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network pharmacology

Akhil Kumar, Ashish Tiwari, Ashok Sharma
Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target...
March 15, 2018: Current Neuropharmacology
Matthew V Green, Jonathan D Raybuck, Xinwen Zhang, Mariah M Wu, Stanley A Thayer
A defining feature of HIV-associated neurocognitive disorder (HAND) is the loss of excitatory synaptic connections. Synaptic changes that occur during exposure to HIV appear to result, in part, from a homeostatic scaling response. Here we discuss the mechanisms of these changes from the perspective that they might be part of a coping mechanism that reduces synapses to prevent excitotoxicity. In transgenic animals expressing the HIV proteins Tat or gp120, the loss of synaptic markers precedes changes in neuronal number...
March 14, 2018: Neurochemical Research
Jiangyong Gu, Li Li, Dongmei Wang, Wei Zhu, Ling Han, Ruizhi Zhao, Xiaojie Xu, Chuanjian Lu
Psoriasis vulgaris is a chronic inflammatory and immune-mediated skin disease. 44 metabonomics biomarkers were identified by high-throughput liquid chromatography coupled to mass spectrometry in our previous work. To further explore the roles of metabonomics biomarkers in the pathogenesis of psoriasis, the metabonomics biomarker-enzyme network was constructed. The key metabonomics biomarkers and enzymes were screened out by network analysis. Long-chain fatty acids, phospholipids, Estradiol and NADH were the most important metabonomics biomarkers...
March 14, 2018: Annals of Medicine
Lakshmi N Yatham, Sidney H Kennedy, Sagar V Parikh, Ayal Schaffer, David J Bond, Benicio N Frey, Verinder Sharma, Benjamin I Goldstein, Soham Rej, Serge Beaulieu, Martin Alda, Glenda MacQueen, Roumen V Milev, Arun Ravindran, Claire O'Donovan, Diane McIntosh, Raymond W Lam, Gustavo Vazquez, Flavio Kapczinski, Roger S McIntyre, Jan Kozicky, Shigenobu Kanba, Beny Lafer, Trisha Suppes, Joseph R Calabrese, Eduard Vieta, Gin Malhi, Robert M Post, Michael Berk
The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments...
March 14, 2018: Bipolar Disorders
Takudzwa J Mtisi, Charles Maponga, Tsitsi G Monera-Penduka, Tinashe Mudzviti, Dexter Chagwena, Faithful Makita-Chingombe, Robin DiFranchesco, Gene D Morse
Background: A growing number of drug development studies that include pharmacokinetic evaluations are conducted in regions lacking a specialised pharmacology laboratory. This necessitated the development of an International Pharmacology Specialty Laboratory (IPSL) in Zimbabwe. Objectives: The aim of this article is to describe the development of an IPSL in Zimbabwe. Methods: The IPSL was developed collaboratively by the University of Zimbabwe and the University at Buffalo Center for Integrated Global Biomedical Sciences...
2018: African Journal of Laboratory Medicine
Mona Dawood, Sami Hamdoun, Thomas Efferth
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug's activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2 O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1...
2018: Frontiers in Pharmacology
Mathias J Aebersold, Greta Thompson-Steckel, Adriane Joutang, Moritz Schneider, Conrad Burchert, Csaba Forró, Serge Weydert, Hana Han, János Vörös
Bottom-up neuroscience aims to engineer well-defined networks of neurons to investigate the functions of the brain. By reducing the complexity of the brain to achievable target questions, such in vitro bioassays better control experimental variables and can serve as a versatile tool for fundamental and pharmacological research. Astrocytes are a cell type critical to neuronal function, and the addition of astrocytes to neuron cultures can improve the quality of in vitro assays. Here, we present cellulose as an astrocyte culture substrate...
2018: Frontiers in Neuroscience
Ashfaqul Hoque, Priyadharshini Sivakumaran, Simon T Bond, Naomi X Y Ling, Anne M Kong, John W Scott, Nadeeka Bandara, Damián Hernández, Guei-Sheung Liu, Raymond C B Wong, Michael T Ryan, Derek J Hausenloy, Bruce E Kemp, Jonathan S Oakhill, Brian G Drew, Alice Pébay, Shiang Y Lim
Human induced pluripotent stem cells (iPSCs) are a valuable tool for studying the cardiac developmental process in vitro, and cardiomyocytes derived from iPSCs are a putative cell source for personalized medicine. Changes in mitochondrial morphology have been shown to occur during cellular reprogramming and pluripotent stem cell differentiation. However, the relationships between mitochondrial dynamics and cardiac mesoderm commitment of iPSCs remain unclear. Here we demonstrate that changes in mitochondrial morphology from a small granular fragmented phenotype in pluripotent stem cells to a filamentous reticular elongated network in differentiated cardiomyocytes are required for cardiac mesodermal differentiation...
December 2018: Cell Death Discovery
Chao-Chieh Lin, Mayumi Kitagawa, Xiaohu Tang, Ming-Hsin Hou, Jianli Wu, Dan Chen Qu, Vinayaka Srinivas, Xiaojing Liu, J Will Thompson, Bernard Mathey-Prevot, Tso-Pang Yao, Sang Hyun Lee, Jen-Tsan Chi
The temporal activation of kinases and timely ubiquitin-mediated degradation is central to faithful mitosis. Here we present evidence that acetylation controlled by Coenzyme A synthase (COASY) and acetyltransferase CBP constitutes a novel mechanism that ensures faithful mitosis. We found that COASY knockdown triggers prolonged mitosis and multinucleation. Acetylome analysis reveals that COASY inactivation leads to hyper-acetylation of proteins associated with mitosis, including CBP and an Aurora A kinase activator, TPX2...
March 12, 2018: Nature Communications
Yanxiong Gan, Shichao Zheng, Jiaqi Zhao, Chen Zhang, Tianhui Gao, Wan Liao, Qiang Fu, Chaomei Fu
ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma phaeocaulis Val. (CP), as the vital medicines for blood-breaking and disorder-eliminating, has been widely used for hepatitis with good curative effects. Owing to the complexity of traditional Chinese medicine, the pharmacological mechanism of CP remains unclear. To solve this problem, a protein network module-based approach was proposed in this study. MATERIALS AND METHODS: Firstly, the content of active components of CP was detected based on HPLC-DAD...
March 8, 2018: Journal of Ethnopharmacology
Graziano Onder, Davide L Vetrano, Alessandra Marengoni, J Simon Bell, Kristina Johnell, Katie Palmer
Chronic diseases are considered to be major determinants of frailty and it could be hypothesized that their treatment may counteract the development of frailty. However, the hypothesis that intensive treatment of chronic diseases might reduce the progression of frailty is poorly supported by existing studies. In contrast, some evidence suggests that intensive treatment of chronic diseases may increase negative health outcomes in frail older adults. In particular, if treatment of symptoms related to chronic diseases (i...
March 8, 2018: European Journal of Internal Medicine
Jin-Jun Wu, Zhen-Zhen Guo, Yuan-Feng Zhu, Zhi-Jian Huang, Xia Gong, Yu-Huan Li, Wen-Jie Son, Xiao-Yan Li, Yan-Mei Lou, Li-Jun Zhu, Lin-Lin Lu, Zhong-Qiu Liu, Liang Liu
BACKGROUND: Fuzi, which is the processed lateral roots of Aconitum carmichaeli Debx. (Ranunculaceae), is a traditional herbal medicine that is well known for its excellent pharmacological effects and acute toxicity. Aconitum alkaloids are responsible for its pharmacological activity and toxicity. Although a large number of studies on Fuzi have been reported, no comprehensive review on its pharmacokinetics has yet been published. PURPOSE: This paper seeks to present a comprehensive review regarding the phytochemistry, pharmacokinetic features and toxicity of Fuzi...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Rui Guo, Xiaoxiao Zhang, Jin Su, Haiyu Xu, Yanqiong Zhang, Fangbo Zhang, Defeng Li, Yi Zhang, Xuefeng Xiao, Shuangcheng Ma, Hongjun Yang
BACKGROUND: Quality marker (Q-markers) has been proposed as a novel concept for quality evaluation and standard elaboration of traditional Chinese medicine (TCM). Xin-Su-Ning capsule (XSNC) has been extensively used for the treatment of arrhythmia with the satisfactory therapeutic effects in clinics. However, it is lack of reliable and effective Q-markers of this prescription. PURPOSE: To identify potential Q-markers of XSNC against arrhythmia. STUDY DESIGN: An integrative pharmacology-based investigation was performed...
February 10, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Kurt Barnhart, Linda Giudice, Steve Young, Tracey Thomas, Michael P Diamond, James Segars, Wahid A Youssef, Stephen Krawetz, Nanette Santoro, Esther Eisenberg, Heping Zhang
OBJECTIVE: Endometriosis is a chronic, estrogen dependent condition that affects 5-10% of reproductive aged women and is associated with pelvic pain and infertility. As the approach to therapy shifts from surgical ablation to pharmacological control, a non-surgical mode of diagnosis would be desirable. The ENDOmarker study was designed by the NICHD Reproductive Medicine Network (RMN) to obtain well characterized and phenotyped bio specimens in a standardized fashion from women with and without endometriosis...
March 7, 2018: Contemporary Clinical Trials
Francesca Martorana, Daniela Gaglio, Maria Rosaria Bianco, Federica Aprea, Assunta Virtuoso, Marcella Bonanomi, Lilia Alberghina, Michele Papa, Anna Maria Colangelo
Neuronal differentiation involves extensive modification of biochemical and morphological properties to meet novel functional requirements. Reorganization of the mitochondrial network to match the higher energy demand plays a pivotal role in this process. Mechanisms of neuronal differentiation in response to nerve growth factor (NGF) have been largely characterized in terms of signaling, however, little is known about its impact on mitochondrial remodeling and metabolic function. In this work, we show that NGF-induced differentiation requires the activation of autophagy mediated by Atg9b and Ambra1, as it is disrupted by their genetic knockdown and by autophagy blockers...
March 9, 2018: Cell Death & Disease
Patricia Barrionuevo, Mohammed Nabhan, Osama Altayar, Zhen Wang, Patricia J Erwin, Noor Asi, Kathryn A Martin, M Hassan Murad
Background: Several pharmacologic treatments for hirsutism are used in practice; however, their relative efficacy is unclear. Methods: We searched MEDLINE, EMBASE, and CENTRAL through January 2017 for randomized controlled trials (RCTs) with follow-up of at least 6 months that evaluated antiandrogens, insulin sensitizers, and oral contraceptives in women with hirsutism. Independent pairs of reviewers selected and appraised trials. Random-effects network meta-analysis was used to compare individual drugs and classes...
March 7, 2018: Journal of Clinical Endocrinology and Metabolism
Xiaowei Niu, Jingjing Zhang, Chun Ling, Ming Bai, Yu Peng, Shaobo Sun, Yingdong Li, Zheng Zhang
Objectives Angelica sinensis exerts various pharmacological effects, such as antioxidant and anti-apoptotic activity. This study aimed to investigate the active ingredients in A. sinensis with antioxidant properties and whether A. sinensis polysaccharide (ASP) protects H9c2 cells against oxidative and endoplasmic reticulum (ER) stress. Methods The ingredients of A. sinensis and their targets and related pathways were determined using web-based databases. Markers of oxidative stress, cell viability, apoptosis, and ER stress-related signalling pathways were measured in H9c2 cells treated with hydrogen peroxide (H2 O2 ) and ASP...
January 1, 2018: Journal of International Medical Research
Karolina Losenkova, Mariachiara Zuccarini, Mikko Helenius, Guillaume Jacquemet, Evgenia Gerasimovskaya, Camilla Tallgren, Sirpa Jalkanen, Gennady G Yegutkin
Intravascular ATP and adenosine have emerged as important regulators of endothelial barrier function, vascular remodeling and neovascularization at various pathological states, including hypoxia, inflammation and oxidative stress. By using human umbilical vein endothelial cells (HUVEC) and bovine vasa vasorum endothelial cells (VVEC) as representatives of macro- and microvessel phenotypes, this study was undertaken to evaluate cellular mechanisms contributing to physiological adaptation of vascular endothelium to hypoxia, with a particular emphasis on ectoenzymatic purine-converting activities and their link to intracellular ATP homeostasis and signaling pathways...
March 4, 2018: Biochimica et Biophysica Acta
Violeta Balbas-Martinez, Leire Ruiz-Cerdá, Itziar Irurzun-Arana, Ignacio González-García, An Vermeulen, José David Gómez-Mantilla, Iñaki F Trocóniz
MOTIVATION: The literature on complex diseases is abundant but not always quantitative. This is particularly so for Inflammatory Bowel Disease (IBD), where many molecular pathways are qualitatively well described but this information cannot be used in traditional quantitative mathematical models employed in drug development. We propose the elaboration and validation of a logic network for IBD able to capture the information available in the literature that will facilitate the identification/validation of therapeutic targets...
2018: PloS One
Saeideh Jalali, Amir Zarrinhaghighi, Saman Sadraei, Younes Ghasemi, Amirhossein Sakhteman, Pouya Faridi
Background The plant Nardostachys jatamansi from Valerianaceae family is a well known antidepressant plant and has historically been used in traditional medicine. As N. jatamansi contains many different compounds, to identify its mechanisms of action, we need a network-based study. Network-based studies are becoming an increasingly important tool in understanding the mechanisms of actions of drugs. Systems pharmacology (SP) and bioinformatics are two emerging tools that use computation to develop an understanding of drug actions in molecular and cellular levels...
March 5, 2018: Current Drug Metabolism
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