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https://www.readbyqxmd.com/read/28630262/dipeptidyl-peptidase-4-inhibitor-anagliptin-prevents-intracranial-aneurysm-growth-by-suppressing-macrophage-infiltration-and-activation
#1
Taichi Ikedo, Manabu Minami, Hiroharu Kataoka, Kosuke Hayashi, Manabu Nagata, Risako Fujikawa, Sei Higuchi, Mika Yasui, Tomohiro Aoki, Miyuki Fukuda, Masayuki Yokode, Susumu Miyamoto
BACKGROUND: Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. METHODS AND RESULTS: IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin...
June 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28626076/cardiac-fibroblast-transcriptome-analyses-support-a-role-for-interferogenic-profibrotic-and-inflammatory-genes-in-anti-ssa-ro-associated-congenital-heart-block
#2
Robert M Clancy, Androo J Markham, Tanisha Jackson, Sara E Rasmussen, Miroslav Blumenberg, Jill P Buyon
The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated hY3. The top ten upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response (e...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28624320/prognostic-value-of-the-vhl-hif-1%C3%AE-and-vegf-signaling-pathway-and-associated-mapk-erk1-2-and-erk5-pathways-in-clear-cell-renal-cell-carcinoma-a-long-term-study
#3
Antonio S Salinas-Sánchez, Leticia Serrano-Oviedo, Syongh Y Nam-Cha, Olga Roche-Losada, Ricardo Sánchez-Prieto, José M Giménez-Bachs
BACKGROUND: The prognostic value of molecular markers in renal cell carcinoma has been investigated in several studies. Although their value is still not confirmed, various proteins are important. We describe the effect on long-term survival of the status of the von Hippel-Lindau (VHL) hypoxia-inducible factor 1-α (HIF1-α) signaling pathway as well as associated mitogen-activated protein kinase (extracellular signal-regulated kinase [ERK]1/2 and ERK5). PATIENTS AND METHODS: A prospective, longitudinal cohort study was conducted with 50 patients diagnosed with clear-cell renal cell carcinoma to analyze VHL mutations and hypermethylation as well as VHL, HIF1-α, vascular endothelial growth factor (VEGF), ERK1/2, and ERK5 protein expression...
May 25, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28603902/extracellular-signal-regulated-kinase-5-associates-with-casein-kinase-ii-to-regulate-gpib-ix-mediated-platelet-activation-via-the-pten-pi3k-akt-pathway
#4
Z Cheng, W Gao, X Fan, X Chen, H Mei, J Liu, X Luo, Y Hu
BACKGROUND: The platelet glycoprotein (GP) Ib-IX complex plays essential roles in thrombosis and hemostasis. The mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 have been shown to be important in the GPIb-IX-mediated signaling leading to integrin activation. However, the roles of the MAPK extracellular signal-regulated kinase 5 (ERK5) in GPIb-IX-mediated platelet activation are unknown. OBJECTIVE: To reveal the function and mechanisms of ERK5 in GPIb-IX-mediated platelet activation...
June 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28592707/endothelial-nitric-oxide-synthase-independent-pleiotropic-effects-of-pitavastatin-against-atherogenesis-and-limb-ischemia-in-mice
#5
Takeshi Mitsuhashi, Ryoko Uemoto, Kazue Ishikawa, Sumiko Yoshida, Yasumasa Ikeda, Shusuke Yagi, Toshio Matsumoto, Masashi Akaike, Ken-Ichi Aihara
AIM: Statins have a protective impact against cardiovascular diseases through not only lipid-lowering effects but also pleiotropic effects, including activation of the endothelial nitric oxide synthase (eNOS) system. We aimed to clarify the protective effects of a statin against atherogenesis and ischemia in eNOS(-/-) mice. METHODS: Study 1. eNOS(-/-) Apolipoprotein E (ApoE)(-/-) mice were treated with a vehicle or pitavastatin (0.3 mg/kg/day) for 4 weeks...
June 6, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28585748/effects-of-curcumin-on-tobacco-smoke-induced-hepatic-mapk-pathway-activation-and-epithelial-mesenchymal-transition-in-vivo
#6
Zhaofeng Liang, Rui Wu, Wei Xie, Chunfeng Xie, Jieshu Wu, Shanshan Geng, Xiaoting Li, Mingming Zhu, Weiwei Zhu, Jianyun Zhu, Cong Huang, Xiao Ma, Wenrong Xu, Caiyun Zhong, Hongyu Han
Tobacco smoke is a major risk factor for hepatic cancer. Epithelial-mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice...
June 6, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28566937/shear-stress-induces-change-in-extracellular-signal-regulated-kinase-5-levels-with-sustained-activation-under-disturbed-and-continuous-laminar-flow
#7
S Y Shalaby, G Chitragari, B J Sumpio, B E Sumpio
Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial integrity and protect from vascular dysfunction under laminar flow. Previously reported research indicates that under laminar flow ERK5 is activated with production of atheroprotective molecules. However, the characterization of ERK5 activation and levels under different flow patterns has not been investigated. Confluent HUVECs were serum-starved then seeded on glass slides. HUVECs incubated in 1% FBS were exposed to continuous laminar flow (CLF), to-and-fro flow (TFF), or pulsatile forward flow (PFF) in a parallel plate flow chamber...
June 2017: International Journal of Angiology: Official Publication of the International College of Angiology, Inc
https://www.readbyqxmd.com/read/28560410/dclk1-is-correlated-with-met-and-erk5-expression-and-associated-with-prognosis-in-malignant-pleural-mesothelioma
#8
Hui Wang, Yu-Yuan Dai, Wen-Qian Zhang, Ping-Chih Hsu, Yi-Lin Yang, Yu-Cheng Wang, Geraldine Chan, Alfred Au, Zhi-Dong Xu, Shu-Juan Jiang, Wei Wang, David M Jablons, Liang You
Malignant pleural mesothelioma (MPM) is an aggressive cancer for which more effective treatments are needed. In this study, strong to moderate staining of MET and ERK5 was detected in 67.1 and 48% of the analyzed 73 human mesothelioma tumors, and significant correlation of MET and ERK5 expression was identified (P<0.05). We evaluated the doublecortin-like kinase 1 (DCLK1) expression in human mesothelioma tumors. Our results showed that 50.7% of the immunohistochemistry analyzed human mesothelioma tumors have strong to moderate staining of DCLK1, and its expression is significantly correlated with MET or ERK5 expression (P<0...
May 26, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28542559/fluvastatin-inhibits-age-induced-cell-proliferation-and-migration-via-an-erk5-dependent-nrf2-pathway-in-vascular-smooth-muscle-cells
#9
Ae-Rang Hwang, Jung-Hwa Han, Jae Hyang Lim, Young Jin Kang, Chang-Hoon Woo
Advanced glycation endproduct (AGE)-induced vascular smooth muscle cell (VSMC) proliferation and reactive oxygen species (ROS) production are emerging as important mechanisms of diabetic vasculopathy, but little is known about the molecular mechanism responsible for the antioxidative effects of statins on AGEs. It has been reported that statins exert pleiotropic effects on the cardiovascular system due to decreases in AGE-induced cell proliferation, migration, and vascular inflammation. Thus, in the present study, the authors investigated the molecular mechanism by which statins decrease AGE-induced cell proliferation and VSMC migration...
2017: PloS One
https://www.readbyqxmd.com/read/28540300/extracellular-signal-regulated-kinase-5-is-required-for-low-concentration-h2o2-induced-angiogenesis-of-human-umbilical-vein-endothelial-cells
#10
Shan Jiang, Dongxin Zhang, Hong Huang, Yonghong Lei, Yan Han, Weidong Han
Background. The aim of this study was to assess the effects of low concentrations of H2O2 on angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro and explore the underlying mechanisms. Methods. HUVECs were cultured and stimulated with different concentrations of H2O2. Flow cytometric analysis was used to select an optimal concentration of H2O2 for the following experiments. Cell proliferation, migration, and tubule formation were evaluated by Cell Counting Kit-8 (CCK-8) assays, scratch wound assays, and Matrigel tubule formation assays, respectively...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28539967/5-7-dihydroxyflavone-analogues-may-regulate-lipopolysaccharide-induced-inflammatory-responses-by-suppressing-i%C3%AE%C2%BAb%C3%AE-linked-akt-and-erk5-phosphorylation-in-raw-264-7-macrophages
#11
Atsuyoshi Nishina, Kazue Shimizu, Mamoru Koketsu, Masayuki Ninomiya, Daisuke Sato, Takashi Suzuki, Satoshi Hayakawa, Hirokazu Kimura
We studied the anti-inflammatory activity of twelve 5,7-dihydroxyflavone analogues in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. We found that chrysin (1) and 4'-methoxytricetin (9) showed relatively significant anti-inflammatory activity and low cytotoxicity. Moreover, 1 and 9 recovered the expression levels of iNOS and COX2, as well as those of the intracellular inflammatory mediators IL-1β and IL-6, which were upregulated by LPS stimulation. In addition, 1 and 9 actively regulated the phosphorylation of IκBα, leading to the activation of NFκB...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28535565/ephrinb-ephb-signaling-induces-hyperalgesia-through-erk5-creb-pathway-in-rats
#12
Li-Na Yu, Li-Hong Sun, Min Wang, Lie-Ju Wang, Ying Wu, Jing Yu, Wen-Na Wang, Feng-Jiang Zhang, Xue Li, Min Yan
BACKGROUND: There are numerous studies implicating that EphB receptors and ephrinB ligands play important roles in modulating the transduction of spinal nociceptive information. EphrinB-EphB signaling may contribute to hyperalgesia via various kinds of downstream molecules, the mechanisms of which have not been completely understood. OBJECTIVE: The aim of the present study was to identify whether ephrinB-EphB signaling could contribute to hyperalgesia through ERK5/CREB pathway...
May 2017: Pain Physician
https://www.readbyqxmd.com/read/28515147/increased-t-cell-infiltration-elicited-by-erk5-deletion-in-a-pten-deficient-mouse-model-of-prostate-carcinogenesis
#13
Carolyn J Loveridge, Ernest J Mui, Rachana Patel, Ee Hong Tan, Imran Ahmad, Michelle Welsh, Julie Galbraith, Ann Hedley, Colin Nixon, Karen Blyth, Owen Sansom, Hing Y Leung
Prostate cancer does not appear to respond to immune checkpoint therapies where T-cell infiltration may be a key limiting factor. Here, we report evidence that ablating the growth regulatory kinase Erk5 can increase T-cell infiltration in an established Pten-deficient mouse model of human prostate cancer. Mice that were doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared with control Pten-mutant mice, the latter of which exhibited increased Erk5 mRNA expression...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28501623/efficient-direct-conversion-of-human-fibroblasts-into-myogenic-lineage-induced-by-co-transduction-with-mycl-and-myod1
#14
Junko Wakao, Tsunao Kishida, Shigehisa Fumino, Koseki Kimura, Kenta Yamamoto, Shin-Ichiro Kotani, Katsura Mizushima, Yuji Naito, Toshikazu Yoshikawa, Tatsuro Tajiri, Osam Mazda
The skeletal muscle consists of contractile myofibers and plays essential roles for maintenance of body posture, movement, and metabolic regulation. During the development and regeneration of the skeletal muscle tissue, the myoblasts fuse into multinucleated myotubes that subsequently form myofibers. Transplantation of myoblasts may make possible a novel regenerative therapy against defects or dysfunction of the skeletal muscle. It is reported that rodent fibroblasts are converted into myoblast-like cells and fuse to form syncytium after forced expression of exogenous myogenic differentiation 1 (MYOD1) that is a key transcription factor for myoblast differentiation...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28440402/erk5-regulates-tobacco-smoke%C3%A2-induced-urocystic-epithelial%C3%A2-mesenchymal-transition-in-balb-c-mice
#15
Jie Min, Hao Geng, Zhiqi Liu, Zhaofeng Liang, Zhiqiang Zhang, Dongdong Xie, Yi Wang, Tao Zhang, Dexin Yu, Caiyun Zhong
Tobacco smoke (TS) is an important risk factor of bladder cancer. Epithelial‑mesenchymal transition (EMT) is involved in the initiation and development of cancer. The role of extracellular signal‑regulated kinase (ERK) 5 in regulating TS‑induced EMT remains to be elucidated. The aim of the present study was to investigate the regulatory role of ERK5 in TS‑triggered EMT in the bladder of mice. BALB/c mice were used for an in vivo TS exposure model. Mice were treated for 6 h a day for 12 weeks. The results demonstrated that mice exposed to TS had decreased mRNA and protein expression levels of the epithelial markers E‑cadherin and zonula occludens‑1, whereas expression levels of the mesenchymal markers Vimentin and N‑cadherin were increased...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28356344/yap-promotes-myogenic-differentiation-via-the-mek5-erk5-pathway
#16
Ting-Huan Chen, Chen-Yu Chen, Hui-Chin Wen, Chia-Chu Chang, Horng-Dar Wang, Chih-Pin Chuu, Chung-Ho Chang
Yes-associated protein (YAP) is a transcriptional coactivator in the Hippo pathway that regulates cell proliferation, differentiation, and apoptosis. The MEK5/ERK5 MAPK cascade is essential for the early step of myogenesis. In this study, we generated C2C12 stable cell lines that expressed YAP (C2C12-YAP cells) and found that ERK5 and MEK5 were activated in C2C12-YAP cells compared with control C2C12 (C2C12-vector) cells. C2C12-YAP stable cells also differentiated into myotubes better than C2C12-vector cells, and expressed elevated levels of myogenin, a transcription factor that regulates myogenesis, as well as elevated levels of myosin heavy chain, a skeletal muscle marker...
March 29, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28336528/platelet-cd36-promotes-thrombosis-by-activating-redox-sensor-erk5-in-hyperlipidemic-conditions
#17
Moua Yang, Brian C Cooley, Wei Li, Yiliang Chen, Jeannette Vasquez-Vivar, Na'il O Scoggins, Scott J Cameron, Craig N Morrell, Roy L Silverstein
Atherothrombosis is a process mediated by dysregulated platelet activation that can cause life-threatening complications and is the leading cause of death by cardiovascular disease. Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein (oxLDL) particles, a process that induces an overt prothrombotic phenotype. The mechanisms by which CD36 promotes platelet activation and thrombosis remain incompletely defined...
May 25, 2017: Blood
https://www.readbyqxmd.com/read/28322346/resveratrol-mitigates-lipopolysaccharide-mediated-acute-inflammation-in-rats-by-inhibiting-the-tlr4-nf-%C3%AE%C2%BAbp65-mapks-signaling-cascade
#18
Guangxi Wang, Zhiqiang Hu, Qiuting Fu, Xu Song, Qiankun Cui, Renyong Jia, Yuanfeng Zou, Changliang He, Lixia Li, Zhongqiong Yin
Resveratrol (RSV) is a natural compound exhibiting anti-inflammatory effect, but the anti-inflammatory mechanism has not been fully understood. This study is aimed to evaluate the anti-inflammatory activity and mechanism of RSV in lipopolysaccharides-induced rats' model. The visceral wet/dry weight ratios and the changes of hematologic and biochemical indices indicated that LPS- stimulation mainly caused damages to liver and lung, while pretreatment with RSV could alleviate the lesions. The cytokine assays showed that RSV could markedly decrease the production of proinflammatory mediators and cytokines (IL-1, IL-1β, IL-6, NO, iNOS and COX-2), and increase the expression of anti-inflammatory mediator (IL-10)...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317898/microrna-roles-in-signalling-during-lactation-an-insight-from-differential-expression-time-course-and-pathway-analyses-of-deep-sequence-data
#19
Duy N Do, Ran Li, Pier-Luc Dudemaine, Eveline M Ibeagha-Awemu
The study examined microRNA (miRNA) expression and regulatory patterns during an entire bovine lactation cycle. Total RNA from milk fat samples collected at the lactogenesis (LAC, day1 [D1] and D7), galactopoiesis (GAL, D30, D70, D130, D170 and D230) and involution (INV, D290 and when milk production dropped to 5 kg/day) stages from 9 cows was used for miRNA sequencing. A total of 475 known and 238 novel miRNAs were identified. Fifteen abundantly expressed miRNAs across lactation stages play regulatory roles in basic metabolic, cellular and immunological functions...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284212/combination-of-glycopyrronium-and-indacaterol-inhibits-carbachol-induced-erk5-signal-in-fibrotic-processes
#20
Yukiko Namba, Shinsaku Togo, Miniwan Tulafu, Kotaro Kadoya, Kumi Yoneda Nagahama, Hikari Taka, Naoko Kaga, Akira Orimo, Xiangde Liu, Kazuhisa Takahashi
BACKGROUND: Airway fibrosis is one of the pathological features of chronic obstructive pulmonary disease (COPD), and recent studies revealed that acetylcholine plays an important role in the development of airway remodeling by stimulating proliferation and collagen synthesis of lung fibroblasts. This study was designed to examine the effects of a long-acting muscarinic receptor antagonist (LAMA) glycopyrronium and a long-acting β2 adrenergic receptor agonist (LABA) indacaterol on acetylcholine-mediated fibrotic responses in lung fibroblasts...
March 11, 2017: Respiratory Research
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