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https://www.readbyqxmd.com/read/28446747/a-systems-pharmacology-approach-to-determine-active-compounds-and-action-mechanisms-of-xipayi-kuijie-an-enema-for-treatment-of-ulcerative-colitis
#1
Wei Yu, Zhihong Li, Fei Long, Wen Chen, Yurong Geng, Zhiyong Xie, Meicun Yao, Bo Han, Teigang Liu
Xipayi Kui Jie'an (KJA), a type of traditional Uygur medicine (TUM), has shown promising therapeutic effects in Ulcerative colitis (UC). Owing to the complexity of TUM, the pharmacological mechanism of KJA remains vague. Therefore, the identification of complex molecular mechanisms is a major challenge and a new method is urgently needed to address this problem. In this study, we established a feasible pharmacological model based on systems pharmacology to identify potential compounds and targets. We also applied compound-target and target-diseases network analysis to evaluate the action mechanisms...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28439271/cross-talk-between-inhibitory-immunoreceptor-tyrosine-based-activation-motif-signaling-and-toll-like-receptor-pathways-in-macrophages-and-dendritic-cells
#2
REVIEW
Ivan Hirsch, Vaclav Janovec, Ruzena Stranska, Nathalie Bendriss-Vermare
The innate immune cells sense microbial infection and self-ligands by pathogen recognition receptors (PRRs), such as toll-like receptors (TLRs) and regulatory receptors (RRs), associated with immunoreceptor tyrosine-based activation motif (ITAM). Rapid activation and concerted action of PRRs signaling and feedback inhibitory mechanisms must be engaged to ensure the host defense functions and to prevent cytotoxicity associated with excessive activation. ITAM-associated RRs can generate stimulatory or, paradoxically, inhibitory signals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28435296/spotlight-on-bevacizumab-and-its-potential-in-the-treatment-of-malignant-pleural-mesothelioma-the-evidence-to-date
#3
REVIEW
Pavel A Levin, Jonathan E Dowell
Malignant pleural mesothelioma (MPM) is a rare, but aggressive cancer. Surgery and radiation offer limited benefit, and systemic chemotherapy remains the primary treatment modality for the majority of patients. Vascular endothelial growth factor (VEGF) and its receptor have been recognized as important players in the biology of this disease. Bevacizumab is a monoclonal antibody that binds VEGF and blocks its interaction with the VEGF receptor. Recent studies have shown benefit with the addition of bevacizumab to the combination of cisplatin and pemetrexed in MPM...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28434616/impaired-tuning-of-neural-ensembles-and-the-pathophysiology-of-schizophrenia-a-translational-and-computational-neuroscience-perspective
#4
REVIEW
John H Krystal, Alan Anticevic, Genevieve J Yang, George Dragoi, Naomi R Driesen, Xiao-Jing Wang, John D Murray
The functional optimization of neural ensembles is central to human higher cognitive functions. When the functions through which neural activity is tuned fail to develop or break down, symptoms and cognitive impairments arise. This review considers ways in which disturbances in the balance of excitation and inhibition might develop and be expressed in cortical networks in association with schizophrenia. This presentation is framed within a developmental perspective that begins with disturbances in glutamate synaptic development in utero...
May 15, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28434615/searching-for-cross-diagnostic-convergence-neural-mechanisms-governing-excitation-and-inhibition-balance-in-schizophrenia-and-autism-spectrum-disorders
#5
REVIEW
Jennifer H Foss-Feig, Brendan D Adkinson, Jie Lisa Ji, Genevieve Yang, Vinod H Srihari, James C McPartland, John H Krystal, John D Murray, Alan Anticevic
Recent theoretical accounts have proposed excitation and inhibition (E/I) imbalance as a possible mechanistic, network-level hypothesis underlying neural and behavioral dysfunction across neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and schizophrenia (SCZ). These two disorders share some overlap in their clinical presentation as well as convergence in their underlying genes and neurobiology. However, there are also clear points of dissociation in terms of phenotypes and putatively affected neural circuitry...
May 15, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28433874/systematically-characterize-the-absorbed-effective-substances-of-wutou-decoction-and-their-metabolic-pathways-in-rat-plasma-using-uhplc-q-tof-ms-combined-with-a-target-network-pharmacological-analysis
#6
Tengfei Xu, Shizhe Li, Yufei Sun, Zifeng Pi, Shu Liu, Fengrui Song, Zhiqiang Liu
Wu-tou Decoction (WTD) is a famous traditional Chinese medicine (TCM) formula which is applied to treat arthritis and pain of joints. In this study, a sensitive and rapid method was developed for the separation and identification of the absorbed constituents and metabolites of WTD in the rats plasma by ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). A total of 22 absorbed prototype constituents and 49 metabolites were identified or tentatively characterized in dosed plasma...
April 13, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28432787/presynaptic-morphology-and-vesicular-composition-determine-vesicle-dynamics-in-mouse-central-synapses
#7
Laurent Guillaud, Dimitar Dimitrov, Tomoyuki Takahashi
Transport of synaptic vesicles (SVs) in nerve terminals is thought to play essential roles in maintenance of neurotransmission. To identify factors modulating SV movements, we performed real-time imaging analysis of fluorescently labeled SVs in giant calyceal and conventional hippocampal terminals. Compared with small hippocampal terminals, SV movements in giant calyceal terminals were faster, longer and kinetically more heterogeneous. Morphological maturation of giant calyceal terminals was associated with an overall reduction in SV mobility and displacement heterogeneity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28431938/selective-inhibition-of-ezh2-by-a-small-molecule-inhibitor-regulates-microglial-gene-expression-essential-for-inflammation
#8
Sarder Arifuzzaman, Amitabh Das, Sun Hwa Kim, Taeho Yoon, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Multiple studies have documented that Enhancer of zeste homolog 2 (EZH2) could play a role in inflammation and a wide range of malignancies; however, the underlying mechanisms remain largely unaddressed. Microglial activation is a key process in the production and release of numerous pro-inflammatory mediators that play important roles in inflammation and neurodegeneration in the central nervous system (CNS). Therefore, our aim was to investigate whether inhibition of EZH2 with the selective small molecule inhibitor EPZ-6438 protects against neonatal microglial activation...
April 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28431202/pharmacological-interventions-for-acute-pancreatitis
#9
REVIEW
Elisabetta Moggia, Rahul Koti, Ajay P Belgaumkar, Federico Fazio, Stephen P Pereira, Brian R Davidson, Kurinchi Selvan Gurusamy
BACKGROUND: In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. OBJECTIVES: To assess the effects of different pharmacological interventions in people with acute pancreatitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs)...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28424576/defensive-vocalizations-and-motor-asymmetry-triggered-by-disinhibition-of-the-periaqueductal-gray-in-non-human-primates
#10
Patrick A Forcelli, Hannah F Waguespack, Ludise Malkova
Rapid and reflexive responses to threats are present across phylogeny. The neural circuitry mediating reflexive defense reactions has been well-characterized in a variety of species, for example, in rodents and cats, the detection of and species-typical response to threats is mediated by a network of structures including the midbrain tectum (deep and intermediate layers of the superior colliculus [DLSC]), periaqueductal gray (PAG), and forebrain structures such as the amygdala and hypothalamus. However, relatively little is known about the functional architecture of defense circuitry in primates...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28424378/-recognition-care-and-prevention-of-suicidal-behaviour-in-adults
#11
Zoltán Rihmer, Attila Németh, Tamás Kurimay, Dóra Perczel-Forintos, György Purebl, Péter Döme
Suicide is a major public health problem everywhere in the world and in the WHO European Region suicide accounts for over 120,000 deaths per year. 1. Recognition and diagnosis: An underlying psychiatric disorder is present in up to 90% of people who completed suicide. Comorbidity with depression, anxiety, substance abuse and personality disorders is high. In order to achieve successful prevention of suicidality, adequate diagnostic procedures and appropriate treatment for the underlying disorder are essential...
2017: Psychiatria Hungarica: A Magyar Pszichiátriai Társaság Tudományos Folyóirata
https://www.readbyqxmd.com/read/28422447/lc-ms-ms-and-chiroptical-spectroscopic-analyses-of-multidimensional-metabolic-systems-of-chiral-thalidomide-and-its-derivatives
#12
Yoshiyuki Ogino, Masahito Tanaka, Togo Shimozawa, Toru Asahi
Enantiomeric thalidomide undergoes various kinds of biotransformations including chiral inversion, hydrolysis, and enzymatic oxidation, which results in several metabolites, thereby adding to the complexity in the understanding of the nature of thalidomide. To decipher this complexity, we analyzed the multidimensional metabolic reaction networks of thalidomide and related molecules in vitro. Characteristic patterns in the amount of various metabolites of thalidomide and related molecules generated during a combination of chiral inversion, hydrolysis, and hydroxylation were observed using liquid chromatography-tandem mass spectrometry and chiroptical spectroscopy...
April 19, 2017: Chirality
https://www.readbyqxmd.com/read/28422371/effects-of-m1-and-m4-activation-on-excitatory-synaptic-transmission-in-ca1
#13
Catherine Thorn, Michael Popiolek, Eda Stark, Jeremy Edgerton
Hippocampal networks are particularly susceptible to dysfunction in many neurodegenerative diseases and neuropsychiatric disorders including Alzheimer's disease, Lewy body dementia, and schizophrenia. CA1, a major output region of the hippocampus, receives glutamatergic input from both hippocampal CA3 and entorhinal cortex, via the Schaffer collateral (SC) and temporoammonic (TA) pathways, respectively. SC and TA inputs to CA1 are thought to be differentially involved in the retrieval of previously stored memories versus the encoding of novel information, and switching between these two crucial hippocampal functions is thought to critically depend on acetylcholine (ACh) acting at muscarinic receptors...
April 19, 2017: Hippocampus
https://www.readbyqxmd.com/read/28421717/cognitive-profiles-in-euthymic-patients-with-bipolar-disorders-results-from-the-face-bd-cohort
#14
Paul Roux, Aurélie Raust, Anne Sophie Cannavo, Valérie Aubin, Bruno Aouizerate, Jean-Michel Azorin, Frank Bellivier, Raoul Belzeaux, Thierry Bougerol, Iréna Cussac, Philippe Courtet, Bruno Etain, Sébastien Gard, Sophie Job, Jean-Pierre Kahn, Marion Leboyer, Emilie Olié, Chantal Henry, Christine Passerieux
OBJECTIVES: Although cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, little is known about cognitive phenotype heterogeneity among patients with BD. METHODS: We investigated neuropsychological performance in 258 euthymic patients with BD recruited via the French network of expert centers for BD. We used a test battery assessing six domains of cognition. Hierarchical cluster analysis of the cross-sectional data was used to determine the optimal number of subgroups and to assign each patient to a specific cognitive cluster...
April 19, 2017: Bipolar Disorders
https://www.readbyqxmd.com/read/28420707/role-of-the-fatty-acid-binding-protein-4-in-heart-failure-and-cardiovascular-disease
#15
Ricardo Rodriguez-Calvo, Josefa Girona, Josep M Alegret, Alba Bosquet, Daiana Ibarretxe, Lluís Masana
Obesity and ectopic fat accumulation in non-adipose tissues are major contributors to heart failure (HF) and cardiovascular disease (CVD). Adipocytes act as endocrine organs by releasing a large number of bioactive molecules into the bloodstream, which participate in a communication network between white adipose tissue and other organs, including the heart. Among these molecules, fatty acid binding protein 4 (FABP4) has been recently shown to increase cardiometabolic risk. Both clinical and experimental evidence have identified FABP4 as a relevant player in atherosclerosis and coronary artery disease, and it has been directly related to cardiac alterations such as left ventricular hypertrophy (LVH) or both systolic and diastolic cardiac dysfunction...
April 18, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28420179/systematic-understanding-of-the-mechanism-of-salvianolic-acid-a-via-computational-target-fishing
#16
Shao-Jun Chen, Ming-Chao Cui
Salvianolic acid A (SAA) is one of the most abundant water-soluble and potent anti-oxidative compounds isolated from Danshen, a traditional Chinese medicine. A systematic overview of its mechanism of action is yet to be performed. In the present study, the druggability of SAA was measured using the TCMSP server, and potential targets of SAA were identified by PharmMapper and DRAR-CPI. Intersecting targets were then assessed by GeneMANIA and GO pathway analysis, and drug-target-pathway networks were constructed to give a visual view...
April 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28420096/a-network-based-pharmacology-study-of-the-herb-induced-liver-injury-potential-of-traditional-hepatoprotective-chinese-herbal-medicines
#17
Ming Hong, Sha Li, Hor Yue Tan, Fan Cheung, Ning Wang, Jihan Huang, Yibin Feng
Herbal medicines are widely used for treating liver diseases and generally regarded as safe due to their extensive use in Traditional Chinese Medicine practice for thousands of years. However, in recent years, there have been increased concerns regarding the long-term risk of Herb-Induced Liver Injury (HILI) in patients with liver dysfunction. Herein, two representative Chinese herbal medicines: one-Xiao-Chai-Hu-Tang (XCHT)-a composite formula, and the other-Radix Polygoni Multiflori (Heshouwu)-a single herb, were analyzed by network pharmacology study...
April 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28420080/delineating-the-common-biological-pathways-perturbed-by-asd-s-genetic-etiology-lessons-from-network-based-studies
#18
REVIEW
Oded Oron, Evan Elliott
In recent decades it has become clear that Autism Spectrum Disorder (ASD) possesses a diverse and heterogeneous genetic etiology. Aberrations in hundreds of genes have been associated with ASD so far, which include both rare and common variations. While one may expect that these genes converge on specific common molecular pathways, which drive the development of the core ASD characteristics, the task of elucidating these common molecular pathways has been proven to be challenging. Several studies have combined genetic analysis with bioinformatical techniques to uncover molecular mechanisms that are specifically targeted by autism-associated genetic aberrations...
April 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28418441/an-integrated-anti-arrhythmic-target-network-of-a-chinese-medicine-compound-wenxin-keli-revealed-by-combined-machine-learning-and-molecular-pathway-analysis
#19
Taiyi Wang, Ming Lu, Qunqun Du, Xi Yao, Peng Zhang, Xiaonan Chen, Weiwei Xie, Zheng Li, Yuling Ma, Yan Zhu
Wenxin Keli (WK), a Chinese patent medicine, is known to be effective against cardiac arrhythmias and heart failure. Although a number of electrophysiological findings regarding its therapeutic effect have been reported, the active components and system-level characterizations of the component-target interactions of WK have yet to be elucidated. In the current study, we present the first report of a new protective effect of WK on suppressing anti-arrhythmic-agent-induced arrhythmias. In a model of isolated guinea pig hearts, rapid perfusion of quinidine altered the heart rate and prolonged the Q-T interval...
April 18, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28417463/pharmacological-interventions-for-primary-sclerosing-cholangitis-an-attempted-network-meta-analysis
#20
REVIEW
Francesca Saffioti, Kurinchi Selvan Gurusamy, Neil Hawkins, Clare D Toon, Emmanuel Tsochatzis, Brian R Davidson, Douglas Thorburn
BACKGROUND: Primary sclerosing cholangitis is a chronic cholestatic liver disease that is associated with both hepatobiliary and colorectal malignancies, which can result in liver cirrhosis and its complications. The optimal pharmacological treatment for patients with primary sclerosing cholangitis remains controversial. OBJECTIVES: To assess the comparative benefits and harms of different pharmacological interventions in people with primary sclerosing cholangitis by performing a network meta-analysis, and to generate rankings of available pharmacological interventions according to their safety and efficacy...
March 28, 2017: Cochrane Database of Systematic Reviews
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