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Mostafa Rezaei Tavirani, Sina Rezaei Tavirani, Fatemeh Tajik Rostami
Aim: Pathway analysis of gastric atrophy to find new molecular prospective of disease. Background: Gastric atrophy as a process which is accompanied with "loss of glans" in stomach can be considered as a risk factor of gastric cancer. Here, the correlated biochemical pathways to the disorder have been analyzed via protein-protein interaction (PPI) network analysis. Methods: The genes related to gastric atrophy were retrieved by STRING database and organized in a network by Cytoscape...
2018: Gastroenterology and Hepatology From Bed to Bench
Ugo Dionne, François J M Chartier, Yossef López de Los Santos, Noémie Lavoie, David N Bernard, Sara L Banerjee, François Otis, Kévin Jacquet, Michel G Tremblay, Mani Jain, Sylvie Bourassa, Gerald D Gish, Jean-Philippe Gagné, Guy G Poirier, Patrick Laprise, Normand Voyer, Christian R Landry, Nicolas Doucet, Nicolas Bisson
Phosphotyrosine (pTyr) signaling has evolved into a key cell-to-cell communication system. Activated receptor tyrosine kinases (RTKs) initiate several pTyr-dependent signaling networks by creating the docking sites required for the assembly of protein complexes. However, the mechanisms leading to network disassembly and its consequence on signal transduction remain essentially unknown. We show that activated RTKs terminate downstream signaling via the direct phosphorylation of an evolutionarily conserved Tyr present in most SRC homology (SH) 3 domains, which are often part of key hub proteins for RTK-dependent signaling...
June 9, 2018: Molecular Cell
Nil Ege, Anna M Dowbaj, Ming Jiang, Michael Howell, Steven Hooper, Charles Foster, Robert P Jenkins, Erik Sahai
The transcriptional regulator YAP1 is critical for the pathological activation of fibroblasts. In normal fibroblasts, YAP1 is located in the cytoplasm, while in activated cancer-associated fibroblasts, it is nuclear and promotes the expression of genes required for pro-tumorigenic functions. Here, we investigate the dynamics of YAP1 shuttling in normal and activated fibroblasts, using EYFP-YAP1, quantitative photobleaching methods, and mathematical modeling. Imaging of migrating fibroblasts reveals the tight temporal coupling of cell shape change and altered YAP1 localization...
June 8, 2018: Cell Systems
Xu Ding, Wei Yang, Xiao-Dan Liu, Xi Yang, Huan-Min Wang, Jun Tai
Neonatal injury-induced exaggeration of pain hypersensitivity after adult trauma is a significant clinical challenge. However, the underlying mechanisms remain poorly understood. Growing evidence shows that spinal Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) contributes to chronic pain in adult rodents. Here we demonstrated that the phosphorylation and expression of SHP2 in synaptosomal fraction of the spinal dorsal horn are elevated in adult rats subjected to neonatal and adult incisions (nIN-IN), and the upregulation of SHP2 is highly correlated with pain hypersensitivity...
June 14, 2018: Neuroscience
Mahmoud El-Daly, Vivek Krishna Pulakazhi Venu, Mahmoud Saifeddine, Koichiro Mihara, Sean Kang, Paul W M Fedak, Laurie A Alston, Simon A Hirota, Hong Ding, Chris R Triggle, Morley D Hollenberg
Hyperglycaemia is a major contributor to diabetic cardiovascular disease with hyperglycaemia-induced endothelial dysfunction recognized as the initiating cause. Coagulation pathway-regulated proteinase-activated receptors (PARs) that can regulate vascular tone in vivo cause eNOS-mediated endothelium-dependent vasodilation; but, the impact of hyperglycaemia on this vasodilatory action of PAR stimulation and the signalling pathways involved are unknown. We hypothesized that vascular sodium-glucose co-transporter 2 activity and hyperglycaemia-induced oxidative stress involving Src-kinase, EGF receptor-kinase, Rho-kinase and protein-kinase-C biochemical signalling pathways would compromise PAR2-mediated endothelium-dependent vasodilation...
June 13, 2018: Vascular Pharmacology
D Prieto, I Urrutxurtu, E Navarro, M B Urrutia, I Ibarrola
The present study aims to test if the environmental conditions prevailing during the growing period can determine the physiological profiles of specimens differentiated as fast (F) or slow (S) growers in the mussel Mytilus galloprovincialis. We reared mussel spats in the laboratory under two different conditions. In Treatment I (continuous feeding during discontinuous immersion), two mussel groups were submitted to a daily air exposure of 8 h and fed continuously during immersion-time, with either high-quality food dosed below the pseudofaeces threshold (BP group) or low organic content food dosed above the pseudofaeces threshold (AP group)...
May 9, 2018: Marine Environmental Research
Laura Hüser, Sachindra, Karol Granados, Aniello Federico, Lionel Larribère, Daniel Novak, Viktor Umansky, Peter Altevogt, Jochen Utikal
Melanoma is often characterized by a constitutively active RAS-RAF-MEK-ERK pathway. For targeted therapy, BRAF inhibitors are available that are powerful in the beginning but resistance occurs rather fast. A better understanding of the mechanisms of resistance is urgently needed to increase the success of the treatment. Here, we observed that SOX2 and CD24 are upregulated upon BRAF inhibitor treatment. A similar upregulation was seen in targeted therapy-resistant, melanoma-derived induced pluripotent cancer cells (iPCCs)...
June 15, 2018: International Journal of Cancer. Journal International du Cancer
Tony Ly, Aki Endo, Alejandro Brenes, Marek Gierlinski, Vackar Afzal, Andrea Pawellek, Angus I Lamond
Background : Viral oncogenes and mutated proto-oncogenes are potent drivers of cancer malignancy. Downstream of the oncogenic trigger are alterations in protein properties that give rise to cellular transformation and the acquisition of malignant cellular phenotypes. Developments in mass spectrometry enable large-scale, multidimensional characterisation of proteomes. Such techniques could provide an unprecedented, unbiased view of how oncogene activation remodels a human cell proteome. Methods : Using quantitative MS-based proteomics and cellular assays, we analysed how transformation induced by activating v-Src kinase remodels the proteome and cellular phenotypes of breast epithelial (MCF10A) cells...
2018: Wellcome Open Research
Weibiao Li, Bo Liao, Wen Zhu, Min Chen, Zejun Li, Xiaohui Wei, Lihong Peng, Guohua Huang, Lijun Cai, HaoWen Chen
Tumor classification is crucial to the clinical diagnosis and proper treatment of cancers. In recent years, sparse representation-based classifier (SRC) has been proposed for tumor classification. The employed dictionary plays an important role in sparse representation-based or sparse coding-based classification. However, sparse representation-based tumor classification models have not used the employed dictionary, thereby limiting their performance. Furthermore, this sparse representation model assumes that the coding residual follows a Gaussian or Laplacian distribution, which may not effectively describe the coding residual in practical tumor classification...
June 14, 2018: Scientific Reports
Takaaki Sugihara, Nathan W Werneburg, Matthew C Hernandez, Lin Yang, Ayano Kabashima, Petra Hirsova, Lavanya Yohanathan, Carlos Sosa, Mark Joseph Truty, George Vasmatzis, Gregory J Gores, Rory L Smoot
The hippo pathway effector, Yes-associated protein (YAP) is a transcriptional co-activator implicated in cholangiocarcinoma (CCA) pathogenesis. YAP is known to be regulated by a serine/threonine kinase relay module (MST1/2 - LATS1/2) culminating in phosphorylation of YAP at Serine 127 (S127) and cytoplasmic sequestration. However, YAP also undergoes tyrosine phosphorylation, and the role of tyrosine phosphorylation in YAP regulation remains unclear. Herein, YAP regulation by tyrosine phosphorylation was examined in human and mouse CCA cells, as well as patient-derived xenograft (PDX) models...
June 14, 2018: Molecular Cancer Research: MCR
Guanhua Rao, In-Kyu Kim, Fabio Conforti, Jing Liu, Yu-Wen Zhang, Giuseppe Giaccone
PURPOSE: Oncogenic KRAS mutations occur frequently in solid tumours, but no clinically applicable targeted strategy is yet available for treating human cancers with mutant KRAS. Here we aimed to identify a strategy for the treatment of KRAS-driven cancers. EXPERIMENTAL DESIGN: Cell viability and colony forming assays were used to assess the in vitro effect of dasatinib and trametinib as single agents or in combination. Western blot was used to analyse the phosphorylated protein and total protein levels...
June 11, 2018: European Journal of Cancer
Roelien A M Meijering, Marit Wiersma, Deli Zhang, Eva A H Lanters, Femke Hoogstra-Berends, Jetse Scholma, Sander Diks, XiaoYan Qi, Natasja M S de Groot, Stanley Nattel, Robert H Henning, Bianca J J M Brundel
BACKGROUND: Dysregulation of protein kinase-mediated signaling is an early event in many diseases, including the most common clinical cardiac arrhythmia, atrial fibrillation (AF). Kinomic profiling represents a promising technique to identify candidate kinases. OBJECTIVE: Here we employ kinomic profiling to identify kinases altered in AF remodeling using atrial tissue from a canine AF-model (atrial tachypacing). METHODS: Left atrial tissue obtained in a previous canine study was used for kinome array (containing 1024 kinase pseudo-substrates) analysis...
June 11, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Ying Xiong, Kai-Xue Li, Hong Wei, Lu Jiao, Shao-Yong Yu, Li Zeng
A growing body of evidence has demonstrated that Eph/ephrin signalling may serve a central role in intestinal diseases. However, whether erythropoietin‑producing hepatocellular (Eph)/ephrin signalling is associated with the development of post‑infectious irritable bowel syndrome (PI‑IBS) is still unknown. In the present study, the role of Eph/Ephrin signalling in lipopolysaccharide (LPS)‑induced intestinal injury was evaluated in vivo and in vitro. LPS treatment significantly increased the levels of proinflammatory mediators [monocyte chemoattractant protein‑1, tumour necrosis factor α, interleukin (IL)‑1β, IL‑6, intercellular adhesion molecule 1 and vascular cell adhesion molecule‑1], activated the EphA2‑Ephrin A1, protein kinase B (Akt)‑nuclear factor (NF)‑κB, Src‑NF‑κB and Wnt/β‑catenin signalling pathways, and inhibited EphB1‑Ephrin B3 signalling in colon tissues, and primary cultured enteric neuronal and glial cells...
June 14, 2018: Molecular Medicine Reports
Nan Guo, Nan Zhang, Liqiu Yan, Zheng Lian, Jiawang Wang, Fengfeng Lv, Yunfei Wang, Xufen Cao
Acute myocardial infarction induces ventricular remodeling, which is implicated in dilated heart and heart failure. The pathogenical mechanism of myocardium remodeling remains to be elucidated. The aim of the present study was to identify key genes and networks for myocardium remodeling following ischemia‑reperfusion (IR). First, the mRNA expression data from the National Center for Biotechnology Information database were downloaded to identify differences in mRNA expression of the IR heart at days 2 and 7...
June 14, 2018: Molecular Medicine Reports
Young Yun Jung, Jong Hyun Lee, Dongwoo Nam, Acharan S Narula, Ojas A Namjoshi, Bruce E Blough, Jae-Young Um, Gautam Sethi, Kwang Seok Ahn
Because of the essential role of signal transducer and activator of transcription 3 (STAT3) in proliferation, anti-apoptosis, and chemoresistance of multiple myeloma (MM), we investigated whether icariin, a prenylated flavonol glycoside, inhibits both constitutive and inducible STAT3 activation in human myeloma cell lines. We noted that icariin could block constitutive STAT3 phosphorylation as well as its nuclear translocation and DNA binding ability in U266 cells. Icariin also suppressed IL-6-induced STAT3 activation through the inhibition of upstream kinases (Janus activated kinase-1 and -2, and c-Src)...
2018: Frontiers in Pharmacology
S M Ashiqul Islam, Christopher Michel Kearney, Erich J Baker
Cystine-stabilized peptides have great utility as they naturally block ion channels, inhibit acetylcholine receptors, or inactivate microbes. However, only a tiny fraction of these peptides has been characterized. Exploration for novel peptides most efficiently starts with the identification of candidates from genome sequence data. Unfortunately, though cystine-stabilized peptides have shared structures, they have low DNA sequence similarity, restricting the utility of BLAST and even more powerful sequence alignment-based annotation algorithms, such as PSI-BLAST and HMMER...
June 13, 2018: Scientific Reports
Gun-Woo Lee, Jun Bum Park, Sung Yeon Park, Jieun Seo, Seung-Hyun Shin, Jong-Wan Park, Sang Jung Kim, Masatoshi Watanabe, Yang-Sook Chun
Neddylation is a cellular process that covalently conjugates substrate proteins with the small ubiquitin-like molecule NEDD8. As neddylation is required for fast turnover of proteins in proliferating cancer cells, the neddylation process is currently regarded as a potential target for cancer therapy. However, little is known about the role of neddylation in cancer invasion and metastasis. Unexpectedly, we here found that the neddylation blockade stimulates migration of lung cancer and glioblastoma cells. Mechanistically, C-CBL acts as the E3 ligase for neddylation of the proto-oncogene c-Src...
June 13, 2018: Oncogene
Joshua Baracks, Douglas J Casa, Tracey Covassin, Ryan Sacko, Samantha E Scarneo, David Schnyer, Susan W Yeargin, Christopher Neville
CONTEXT:   Without a true criterion standard assessment, the sport-related concussion (SRC) diagnosis remains subjective. Inertial balance sensors have been proposed to improve acute SRC assessment, but few researchers have studied their clinical utility. OBJECTIVE:   To determine if group differences exist when using objective measures of balance in a sample of collegiate athletes with recent SRCs and participants serving as the control group and to calculate sensitivity and specificity to determine the diagnostic utility of the inertial balance sensor for acute SRC injuries...
June 13, 2018: Journal of Athletic Training
Dan Luo, Shaohua Zhan, Wenchao Xia, Liang Huang, Wei Ge, Tianxiao Wang
Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) is related to increased risk of recurrence and poor prognosis. Tumor exosomes have been shown to be associated with metastasis of cancer cells. Therefore, we aim to identify the characteristics and biological functions of serum exosomes in lymph node metastases of PTC. We compared proteome profiles of serum-purified exosomes (SPEs) from PTC patients with LNM, PTC patients without LNM, and healthy donors, using a combination of liquid chromatography-tandem mass spectroscopy analyses and Tandem Mass Tag label quantitation analysis...
June 12, 2018: Endocrine-related Cancer
Juthika Kundu, Do-Hee Kim, In Gyeong Chae, Jong Kwon Lee, Sooyeun Lee, Chul-Ho Jeong, Kyung-Soo Chun
Silicon dioxide nanoparticles (SiO2 -NPs) are widely used in biomedicines and consumer products, such as sunscreens and cosmetics. However, SiO2 -NPs can cause adverse effects on human health, depending on the size and concentration of nanoparticles. The present study was aimed at investigating the molecular mechanism underlying SiO2 -NPs-induced inflammation in human keratinocyte (HaCaT) cells. Incubation of HaCaT cells with SiO2 -NPs induced the expression of cyclooxygenase-2 (COX-2) mRNA and protein. Treatment of cells with SiO2 -NPs also induced the phosphorylation, DNA binding and the reporter gene activity of signal transducer and activator of transcription-3 (STAT3)...
June 9, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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