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https://www.readbyqxmd.com/read/28922333/rock-inhibitor-ripasudil-as-coadjuvant-after-descemetorhexis-without-an-endothelial-graft
#1
Virgilio Galvis, Alejandro Tello, Johanna P Fuquen, Carlos A Rodríguez-Barrientos, Juan Martín Grice
No abstract text is available yet for this article.
September 14, 2017: Cornea
https://www.readbyqxmd.com/read/28921504/g%C3%AE-12-facilitates-carbachol-induced-shortening-in-human-airway-smooth-muscle-by-modulating-phosphoinositide-3-kinase-mediated-activation-in-a-rhoa-dependent-manner
#2
Edwin J Yoo, Gaoyuan Cao, Cynthia J Koziol-White, Christie A Ojiaku, Krishna Sunder, Joseph A Jude, James V Michael, Hong Lam, Ivan Pushkarsky, Robert Damoiseaux, Dino Di Carlo, Kwangmi Ahn, Steven S An, Raymond B Penn, Reynold A Panettieri
BACKGROUND AND PURPOSE: Phosphoinositide 3-kinase (PI3K)-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The upstream mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given the capacity of G12 family proteins to activate ROCK pathways in other cell types (Riobo and Manning, 2005), the role of G12 proteins in modulating M3 muscarinic acetylcholine receptor (M3R)-stimulated PI3K/ROCK activation and HASMC contraction was examined...
September 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28919351/suspension-state-increases-reattachment-of-breast-cancer-cells-by-up-regulating-lamin-a-c
#3
Xiaomei Zhang, Yonggang Lv
Extravasation is a rate-limiting step of tumor metastasis, for which adhesion to endothelium of circulating tumor cells (CTCs) is the prerequisite. The suspension state of CTCs undergoing detachment from primary tumor is a persistent biomechanical cue, which potentially regulates the biophysical characteristics and cellular behaviors of tumor cells. In this study, breast tumor cells MDA-MB-231 in suspension culture condition were used to investigate the effect of suspension state on reattachment of CTCs. Our study demonstrated that suspension state significantly increased the adhesion ability of breast tumor cells...
September 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28916199/erk-and-rock-functionally-interact-in-a-signaling-network-that-is-compensationally-upregulated-in-spinal-muscular-atrophy
#4
Niko Hensel, Svetlana Baskal, Lisa Marie Walter, Hella Brinkmann, Manuela Gernert, Peter Claus
Spinal Muscular Atrophy (SMA) is a motoneuron disease caused by low levels of functional survival of motoneuron protein (SMN). Molecular disease mechanisms downstream of functional SMN loss are still largely unknown. Previous studies suggested an involvement of Rho kinase (ROCK) as well as the extracellular signal-regulated kinases (ERK) pathways in the pathomechanism. Both pathways are bi-directionally linked and inhibit each other. Thus, we hypothesize that both pathways regulate SMA pathophysiology in vivo in a combined manner rather than acting separately...
September 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28914001/comparative-study-of-the-effects-of-trabecular-meshwork-outflow-drugs-on-the-permeability-and-nitric-oxide-production-in-trabecular-meshwork-cells
#5
Jae Woo Kim
PURPOSE: To compare the effects of the barrier function in human trabecular meshwork (TM) cells monolayer and the production of nitric oxide (NO) between trabecular outflow drugs, Rho-associated kinase (ROCK) inhibitors, adenosine, and statin. METHODS: Primary cultured TM cells were exposed to 10 or 25 μM Y-27632, 0.1 or 1 μM N6-cyclohexyladenosine (CHA), or 15 or 30 μM simvastatin for 24 hours. NO production and expression of endothelial nitric oxide synthase mRNA were measured by Griess assay and reverse transcription polymerase chain reaction, respectively...
July 25, 2017: Korean Journal of Ophthalmology: KJO
https://www.readbyqxmd.com/read/28902377/-implementation-of-the-national-guidelines-for-the-treatment-of-diabetes-mellitus-type-2-in-secondary-diabetes-centers
#6
Lydia Marahrens, Daniel Röck, Tjalf Ziemssen, Raimar Kern, Focke Ziemssen, Andreas Fritsche
Background The German National Disease Management Guideline (NVL) on treatment of Type 2 Diabetes recommends lowering of blood glucose in four therapy steps. There is little evidence, how NVL is implemented for the individual patients. Methods 810 patients in secondary diabetes centers were examined within the DiabCheck(OCTplus) trial. Data about the patient's health status (electronic medical record) were classified according to the NVL treatment steps. The degree of implementation was assessed for every person with diabetes type 2 (NCT02 311 504)...
September 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28893104/ripasudil-hydrochloride-hydrate-targeting-rho-kinase-in-the-treatment-of-glaucoma
#7
Toshihiro Inoue, Hidenobu Tanihara
Among the intraocular pressure (IOP)-lowering drugs used in a clinical setting, Rho kinase (ROCK) inhibitors lower IOP by a unique mechanism, namely the depolymerization of intracellular actin in the conventional outflow tissues: the trabecular meshwork (TM) and Schlemm's canal (SC). Furthermore, ROCK inhibitors suppress the production of extracellular matrix by TM cells, which represents a potential alternative method of lowering IOP. Considering that conventional outflow is a dominant pathway in humans, IOP-lowering ROCK inhibitors, delivered in conjunction with other drugs, may be able to treat the glaucomatous eye...
September 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28882559/enhancement-of-s1p-induced-contractile-response-in-detrusor-smooth-muscle-of-rats-having-cystitis
#8
Irfan Anjum, Merve Denizalti, Hilmi Burak Kandilci, Nezahat Tugba Durlu-Kandilci, Inci Sahin-Erdemli
Interstitial cystitis is a chronic disease characterized by lower abdominal pain and some nonspecific symptoms including an increase in urinary frequency and urgency. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that controls smooth muscle tone via G-protein coupled receptors (S1P1-3 receptors). S1P production is known to take place both in physiological states and some pathological situations, such as in overactive bladder syndrome. The intracellular mechanism of S1P-induced contractile response was investigated in β-escin permeabilized detrusor smooth muscle of rats having cyclophosphamide-induced cystitis...
September 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28881620/eets-reduces-lps-induced-hyperpermeability-by-targeting-grp78-mediated-src-activation-and-subsequent-rho-rock-signaling-pathway
#9
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...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878396/rhoa-rock-inhibition-reverses-synaptic-remodeling-and-motor-and-cognitive-deficits-caused-by-traumatic-brain-injury
#10
Shalaka Mulherkar, Karen Firozi, Wei Huang, Mohammad Danish Uddin, Raymond J Grill, Mauro Costa-Mattioli, Claudia Robertson, Kimberley F Tolias
Traumatic brain injury (TBI) causes extensive neural damage, often resulting in long-term cognitive impairments. Unfortunately, effective treatments for TBI remain elusive. The RhoA-ROCK signaling pathway is a potential therapeutic target since it is activated by TBI and can promote the retraction of dendritic spines/synapses, which are critical for information processing and memory storage. To test this hypothesis, RhoA-ROCK signaling was blocked by RhoA deletion from postnatal neurons or treatment with the ROCK inhibitor fasudil...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28845297/discovery-of-a-rock-inhibitor-fpnd-which-prevents-cerebral-hemorrhage-through-maintaining-vascular-integrity-by-interference-with-ve-cadherin
#11
Shang Li, Nana Ai, Mingyun Shen, Yuanye Dang, Cheong-Meng Chong, Peichen Pan, Yiu Wa Kwan, Shun Wan Chan, George Pak Heng Leung, Maggie Pui Man Hoi, Tingjun Hou, Simon Ming-Yuen Lee
Hemorrhagic stroke occurs when a weakened vessel ruptures and bleeds into the surrounding brain, leading to high rates of death and disability worldwide. A series of complex pathophysiological cascades contribute to the risk of hemorrhagic stroke, and no therapies have proven effective to prevent hemorrhagic stroke. Stabilization of vascular integrity has been considered as a potential therapeutic target for hemorrhagic stroke. ROCKs, which belong to the serine/threonine protein kinase family and participate in the organization of actin cytoskeleton, have become attractive targets for the treatment of strokes...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28841710/inhibition-of-rock1-kinase-modulates-both-tumor-cells-and-stromal-fibroblasts-in-pancreatic-cancer
#12
Clifford J Whatcott, Serina Ng, Michael T Barrett, Galen Hostetter, Daniel D Von Hoff, Haiyong Han
ROCK, or Rho-associated coiled coil-containing protein kinase, is a member of the AGC kinase family and has been shown to play a role in cell migration, ECM synthesis, stress-fiber assembly, and cell contraction. Increased ROCK expression has been reported in multiple pathological conditions, including cancer. Here, we report increased expression of ROCK 1 in pancreatic tumor epithelial cells as well as in cancer associated fibroblasts (CAF). In our analysis, 62% of tumor samples exhibited ≥2+ in staining intensity by IHC analysis, versus 40% of adjacent normal tissue samples (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28826686/cofilin-is-a-camp-effector-in-mediating-actin-cytoskeleton-reorganization-and-steroidogenesis-in-mouse-and-human-adrenocortical-tumor-cells
#13
E Peverelli, R Catalano, E Giardino, D Treppiedi, V Morelli, C L Ronchi, A Vaczlavik, N Fusco, S Ferrero, J Bertherat, F Beuschlein, I Chiodini, M Arosio, A Spada, G Mantovani
cAMP pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). cAMP-induced steroidogenesis is preceded by actin cytoskeleton reorganization, a process regulated by cofilin activity. In this study we investigated cofilin role in mediating cAMP effects on cell morphology and steroidogenesis in adrenocortical tumor cells. We demonstrated that forskolin induced cell rounding and strongly reduced phosphorylated (P)-cofilin/total cofilin ratio in Y1 (-52 ± 16%, p < 0...
August 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28821556/dasatinib-reversibly-disrupts-endothelial-vascular-integrity-by-increasing-non-muscle-myosin-ii-contractility-in-a-rock-dependent-manner
#14
Anna Kreutzman, Beatriz Colom-Fernández, Ana Marcos Jiménez, Mette Ilander, Carlos Cuesta-Mateos, Yaiza Perez-García, Cristina Delgado Arévalo, Oscar Brück, Henna Hakanen, Jani Saarela, Alvaro Ortega-Carrión, Ana de Rosendo, Alba Juanes-García, Juan Luis Steegmann, Satu Mustjoki, Miguel Vicente-Manzanares, Cecilia Muñoz-Calleja
Purpose: Dasatinib is a short-acting dual ABL/SRC family tyrosine kinase inhibitor (TKI), which is frequently used to treat chronic myeloid leukemia. Although very effective, dasatinib often displays severe adverse effects, including pleural effusions and increased risk of bleeding primarily in the gastrointestinal tract. The actual causes of these side effects are currently undetermined. We hypothesize that endothelial cells (ECs) that line the inner walls of blood vessels and control the traffic to the underlying tissues, might be involved...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28820400/alteration-in-expressions-of-rhoa-and-rho-kinases-during-pregnancy-in-rats-their-roles-in-uterine-contractions-and-onset-of-labour
#15
D Domokos, E Ducza, G Falkay, R Gaspar
Activation of RhoA and Rho-associated kinases (ROCKs) is known to play a pivotal role in the regulation of smooth muscle contraction via phosphorylation of myosin-light chain and myosin phosphatase. There are few data on the RhoA and ROCKs expression levels in rat uteri. Therefore, our aim was to investigate the mRNA and protein concentration of RhoA and ROCKs in rat uterus during pregnancy, during parturition and post-partum using real time PCR and Western blot analysis. The other purpose was to evaluate the effects of the ROCK (Y-27632, fasudil and RKI 1441) and RhoA inhibitors (simvastatin) on uterine contractility in isolated organ bath experiments...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819566/development-of-poly-lactic-glycolic-acid-plga-microspheres-for-controlled-release-of-rho-associated-kinase-inhibitor
#16
Sho Koda, Naoki Okumura, Junji Kitano, Noriko Koizumi, Yasuhiko Tabata
PURPOSE: The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA) as a drug delivery carrier of Rho kinase (ROCK) inhibitor for the treatment of corneal endothelial disease. METHOD: ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1), and a double emulsion [(W1/O)/W2] was formed with dichloromethane (O) and polyvinyl alcohol (W2). Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/28815725/p2y6-regulates-cytoskeleton-reorganization-and-cell-migration-of-c2c12-myoblasts-via-rock-pathway
#17
Wei Wang, Mengjie Chen, Yingna Gao, Xianmin Song, Hongliang Zheng, Kaiyong Zhang, Bimeng Zhang, Donghui Chen
Migration of skeletal muscle precursor cells is required for limb muscle development and skeletal muscle repair. This study aimed to examine the role of P2Y6 receptor in C2C12 myoblasts migration. C2C12 myoblasts were treated with P2Y6 agonist UDP, P2Y6 antagonist MRS2578, Ca(2+) channel blocker BTP2, or ROCK inhibitor GSK269962 or Y27632, and the migration ability of C2C12 cells was assessed by wound healing assay. The cellular Ca(2+) content was analyzed with fluo-4 probe and the activation of ROCK (phosphorlyation of LIMK and cofilin) was assayed by western blot...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28805944/suppression-of-acute-and-anticipatory-nausea-by-peripherally-restricted-faah-inhibitor-in-animal-models-role-of-ppar%C3%AE-and-cb1-receptors
#18
Erin M Rock, Guillermo Moreno-Sanz, Cheryl L Limebeer, Gavin N Petrie, Roberto Angelini, Daniele Piomelli, Linda A Parker
To evaluate the ability of the peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor, URB937 (cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) to suppress acute and anticipatory nausea in rats, and to examine the pharmacological mechanism of such an effect. EXPERIMENTAL APPROACH: We investigated the potential of URB937 to reduce the establishment of lithium chloride (LiCl)-induced conditioned gaping (a model of acute nausea) and to reduce the expression of contextually elicited conditioned gaping (a model of anticipatory nausea) in rats...
August 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28804108/effects-of-vitrification-and-a-rho-associated-coiled-coil-containing-protein-kinase-1-inhibitor-on-the-meiotic-and-developmental-competence-of-feline-oocytes
#19
Saengtawan Arayatham, Narong Tiptanavattana, Theerawat Tharasanit
Oocyte cryopreservation is the technique of choice for the long-term storage of female gametes. However, it induces an irreversible loss of oocyte viability and function. We examined the effects of vitrification and a Rho-associated coiled-coil containing protein kinase 1 (ROCK1) inhibitor (ROCKi) on the meiotic and developmental competence of feline oocytes. We examined the expression of LIM kinase (LIMK) 1 and 2, with and without ROCKi treatment. Cumulus oocyte complexes (COCs) were matured in vitro with 0, 10, 20, and 40 µM ROCKi...
August 11, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28803065/flow-induced-adherens-junction-remodeling-driven-by-cytoskeletal-forces
#20
Deepika Verma, Vivek K Bajpai, Nannan Ye, Mohammad M Maneshi, Deekshitha Jetta, Stelios T Andreadis, Frederick Sachs, Susan Z Hua
Adherens junctions (AJs) are a key structural component for tissue organization and function. Under fluid shear stress, AJs exhibit dynamic assembly/disassembly, but how shear stress couples to AJs is unclear. In MDCK cells we measured simultaneously the forces in cytoskeletal α-actinin and the density and length of AJs using a genetically coded optical force sensor, actinin-sstFRET, and fluorescently labeled E-cadherin (E-cad). We found that shear stress of 0.74dyn/cm(2) for 3h significantly enhanced E-cad expression at cell-cell contacts and this phenomenon has two phases...
August 10, 2017: Experimental Cell Research
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