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https://www.readbyqxmd.com/read/29351444/activated-human-t-lymphocytes-inhibit-tgf%C3%AE-induced-fibroblast-to-myofibroblast-differentiation-via-prostaglandins-d2-and-e2
#1
Shannon H Lacy, Amali P Epa, Stephen J Pollock, Collynn F Woeller, Thomas H Thatcher, Richard P Phipps, Patricia J Sime
In pulmonary fibrosis (PF), fibroblasts and myofibroblasts proliferate and deposit excessive extracellular matrix in the interstitium, impairing normal lung function. As most forms of PF have a poor prognosis and limited treatment options, PF represents an urgent unmet need for novel, effective therapeutics. While the role of immune cells in lung fibrosis is unclear, recent studies suggest that T lymphocyte (T cell) activation may be impaired in PF patients. Further, we have previously shown that activated T cells can produce prostaglandins with anti-scarring potential...
December 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29350907/excitatory-and-inhibitory-neuronal-circuits-in-the-spinal-cord-and-their-role-in-the-control-of-motor-neuron-function-and-degeneration
#2
Uri Nimrod Ramírez-Jarquín, Ricardo Tapia
The complex neuronal networks of the spinal cord coordinate a wide variety of motor functions, including walking, running and voluntary and involuntary movements. This is accomplished by different groups of neurons, called center pattern generators, which control left-right alternation and flexor-extensor patterns. These spinal circuits, located in the ventral horns, are formed by several neuronal types, and the specific function of most of them has been identified by means of studies in vivo and in the isolated spinal cord of mice harboring genetically induced ablation of specific neuronal populations...
January 19, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29348728/systems-level-mechanisms-of-action-of-panax-ginseng-a-network-pharmacological-approach
#3
REVIEW
Sa-Yoon Park, Ji-Hun Park, Hyo-Su Kim, Choong-Yeol Lee, Hae-Jeung Lee, Ki Sung Kang, Chang-Eop Kim
Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases...
January 2018: Journal of Ginseng Research
https://www.readbyqxmd.com/read/29341478/translational-systems-pharmacology-based-predictive-assessment-of-drug-induced-cardiomyopathy
#4
Dimitris E Messinis, Ioannis N Melas, Junguk Hur, Navya Varshney, Leonidas G Alexopoulos, Jane P F Bai
Drug-induced cardiomyopathy contributes to drug attrition. We compared two pipelines of predictive modeling: (1) applying elastic net (EN) to differentially expressed genes (DEGs) of drugs; (2) applying integer linear programming (ILP) to construct each drug's signaling pathway starting from its targets to downstream proteins, to transcription factors, and to its DEGs in human cardiomyocytes, and then subjecting the genes/proteins in the drugs' signaling networks to EN regression. We classified 31 drugs with availability of DEGs into 13 toxic and 18 nontoxic drugs based on a clinical cardiomyopathy incidence cutoff of 0...
January 17, 2018: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29337905/the-role-of-mirnas-in-the-pathophysiology-of-liver-diseases-and-toxicity
#5
REVIEW
Florian Schueller, Sanchari Roy, Mihael Vucur, Christian Trautwein, Tom Luedde, Christoph Roderburg
Both acute and chronic liver toxicity represents a major global health burden and an important cause of morbidity and lethality worldwide. Despite epochal progress in the treatment of hepatitis C virus infections, pharmacological treatment strategies for most liver diseases are still limited and new targets for prevention or treatment of liver disease are urgently needed. MicroRNAs (miRNAs) represent a new class of highly conserved small non-coding RNAs that are involved in the regulation of gene expression by targeting whole networks of so called "targets"...
January 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29336875/systems-pharmacology-dissection-of-the-anti-stroke-mechanism-for-the-chinese-traditional-medicine-xing-nao-jing
#6
Yuhua Chen, Yue Sun, Wende Li, Hong Wei, Tianlin Long, Hua Li, Quanhua Xu, Wei Liu
Xing-Nao-Jing (XNJ) is a well-known injection that has been extensively applied in clinical treatment of stroke in China. However, the underlying mechanism of clinical administration of XNJ in stroke remains unclear. In this study, a systems pharmacology strategy based on pharmacokinetic and pharmacodynamics data was applied to analyze the pharmacological effect of XNJ on stroke. Sixteen active compounds were filtered from XNJ through Drug-likeness (DL) and Brain-blood-barrier (BBB) evaluations. Ninety-four potential targets of these active components were identified by SysDT and SEA...
December 20, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29335507/highly-conserved-molecular-pathways-including-wnt-signaling-promote-functional-recovery-from-spinal-cord-injury-in-lampreys
#7
Paige E Herman, Angelos Papatheodorou, Stephanie A Bryant, Courtney K M Waterbury, Joseph R Herdy, Anthony A Arcese, Joseph D Buxbaum, Jeramiah J Smith, Jennifer R Morgan, Ona Bloom
In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and synaptic connections, and consequently function. Unlike mammals, lampreys are vertebrates that undergo spontaneous regeneration and achieve functional recovery after SCI. Therefore our goal was to determine the complete transcriptional responses that occur after SCI in lampreys and to identify deeply conserved pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord and brain throughout the course of functional recovery...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334873/nobiletin-prevents-cadmium-induced-neuronal-apoptosis-by-inhibiting-reactive-oxygen-species-and-modulating-jnk-erk1-2-and-akt-mtor-networks-in-rats
#8
Youyang Qu, Yu Liu, Li Chen, Yanmei Zhu, Xingjun Xiao, Di Wang, Yulan Zhu
Objectives Cadmium (Cd), an extremely noxious environmental pollutant is known to induce oxidative stress leading to neurodegenerative diseases. Nobiletin, a citrus flavonoid is reported to possess various pharmacological properties. This study investigates the effects of nobiletin over Cd-induced neuronal apoptosis in rodent experimental model. Methods To separate group of male Sprague Dawley rats, Cd (2 mL/kg/day) was subcutaneously injected for one month which results in a dose level of 1 mg/kg Cd. Couple of days prior to Cd injection, the treatment group rats regularly received nobiletin (50, 100, or 200 mg/kg b...
January 16, 2018: Neurological Research
https://www.readbyqxmd.com/read/29332256/dopamine-dependent-social-information-processing-in-non-human-primates
#9
Young-A Lee, Sarah Lionnet, Akemi Kato, Yukiori Goto
RATIONALE: Dopamine (DA) is a neurotransmitter whose roles have been suggested in various aspects of brain functions. Recent studies in rodents have reported its roles in social function. However, how DA is involved in social information processing in primates has largely remained unclear. OBJECTIVES: We investigated prefrontal cortical (PFC) activities associated with social vs. nonsocial visual stimulus processing. METHODS: Near-infrared spectroscopy (NIRS) was applied to Japanese macaques, along with pharmacological manipulations of DA transmission, while they were gazing at social and nonsocial visual stimuli...
January 14, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29330787/mass-spectrometry-and-bioinformatic-analysis-of-hydroxylation-dependent-protein-protein-interactions
#10
Javier Rodriguez, Alex von Kriegsheim
Characterization of how a stimulus regulates the dynamics of protein-protein interaction is critical for understanding how a particular protein is regulated in an intracellular signaling network. Protein hydroxylation, which is a posttranslational modification catalyzed by oxygen-dependent enzymes, is a crucial regulator of protein-protein interactions. Under low oxygen conditions, the activity of many hydroxylases is inhibited, which results in a reduction of substrate hydroxylation. These changes alter the interactome of the substrate, and this dynamic rewiring of signaling networks explains crucial aspects of the adaptive response to hypoxia...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330507/uncovering-the-anticancer-mechanism-of-compound-kushen-injection-against-hcc-by-integrating-quantitative-analysis-network-analysis-and-experimental-validation
#11
Li Gao, Ke-Xin Wang, Yu-Zhi Zhou, Jian-Song Fang, Xue-Mei Qin, Guan-Hua Du
Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM) preparation that has been clinically used in China to treat various types of solid tumours. Although several studies have revealed that CKI can inhibit the proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds, potential targets and pathways involved in these effects have not been systematically investigated. Here, we proposed a novel idea of "main active compound-based network pharmacology" to explore the anti-cancer mechanism of CKI...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330217/a-systematic-review-of-network-meta-analyses-for-pharmacological-treatment-of-common-mental-disorders
#12
REVIEW
Taryn Williams, Dan J Stein, Jonathan Ipser
QUESTION: Network meta-analyses (NMAs) of treatment efficacy across different pharmacological treatments help inform clinical decision-making, but their methodological quality may vary a lot depending also on the quality of the included primary studies. We therefore conducted a systematic review of NMAs of pharmacological treatment for common mental disorders in order to assess the methodological quality of these NMAs, and to relate study characteristics to the rankings of efficacy and tolerability...
January 12, 2018: Evidence-based Mental Health
https://www.readbyqxmd.com/read/29329355/when-the-brain-changes-its-mind-oscillatory-dynamics-of-conflict-processing-and-response-switching-in-a-flanker-task-during-alcohol-challenge
#13
Lauren E Beaton, Sheeva Azma, Ksenija Marinkovic
Despite the subjective experience of being in full and deliberate control of our actions, our daily routines rely on a continuous and interactive engagement of sensory evaluation and response preparation streams. They unfold automatically and unconsciously and are seamlessly integrated with cognitive control which is mobilized by stimuli that evoke ambiguity or response conflict. Methods with high spatio-temporal sensitivity are needed to provide insight into the interplay between automatic and controlled processing...
2018: PloS One
https://www.readbyqxmd.com/read/29327758/a-computational-analysis-of-pro-angiogenic-therapies-for-peripheral-artery-disease
#14
Lindsay E Clegg, Feilim Mac Gabhann
Inducing therapeutic angiogenesis to effectively form hierarchical, non-leaky networks of perfused vessels in tissue engineering applications and ischemic disease remains an unmet challenge, despite extensive research and multiple clinical trials. Here, we use a previously-developed, multi-scale, computational systems pharmacology model of human peripheral artery disease to screen a diverse array of promising pro-angiogenic strategies, including gene therapy, biomaterials, and antibodies. Our previously-validated model explicitly accounts for VEGF immobilization, Neuropilin-1 binding, and weak activation of VEGF receptor 2 (VEGFR2) by the "VEGFxxxb" isoforms...
January 12, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29327005/vivo-complexes-with-antibacterial-quinolone-ligands-and-their-interaction-with-serum-proteins
#15
Daniele Sanna, Valeria Ugone, Giuseppe Sciortino, Péter Buglyó, Zsolt Bihari, Péter László Parajdi-Losonczi, Eugenio Garribba
Quinolone derivatives are among the most commonly prescribed antibacterials in the world and could also attract interest as organic ligands in the design of metal complexes with potential pharmacological activity. In this study, five compounds, belonging to the first (nalidixic acid or Hnal), second (ciprofloxacin or Hcip, and norfloxacin or Hnor) and third generation (levofloxacin or Hlev, and sparfloxacin or Hspar) of quinolones, were used as ligands to bind the VIVO2+ ion. In aqueous solution, mono- and bis-chelated species were formed as a function of pH, with cis-[VOHxL2(H2O)]x+ and [VOHxL2]x+, x = 0-2, being the major complexes at pH 7...
January 12, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29325568/pink1-import-regulation-a-fine-system-to-convey-mitochondrial-stress-to-the-cytosol
#16
REVIEW
Shiori Sekine, Richard J Youle
Insights from inherited forms of parkinsonism suggest that insufficient mitophagy may be one etiology of the disease. PINK1/Parkin-dependent mitophagy, which helps maintain a healthy mitochondrial network, is initiated by activation of the PINK1 kinase specifically on damaged mitochondria. Recent investigation of this process reveals that import of PINK1 into mitochondria is regulated and yields a stress-sensing mechanism. In this review, we focus on the mechanisms of mitochondrial stress-dependent PINK1 activation that is exerted by regulated import of PINK1 into different mitochondrial compartments and how this offers strategies to pharmacologically activate the PINK1/Parkin pathway...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29323708/microrna501-5p-induces-p53-proteasome-degradation-through-the-activation-of-the-mtor-mdm2-pathway-in-adpkd-cells
#17
Lucia de Stephanis, Alessandra Mangolini, Miriam Servello, Peter C Harris, Lucio Dell'Atti, Paolo Pinton, Gianluca Aguiari
Cell proliferation and apoptosis are typical hallmarks of autosomal dominant polycystic kidney disease (ADPKD) and cause the development of kidney cysts that lead to end-stage renal disease (ESRD). Many factors, impaired by polycystin complex loss of function, may promote these biological processes, including cAMP, mTOR and EGFR signalling pathways. In addition, microRNAs (miRs) may also regulate the ADPKD related signalling network and their dysregulation contributes to disease progression. However, the role of miRs in ADPKD pathogenesis has not been fully understood, but also the function of p53 is quite obscure, especially its regulatory contribution on cell proliferation and apoptosis...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29321678/systems-pharmacology-analysis-of-synergy-of-tcm-an-example-using-saffron-formula
#18
Jianling Liu, Jingjing Liu, Fengxia Shen, Zonghui Qin, Meng Jiang, Jinglin Zhu, Zhenzhong Wang, Jun Zhou, Yingxue Fu, Xuetong Chen, Chao Huang, Wei Xiao, Chunli Zheng, Yonghua Wang
Traditional Chinese medicine (TCM) follows the principle of formulae, in which the pharmacological activity of a single herb can be enhanced or potentiated by addition of other herbs. Nevertheless, the involved synergy mechanisms in formulae remain unknown. Here, a systems-based method is proposed and applied to three representative Chinese medicines in compound saffron formula (CSF): two animal spices (Moschus, Beaver Castoreum), and one herb Crocus sativus which exert synergistic effects for cardiovascular diseases (CVDs)...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320554/a-census-of-p-longum-s-phytochemicals-and-their-network-pharmacological-evaluation-for-identifying-novel-drug-like-molecules-against-various-diseases-with-a-special-focus-on-neurological-disorders
#19
Neha Choudhary, Vikram Singh
Piper longum (P. longum, also called as long pepper) is one of the common culinary herbs that has been extensively used as a crucial constituent in various indigenous medicines, specifically in traditional Indian medicinal system known as Ayurveda. For exploring the comprehensive effect of its constituents in humans at proteomic and metabolic levels, we have reviewed all of its known phytochemicals and enquired about their regulatory potential against various protein targets by developing high-confidence tripartite networks consisting of phytochemical-protein target-disease association...
2018: PloS One
https://www.readbyqxmd.com/read/29317611/metabotropic-glutamate-receptor-5-binding-in-male-patients-with-alcohol-use-disorder
#20
Funda Akkus, Yoan Mihov, Valerie Treyer, Simon M Ametamey, Anass Johayem, Smeralda Senn, Susanne Rösner, Alfred Buck, Gregor Hasler
Glutamate signaling plays a major role in addiction. Preclinical research strongly suggests an implication of G-protein-coupled metabotropic glutamate receptor subtype 5 (mGluR5) in nicotine addiction and alcohol use disorder. In humans, smoking is related to a global reduction in mGluR5 availability. In the present study, we investigated mGluR5 in vivo in patients with alcohol use disorder without the confounding effects of smoking. A total of 14 male subjects with alcohol use disorder and at least a 25-day abstinence and 14 matched male non-smoking healthy controls were included in the study...
January 10, 2018: Translational Psychiatry
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