1 receptor (CB1R) is one of the most widely expressed metabotropic G protein-coupled receptors in brain, and its participation in various (patho)physiological processes has made CB1R activation a viable therapeutic modality. Adverse psychotropic effects limit the clinical utility of CB1R orthosteric agonists and have promoted the search for CB1R positive allosteric modulators (PAMs) with the promise of improved drug-like pharmacology and enhanced safety over typical CB1R agonists. In this study, we describe the synthesis and in vitro and ex vivo pharmacology of the novel allosteric CB1R modulator GAT211 (racemic) and its resolved enantiomers, GAT228 (R) and GAT229 (S)...
January 19, 2017: ACS Chemical Neuroscience
keyword
keyword
48136
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"