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Fasudil

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https://www.readbyqxmd.com/read/29660902/effect-of-rho-kinase-inhibitor-fasudil-on-the-expression-et-1-and-no-in-rats-with-hypoxic-pulmonary-hypertension
#1
Xing-Zhen Sun, Shu-Yan Li, Xiang-Yang Tian, Ze Hong, Jia-Xin Li
OBJECTIVE: This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH). METHODS: Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups...
April 12, 2018: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/29599137/afadin-facilitates-vascular-endothelial-growth-factor-induced-network-formation-and-migration-of-vascular-endothelial-cells-by-inactivating-rho-associated-kinase-through-arhgap29
#2
Toru Tagashira, Terunobu Fukuda, Muneaki Miyata, Kazuha Nakamura, Hidenobu Fujita, Yoshimi Takai, Ken-Ichi Hirata, Yoshiyuki Rikitake
OBJECTIVE: We previously reported that afadin, an actin filament-binding protein, regulated vascular endothelial growth factor-induced angiogenesis. However, the underlying molecular mechanisms are poorly understood. Here, we investigated the mechanisms of how Rho-associated kinase is activated in afadin-knockdown human umbilical vein endothelial cells (HUVECs) and how its activation is involved in defects of vascular endothelial growth factor-induced network formation and migration of the cells...
March 29, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29581852/rhoa-rho-kinase-triggers-epithelial-mesenchymal-transition-in-mesothelial-cells-and-contributes-to-the-pathogenesis-of-dialysis-related-peritoneal-fibrosis
#3
Qinglian Wang, Xiaowei Yang, Ying Xu, Zhenwei Shen, Hongxia Cheng, Fajuan Cheng, Xiang Liu, Rong Wang
Peritoneal fibrosis (PF) with associated peritoneal dysfunction is almost invariably observed in long-term peritoneal dialysis (PD) patients. Advanced glycation end products (AGEs) are pro-oxidant compounds produced in excess during the metabolism of glucose and are present in high levels in standard PD solutions. The GTPase RhoA has been implicated in PF, but its specific role remains poorly understood. Here, we studied the effects of RhoA/Rho-kinase signaling in AGEs-induced epithelial-mesenchymal transition (EMT) in human peritoneal mesothelial cells (HPMCs), and evaluated morphological and molecular changes in a rat model of PD-related PF...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29581784/autophagy-inhibition-stimulates-apoptosis-in-oesophageal-squamous-cell-carcinoma-treated-with-fasudil
#4
Fa-Jun Xie, Qiu-Qing Zheng, Jing Qin, Ling-Ling Zhang, Na Han, Wei-Min Mao
Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both treatments also significantly sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29554661/alkannin-inhibited-hepatic-inflammation-in-diabetic-db-db-mice
#5
Wenhua Xue, Zhirui Fan, Yuanzhe Li, Lifeng Li, Tengfei Zhang, Jingli Lu, Bingjun Ma, Zijia Zhu, Jingyao Lian, Chaoqi Zhang, Xiaoqin Song, Dongxu Sun, Yunkai Zhai, Ruitai Fan, Yang Cao, Xiaoming Deng, Jie Zhao
BACKGROUND/AIMS: The current study was designed to investigate the protective role of alkannin (ALK) on liver injury in diabetic C57BL/KsJ-db/db mice and explore its potential mechanisms. METHODS: An oral glucose tolerance test (OGTT) was performed. The levels of insulin, alanine aminotransferase (ALT), aspartate aminotransaminase (AST), total cholesterol (TC) and triglyceride (TG) were determined by commercial kits. The pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were determined by ELISA...
March 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29534403/-acute-effects-of-intravenous-fasudil-with-different-dosage-on-patients-with-congenital-heart-defects-and-severe-pulmonary-arterial-hypertension
#6
H Y Ruan, Y G Zhang, R Liu
Objective: To compare the acute hemodynamic effects of intravenous fasudil with different dosage on patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). Methods: Sixty patients (37±17 years old) with CHD and PAH were consecutively enrolled. All patients underwent heart catheterization. The patients were randomly divided into two groups: the regular dosage group and the large dosage group. At initiation and 30 min after intravenous fasudil(30 mg and 60 mg respectively), the following hemodynamic parameters were measured and calculated: right atrial pressure(RAP), pulmonary arterypressure(PAP) , systemic artery pressure (SAP), pulmonary capillary wedge pressure(PCWP) , pulmonary vascular resistance(PVR) and systemic vascular resistance( SVR), cardiac index (CI) and artery oxygen saturation (SaO(2))...
March 6, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29530787/altered-ureteral-contractility-with-ageing-role-of-the-rho-kinase-pathway
#7
Iris Lim, Russ Chess-Williams, Donna Sellers
This study investigated the role of calcium sensitisation in the regulation of ureteral contractility with ageing. Isolated ureteral strips from young (6-month old) and older (3-year old) pigs were mounted in Krebs bicarbonate solution and contractility induced by the α1-adrenoceptor agonist phenylephrine (30 and 300 μM) and 5-HT (10 and 100 μM), recorded in the absence and presence of the rho-kinase inhibitors Y-27632 (10 μM) and fasudil (30 μM). Ureteral strips developed bursts of contractile activity which was measured as area under the curve (AUC) and frequency...
March 9, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29528655/fasudil-and-deta-nonoate-loaded-in-a-peptide-modified-liposomal-carrier-slows-pah-progression-upon-pulmonary-delivery
#8
Jahidur Rashid, Kamrun Nahar, Snehal Raut, Ali Keshavarz, Fakhrul Ahsan
We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long acting nitric oxide donorboth loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC)in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified- and CAR-modified-liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia induced PAH rats...
March 12, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29527586/rho-kinase-signaling-and-cardiac-physiology
#9
Yuan Dai, Weijia Luo, Jiang Chang
Rho kinases (ROCKs) are the first discovered RhoA effectors that are now widely known for their effects on actin organization. Recent studies have shown that ROCKs play important roles in cardiac physiology. Abnormal activation of ROCKs participate in multiple cardiovascular pathological processes, including cardiac hypertrophy, apoptosis, fibrosis, systemic hypertension, and pulmonary hypertension. ROCK inhibitors, fasudil and statins, have shown beneficial cardiovascular effects in many animal studies, clinical trials, and applications...
February 2018: Current Opinion in Physiology
https://www.readbyqxmd.com/read/29503530/fasudil-inhibits-proliferation-and-migration-of-hep-2-laryngeal-carcinoma-cells
#10
Xiaowen Zhang, Nan Wu
Background: Rho-kinase signal pathway is a new target for cancer therapy. Fasudil, a selective Rho-kinase inhibitor, is found to exert antitumor effects on several types of cancer, but whether fasudil has antitumor effects on laryngeal carcinoma is still unknown. The aim of this study was to determine the effects of fasudil on laryngeal carcinoma and explore the underlying molecular mechanisms in this process. Methods: After treatment with fasudil, changes in biological behaviors, including the growth, proliferation, clone formation, apoptosis, and migration of human laryngeal carcinoma cells (Hep-2 cells) were observed...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29487527/rhoa-rock-signaling-pathway-mediates-shuanghuanglian-injection-induced-pseudo-allergic-reactions
#11
Jiayin Han, Yong Zhao, Yushi Zhang, Chunying Li, Yan Yi, Chen Pan, Jingzhuo Tian, Yifei Yang, Hongyu Cui, Lianmei Wang, Suyan Liu, Jing Liu, Nuo Deng, Aihua Liang
Background: Shuanghuanglian injection (SHLI) is a famous Chinese medicine used as an intravenous preparation for the treatment of acute respiratory tract infections. In the recent years, the immediate hypersensitivity reactions induced by SHLI have attracted broad attention. However, the mechanism involved in these reactions has not yet been elucidated. The present study aims to explore the characteristics of the immediate hypersensitivity reactions induced by SHLI and deciphers the role of the RhoA/ROCK signaling pathway in these reactions...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29486854/pregestational-diabetes-increases-fetoplacental-vascular-resistance-in-rats
#12
Olga Vajnerova, Petr Kafka, Tereza Kratzerova, Karel Chalupsky, Vaclav Hampl
INTRODUCTION: Diabetes is a well-known risk factor in pregnancy. Because maternal diabetes involves oxidative stress that is also induced by chronic hypoxia and can alter vascular function, we sought to determine the effects of chronic maternal hyperglycemia on the fetoplacental vasculature in rats and to compare it with the effects of chronic hypoxia. METHODS: Diabetes was induced in female rats by a streptozotocin injection at a neonatal age. When these animals reached adulthood, their hyperglycemia was confirmed and they were inseminated...
March 2018: Placenta
https://www.readbyqxmd.com/read/29481792/fasudil-inhibits-neutrophil-endothelial-cell-interactions-by-regulating-the-expressions-of-grp78-and-bmpr2
#13
Jingjing Wang, Jian Xu, Xinyun Zhao, Weiping Xie, Hong Wang, Hui Kong
Regulation of leukocyte-endothelial cell interactions and of vascular permeability plays a critical role in the maintenance of functional pulmonary microvascular barriers. Little is yet known about the effect of the Rho-associated protein kinase (ROCK) inhibitor fasudil on leukocyte-endothelial cell interactions or the underlying mechanism. In the present study, as evaluated using co-culture systems of neutrophils and human pulmonary microvascular endothelial cells (HPMECs), fasudil dose-dependently suppressed neutrophil chemotaxis by decreasing the production of chemotactic factors in lipopolysaccharide (LPS)-treated HPMECs...
February 23, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29475961/alterations-in-the-rho-pathway-contribute-to-epstein-barr-virus-induced-lymphomagenesis-in-immunosuppressed-environments
#14
Sung-Yup Cho, Chang Ohk Sung, Jeesoo Chae, Jieun Lee, Deukchae Na, Wonyoung Kang, Jinjoo Kang, Seoyeon Min, Ahra Lee, Eunhye Kwak, Jooyoung Kim, Boram Choi, Hyunsoo Kim, Jeffrey H Chuang, Hyo-Kyung Pak, Chan-Sik Park, Sanghui Park, Young Hyeh Ko, Dakeun Lee, Jin Roh, Min-Sun Cho, Seongyeol Park, Young Seok Ju, Yun-Suhk Suh, Seong-Ho Kong, Hyuk-Joon Lee, James Keck, Jacques Banchereau, Edison T Liu, Woo-Ho Kim, Hansoo Park, Han-Kwang Yang, Jong-Il Kim, Charles Lee
Epstein-Barr virus (EBV)-positive diffuse large B cell lymphomas (EBV+ -DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV+ -DLBLs are largely unknown because of the limited availability of human samples and lack of experimental animal models. We observed the development of 25 human EBV+ -DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV+ -DLBLs revealed enrichment of mutations in Rho pathway genes, including RHPN2 , and Rho pathway transcriptomic activation...
February 23, 2018: Blood
https://www.readbyqxmd.com/read/29474864/a-crucial-role-of-rock-for-alleviation-of-senescence-associated-phenotype
#15
Joon Tae Park, Hyun Tae Kang, Chi Hyun Park, Young-Sam Lee, Kyung A Cho, Sang Chul Park
In our previous study, we uncovered a novel mechanism in which amelioration of Hutchinson-Gilford progeria syndrome (HGPS) phenotype is mediated by mitochondrial functional recovery upon rho-associated protein kinase (ROCK) inhibition. However, it remains elusive whether this mechanism is also applied to the amelioration of normal aging cells. In this study, we used Y-27632 and fasudil as effective ROCK inhibitors, and examined their role in senescence. We found that ROCK inhibition induced the functional recovery of the mitochondria as well as the metabolic reprogramming, which are two salient features that are altered in normal aging cells...
February 20, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29451818/overexpression-of-heart-specific-small-subunit-of-myosin-light-chain-phosphatase-results-in-heart-failure-and-conduction-disturbance
#16
Takuro Arimura, Antoine Muchir, Masayoshi Kuwahara, Sachio Morimoto, Taisuke Ishikawa, Cheng-Kun Du, Dong-Yun Zhan, Shu Nakao, Noboru Machida, Ryo Tanaka, Yoshihisa Yamane, Takeharu Hayashi, Akinori Kimura
Mutations in genes encoding components of sarcomere cause cardiomyopathy, which is often associated with abnormal Ca 2+ sensitivity of muscle contraction. We previously showed that a heart-specific myosin light chain phosphatase small subunit, hHS-M 21 , increases the Ca 2+ -sensitivity of muscle contraction. The aim of this study was to investigate the function of hHS-M 21 in vivo and the causative role of abnormal Ca 2+ sensitivity in cardiomyopathy. We generated transgenic (Tg) mice with cardiac-specific overexpression of hHS-M 21 ...
February 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29448133/exposure-to-the-rock-inhibitor-fasudil-promotes-gliogenesis-of-neural-stem-cells-in-vitro
#17
Zubair Ahmed Nizamudeen, Lisa Chakrabarti, Virginie Sottile
Fasudil is a clinically approved Rho-associated protein kinase (ROCK) inhibitor that has been used widely to treat cerebral consequences of subarachnoid hemorrhage. It is known to have a positive effect on animal models of neurological disorders including Parkinson's disease and stroke. However, its cellular effect on progenitor populations and differentiation is not clearly understood. While recent studies suggest that fasudil promotes the mobilization of neural stem cells (NSCs) from the subventricular zone in vivo and promotes the differentiation of the C17...
April 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29440699/vascular-dysfunction-in-obese-diabetic-db-db-mice-involves-the-interplay-between-aldosterone-mineralocorticoid-receptor-and-rho-kinase-signaling
#18
Aurelie Nguyen Dinh Cat, Glaucia E Callera, Malou Friederich-Persson, Ana Sanchez, Maria Gabriela Dulak-Lis, Sofia Tsiropoulou, Augusto C Montezano, Ying He, Ana M Briones, Frederic Jaisser, Rhian M Touyz
Activation of aldosterone/mineralocorticoid receptors (MR) has been implicated in vascular dysfunction of diabetes. Underlying mechanisms are elusive. Therefore, we investigated the role of Rho kinase (ROCK) in aldosterone/MR signaling and vascular dysfunction in a model of diabetes. Diabetic obese mice (db/db) and control counterparts (db/+) were treated with MR antagonist (MRA, potassium canrenoate, 30 mg/kg/day, 4 weeks) or ROCK inhibitor, fasudil (30 mg/kg/day, 3 weeks). Plasma aldosterone was increased in db/db versus db/+...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29440458/macrophage-targeting-fasudil-treatment-protects-liver-from-the-ischemia-reperfusion-injury-by-promoting-m2-macrophage-polarization
#19
Yingli Xie, Di Zhao, Pingshuan Dong, Lihong Lai
Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure. During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension...
February 12, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29416017/fasudil-increases-temozolomide-sensitivity-and-suppresses-temozolomide-resistant-glioma-growth-via-inhibiting-rock2-abcg2
#20
Xin Zhang, Xiuting Liu, Wei Zhou, Mengdi Yang, Yang Ding, Qing Wang, Rong Hu
Resistance to temozolomide (TMZ) is a major clinical challenge in glioma treatment, but the mechanisms of TMZ resistance are poorly understood. Here, we provided evidence that ROCK2 acted redundantly to maintain resistance of TMZ in TMZ-resistant gliomas, and as a ROCK2 phosphorylation inhibitor, fasudil significantly suppressed proliferation of TMZ-resistant gliomas in vivo and vitro via enhancing the chemosensitivity of TMZ. Additionally, the membrane translocation of ABCG2 was decreased with fasudil by ROCK2/moesin pathway...
February 7, 2018: Cell Death & Disease
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