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https://www.readbyqxmd.com/read/29150975/downregulation-of-dusp4-enhances-cell-proliferation-and-invasiveness-in-colorectal-carcinomas
#1
Michihiro Ichimanda, Naoki Hijiya, Yoshiyuki Tsukamoto, Tomohisa Uchida, Chisato Nakada, Tomonori Akagi, Tsuyoshi Etoh, Hidekatsu Iha, Masafumi Inomata, Mutsuhiro Takekawa, Masatsugu Moriyama
It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas...
November 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/29150960/epithelial-cell-adhesion-molecule-fragments-and-signaling-in-primary-human-liver-cells
#2
Jörg C Gerlach, Hubert G Foka, Robert L Thompson, Bruno Gridelli, Eva Schmelzer
Epithelial Cell Adhesion Molecule (EpCAM), or CD326, is a trans-membrane glycoprotein expressed by multiple normal epithelia as well as carcinoma. Human hepatic stem cells and bile duct epithelium of the liver are EpCAM positive. In tumor cell lines, its intracellular domain can be released after cleavage of the extracellular domain. Within the cell nucleus it induces cell proliferation, but cleavage depends on cell contact. Fragments of various lengths have been described in tumor cells. Despite of its described important role in proliferation in tumor cells, there is not much known about the expression and role of EpCAM fragments in primary human liver cells...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150940/tumor-suppressive-roles-of-%C3%AE-np63%C3%AE-mir-205-axis-in-epithelial-mesenchymal-transition-of-oral-squamous-cell-carcinoma-via-targeting-zeb1-and-zeb2
#3
Yuma Hashiguchi, Shintaro Kawano, Yuichi Goto, Kaori Yasuda, Naoki Kaneko, Taiki Sakamoto, Ryota Matsubara, Teppei Jinno, Yasuyuki Maruse, Hideaki Tanaka, Masahiko Morioka, Taichi Hattori, Shoichi Tanaka, Tamotsu Kiyoshima, Seiji Nakamura
We previously revealed that epithelial-to-mesenchymal transition (EMT) was mediated by ΔNp63β, a splicing variant of ΔNp63, in oral squamous cell carcinoma (OSCC). Recent studies have highlighted the involvement of microRNA (miRNA) in EMT of cancer cells, though the mechanism remains unclear. To identify miRNAs responsible for ΔNp63β-mediated EMT, miRNA microarray analyses were performed by ΔNp63β-overexpression in OSCC cells; SQUU-B, which lacks ΔNp63 expression and displays EMT phenotypes. miRNAs microarray analyses revealed miR-205 was the most up-regulated following ΔNp63β-overexpression...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150939/mir-34b-5p-inhibition-attenuates-lung-inflammation-and-apoptosis-in-an-lps-induced-acute-lung-injury-mouse-model-by-targeting-progranulin
#4
Wang Xie, Qingchun Lu, Kailing Wang, Jingjing Lu, Xia Gu, Dongyi Zhu, Fanglei Liu, Zhongliang Guo
BACKGROUND: Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS-induced ALI. Here, we have investigated the potential roles of PGRN-targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. METHODS: LPS-induced lung injury and the protective roles of PGRN in ALI were first confirmed...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150931/microrna-497-accelerates-apoptosis-while-inhibiting-proliferation-migration-and-invasion-through-negative-regulation-of-the-mapk-erk-signaling-pathway-via-raf-1
#5
Ling Tao, Xia Li, Na-Na Han, Qi Zhou, Zhi-Le Liu
The aim of this study is to explore the various modes of action miR-497 has on human cervical cancer (CC) cell behavior. We also speculate that miR-497 achieves its anti-tumor role by governing RAF-1 via MAPK/ERK signaling pathway. CC tissues with corresponding adjacent normal tissues were collected from 168 CC patients. RAF-1-positive cells were identified by means of immunohistochemistry in tissues. A series of inhibitors, mimics and siRNA against RAF-1 were introduced to validate regulatory mechanisms for miR-497 and RAF-1...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150880/a-slowly-developed-severe-cutaneous-adverse-reaction-to-idelalisib
#6
L Huilaja, O Lindgren, M Soronen, T Siitonen, K Tasanen
Intracellular signal mediator phosphatidylinositol-3-kinase (PIK3K) -δ, an isoform of PIK3K, is expressed in hematopoietic cells especially in lymphoid lineage 1. Idelalisib is a novel PIK3K-δ targeted kinase inhibitor which is approved for relapsed follicular B-cell non-Hodgkin lymphoma as a monotherapy and in combination with rituximab, an anti-CD20 antibody, for relapsed chronic lymphocytic leukemia (CLL) 2. Only one case describing the clinical features of severe cutaneous adverse reaction (SCAR) of idelalisib in detail has been previously published 3...
November 17, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29150850/comparison-of-pharmacodynamic-effects-of-ticagrelor-vs-prasugrel-in-type-2-diabetes-mellitus-patients-with-coronary-heart-disease
#7
L-L Shang, D-D Guo, H-Y Zhao, A-J Quan, P-G Cao
WHAT IS KNOWN AND OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of thrombotic complications. Studies have indicated that patients with T2DM have impaired clopidogrel-induced antiplatelet effect. Ticagrelor and prasugrel are two latest generation P2Y12 inhibitors with advantageous platelet inhibitory profiles. However, the pharmacodynamic differences between the two drugs in patients with T2DM remain poorly explored. METHODS: This study, involving 140 patients with T2DM following percutaneous coronary intervention (PCI), evaluated the efficacy of aspirin upon concomitant use of prasugrel (10 mg/d) or ticagrelor (90 mg/d)...
November 17, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29150838/gi-530159-a-novel-selective-mechano-sensitive-k2p-channel-opener-reduces-rat-dorsal-root-ganglion-drg-neuron-excitability
#8
Alexandre J C Loucif, Pierre-Philippe Saintot, Jia Liu, Brett M Antonio, Shannon G Zellmer, Katrina Yoger, Emma L Veale, Anna Wilbrey, Kiyoyuki Omoto, Lishuang Cao, Alex Gutteridge, Neil A Castle, Edward B Stevens, Alistair Mathie
BACKGROUND AND PURPOSE: TREK two pore domain potassium channels play a critical role in regulating the excitability of somatosensory nociceptive neurons and are important mediators of pain perception. An understanding of the roles of TREK channels in pain perception and, indeed, in other pathophysiological conditions, has been severely hampered by the lack of potent and/or selective activators and inhibitors. In this study we describe a new, selective opener of TREK channels, GI-530159 (4,4'-(Hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline)...
November 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29150830/does-preoperative-use-of-dutasteride-decrease-bleeding-during-open-prostatectomy
#9
Arif Demirbas, Berkan Resorlu, Murat Tolga Gulpinar, Sina Kardas, Omer Gokhan Doluoglu, Abdulkadir Tepeler, Muhammet Fatih Kilinc, Tolga Karakan, Serkan Ozcan
PURPOSE: To investigate whether use of dutasteride, a 5-alpha reductase inhibitor, for at least four weeks preoperatively affected the blood loss during open prostatectomy (OP). MATERIALS AND METHODS: Retrospective analysis was made of the data of 110 patients who had undergone OP. Group I comprised 50 patients that used dutasteride for 4 weeks preoperatively, and Group II comprised 60 patients that did not use the drug. The groups were compared in respect of age, total prostate specific antigen (TPSA) levels, prostate volumes, preoperative hemoglobin (Hgb) and hematocrit (Hct) levels, postoperative reduction of Hgb and Hct, percentage reduction in Hgb and Hct, and the administration of postoperative blood products...
November 15, 2017: Urology Journal
https://www.readbyqxmd.com/read/29150806/ticagrelor-a-review-in-long-term-secondary-prevention-of-cardiovascular-events
#10
Zaina T Al-Salama, Gillian M Keating, Susan J Keam
Ticagrelor (Brilique(®)) is an orally administered P2Y12 inhibitor. A long-term (maintenance) regimen of ticagrelor 60 mg twice daily is indicated in the EU for coadministration with low-dose aspirin 75-150 mg/day for the secondary prevention of atherothrombotic events in high-risk patients with a history of myocardial infarction (MI) of at least 1 year. Approval is based on the results of the PEGASUS-TIMI 54 trial that compared ticagrelor with placebo (in conjunction with low-dose aspirin) in stable patients who had had a spontaneous MI 1-3 years prior to enrolment and were at high risk of atherothrombotic events...
November 18, 2017: Drugs
https://www.readbyqxmd.com/read/29150788/ck4-ck6-cyclin-d1-p16-ink4a-and-egfr-expression-in-glioblastoma-with-a-primitive-neuronal-component
#11
Guiyan Xu, Jian Yi Li
Glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) is a rare variant of glioblastoma, which was renamed as glioblastoma with a primitive neuronal component (GBM-PN) in new WHO classification of tumours of the central nervous system in 2016. There are few publications on the investigation of GBM-PN. In this study, PCR mRNA arrays on 6 cases of conventional GBM and 10 cases of GBM-PN showed high mRNA level of CDK4 in GBM-PN and low mRNA level of EGFR in GBM-PN. Immunohistochemical stains on tissue microarrays with 28 cases of conventional GBM and 13 cases of GBM-PN demonstrated that CDK4 was selectively expressed in the primitive neuronal component of all GBM-PN cases while EGFR was positive in conventional GBM and glial component of GBM-PN, but was negative in the primitive neuronal component of all GBM-PN cases...
November 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29150777/glibenclamide-and-therapeutic-hypothermia-have-comparable-effect-on-attenuating-global-cerebral-edema-following-experimental-cardiac-arrest
#12
Shin Nakayama, Noriko Taguchi, Yumi Isaka, Takako Nakamura, Makoto Tanaka
BACKGROUND: Cerebral edema is one of the major causes of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). A subunit of the sulfonylurea receptor 1-transient receptor potential M4 (Sur1-TRPM4) channel has been implicated in the pathogenesis of ischemia-evoked cerebral edema. In this study, we examined whether glibenclamide (GBC), a Sur1-TRPM4 channel inhibitor, attenuates cerebral edema following CA/CPR and further examined the efficacy of GBC combined with therapeutic hypothermia...
November 17, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/29150737/risk-of-active-tuberculosis-in-patients-with-inflammatory-arthritis-receiving-tnf-inhibitors-a-look-beyond-the-baseline-tuberculosis-screening-protocol
#13
Alina Soare, Ana Maria Gheorghiu, Victoria Aramă, Dragoș Bumbăcea, Rucsandra Dobrotă, Raida Oneaţă, Simona Pintilie, Mihaela Milicescu, Ioan Ancuţa, Andrei Martin, Mariana Sasu, Claudia Ciofu, Liviu Macovei, Victor Stoica, Mihai Bojincă, Carina Mihai
Tuberculosis (TB) is a major concern in patients receiving TNF inhibitors (TNFi). This study aimed to assess the incidence of active TB and the efficacy of TB prevention measures used over the years, and to determine risk factors for developing TB, in a single-centre cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNFi. Data of all patients in whom treatment with TNFi was initiated in our rheumatology clinic until December 1st 2014 have been retrospectively analysed...
November 17, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/29150734/the-sirtuin-1-2-inhibitor-tenovin-1-induces-a-nonlinear-apoptosis-inducing-factor-dependent-cell-death-in-a-p53-null-ewing-s-sarcoma-cell-line
#14
Christian Marx, Lisa Marx-Blümel, Nora Lindig, René Thierbach, Doerte Hoelzer, Sabine Becker, Susan Wittig, Roland Lehmann, Hortense Slevogt, Thorsten Heinzel, Zhao-Qi Wang, James F Beck, Jürgen Sonnemann
The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting...
November 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29150732/dimethylarginine-dimethylaminohydrolase-1-ddah1-is-frequently-upregulated-in-prostate-cancer-and-its-overexpression-conveys-tumor-growth-and-angiogenesis-by-metabolizing-asymmetric-dimethylarginine-adma
#15
Karthik Reddy Kami Reddy, Chandrashekhar Dasari, Divya Duscharla, Bhukya Supriya, N Sai Ram, M V Surekha, Jerald Mahesh Kumar, Ramesh Ummanni
Tissue microarray analysis confirmed higher dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression in prostate cancer (PCa) compared to benign and normal prostate tissues. DDAH1 regulates nitric oxide (NO) production by degrading endogenous nitric oxide synthase (NOS) inhibitor, asymmetric dimethylarginine (ADMA). This study examined whether DDAH1 has any physiological role in PCa progression. Using overexpression of DDAH1 in PCa (PC3 and LNCaP) cell lines, we found that DDAH1 promotes cell proliferation, migration and invasion by lowering ADMA levels, as well as increasing NO production...
November 17, 2017: Angiogenesis
https://www.readbyqxmd.com/read/29150694/inhibition-of-intimal-hyperplasia-in-murine-aortic-allografts-by-administration-of-a-small-molecule-tlr4-inhibitor-tak-242
#16
Chuangyan Wu, Xiangchao Ding, Cheng Zhou, Ping Ye, Yuan Sun, Jie Wu, Anchen Zhang, Xiaofan Huang, Lingyun Ren, Ke Wang, Peng Deng, Zhang Yue, Jiuling Chen, Sihua Wang, Jiahong Xia
Graft arteriosclerosis (GA) is the leading cause of late cardiac allograft dysfunction. The innate immune system plays a major role in GA, paprticularly Toll-like receptor 4 (TLR4) signaling. Here we characterized the role of TLR4 and its antagonist TAK-242 in a mouse model of GA. BALB/c (H-2d) donor aortas were transplanted into C57BL/6 (H-2b) recipients, and the mice received intraperitoneal injection of 3 or 10 mg/kg of TAK-242 or vehicle every other day for 1, 2, 4, 6, 8 and 12 weeks. With TAK-242 administration, intimal hyperplasia initially appeared at 2 weeks after transplantation, and TAK-242 postponed the progression of neointimal formation in allogeneic aortic grafts...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150677/phosphatidylserine-decarboxylase-ct699-lysophospholipid-acyltransferase-ct775-and-acyl-acp-synthase-ct776-provide-membrane-lipid-diversity-to-chlamydia-trachomatis
#17
Eric Soupene, Frans A Kuypers
De novo lipid synthesis and scavenging of fatty acids (FA) are processes essential for the formation of the membrane of the human pathogen Chlamydia trachomatis (C.t.). Host FA are assimilated via esterification by the bacterial acyl-acyl carrier protein (ACP) synthase AasC but inhibitors of the host acyl-CoA synthetase enymes ACSL also impaired growth of C.t. in human cells. In E. coli, activity of AasC was sensitive to triacsin C and rosiglitazone G. The absence of a triacsin C-insensitive pathway and the increased inhibition by rosiglitazone G confirmed the sensitivity of the bacterial acyl-ACP synthase to these drugs in infected human cells...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150659/ectopic-foxp3-expression-preserves-primitive-features-of-human-hematopoietic-stem-cells-while-impairing-functional-t-cell-differentiation
#18
F R Santoni de Sio, L Passerini, M M Valente, F Russo, L Naldini, M G Roncarolo, R Bacchetta
FOXP3 is the transcription factor ruling regulatory T cell function and maintenance of peripheral immune tolerance, and mutations in its coding gene causes IPEX autoimmune syndrome. FOXP3 is also a cell-cycle inhibitor and onco-suppressor in different cell types. In this work, we investigate the effect of ectopic FOXP3 expression on HSC differentiation and we challenged this approach as a possible HSC-based gene therapy for IPEX. FOXP3-expressing HSC showed reduced proliferation ability and increased maintenance of primitive markers in vitro in both liquid and OP9-ΔL1 co-cultures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150643/%C3%AE-eudesmol-an-oxygenized-sesquiterpene-stimulates-appetite-via-trpa1-and-the-autonomic-nervous-system
#19
Kazuaki Ohara, Takafumi Fukuda, Yuko Ishida, Chika Takahashi, Rena Ohya, Mikio Katayama, Kunitoshi Uchida, Makoto Tominaga, Katsuya Nagai
Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature. TRPA1 activators have been generally recognized as noxious, however, foods and beverages containing TRPA1 activators are preferably consumed; the reasons for this discrepancy are not well understood. We demonstrate that TRPA1 is involved in the stimulatory appetite control mechanism. β-Eudesmol is an oxygenated sesquiterpene contained in medicinal or edible plants which activates TRPA1...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150631/effect-of-long-term-incretin-based-therapies-on-ischemic-heart-diseases-in-patients-with-type-2-diabetes-mellitus-a-network-meta-analysis
#20
Che-Yi Chou, Ying-Tzu Chang, Jia-Lian Yang, Jiun-Yi Wang, Tsui-Er Lee, Ruey-Yun Wang, Chin-Chuan Hung
Patients with type 2 diabetes mellitus (T2DM) experience many cardiovascular complications. Several studies have demonstrated the cardioprotective effects of incretin-based therapies; however, there are few studies on the effects of long-term incretin-based therapies on cardiovascular events. Therefore, the present study conducted a systematic review and network meta-analysis to evaluate the effects of long-term incretin-based therapies on ischaemic diseases. We searched PubMed, CENTRAL, and Clinicaltrial.gov to retrieve randomised control trials reported until December 2016 and enrolled only RCTs with more than a 1-year follow-up...
November 17, 2017: Scientific Reports
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