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https://www.readbyqxmd.com/read/28416371/modulation-by-nadph-oxidase-of-the-chronic-cardiovascular-and-autonomic-interaction-between-cyclosporine-and-nsaids-in-female-rats
#1
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/28396402/apc-c-cdh1-rock2-pathway-controls-dendritic-integrity-and-memory
#2
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/28387604/des-ncrna-a-knowledgebase-for-exploring-information-about-human-micro-and-long-noncoding-rnas-based-on-literature-mining
#3
Adil Salhi, Magbubah Essack, Tanvir Alam, Vladan P Bajic, Lina Ma, Aleksandar Radovanovic, Benoit Marchand, Sebastian Schmeier, Zhang Zhang, Vladimir B Bajic
Noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long ncRNAs (lncRNAs), are important players in diseases and emerge as novel drug targets. Thus, unraveling the relationships between ncRNAs and other biomedical entities in cells are critical for better understanding ncRNA roles that may eventually help develop their use in medicine. To support ncRNA research and facilitate retrieval of relevant information regarding miRNAs and lncRNAs from the plethora of published ncRNA-related research, we developed DES-ncRNA ( www...
April 7, 2017: RNA Biology
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
#4
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/28381539/transient-tissue-priming-via-rock-inhibition-uncouples-pancreatic-cancer-progression-sensitivity-to-chemotherapy-and-metastasis
#5
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
https://www.readbyqxmd.com/read/28363184/treatment-with-platelet-derived-growth-factor-pdgf-and-rock-inhibitors-is-related-to-declined-nerve-growth-factor-ngf-signaling-in-an-experimental-model-of-rat-pulmonary-hypertension
#6
Magdalena Jasińska-Stroschein, Katarzyna Oszajca, Weronika Świtlik, Justyna Ruchwa, Daria Orszulak-Michalak
BACKGROUND: Recent studies reveal that nerve growth factor (NGF) plays a critical role in the pathobiology of pulmonary hypertension (PH). The aim of the present study is to clarify the relationship between NGF signaling and treatment with PDGF or ROCK inhibitors in an animal model of PH. METHODS: Lung tissues were obtained from animals with monocrotaline (MCT)-challenged PH which had been administered long term imatinib, fasudil or statin. Reversal of disease was indicated by decreases in right ventricle pressure (RVP) and hypertrophy...
February 1, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28284330/inhibition-of-ages-rage-rho-rock-pathway-suppresses-non-specific-neuroinflammation-by-regulating-bv2-microglial-m1-m2-polarization-through-the-nf-%C3%AE%C2%BAb-pathway
#7
Jingkao Chen, Zhaowei Sun, Minghua Jin, Yalin Tu, Shengnan Wang, Xiaohong Yang, Qiuhe Chen, Xiao Zhang, Yifan Han, Rongbiao Pi
The microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) or Rho/Rho kinase (ROCK) are both involved in the development of non-specific inflammation. However, there are few reports about their effects on neuroinflammation. Here, we explored the mechanism of AGEs/RAGE/Rho/ROCK pathway underlying the non-specific inflammation and microglial polarization in BV2 cells...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28277985/indoxyl-sulfate-potentiates-endothelial-dysfunction-via-reciprocal-role-for-reactive-oxygen-species-and-rhoa-rock-signaling-in-5-6-nephrectomized-rats
#8
Shuang Chu, Xiaodong Mao, Hengjiang Guo, Li Wang, Zezheng Li, Yang Zhang, Yunman Wang, Hao Wang, Xuemei Zhang, Wen Peng
Accumulative indoxyl sulfate (IS) retained in chronic kidney disease (CKD) can potentiate vascular endothelial dysfunction, and herein, we aim at elucidating the underlying mechanisms from the perspective of possible association between reactive oxygen species (ROS) and RhoA/ROCK pathway. IS-treated nephrectomized rats are administered with antioxidants including NADPH oxidase inhibitor apocynin, SOD analog tempol, and mitochondrion-targeted SOD mimetic mito-TEMPO to scavenge ROS, or ROCK inhibitor fasudil to obstruct RhoA/ROCK pathway...
March 13, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28225457/rhoa-rock-pathway-inhibition-by-fasudil-suppresses-the-vasculogenic-mimicry-of-u2os-osteosarcoma-cells-in-vitro
#9
Yun Xia, Xianyi Cai, Jiquan Fan, Liling Zhang, Zhenyu Li, Jinghua Ren, Gang Wu, Fang Zhu
GTPase RhoA and its downstream Rho-associated coiled-coil-containing protein kinases (ROCKs) are frequently overexpressed in human cancers. Inhibition of the RhoA/ROCK pathway blocks angiogenesis mediated by the vascular endothelial growth factor, which led us to investigate the role of this pathway in vasculogenic mimicry (VM) - a process by which aggressive cancer cells form vessel-like structures that provide adequate blood supply for tumor growth. We showed that the expression of RhoA and its effector kinases ROCK1/2 was much higher in human osteosarcoma (OS) tissues and the human OS cell line U2OS than in nontumorous tissues and cell line hFOB 1...
June 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28223486/serum-borne-bioactivity-caused-by-pulmonary-multiwalled-carbon-nanotubes-induces-neuroinflammation-via-blood-brain-barrier-impairment
#10
Mario J Aragon, Lauren Topper, Christina R Tyler, Bethany Sanchez, Katherine Zychowski, Tamara Young, Guy Herbert, Pamela Hall, Aaron Erdely, Tracy Eye, Lindsey Bishop, Samantha A Saunders, Pretal P Muldoon, Andrew K Ottens, Matthew J Campen
Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28197417/basal-and-activated-calcium-sensitization-mediated-by-rhoa-rho-kinase-pathway-in-rats-with-genetic-and-salt-hypertension
#11
Michal Behuliak, Michal Bencze, Ivana Vaněčková, Jaroslav Kuneš, Josef Zicha
Calcium sensitization mediated by RhoA/Rho kinase pathway can be evaluated either in the absence (basal calcium sensitization) or in the presence of endogenous vasoconstrictor systems (activated calcium sensitization). Our aim was to compare basal and activated calcium sensitization in three forms of experimental hypertension with increased sympathetic tone and enhanced calcium entry-spontaneously hypertensive rats (SHR), heterozygous Ren-2 transgenic rats (TGR), and salt hypertensive Dahl rats. Activated calcium sensitization was determined as blood pressure reduction induced by acute administration of Rho kinase inhibitor fasudil in conscious rats with intact sympathetic nervous system (SNS) and renin-angiotensin system (RAS)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28197100/rho-kinase-inhibition-with-fasudil-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis-symptomatic-treatment-potential-after-disease-onset
#12
René Günther, Alexander Balck, Jan C Koch, Tobias Nientiedt, Michael Sereda, Mathias Bähr, Paul Lingor, Lars Tönges
Despite an improved understanding of the genetic background and the pathomechanisms of amyotrophic lateral sclerosis (ALS) no novel disease-modifying therapies have been successfully implemented in clinical routine. Riluzole still remains the only clinically approved substance in human ALS treatment with limited efficacy. We have previously identified pharmacological rho kinase (ROCK) inhibitors as orally applicable substances in SOD1.G93A transgenic ALS mice (SOD1(G93A)), which are able to extend survival time and improve motor function after presymptomatic treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28178410/strategies-to-extend-thrombolytic-time-window-for-ischemic-stroke-treatment-an-unmet-clinical-need
#13
REVIEW
Ike Dela Peña, Cesar Borlongan, Guofang Shen, Willie Davis
To date, reperfusion with tissue plasminogen activator (tPA) remains the gold standard treatment for ischemic stroke. However, when tPA is given beyond 4.5 hours of stroke onset, deleterious effects of the drug ensue, especially, hemorrhagic transformation (HT), which causes the most significant morbidity and mortality in stroke patients. An important clinical problem at hand is to develop strategies that will enhance the therapeutic time window for tPA therapy and reduce the adverse effects (especially HT) of delayed tPA treatment...
January 2017: Journal of Stroke
https://www.readbyqxmd.com/read/28166443/aldehyde-oxidase-dependent-species-difference-in-hepatic-metabolism-of-fasudil-to-hydroxyfasudil
#14
Zhengsheng Mao, Yali Wu, Qiuying Li, Xin Wang, Youping Liu, Xin Di
1. An investigation on the metabolic mechanism of fasudil to hydroxyfasudil was conducted in vitro using liver subcellular fractions of different species. Hydroxyfasudil was generated in large amounts by male rat liver S9 and to a similar extent by human liver S9 but was not detected in dog liver S9 incubations. 2. Studies with various molybdenum hydroxylase inhibitors demonstrated that aldehyde oxidase (AO), but not xanthine oxidase (XO), selectively catalyzed fasudil to hydroxyfasudil in both rat and human liver cytosol...
February 6, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28165252/cocktail-of-superoxide-dismutase-and-fasudil-encapsulated-in-targeted-liposomes-slows-pah-progression-at-a-reduced-dosing-frequency
#15
Nilesh Gupta, Jahidur Rashid, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan
Currently, two or more pulmonary vasodilators are used to treat pulmonary arterial hypertension (PAH), but conventional vasodilators alone cannot reverse disease progression. In this study, we tested the hypothesis that a combination therapy comprising a vasodilator plus a therapeutic agent that slows pulmonary arterial remodeling and right heart hypertrophy is an efficacious alternative to current vasodilator-based PAH therapy. Thus, we encapsulated a cocktail of superoxide dismutase (SOD), a superoxide scavenger, and fasudil, a specific rho-kinase inhibitor, into a liposomal formulation equipped with a homing peptide, CAR...
March 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28112256/fsd-c10-a-fasudil-derivative-promotes-neuroregeneration-through-indirect-and-direct-mechanisms
#16
Yan-Hua Li, Chong Xie, Yuan Zhang, Xing Li, Hai-Fei Zhang, Qing Wang, Zhi Chai, Bao-Guo Xiao, Rodolfo Thome, Guang-Xian Zhang, Cun-Gen Ma
FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104123/diffusion-tensor-imaging-mri-with-spin-echo-sequence-and-long-duration-measurement-for-evaluation-of-renal-fibrosis-in-a-rat-fibrosis-model
#17
J-Y Kaimori, Y Isaka, M Hatanaka, S Yamamoto, N Ichimaru, A Fujikawa, H Shibata, A Fujimori, S Miyoshi, T Yokawa, K Kuroda, T Moriyama, H Rakugi, S Takahara
BACKGROUND: Renal fibrosis (RF) is a well-known marker for chronic kidney disease (CKD) progression, including chronic renal injury after renal transplantation. However, invasive biopsy is an available examination for evaluation of RF. Diffusion MRI was once recognized as a promising option for RF. However, it is now controversial for RF evaluation in a unilateral ureteral obstruction (UUO) model. METHODS: To seek an optimal imaging method applicable for RF in UUO model kidneys, we attempted a series of MRI methods, including proton density-weighted imaging, T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, diffusion-weighted imaging, and diffusion tensor imaging (DTI)...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28101628/rho-kinase-inhibitor-fasudil-mitigates-high-cholesterol-diet-induced-hypercholesterolemia-and-vascular-damage
#18
Nibrass Taher Abdali, Awny H Yaseen, Eman Said, Tarek M Ibrahim
The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2...
April 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28088401/pharmacological-rescue-of-adult-hippocampal-neurogenesis-in-a-mouse-model-of-x-linked-intellectual-disability
#19
Manuela Allegra, Cristina Spalletti, Beatrice Vignoli, Stefano Azzimondi, Irene Busti, Pierre Billuart, Marco Canossa, Matteo Caleo
Oligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophn1 affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophn1 display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CA3, and showed an altered density of dendritic protrusions...
April 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28054559/the-rhoa-rock-pathway-ameliorates-adhesion-and-inflammatory-infiltration-induced-by-ages-in-glomerular-endothelial-cells
#20
Jialing Rao, Zengchun Ye, Hua Tang, Cheng Wang, Hui Peng, Weiyan Lai, Yin Li, Wanbing Huang, Tanqi Lou
A recent study demonstrated that advanced glycation end products (AGEs) play a role in monocyte infiltration in mesangial areas in diabetic nephropathy. The Ras homolog gene family, member A Rho kinase (RhoA/ROCK) pathway plays a role in regulating cell migration. We hypothesized that the RhoA/ROCK pathway affects adhesion and inflammation in endothelial cells induced by AGEs. Rat glomerular endothelial cells (rGECs) were cultured with AGEs (80 μg/ml) in vitro. The ROCK inhibitor Y27632 (10 nmol/l) and ROCK1-siRNA were used to inhibit ROCK...
January 5, 2017: Scientific Reports
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