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https://www.readbyqxmd.com/read/28446461/developmental-changes-of-contractile-responses-to-cholinergic-stimuli-role-of-calcium-sensitization-and-related-pathways
#1
Young Jae Im, Jung Keun Lee, Sun Hee Lee, Seung-June Oh, Kwanjin Park
This study was carried out to analyze the developmental changes of bladder response to cholinergic stimulation in detail, highlighting calcium sensitization (CS) and its related pathways. Rats were divided into three groups in accordance with reported time of developmental milestones (newborn: day 1-4, youngster: day 5-14 and grown-up: day 15-21). Following cholinergic stimulation (carbachol 5 uM) the contractile response to detrusor were analyzed with respect to three phases (initial phasic, tonic and superimposed phasic contractions)...
April 26, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28445805/fak-phosphorylation-plays-a-central-role-in-thrombin-induced-rpe-cell-migration
#2
E D Aguilar-Solis, A M López-Colomé, I Lee-Rivera, A Alvarez-Arce, E López
The migration of retinal pigment epithelial (RPE) cells is an important step in various pathologic conditions including subretinal neovascularization (SRN), proliferative vitreoretinopathy (PVR) and, importantly, as a consequence of retinal surgery. Therefore, the elucidation of the mechanisms underlying RPE trans-differentiation and migration is essential for devising effective treatments aimed to the prevention of these disorders. A common event in these pathologies is the alteration of the blood-retina barrier (BRB), which allows the interaction of RPE cells with thrombin, a pro-inflammatory protease contained in serum...
April 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28442357/dl-3-n-butylphthalide-promotes-neuroplasticity-and-motor-recovery-in-stroke-rats
#3
Yefei Sun, Xi Cheng, Huibin Wang, Xiaopeng Mu, Yifan Liang, YuJia Luo, Huiling Qu, Chuansheng Zhao
BACKGROUNDS AND AIMS: Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease. In this study, we investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia. METHODS: Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70mg/kg dl-NBP by oral gavage for two weeks...
April 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28438902/crucial-role-of-rock2-mediated-phosphorylation-and-upregulation-of-fhod3-in-the-pathogenesis-of-angiotensin-ii-induced-cardiac-hypertrophy
#4
Qing Zhou, Si-Si Wei, Hong Wang, Qian Wang, Wei Li, Gang Li, Jian-Wen Hou, Xiao-Meng Chen, Jie Chen, Wei-Ping Xu, Yi-Gang Li, Yue-Peng Wang
Cardiac hypertrophy is characterized by increased myofibrillogenesis. Angiotensin II (Ang-II) is an essential mediator of the pressure overload-induced cardiac hypertrophy in part through RhoA/ROCK (small GTPase/Rho-associated coiled-coil containing protein kinase) pathway. FHOD3 (formin homology 2 domain containing 3), a cardiac-restricted member of diaphanous-related formins, is crucial in regulating myofibrillogenesis in cardiomyocytes. FHOD3 maintains inactive through autoinhibition by an intramolecular interaction between its C- and N-terminal domains...
April 24, 2017: Hypertension
https://www.readbyqxmd.com/read/28437280/inhibition-of-rho-kinase-attenuates-left-ventricular-remodeling-caused-by-chronic-intermittent-hypoxia-in-rats-via-suppressing-myocardial-inflammation-and-apoptosis
#5
Zhi-Hua Wang, Die Zhu, Sheng Xie, Yan Deng, Yueying Pan, Jie Ren, Hui-Guo Liu
Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea syndrome (OSAS), has been reported to play a key role in the development of OSAS-associated cardiovascular diseases including cardiac remodeling. RhoA/Rho-kinase (ROCK) pathway has also been implicated in myocardial remodeling, but the exact mechanisms are not fully elucidated. The current study's purpose is to investigate the influence of fasudil, a selective ROCK inhibitor, on CIH-induced left ventricular remodeling in rats and its possible mechanisms...
April 18, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28434818/expression-of-a-kinase-anchor-protein-13-and-rho-associated-coiled-coil-containing-protein-kinase-in-restituted-and-regenerated-mucosal-epithelial-cells-following-mucosal-injury-and-colorectal-cancer-cells-in-mouse-models
#6
Yumi Kangawa, Toshinori Yoshida, Takeshi Tanaka, Akira Kataoka, Naomi Koyama, Tomoka Ohsumi, Shim-Mo Hayashi, Makoto Shibutani
We demonstrate the expression patterns of A-kinase anchor protein 13 (AKAP13), a scaffold protein that acts upstream of Rho signaling, and Rho-associated coiled-coil containing protein kinase (ROCK) 1/2 in mouse colorectal cancer and during the healing stage of mouse colitis. BALB/c mice received an intraperitoneal injection of azoxymethane at 10mg/kg, followed by two 7-day cycles of 3% dextran sulfate sodium (DSS) administered through their drinking water to induce colon cancer, or a 7-day administration of 4% DSS to induce colitis...
April 20, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28431548/water-pipe-smoke-condensate-increases-the-internalization-of-mycobacterium-bovis-of-type-ii-alveolar-epithelial-cells-a549
#7
Esmaeil Mortaz, Shamila D Alipoor, Masoud Movassaghi, Mohammad Varahram, Jahangir Ghorbani, Gert Folkerts, Johan Garssen, Ian M Adcock
BACKGROUND: Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection...
April 21, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28430966/decreased-thromboembolic-stroke-but-not-atherosclerosis-or-vascular-remodeling-in-mice-with-rock2-deficient-platelets
#8
Nikola Sladojevic, Goo Taeg Oh, Hyung-Hwan Kim, Lea M Beaulieu, Hervé Falet, Karol Kaminski, Jane E Freedman, James K Liao
Aims: Rho-associated coiled-coil containing kinase (ROCK)-2 is an important mediator of the actin cytoskeleton. Because changes in the actin cytoskeleton are critical for platelet function, we hypothesized that ROCK2 in platelets will play important role in thrombosis and can be potentially a target for therapeutic intervention in thromboembolic stroke. Methods and Results: We generated platelet-specific ROCK2-deficient mice (ROCK2 Plt-/- ) from conditional ROCK2 fl°x/fl°x and platelet factor (PF)-4-Cre transgenic mice...
April 14, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430879/role-of-phosphatase-and-tensin-homolog-pten-in-hypoxic-pulmonary-vasoconstriction
#9
Adrienn Krauszman, Tak Mak, Katalin Szaszi, Wolfgang M Kuebler
AIMS: Hypoxic pulmonary vasoconstriction (HPV) redistributes blood flow from poorly ventilated to better aerated areas in the lung, thereby optimizing ventilation-perfusion ratio (V/Q). Pulmonary artery smooth muscle cell (PASMC) contraction in response to hypoxia is triggered by Ca2+ influx via transient receptor potential canonical 6 (TRPC6) cation channels that have translocated to caveolae in the plasma membrane. Since phosphatase and tensin homolog (PTEN) was suggested to regulate TRPC6 in endothelial cells, we aimed to define its role in the hypoxic response of PASMCs and as a putative mediator of HPV...
April 18, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28420986/modulation-of-microglial-activity-by-rho-kinase-rock-inhibition-as-therapeutic-strategy-in-parkinson-s-disease-and-amyotrophic-lateral-sclerosis
#10
REVIEW
Anna-Elisa Roser, Lars Tönges, Paul Lingor
Neurodegenerative diseases are characterized by the progressive degeneration of neurons in the central and peripheral nervous system (CNS, PNS), resulting in a reduced innervation of target structures and a loss of function. A shared characteristic of many neurodegenerative diseases is the infiltration of microglial cells into affected brain regions. During early disease stages microglial cells often display a rather neuroprotective phenotype, but switch to a more pro-inflammatory neurotoxic phenotype in later stages of the disease, contributing to the neurodegeneration...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28416371/modulation-by-nadph-oxidase-of-the-chronic-cardiovascular-and-autonomic-interaction-between-cyclosporine-and-nsaids-in-female-rats
#11
Ahmed F El-Yazbi, Karim S Ibrahim, Hanan M El-Gowelli, Nevine M El-Deeb, Mahmoud M El-Mas
Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used together to manage arthritic disorders with an immune component. Previous reports showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations in blood pressure. Both effects were ameliorated or exaggerated after selective cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively. Here we investigated: (i) the interaction of CSA with NSAIDs possessing variable COX1/COX2 selectivities on hemodynamic, left ventricular (LV) and cardiac autonomic and histologic profiles, and (ii) role of NADPH-oxidase (NOX)/Rho-kinase (ROCK) pathway in the interaction...
April 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28415790/hyperglycemia-via-activation-of-thromboxane-a2-receptor-impairs-the-integrity-and-function-of-blood-brain-barrier-in-microvascular-endothelial-cells
#12
Zhihong Zhao, Jue Hu, Xiaoping Gao, Hui Liang, Haiya Yu, Suosi Liu, Zhan Liu
Diabetes is one of high risk factors for cardio- and cerebra-vascular diseases, including stroke, atherosclerosis and hypertension. This study was conducted to elucidate whether and how thromboxane receptor (TPr) activation contributes to blood-brain barrier (BBB) dysfunction in diabetes. Human brain microvascular endothelial cells (HBMECs) were cultured. The levels of phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 (p-eNOS) and Akt at Ser473 (p-Akt) were assayed by western blot. Exposure of HBMECs to either high glucose (HG) or thromboxane A2 (TxA2) mimetic U46619, significantly reduced p-eNOS and p-Akt...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411398/bud-detachment-in-hydra-requires-activation-of-fgfr-and-a-rho-rock-myosin-ii-signaling-pathway-to-ensure-formation-of-a-basal-constriction
#13
Oliver Holz, David Apel, Patrick Steinmetz, Ellen Lange, Simon Hopfenmüller, Kerstin Ohler, Stefanie Sudhop, Monika Hassel
BACKGROUND: Hydra propagates asexually by exporting tissue into a bud, which detaches four days later as a fully differentiated young polyp. Prerequisite for detachment is activation of fibroblast growth factor receptor (FGFR) signaling. The mechanism which enables constriction and tissue separation within the monolayered ecto- and endodermal epithelia is unknown. RESULTS: Histological sections and staining of F-actin by phalloidin revealed conspicuous cell shape changes at the bud detachment site indicating a localized generation of mechanical forces and the potential enhancement of secretory functions in ectodermal cells...
April 15, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28402705/interaction-of-factor-h-binding-protein-of-streptococcus-suis-with-globotriaosylceramide-promotes-the-development-of-meningitis
#14
Decong Kong, Zhe Chen, Junping Wang, Qingyu Lv, Hua Jiang, Yuling Zheng, Maokai Xu, Xuyu Zhou, Huaijie Hao, Yongqiang Jiang
Streptococcus suis is an important emerging zoonotic agent that causes acute bacterial meningitis in humans with high mortality and morbidity. Our previous work showed that factor H-binding protein (Fhb) contributed to virulence of S. suis, but the role of Fhb in the development of S. suis meningitis remained unclear. In this study, we demonstrated for the first time that Fhb contributed to the traversal of S. suis across the human blood-brain barrier by allelic-exchange mutagenesis, complementation and specific antibody blocking studies...
April 12, 2017: Virulence
https://www.readbyqxmd.com/read/28400811/effect-of-electroacupuncture-on-the-mrna-and-protein-expression-of-rho-a-and-rho-associated-kinase-ii-in-spinal-cord-injury-rats
#15
You-Jiang Min, Li-Li-Qiang Ding, Li-Hong Cheng, Wei-Ping Xiao, Xing-Wei He, Hui Zhang, Zhi-Yun Min, Jia Pei
Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase (ROCK) signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury...
February 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28396402/apc-c-cdh1-rock2-pathway-controls-dendritic-integrity-and-memory
#16
Verónica Bobo-Jiménez, María Delgado-Esteban, Julie Angibaud, Irene Sánchez-Morán, Antonio de la Fuente, Javier Yajeya, U Valentin Nägerl, José Castillo, Juan P Bolaños, Angeles Almeida
Disruption of neuronal morphology contributes to the pathology of neurodegenerative disorders such as Alzheimer's disease (AD). However, the underlying molecular mechanisms are unknown. Here, we show that postnatal deletion of Cdh1, a cofactor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase in neurons [Cdh1 conditional knockout (cKO)], disrupts dendrite arborization and causes dendritic spine and synapse loss in the cortex and hippocampus, concomitant with memory impairment and neurodegeneration, in adult mice...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28389592/cutting-edge-selective-oral-rock2-inhibitor-reduces-clinical-scores-in-patients-with-psoriasis-vulgaris-and-normalizes-skin-pathology-via-concurrent-regulation-of-il-17-and-il-10
#17
Alexandra Zanin-Zhorov, Jonathan M Weiss, Alissa Trzeciak, Wei Chen, Jingya Zhang, Melanie S Nyuydzefe, Carmen Arencibia, Seetharam Polimera, Olivier Schueller, Judilyn Fuentes-Duculan, Kathleen M Bonifacio, Norma Kunjravia, Inna Cueto, Jennifer Soung, Roy M Fleischmann, Alan Kivitz, Mark Lebwohl, Margarita Nunez, Johnnie Woodson, Shondra L Smith, Robert F West, Mark Berger, James G Krueger, John L Ryan, Samuel D Waksal
Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin...
April 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28386357/fasudil-inhibits-proliferation-and-collagen-synthesis-and-induces-apoptosis-of-human-fibroblasts-derived-from-urethral-scar-via-the-rho-rock-signaling-pathway
#18
Ning Xu, Shao-Hao Chen, Gen-Yi Qu, Xiao-Dong Li, Wen Lin, Xue-Yi Xue, Yun-Zhi Lin, Qing-Shui Zheng, Yong Wei
Fasudil has shown antifibrotic effects in various fibrotic diseases. However, its effects on human urethral fibroblasts are unknown. This study evaluated the effects of fasudil on cellular proliferation, migration, apoptosis, and collagen synthesis in human fibroblasts derived from urethral scar tissues. Human urethral scar fibroblasts were cultured by explant and incubated for 24 h or 48 h with fasudil (12.5, 25, 50 µmol/L) with or without transforming growth factor β1 (TGF-β1, 10 ng/mL), or left untreated (control)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28384722/production-of-homogeneous-cultured-human-corneal-endothelial-cells-indispensable-for-innovative-cell-therapy
#19
Munetoyo Toda, Morio Ueno, Asako Hiraga, Kazuko Asada, Monty Montoya, Chie Sotozono, Shigeru Kinoshita, Junji Hamuro
Purpose: Cultured human corneal endothelial cells (cHCECs) are anticipated to become an alternative to donor corneas for the treatment of corneal endothelial dysfunction. The aim of this study was to establish proper culture protocols to successfully obtain a reproducibly homogeneous subpopulation (SP) with matured cHCEC functions and devoid of cell-state transition suitable for cell-injection therapy. Methods: The presence of SPs in cHCECs was investigated in terms of surface cluster-of-differentiation (CD) marker expression level by flow cytometry, as combined analysis of CD markers can definitively specify the SP (effector cells) conceivably the most suitable for cell therapy among diverse SPs...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28381539/transient-tissue-priming-via-rock-inhibition-uncouples-pancreatic-cancer-progression-sensitivity-to-chemotherapy-and-metastasis
#20
Claire Vennin, Venessa T Chin, Sean C Warren, Morghan C Lucas, David Herrmann, Astrid Magenau, Pauline Melenec, Stacey N Walters, Gonzalo Del Monte-Nieto, James R W Conway, Max Nobis, Amr H Allam, Rachael A McCloy, Nicola Currey, Mark Pinese, Alice Boulghourjian, Anaiis Zaratzian, Arne A S Adam, Celine Heu, Adnan M Nagrial, Angela Chou, Angela Steinmann, Alison Drury, Danielle Froio, Marc Giry-Laterriere, Nathanial L E Harris, Tri Phan, Rohit Jain, Wolfgang Weninger, Ewan J McGhee, Renee Whan, Amber L Johns, Jaswinder S Samra, Lorraine Chantrill, Anthony J Gill, Maija Kohonen-Corish, Richard P Harvey, Andrew V Biankin, T R Jeffry Evans, Kurt I Anderson, Shane T Grey, Christopher J Ormandy, David Gallego-Ortega, Yingxiao Wang, Michael S Samuel, Owen J Sansom, Andrew Burgess, Thomas R Cox, Jennifer P Morton, Marina Pajic, Paul Timpson
The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy...
April 5, 2017: Science Translational Medicine
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