keyword
MENU ▼
Read by QxMD icon Read
search

Rock inhibitor

keyword
https://www.readbyqxmd.com/read/28317242/chemical-screening-identifies-rock-as-a-target-for-recovering-mitochondrial-function-in-hutchinson-gilford-progeria-syndrome
#1
Hyun Tae Kang, Joon Tae Park, Kobong Choi, Hyo Jei Claudia Choi, Chul Won Jung, Gyu Ree Kim, Young-Sam Lee, Sang Chul Park
Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. In this study, we performed high-throughput screening to find compounds that could reduce ROS levels in HGPS fibroblasts and identified rho-associated protein kinase (ROCK) inhibitor (Y-27632) as an effective agent...
March 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28316141/dasatinib-inhibits-actin-fiber-reorganization-and-promotes-endothelial-cell-permeability-through-rhoa-rock-pathway
#2
Swapan K Dasgupta, Anhquyen Le, K Vinod Vijayan, Perumal Thiagarajan
Treatment with dasatinib, a tyrosine kinase inhibitor, is associated with edema, pleural effusion, and pulmonary edema. We investigated the effect of dasatinib on the barrier function of human microvascular endothelial cells-1 (HMEC-1) in vitro and in vivo. The permeability of HMEC-1 to fluorescein isothiocyante (FITC)-dextran increased in Transwell chambers within 5 min following the addition of therapeutic concentrations of dasatinib. The change in permeability was associated with increased activation of RhoA GTPase and its effector Rho-associated coiled-coil kinase 1(ROCK1)...
March 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28297567/developing-a-novel-two-dimensional-culture-system-to-enrich-human-prostate-luminal-progenitors-that-can-function-as-a-cell-of-origin-for-prostate-cancer
#3
Dingxiao Zhang, Kevin Lin, Yue Lu, Kiera Rycaj, Yi Zhong, Hsueh-Ping Chao, Tammy Calhoun-Davis, Jianjun Shen, Dean G Tang
Elucidating the cell of origin of cancer has great significance in stratifying patients into appropriate treatment groups and for developing novel targeted therapies. Early studies demonstrate that only stem-like basal cells in the normal human prostate (NHP) can function as the cell of origin for prostate cancer (PCa). Here, we show that the organoids derived from bulk NHP luminal cells can also be tumorigenically transformed. We further show that the WIT medium, which is used to culture human mammary epithelial progenitor cells, when combined with the ROCK inhibitor, can readily propagate a population of progenitor-like cells from the primary NHP luminal cell isolates...
March 2017: Stem Cells Translational Medicine
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
#4
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/28283529/targeting-the-rhoa-rock-pathway-to-reverse-t-cell-dysfunction-in-sle
#5
Cristina Rozo, Yurii Chinenov, Reena Khianey Maharaj, Sanjay Gupta, Laura Leuenberger, Kyriakos A Kirou, Vivian P Bykerk, Susan M Goodman, Jane E Salmon, Alessandra B Pernis
OBJECTIVES: Deregulated production of interleukin (IL)-17 and IL-21 contributes to the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Production of IL-17 and IL-21 can be regulated by ROCK2, one of the two Rho kinases. Increased ROCK activation was previously observed in an SLE cohort. Here, we evaluated ROCK activity in a new SLE cohort, and an RA cohort, and assessed the ability of distinct inhibitors of the ROCK pathway to suppress production of IL-17 and IL-21 by SLE T cells or human Th17 cells...
April 2016: Annals of the Rheumatic Diseases
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
#6
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/28273942/human-corneal-endothelial-cell-cultivation-from-old-donor-corneas-with-forced-attachment
#7
Mohit Parekh, Sajjad Ahmad, Alessandro Ruzza, Stefano Ferrari
Human corneal endothelial cells (HCEnCs) are responsible for maintaining the transparency of the cornea. Damaged or diseased HCEnCs may cause blindness. Replacement of the diseased cells with a healthy donor endothelium is the only currently available treatment. Tissue-engineering can serve as an alternative to conventional donor corneal transplantation. Due to the global shortage of donor corneas, a wide interest in the development of cultured graft substitutes and artificial corneas has increased. Availability of the old donor corneas is higher especially for research...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28266583/zyz-168-alleviates-cardiac-fibrosis-after-myocardial-infarction-through-inhibition-of-erk1-2-dependent-rock1-activation
#8
Shanshan Luo, Tran Ba Hieu, Fenfen Ma, Ying Yu, Zhonglian Cao, Minjun Wang, Weijun Wu, Yicheng Mao, Peter Rose, Betty Yuen-Kwan Law, Yi Zhun Zhu
Selective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α-smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9)...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265821/suppression-of-rho-kinase-1-is-responsible-for-insulin-regulation-of-the-ampk-srebp-1c-pathway-in-skeletal-muscle-cells-exposed-to-palmitate
#9
Sunyinyan Tang, Wenjun Wu, Wenjuan Tang, Zhijuan Ge, Hongdong Wang, Ting Hong, Dalong Zhu, Yan Bi
AIMS: Clinical and experimental data suggest that early insulin therapy could reduce lipotoxicity in subjects and animal models with type 2 diabetes mellitus. However, the underlying mechanisms need to be clarified. Sterol regulatory element-binding protein 1c (SREBP-1c), which is negatively regulated by AMP-activated protein kinase (AMPK), plays a critical role in lipotoxicity and insulin resistance in skeletal muscle cells. Here, we investigated the effect and molecular mechanism of insulin intervention on the AMPK/SREBP-1c pathway in skeletal muscle cells with chronic exposure to palmitic acid (PA)...
March 7, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28260321/-hydroxyfasudi-attenuates-lipopolysaccharide-induced-endothelial-dysfunction-via-suppressing-the-expression-of-rho-associated-coiled-coil-protein-kinase-1-connexin-43-and-caveolin-1
#10
P F Zheng, X H Wu, W Huang, G T Ma, Q Bi
Objective: To investigate the effect and mechanism of hydroxyfasudi (HF), a specific Rho kinase inhibitor, on lipopolysaccharide(LPS)induced endothelial dysfunction. Methods: A total of 24 male Sprague Dawley rats were randomly divided into control group(n=6), HF group(n=6), LPS group(n=6) and LPS + HF group(n=6) with random number table method. There was no special treatment in control group. HF (30 mg/kg) was injected intraperitoneally in HF group. LPS (1 mg/kg) were injected intravenously in LPS group. In LPS+ HF group, HF (30 mg/kg) was injected intraperitoneally, followed by intravenous LPS injection (1 mg/kg) 30 minutes later...
February 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28259960/rock-actin-mrtf-signaling-promotes-the-fibrogenic-phenotype-of-fibroblast-like-synoviocytes-derived-from-the-temporomandibular-joint
#11
Seiji Yokota, Naoyuki Chosa, Seiko Kyakumoto, Hitomichi Kimura, Miho Ibi, Masaharu Kamo, Kazuro Satoh, Akira Ishisaki
Malocclusion caused by abnormal jaw development or muscle overuse during mastication results in abnormal mechanical stress to the tissues surrounding the temporomandibular joint (TMJ). Excessive mechanical stress against soft and hard tissues around the TMJ is involved in the pathogenesis of inflammatory diseases, including osteoarthritis (OA). OA-related fibrosis is a possible cause of joint stiffness in OA. However, cellular and molecular mechanisms underlying fibrosis around the TMJ remain to be clarified...
February 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28241317/tgf%C3%AE-2-induces-the-formation-of-cross-linked-actin-networks-clans-in-human-trabecular-meshwork-cells-through-the-smad-and-non-smad-dependent-pathways
#12
Michela Montecchi-Palmer, Jaclyn Y Bermudez, Hannah C Webber, Gaurang C Patel, Abbot F Clark, Weiming Mao
Purpose: Increased intraocular pressure results from increased aqueous humor (AH) outflow resistance at the trabecular meshwork (TM) due to pathologic changes including the formation of cross-linked actin networks (CLANs). Transforming growth factor β2 (TGFβ2) is elevated in the AH and TM of primary open angle glaucoma (POAG) patients and induces POAG-associated TM changes, including CLANs. We determined the role of individual TGFβ2 signaling pathways in CLAN formation. Methods: Cultured nonglaucomatous human TM (NTM) cells were treated with control or TGFβ2, with or without the inhibitors of TGFβ receptor, Smad3, c-Jun N-terminal kinases (JNK), extracellular signal regulated kinase (ERK), P38, or Rho-associated protein kinase (ROCK)...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28225457/rhoa-rock-pathway-inhibition-by-fasudil-suppresses-the-vasculogenic-mimicry-of-u2os-osteosarcoma-cells-in-vitro
#13
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...
February 20, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28225294/role-of-rock-isoforms-in-regulation-of-stiffness-induced-myofibroblast-differentiation-in-lung-fibrosis
#14
Su S Htwe, Byung H Cha, Kan Yue, Ali Khademhosseini, Alan J Knox, Amir M Ghaemmaghami
Fibrosis is a major cause of progressive organ dysfunction in several chronic pulmonary diseases. Rho associated coiled-coil forming kinase (ROCK) has shown to be involved in myofibroblast differentiation driven by altered matrix stiffness in fibrotic state. There are two known ROCK isoforms in human, ROCK1 (ROKβ) and ROCK2 (ROKα), but specific role of each isoform in myofibroblast differentiation in lung fibrosis remains unknown. To study this, we developed a Gelatin methacryloyl (GelMA) hydrogel based culture system with different stiffness levels relevant to healthy and fibrotic lungs...
February 22, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28220212/rho-kinase-inhibition-ameliorates-cyclophosphamide-induced-cystitis-in-rats
#15
Andrzej Wróbel, Urszula Doboszewska, Ewa Rechberger, Karol Rojek, Anna Serefko, Ewa Poleszak, Krystyna Skalicka-Woźniak, Jarosław Dudka, Piotr Wlaź
Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CYP). Studies have indicated that Rho kinase (ROCK) inhibitors may suppress detrusor overactivity symptoms and possess anti-inflammatory properties. The aim of the present study was to investigate whether inhibition of ROCK reduces cystometric and histopathological changes associated with CYP-induced cystitis. The rats received GSK 269962, a ROCK inhibitor, at a dose of 30 mg/kg daily, or vehicle for 7 days. Then, acute chemical cystitis leading to bladder overactivity was induced by CYP injection (200 mg/kg i...
February 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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
#16
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/28165055/human-embryonic-and-induced-pluripotent-stem-cells-maintain-phenotype-but-alter-their-metabolism-after-exposure-to-rock-inhibitor
#17
Spyros I Vernardis, Konstantinos Terzoudis, Nicki Panoskaltsis, Athanasios Mantalaris
Human pluripotent stem cells (hPSCs) are adhesion-dependent cells that require cultivation in colonies to maintain growth and pluripotency. Robust differentiation protocols necessitate single cell cultures that are achieved by use of ROCK (Rho kinase) inhibitors. ROCK inhibition enables maintenance of stem cell phenotype; its effects on metabolism are unknown. hPSCs were exposed to 10 μM ROCK inhibitor for varying exposure times. Pluripotency (TRA-1-81, SSEA3, OCT4, NANOG, SOX2) remained unaffected, until after prolonged exposure (96 hrs)...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28157424/a-rho-associated-kinase-inhibitor-protects-permeability-in-a-cell-culture-model-of-ocular-disease-and-reduces-aqueous-flare-in-anterior-uveitis
#18
Hiroshi Yamada, Masahiko Yoneda, Shingo Inaguma, Masahiko Gosho, Yusuke Murasawa, Zenzo Isogai, Masahiro Zako
PURPOSE: Recent clinical and experimental studies have reported favorable results when using Rho-associated kinase (ROCK) inhibitors for ocular disease, and in cell culture. Disruption of the human, nonpigmented ciliary epithelial cells (HNPCECs) that comprise the blood-aqueous barrier (BAB) induces anterior uveitis; these cells therefore provide a useful cell model of ocular disease. In this study, we examined the effects of ROCK inhibitors in anterior uveitis and in HNPCECs. METHODS: Aqueous flare values and intraocular pressures (IOPs) were determined in patients with anterior uveitis, 2 weeks after administration of ripasudil hydrochloride hydrate, a commercial ROCK inhibitor used to treat glaucoma or ocular hypertension...
February 3, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28155615/the-protective-effect-of-dl0805-derivatives-on-pulmonary-artery-cells-and-the-underlying-mechanisms-study
#19
Tianyi Yuan, Huifang Zhang, Yucai Chen, Xiaozhen Jiao, Ping Xie, Lianhua Fang, Guanhua Du
Pulmonary hypertension (PH) is a severe disease characterized by a progressive increase in pulmonary vascular resistance, initially due to abnormal pulmonary vasoconstriction in response to endothelial and smooth muscle cells injury. The discovery of new chemical entities having a protective effect on pulmonary artery cells could be meaningful for the treatment of PH. We evaluated the protective effect of DL0805 derivatives (DL0805-1 and DL0805-2) on pulmonary artery vascular cells, including human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs)...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28122303/icariin-promotes-proliferation-and-osteogenic-differentiation-of-rat-adipose-derived-stem-cells-by-activating-the-rhoa-taz-signaling-pathway
#20
Yaping Ye, Xingzhi Jing, Na Li, Yingxing Wu, Bingbing Li, Tao Xu
Icariin, the main active flavonoid glucoside isolated from Herba epimedii, has been demonstrated to be a potential alternative therapy to prevent postmenopausal osteoporosis. Icariin has also been shown to regulate the proliferation and osteogenic differentiation of rat bone marrow stromal cells (rBMSCs). However, the detailed molecular mechanism of icariin has remained largely unknown. Besides, no investigation has focused on the relevance of icariin in the regulation of rat adipose-derived stem cells (rASCs) proliferation and osteogenic differentiation...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
keyword
keyword
65432
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"