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https://www.readbyqxmd.com/read/28534935/effect-of-fasudil-on-cognitive-function-following-status-convulsion-in-rats
#1
Rong He, Wei Han, Xiaojie Song, Xiaoju Tang, Li Cheng, Li Jiang
Fasudil has been demonstrated to possess a protective effect in neural injury; however, its protective effect on convulsive brain injury remains to be assessed. The aim of the present study was to investigate the latent mechanism and effect of fasudil on cognitive function following status convulsion (SC) in rats. Initially, to determine the effects of SC, the expression levels of Ras homolog gene family, member A (RhoA)/Rho‑associated protein kinase (ROCK) signaling pathway‑associated proteins were measured by western blot analysis in 16 rats...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28531660/carbon-black-aggregates-cause-endothelial-dysfunction-by-activating-rock
#2
Junyan Yan, Chia-Hsiang Lai, Shih-Chun Candice Lung, Wen-Cheng Wang, Chih-Ching Huang, Guan-Wen Chen, Guangli Suo, Cheng-Tai Choug, Chia-Hua Lin
Carbon black nanoparticles (CBNs) have been associated with the progression of atherosclerosis. CBNs normally enter the bloodstream and crosslink together to form agglomerates. However, most studies have used nano-sized CB particles to clarify the involvement of CBN exposure in CBN-induced endothelial dysfunction. Herein, we studied endothelial toxicity of CBN aggregates (CBA) to human EA.hy926 vascular cells. Cell viability, lactate dehydrogenase leakage, and oxidative stress were affected by the highest concentration of CBA...
May 15, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28526517/regulation-of-rhoa-rock-and-sustained-arterial-contraction-by-low-cytosolic-ca-2-levels-during-prolonged-depolarization-of-arterial-smooth-muscle
#3
Cristina Porras-González, Antonio Ordóñez, Antonio Castellano, Juan Ureña
The role of L-type Ca(2+) channels (LTCCs) and RhoA/Rho kinase (ROCK) on depolarization-induced sustained arterial contraction lasting several minutes is already known. However, in vivo, vascular smooth muscle cells can be depolarized for longer periods, inducing substantial inactivation of LTCCs and markedly reducing Ca(2+) influx into the myocytes. We have examined, in femoral arterial rings, the role of LTCCs and RhoA/ROCK during long-lasting depolarization. Our results reveal a new vasoreactive response after 20-30min of depolarization in 2...
May 16, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28515690/brain-renin-angiotensin-system-and-microglial-polarization-implications-for-aging-and-neurodegeneration
#4
REVIEW
Jose L Labandeira-Garcia, Ana I Rodríguez-Perez, Pablo Garrido-Gil, Jannette Rodriguez-Pallares, Jose L Lanciego, Maria J Guerra
Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28513223/activation-of-thromboxane-a2-receptors-mediates-endothelial-dysfunction-in-diabetic-mice
#5
Xiaona Xie, Wanchun Sun, Jun Wang, Xiaoou Li, Xiaofeng Liu, Ning Liu
BACKGROUND: Diabetes is one of high-risk factors for cardiovascular disease. Improvement of endothelial dysfunction in diabetes reduces vascular complications. However, the underlying mechanism needs to be uncovered. This study was conducted to elucidate whether and how thromboxane A2 receptor (TPr) activation contributes to endothelial dysfunction in diabetes. METHODS AND RESULTS: Exposure of human umbilical vein endothelial cells (HUVECs) to either TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics, significantly reduced phosphorylations of endothelial nitric oxide synthase (eNOS) at Ser(1177) and Akt at Ser(473)...
May 17, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28510599/selective-inhibition-of-brain-endothelial-rho-kinase-2-provides-optimal-protection-of-an-in-vitro-blood-brain-barrier-from-tissue-type-plasminogen-activator-and-plasmin
#6
Be'eri Niego, Natasha Lee, Pia Larsson, T Michael De Silva, Amanda E-Ling Au, Fiona McCutcheon, Robert L Medcalf
Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model...
2017: PloS One
https://www.readbyqxmd.com/read/28509344/cgmp-signalling-inhibits-platelet-shape-change-through-regulation-of-the-rhoa-rho-kinase-mlc-phosphatase-signalling-pathway
#7
Ahmed Aburima, Kochar Walladbegi, Jonathan D Wake, Khalid M Naseem
BACKGROUND: Platelet shape change, spreading and thrombus stability requires activation of the actin cytoskeleton contractile machinery. The mechanisms controlling actin assembly to prevent unwanted platelet activation are unclear. OBJECTIVES: We examined the effects of nitric oxide on the signalling pathways regulating platelet actin-myosin activation. RESULTS: S-nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and myosin phosphorylation of myosin light chain (MLC)...
May 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28493050/fasudil-ameliorates-endothelial-dysfunction-in-streptozotocin-induced-diabetic-rats-a-possible-role-of-rho-kinase
#8
Amal Hofni, Basim A Shehata Messiha, Safwat A Mangoura
Endothelial dysfunction is a major contributor to the pathogenesis of vascular disease in diabetes mellitus and RhoA/Rho-kinase (ROCK) system appears to play a crucial role in this setting. The present study was conducted to investigate the effect of the selective ROCK inhibitor, fasudil, on diabetes-related endothelial dysfunction and elucidated its underlying mechanism(s). Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg), and fasudil (5 mg/kg per day) was orally administered for 8 weeks...
May 11, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28489579/transforming-growth-factor-%C3%AE-a-potential-biomarker-and-therapeutic-target-of-ventricular-remodeling
#9
REVIEW
Yuan Ma, Hai Zou, Xing-Xing Zhu, Jie Pang, Qiang Xu, Qin-Yang Jin, Ya-Hui Ding, Bing Zhou, Dong-Sheng Huang
Transforming growth factor β (TGF-β) is a multifunctional cytokine that is synthesized by many types of cells and regulates the cell cycle. Increasing evidence has led to TGF-β receiving increased and deserved attention in recent years because it may play a potentially novel and critical role in the development and progression of myocardial fibrosis and the subsequent progress of ventricular remodeling (VR). Numerous studies have highlighted a crucial role of TGF-β in VR and suggest potential therapeutic targets of the TGF-β signaling pathways for VR...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488809/optimized-isolation-and-expansion-of-human-airway-epithelial-basal-cells-from-endobronchial-biopsy-samples
#10
Kate H C Gowers, Robert E Hynds, Ricky M Thakrar, Bernadette Carroll, Martin A Birchall, Sam M Janes
Autologous airway epithelial cells have been used in clinical tissue-engineered airway transplantation procedures with a view to assisting mucosal regeneration and restoring mucociliary escalator function. However, limited time is available for epithelial cell expansion due to the urgent nature of these interventions and slow epithelial regeneration has been observed in patients. Human airway epithelial cells can be expanded from small biopsies or brushings taken during bronchoscopy procedures but the optimal mode of tissue acquisition from patients has not been investigated...
May 10, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28488585/eets-reduces-lps-induced-hyperpermeability-by-targeting-grp78-mediated-src-activation-and-subsequent-rho-rock-signaling-pathway
#11
Ruolan Dong, Danli Hu, Yan Yang, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
Integrity of endothelial barrier is a determinant of the prognosis in the acute lung injury caused by sepsis. The epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, exhibit protective effects in various pathogenic states, however, whether EETs play a role in endothelial barrier enhancement and the involved mechanisms remain to be investigated. Here, we show that increased EETs level by endothelial specific cytochrome P450 epoxygenase 2J2 over-expression and soluble epoxide hydrolase (sEH) inhibitor TPPU reduced lipopolysaccharide-induced endothelial hyper-permeability in vivo, accompanied by improved survival of septic mice...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487419/membrane-depolarization-activates-bk-channels-through-rock-mediated-%C3%AE-1-subunit-surface-trafficking-to-limit-vasoconstriction
#12
M Dennis Leo, Xue Zhai, Padmapriya Muralidharan, Korah P Kuruvilla, Simon Bulley, Frederick A Boop, Jonathan H Jaggar
Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca(2+))-activated potassium (BK) channels, which limits Ca(2+) channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels...
May 9, 2017: Science Signaling
https://www.readbyqxmd.com/read/28487281/filamin-a-is-required-for-spindle-migration-and-asymmetric-division-in-mouse-oocytes
#13
HaiYang Wang, Jing Guo, ZiLi Lin, Suk Namgoong, Jeong Su Oh, Nam-Hyung Kim
Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels...
May 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28487031/hmec-1-adopt-the-mixed-amoeboid-mesenchymal-migration-type-during-endmt
#14
Jakub Kryczka, Patrycja Przygodzka, Helena Bogusz, Joanna Boncela
The contribution of endothelial cells to scar and fibrotic tissue formation is undisputedly connected to their ability to undergo the endothelial-to-mesenchymal transition (EndMT) towards fibroblast phenotype-resembling cells. The migration model of fibroblasts and fibroblast-resembling cells is still not fully understood. It may be either a Rho/ROCK-independent, an integrin- and MMP-correlated ECM degradation-dependent, a mesenchymal model or Rho/ROCK-dependent, integrin adhesion- and MMP activity-independent, an amoeboid model...
April 24, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28483592/erectile-dysfunction-in-wistar-audiogenic-rats-war-is-associated-with-increased-cavernosal-contraction-and-decreased-nnos-protein-expression
#15
Fernanda Luciano Rodrigues, Rafael S Fais, Marília G A G Pereira, Norberto Garcia-Cairasco, Rita C Tostes, Fernando S Carneiro
OBJECTIVE: To test the hypothesis that naïve Wistar audiogenic rats (WAR) display ED, which is associated with increased sympathetic-mediated contractile tone and/or decreased NO-mediated relaxation responses of the cavernous tissue. METHODS: Changes in the ratio of the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of the right major pelvic ganglion were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine...
May 5, 2017: Urology
https://www.readbyqxmd.com/read/28477431/ehrho1-regulates-plasma-membrane-blebbing-through-pi3-kinase-in-entamoeba-histolytica
#16
Ravi Bharadwaj, Ranjana Arya, Sudha Bhattacharya, Alok Bhattacharya
The protozoan parasite Entamoeba histolytica causes amoebiasis, a major public health problem in developing countries. Motility of E. histolytica is important for its pathogenesis. Blebbing is an essential process contributing to cellular motility in many systems. In mammalian cells, formation of plasma membrane blebs is regulated by Rho-GTPases through its effectors, such as ROCK, mDia1 and acto-myosin proteins. In the present study, we have illuminated the role of EhRho1 in bleb formation and motility of E...
May 6, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28476048/descemetorhexis-without-grafting-for-fuchs-endothelial-dystrophy-supplementation-with-topical-ripasudil
#17
Gregory Moloney, Constantinos Petsoglou, Matthew Ball, Yves Kerdraon, Roland Höllhumer, Natasha Spiteri, Simone Beheregaray, Judith Hampson, Mario DʼSouza, Raj N Devasahayam
PURPOSE: To report the safety and efficacy of descemetorhexis without grafting as a primary intervention in Fuchs dystrophy, and the use of a ROCK inhibitor, ripasudil as a salvage agent in failing cases. METHODS: Twelve eyes of 11 patients underwent central descemetorhexis not exceeding 4 mm. All had Fuchs dystrophy-producing visual symptoms, requesting intervention. Exclusion criteria were a peripheral endothelial cell count <1000 and central edema. Corneal clearance and visual parameters were recorded monthly until corneal clearance was observed, then at intervals of 6 months...
June 2017: Cornea
https://www.readbyqxmd.com/read/28472098/t1r3-homomeric-sweet-taste-receptor-regulates-adipogenesis-through-g%C3%AE-s-mediated-microtubules-disassembly-and-rho-activation-in-3t3-l1-cells
#18
Yosuke Masubuchi, Yuko Nakagawa, Johan Medina, Masahiro Nagasawa, Itaru Kojima, Mark M Rasenick, Takeshi Inagaki, Hiroshi Shibata
We previously reported that 3T3-L1 cells express a functional sweet taste receptor possibly as a T1R3 homomer that is coupled to Gs and negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. Here, we show that stimulation of this receptor with sucralose or saccharin induced disassembly of the microtubules in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A). In contrast, overexpression of the constitutively active mutant of Gαs (Gαs-Q227L) as well as treatment with cholera toxin or isoproterenol but not with forskolin caused disassembly of the microtubules...
2017: PloS One
https://www.readbyqxmd.com/read/28472054/a-mathematical-model-coupling-polarity-signaling-to-cell-adhesion-explains-diverse-cell-migration-patterns
#19
William R Holmes, JinSeok Park, Andre Levchenko, Leah Edelstein-Keshet
Protrusion and retraction of lamellipodia are common features of eukaryotic cell motility. As a cell migrates through its extracellular matrix (ECM), lamellipod growth increases cell-ECM contact area and enhances engagement of integrin receptors, locally amplifying ECM input to internal signaling cascades. In contrast, contraction of lamellipodia results in reduced integrin engagement that dampens the level of ECM-induced signaling. These changes in cell shape are both influenced by, and feed back onto ECM signaling...
May 4, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28470935/targeting-yap-in-malignant-pleural-mesothelioma
#20
Wen-Qian Zhang, Yu-Yuan Dai, Ping-Chih Hsu, Hui Wang, Li Cheng, Yi-Lin Yang, Yu-Cheng Wang, Zhi-Dong Xu, Shu Liu, Geraldine Chan, Bin Hu, Hui Li, David M Jablons, Liang You
Malignant mesothelioma is an aggressive cancer that is resistant to current therapy. The poor prognosis of mesothelioma has been associated with elevated Yes-associated protein (YAP) activity. In this study, we evaluated the effect of targeting YAP in mesothelioma. First, we comprehensively studied YAP activity in five mesothelioma cell lines (211H, H2052, H290, MS-1 and H2452) and one normal mesothelial cell line (LP9). We found decreased phospho-YAP to YAP protein ratio and consistently increased GTIIC reporter activity in 211H, H2052 and H290 compared to LP9...
May 4, 2017: Journal of Cellular and Molecular Medicine
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