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https://www.readbyqxmd.com/read/28643328/drug-repurposing-by-simulating-flow-through-protein-protein-interaction-networks
#1
M Manczinger, V Bodnár, B T Papp, B Sz Bolla, K Szabó, B Balázs, E Csányi, E Szél, G Erős, L Kemény
As drug development is extremely expensive, the identification of novel indications for in-market drugs is financially attractive. Multiple algorithms are used to support such drug repurposing, but highly reliable methods combining simulation of intracellular networks and machine learning are currently not available. We developed an algorithm that simulates drug effects on the flow of information through protein-protein interaction networks, and uses Support Vector Machine to identify potentially effective drugs in our model disease, psoriasis...
June 23, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28643236/multi-reservoir-phospholipid-shell-encapsulating-protamine-nanocapsules-for-co-delivery-of-letrozole-and-celecoxib-in-breast-cancer-therapy
#2
Ahmed O Elzoghby, Shaimaa K Mostafa, Maged W Helmy, Maha A ElDemellawy, Salah A Sheweita
PURPOSE: In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). METHODS: Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. RESULTS: Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28641979/sexual-dimorphism-in-the-fetal-cardiac-response-to-maternal-nutrient-restriction
#3
Sribalasubashini Muralimanoharan, Cun Li, Ernesto S Nakayasu, Cameron P Casey, Thomas O Metz, Peter W Nathanielsz, Alina Maloyan
Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight...
June 19, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28637879/platelets-express-activated-p2y12-receptor-in-patients-with-diabetes
#4
Liang Hu, Lin Chang, Yan Zhang, Lili Zhai, Shenghui Zhang, Zhiyong Qi, Hongmei Yan, Yan Yan, Xinping Luo, Si Zhang, Yiping Wang, Satya P Kunapuli, Hongying Ye, Zhongren Ding
Background -Platelets from patients with diabetes are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes. However, the underlying mechanism of hyperactivated platelets is not completely understood. Methods -We measured P2Y12 expression on platelets from patients with type 2 diabetes mellitus (T2DM) and on platelets from rats with diabetes. We also assayed platelet P2Y12 activation by measuring cAMP and VASP phosphorylation...
June 21, 2017: Circulation
https://www.readbyqxmd.com/read/28636994/a-novel-ampk-activator-hernandezine-inhibits-lps-induced-tnf%C3%AE-production
#5
Ping Li, Xiaofang Li, Yonghong Wu, Manxiang Li, Xiaochuang Wang
Here, we found that hernandezine, a novel AMPK activator, inhibited LPS-induced TNFα expression/production in human macrophage cells (THP-1 and U937 lines). Activation of AMPK is required for hernandezine-induced anti-LPS response. AMPKα shRNA or dominant negative mutation (T172A) blocked hernandezine-induced AMPK activation, which almost completely reversed anti-LPS activity by hernandezine. Exogenous expression of the constitutively activate AMPKα (T172D, caAMPKα) also suppressed TNFα production by LPS...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633482/markers-of-adipogenesis-but-not-inflammation-in-adipose-tissue-are-independently-related-to-insulin-sensitivity
#6
Natalia Matulewicz, Magdalena Stefanowicz, Agnieszka Nikolajuk, Monika Karczewska-Kupczewska
Context: In obesity, adipose tissue (AT) undergoes dynamic remodeling, including an alternations in adipogenesis, AT-resident cell content, angiogenesis and turnover of extracellular matrix (ECM) components. Studies on AT in humans have been carried out mostly on people with severe metabolic abnormalities, like type 2 diabetes or morbid obesity. Objective: The purpose of the present study was to investigate subcutaneous AT gene expression of markers of adipogenesis, ECM remodeling and inflammation in young, healthy, overweight or obese subjects...
June 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28632747/selective-cyclooxygenase-inhibition-by-sc-560-improves-hepatopulmonary-syndrome-in-cirrhotic-rats
#7
Ching-Chih Chang, Wen-Shin Lee, Hsian-Guey Hsieh, Chiao-Lin Chuang, Hui-Chun Huang, Fa-Yauh Lee, Shou-Dong Lee
OBJECTIVE: Hepatopulmonary syndrome (HPS) is characterized by hypoxia in patients with chronic liver disease. The mechanism of HPS includes pulmonary vasodilatation, inflammation, and angiogenesis. Prostaglandins synthesized by cyclooxygenases (COX) participate in vascular responsiveness, inflammation and angiogenesis, which can be modulated by COX inhibitors. We therefore evaluated the impact of COX inhibition in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS...
2017: PloS One
https://www.readbyqxmd.com/read/28629363/fibroblast-paracrine-tnf-%C3%AE-signaling-elevates-integrin-a5-expression-in-idiopathic-pulmonary-fibrosis-ipf
#8
Gali Epstein Shochet, Elizabetha Brook, Lilach Israeli-Shani, Evgeny Edelstein, David Shitrit
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. Inflammatory cytokines play a significant role in IPF pathology. However, the fibroblast itself is also believed to be the primary effector in IPF. We hypothesized that the fibroblasts themselves secrete pro-inflammatory cytokines that could propagate IPF by affecting normal neighboring cells. Thus, we explored the effects of IPF fibroblast derived media on normal fibroblast characteristics...
June 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28627705/targeting-the-pd-l1-dnmt1-axis-in-acquired-resistance-to-sorafenib-in-human-hepatocellular-carcinoma
#9
Jianhua Liu, Yahui Liu, Lingyu Meng, Kai Liu, Bai Ji
Molecule-targeted therapy, such as sorafenib, is one of the effectively therapeutic options for advanced hepatocellular carcinoma (HCC). However, acquired resistance to sorafenib has been found in some HCC patients, resulting in poor prognosis. It is reported that PD-L1 and DNA methyltransferases (DNMTs) contribute to drug resistance. In this study, by inducing sorafenib-resistant HCC cell lines, we investigated their molecular and functional characteristics. Our data indicated that highly upregulated DNMT1 was positively correlated with PD-L1 overexpression in sorafenib-resistant HCC cells...
June 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28626833/the-lung-is-a-host-defense-niche-for-immediate-neutrophil-mediated-vascular-protection
#10
Bryan G Yipp, Jung Hwan Kim, Ronald Lima, Lori D Zbytnuik, Björn Petri, Nick Swanlund, May Ho, Vivian G Szeto, Tamar Tak, Leo Koenderman, Peter Pickkers, Anton T J Tool, Taco W Kuijpers, Timo K van den Berg, Mark R Looney, Matthew F Krummel, Paul Kubes
Bloodstream infection is a hallmark of sepsis, a medically emergent condition requiring rapid treatment. However, upregulation of host defense proteins through toll-like receptors and NFκB requires hours after endotoxin detection. Using confocal pulmonary intravital microscopy, we identified that the lung provides a TLR4-Myd88-and abl tyrosine kinase-dependent niche for immediate CD11b-dependent neutrophil responses to endotoxin and Gram-negative bloodstream pathogens. In an in vivo model of bacteremia, neutrophils crawled to and rapidly phagocytosed Escherichia coli sequestered to the lung endothelium...
April 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28622577/hyperoside-inhibits-lipopolysaccharide-induced-inflammatory-responses-in-microglial-cells-via-p38-and-nf%C3%AE%C2%BAb-pathways
#11
Hui-Hui Fan, Lan-Bing Zhu, Ting Li, Hui Zhu, Ya-Nan Wang, Xiao-Li Ren, Bei-Lei Hu, Chen-Ping Huang, Jian-Hong Zhu, Xiong Zhang
Hyperoside (quercetin-3-O-β-d-galactoside) is an active compound isolated from herbs. Neuroinflammation is a key mechanism involved in neurodegenerative disorders including Parkinson's disease. In this study, we aimed to investigate the potentiality of hyperoside in inhibiting microglia-mediated neuroinflammation. BV2 microglial cells were pretreated with hyperoside and stimulated with lipopolysaccharide (LPS). The results showed that hyperoside significantly inhibited LPS-induced production of nitric oxide and pro-inflammatory cytokines including IL-1β and TNF-α, as well as the expression of inducible nitric oxide synthase...
June 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28619309/scalp-acupuncture-attenuates-neurological-deficits-in-a-rat-model-of-hemorrhagic-stroke
#12
Hao Liu, Xiaowei Sun, Wei Zou, Mengtong Leng, Beng Zhang, Xiaoyu Kang, Tao He, Hui Wang
BACKGROUND: Hemorrhagic stroke accounts for approximately 15% of all stroke cases, and is associated with high morbidity and mortality. Limited human studies suggested that scalp acupuncture could facilitate functional recovery after cerebral hemorrhage. In the current study, we used an animal model of cerebral hemorrhage to examine the potential effects of scalp acupuncture. METHODS: Adult male Sprague-Dawley rats received autologous blood (50μL) into the right caudate nucleus on the right side under pentobarbital anesthesia, and then received scalp acupuncture (DU20 through GB7 on the lesion side) or sham acupuncture (1cm to the right side of the acupoints) (n=10 per group)...
June 2017: Complementary Therapies in Medicine
https://www.readbyqxmd.com/read/28617329/hepatoprotective-effect-of-aqueous-extract-from-the-seeds-of-orychophragmus-violaceus-against-liver-injury-in-mice-and-hepg2-cells
#13
Xiaowei Huo, Chenqi Liu, Li Gao, Xudong Xu, Nailiang Zhu, Li Cao
Orychophragmus violaceus (O. violaceus) is a kind of edible wild herb in north China and its seeds have medical potential, however, the effect of O. violaceus seeds on liver injury and the mechanism of action remains poorly understood. Thus, the purpose of the present study is to investigate the effect of O. violaceus seeds on liver injury and further explore the molecular mechanism of the beneficial effects using aqueous extract from the seeds of O. violaceus (AEOV). Mice were orally administrated with saline, AEOV, and biphenyldicarboxylate for 4 days, and were then injected subcutaneously with 0...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28617068/nuclear-factor-%C3%AE%C2%BAb-expression-in-the-endometrium-of-normal-and-overweight-women-with-polycystic-ovary-syndrome
#14
Onder Koc, Safak Ozdemirici, Mustafa Acet, Ummugulsum Soyturk, Suleyman Aydin
The aim of this study was to investigate whether the expression levels of endometrial NFκB p65 differ between normal weight and overweight PCOS women and to compare them with BMI-matched control subjects without PCOS. The study group comprised 20 normal weight (BMI: 18.5-24.9 kg/m(2)) and 15 overweight PCOS women (BMI: 25-29.9 kg/m(2)) with infertility. Healthy fertile women without PCOS were recruited as the control group. The patients in the normal weight PCOS group and control group were age and BMI-matched...
June 15, 2017: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28615349/cftr-protects-against-vascular-inflammation-and-atherogenesis-in-apolipoprotein-e-deficient-mice
#15
Zhengzhang Li, Zhe Shen, Haoping Xue, Shi Cheng, Qun Ji, Yutan Liu, Xiangjun Yang
Atherosclerosis is a chronic inflammatory disease of the vascular wall. Dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to result in inflammatory responses in cystic fibrosis (CF) patients. However, little is known about the role of CFTR in vascular inflammation and atherogenesis. Our results showed that CFTR was dominantly expressed in macrophages of atherosclerotic plaque and reduced in aorta and aortic sinus from atherosclerotic apolipoprotein E-deficient (apoE-/-) mice...
June 14, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28614774/new-insight-into-the-direct-anti-inflammatory-activity-of-a-myokine-irisin-against-proinflammatory-activation-of-adipocytes-implication-for-exercise-in-obesity
#16
A I Mazur-Bialy, J Bilski, E Pochec, T Brzozowski
A biological activity of myokine irisin, has been intensively investigated in the context of a browning process occurring in white adipose tissue, but its role as a modulator of immune response has been little studied. The aim of our study was to determine the impact of irisin (0 - 100 nM) on pro-inflammatory activation of adipocyte 3T3 L1 cell line. Irisin reduced in a concentration-dependent manner the expression and activity of major proinflammatory cytokines, e.g. tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) expression and their secretion into cell medium...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28611044/characterization-of-mk-4166-a-clinical-agonistic-antibody-that-targets-human-gitr-and-inhibits-the-generation-and-suppressive-effects-of-t-regulatory-cells
#17
Selvakumar Sukumar, Douglas C Wilson, Ying Yu, Jerelyn Wong, Saraswathi Naravula, Grigori Ermakov, Romina Riener, Bhagyashree Bhagwat, Antoaneta S Necheva, Jeff Grein, Tatyana Churakova, Ruban Mangadu, Peter Georgiev, Denise Manfra, Elaine M Pinheiro, Venkataraman Sriram, Wendy J Bailey, Danuta Herzyk, Terrill K McClanahan, Aarron Willingham, Amy M Beebe, Svetlana Sadekova
GITR is a T cell co-stimulatory receptor that enhances cellular and humoral immunity. The agonist anti-mouse GITR antibody DTA-1 has demonstrated efficacy in murine models of cancer primarily by attenuation of Treg-mediated immune suppression, but the translatability to human GITR biology has not been fully explored. Here we report the potential utility of MK-4166, a humanized GITR monoclonal antibody selected to bind to an epitope analogous to the DTA-1 epitope, which enhances the proliferation of both naïve and tumor-infiltrating T lymphocytes (TILs)...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28610547/human-plasma-rich-in-growth-factors-improves-survival-and-neurite-outgrowth-of-spiral-ganglion-neurons-in-vitro
#18
Michael Stolle, Jennifer Schulze, Ariane Römer, Thomas Lenarz, Martin Durisin, Athanasia Warnecke
BACKGROUND: Platelet-rich and platelet poor plasma (PRP and PPP) are autologous preparations from peripheral blood and contain several growth factors and cytokines involved in tissue repair. Although their neuroprotective and -regenerative properties have been already described, little is known about their effects in the inner ear. We therefore examined the effects of PRP and PPP on spiral ganglion neurons (SGN) in vitro. RESULTS: For all experiments, spiral ganglia were isolated from neonatal rats and were cultured in serum-free medium...
June 13, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28607508/systematic-review-and-meta-analysis-pharmacogenetics-of-anti-tnf-treatment-response-in-rheumatoid-arthritis
#19
REVIEW
S Bek, A B Bojesen, J V Nielsen, J Sode, S Bank, U Vogel, V Andersen
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis...
June 13, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28607410/dc-sign-and-toll-like-receptor-4-mediate-oxidized-low-density-lipoprotein-induced-inflammatory-responses-in-macrophages
#20
Ke Yang, Xinhe Liu, Yan Liu, Xinqiong Wang, Lijuan Cao, Xiaojie Zhang, Chundi Xu, Weifeng Shen, Tong Zhou
The regulation of inflammatory responses by innate immune receptors is recognized as a crucial step in the development of atherosclerosis, although the precise molecular mechanisms remain to be elucidated. This study focused on illustrating the roles of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)- and Toll-like receptor 4 (TLR4)-regulated inflammatory responses in macrophages. We found that DC-SIGN expression levels were increased in macrophages of atherosclerotic plaques...
June 12, 2017: Scientific Reports
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