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https://www.readbyqxmd.com/read/28339541/vitamin-d-suppresses-oxidative-stress-induced-microparticle-release-by-human-umbilical-vein-endothelial-cells
#1
Xiuyue Jia, Jie Xu, Yang Gu, Xin Gu, Weimin Li, Yuping Wang
Endothelial microparticle (MP) release was increased in numerous cardiovascular diseases including preeclampsia. Oxidative stress is a potent inducer of endothelial dysfunction. In this study, we aimed to investigate if vitamin D could protect endothelial cells (ECs) from MP release induced by oxidative stress. Endothelial cell (from human umbilical vein) oxidative stress was induced by cultivation of cells under lowered oxygen condition (2%O2) for 48 h and cells cultured under standard condition (21%O2) served as control...
December 27, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/28339093/rock-inhibition-as-a-potential-therapeutic-target-involved-in-apoptosis-in-hemangioma
#2
Ming-Ke Qiu, Shu-Qing Wang, Chang Pan, Yang Wang, Zhi-Wei Quan, Ying-Bin Liu, Jing-Min Ou
Gene expression was examined in hemangiomas (HA), benign, birthmark-like tumors occurring in infancy, and confirmed in HA-derived endothelial cells (HDEC), for which cell proliferation and apoptosis were also assessed. Protein and mRNA accumulation of Rho-associated protein kinase (ROCK), vascular endothelial growth factor (VEGF), Ki-67 and proliferating cell nuclear antigen was significantly higher in proliferating phase HAs than in involuting phase HAs. In contrast, p53 and caspase-3 exhibited higher levels of accumulation in involuting than proliferating HAs...
March 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28337305/rho-kinase-regulates-neurite-outgrowth-of-hippocampal-neurons-via-calcium-dependent-cytoskeleton-regulation
#3
Zhisheng Ji, Zhenbin Cai, Jifeng Zhang, Nannuan Liu, Jing Chen, Minghui Tan, Hongsheng Lin, Guoqing Guo
OBJECTIVE: To investigate whether calcium is involved in downstream signal transduction in neurite outgrowth regulated by Rho kinase. METHODS: In vitro primary hippocampal neurons were cultured and treated with Rho kinase agonist (LPA) or antagonist (Y-27632). Then, the cytoskeleton and neurite outgrowth were observed. After addition of calcium antagonist BAPTA/AM to reduce intracellular calcium, the cytoskeleton distribution and neurite outgrowth were observed...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28332240/lower-urinary-tract-symptoms-benign-prostatic-hypertrophy-and-vascular-function-role-of-the-nitric-oxide-phosphodiesterase-type-5-cyclic-guanosine-3-5-monophosphate-pathway
#4
REVIEW
Yukihito Higashi
It is well known that there is an association of lower urinary tract symptoms/benign prostatic hypertrophy with cardiovascular disease, suggesting that lower urinary tract symptoms/benign prostatic hypertrophy is a risk factor for cardiovascular events. Vascular function, including endothelial function and vascular smooth muscle function, is involved in the pathogenesis, maintenance and development of atherosclerosis, leading to cardiovascular events. Vascular dysfunction per se should also contribute to lower urinary tract symptoms/benign prostatic hypertrophy...
March 22, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28330614/a-predictive-3d-multi-scale-model-of-biliary-fluid-dynamics-in-the-liver-lobule
#5
Kirstin Meyer, Oleksandr Ostrenko, Georgios Bourantas, Hernan Morales-Navarrete, Natalie Porat-Shliom, Fabian Segovia-Miranda, Hidenori Nonaka, Ali Ghaemi, Jean-Marc Verbavatz, Lutz Brusch, Ivo Sbalzarini, Yannis Kalaidzidis, Roberto Weigert, Marino Zerial
Bile, the central metabolic product of the liver, is transported by the bile canaliculi network. The impairment of bile flow in cholestatic liver diseases has urged a demand for insights into its regulation. Here, we developed a predictive 3D multi-scale model that simulates fluid dynamic properties successively from the subcellular to the tissue level. The model integrates the structure of the bile canalicular network in the mouse liver lobule, as determined by high-resolution confocal and serial block-face scanning electron microscopy, with measurements of bile transport by intravital microscopy...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28328290/cross-talk-between-rho-gtpases-and-pi3k-in-the-neutrophil
#6
Barry McCormick, Julia Y Chu, Sonja Vermeren
Neutrophils are short-lived, abundant peripheral blood leukocytes that provide a first line of defense against bacterial and fungal infections whilst also being a key part of the inflammatory response. Chemokines induce neutrophil recruitment to inflammatory sites, where neutrophils perform a number of diverse functions that are aimed at fighting infections. Neutrophil effector functions are tightly regulated processes that are governed by an array of intracellular signaling pathways and initiated by receptor-ligand binding events...
March 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28320516/l-f001-a-novel-multifunctional-rock-inhibitor-suppresses-neuroinflammation-in-vitro-and-in-vivo-involvement-of-nf-%C3%AE%C2%BAb-inhibition-and-nrf2-pathway-activation
#7
Jingkao Chen, Wei Yin, Yalin Tu, Shengnan Wang, Xiaohong Yang, Qiuhe Chen, Xiao Zhang, Yifan Han, Rongbiao Pi
Microglia and astrocytes are largely responsible for inflammatory injury in the brain of Alzheimer's disease (AD). Increasing evidence has indicated that Rho kinase (ROCK) plays an important role in the regulation of neuroinflammation. Previously, we synthesized a new chemical entity L-F001 and proved its potential inhibitory effects on ROCK and oxidative stress. Here, we investigated the anti-inflammatory effects and the molecular mechanisms of L-F001 in vitro and in vivo. L-F001 remarkably suppressed lipopolysaccharides (LPS)-elevated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as LPS-induced production of nitric oxide (NO), reactive oxygen species, interleukin-6 (IL-6) and tumor necreactive oxygen speciesis factor-α (TNF-α) in microglial BV-2 cells and in cultured astrocytes...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28319644/the-retinal-relaxing-factor-update-on-an-enigmatic-regulator-of-the-retinal-circulation
#8
Laura Vanden Daele, Charlotte Boydens, Bart Pauwels, Johan Van de Voorde
The retinal circulation is regulated by different local factors and might include the retinal relaxing factor (RRF). This factor is found to be continuously released by the retina and relaxes smooth muscle cells. This review describes the current knowledge about the RRF. Despite many research efforts, the cellular source, identity, mechanism, and physiological role of the RRF remain largely unknown. Thus far, it seems that the RRF is a hydrophilic, thermostable, diffusible chemical messenger, which characteristics do not correspond with most well-known endogenous vasorelaxants...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28317242/chemical-screening-identifies-rock-as-a-target-for-recovering-mitochondrial-function-in-hutchinson-gilford-progeria-syndrome
#9
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
#10
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/28303627/camp-dependent-regulation-of-rhoa-rho-kinase-attenuates-detrusor-overactivity-in-a-novel-mouse-experimental-model
#11
William Akakpo, Biljana Musicki, Arthur L Burnett
OBJECTIVES: To investigate detrusor function and cAMP activation as a possible target for detrusor overactivity in an experimental model lacking a key denitrosylation enzyme, S-nitrosoglutathione reductase (GSNOR). MATERIALS AND METHODS: GSNOR-deficient (GSNOR(-/-) ) (n=30) and wild-type (WT) mice (n=26) were treated for 7 days with the cAMP activator, colforsin (1mg/kg), or vehicle intraperitoneally. Cystometric studies or molecular analyses of bladder specimens were performed...
March 16, 2017: BJU International
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#12
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28301357/the-effect-of-microporous-polysaccharide-hemospheres-on-wound-healing-and-scarring-in-wild-type-and-db-db-mice
#13
Kyle J Miller, Wei Cao, Mohamed M Ibrahim, Howard Levinson
BACKGROUND: Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process. OBJECTIVE: This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model. METHODS: The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice...
April 2017: Advances in Skin & Wound Care
https://www.readbyqxmd.com/read/28300846/regulation-of-rhoa-activity-by-the-cellular-prion-protein
#14
Hee-Jun Kim, Hong-Seok Choi, Jeong-Ho Park, Mo-Jong Kim, Hyoung-Gon Lee, Robert Bob Petersen, Yong-Sun Kim, Jae-Bong Park, Eun-Kyoung Choi
The cellular prion protein (PrP(C)) is a highly conserved glycosylphosphatidylinositol (GPI)-anchored membrane protein that is involved in the signal transduction during the initial phase of neurite outgrowth. The Ras homolog gene family member A (RhoA) is a small GTPase that is known to have an essential role in regulating the development, differentiation, survival, and death of neurons in the central nervous system. Although recent studies have shown the dysregulation of RhoA in a variety of neurodegenerative diseases, the role of RhoA in prion pathogenesis remains unclear...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28288476/the-role-of-rho-rho-kinase-pathway-in-the-pathogenesis-of-cholesteatoma
#15
Mesut Yeşilova, Kemal Görür, Onur Ismi, Cengiz Özcan, Kansu Büyükafşar
OBJECTIVE: To assess the role of Rho/Rho-kinase pathway in the pathogenesis of cholesteatoma. MATERIALS AND METHODS: Thirty-eight patients with cholesteatoma, who had gone mastoidectomies were enrolled in this prospective study. Cholesteatomas matrix (CM) and a piece of the external ear canal skin (EECS as control) were taken and transferred to the liquid nitrogen and kept at -86 °C for Rho A and Rho-kinase (ROCK) analysis with Western blotting and commercial ELISA kits (Cell Biolabs Inc...
April 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28287465/serine-threonine-kinase-3-phosphoinositide-dependent-protein-kinase-1-pdk1-as-a-key-regulator-of-cell-migration-and-cancer-dissemination
#16
REVIEW
Laura Di Blasio, Paolo A Gagliardi, Alberto Puliafito, Luca Primo
Dissecting the cellular signaling that governs the motility of eukaryotic cells is one of the fundamental tasks of modern cell biology, not only because of the large number of physiological processes in which cell migration is crucial, but even more so because of the pathological ones, in particular tumor invasion and metastasis. Cell migration requires the coordination of at least four major processes: polarization of intracellular signaling, regulation of the actin cytoskeleton and membrane extension, focal adhesion and integrin signaling and contractile forces generation and rear retraction...
March 11, 2017: Cancers
https://www.readbyqxmd.com/read/28284975/chronic-treatment-with-taurine-after-intracerebroventricular-streptozotocin-injection-improves-cognitive-dysfunction-in-rats-by-modulating-oxidative-stress-cholinergic-functions-and-neuroinflammation
#17
K H Reeta, Devendra Singh, Y K Gupta
The present study investigated the neuroprotective effects of taurine, an essential amino acid for growth and development of central nervous system. Intracerebroventricular streptozotocin (ICV-STZ) model of cognitive impairment was used in male Wistar rats (270 ± 20 g). Morris water maze, elevated plus maze and passive avoidance paradigm were used to assess cognitive performance. Taurine (40, 60 and 120 mg/kg) was administered orally for 28 days following STZ administration on day 1. Oxidative stress parameters (malondialdehyde, glutathione, nitric oxide and superoxide dismutase) and cholinesterases (acetylcholinesterase and butyrylcholinesterase) activity were measured at end of the study in the cortex and hippocampus...
March 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28284870/identification-of-a-new-class-of-potent-cdc7-inhibitors-designed-by-putative-pharmacophore-model-synthesis-and-biological-evaluation-of-2-3-dihydrothieno-3-2-d-pyrimidin-4-1h-ones
#18
Osamu Kurasawa, Yuya Oguro, Tohru Miyazaki, Misaki Homma, Kouji Mori, Kenichi Iwai, Hideto Hara, Robert Skene, Isaac Hoffman, Akihiro Ohashi, Sei Yoshida, Tomoyasu Ishikawa, Nobuo Cho
Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. In order to identify a new class of potent Cdc7 inhibitors, we generated a putative pharmacophore model based on in silico docking analysis of a known inhibitor with Cdc7 homology model. The pharmacophore model provided a minimum structural motif of Cdc7 inhibitor, by which preliminary medicinal chemistry efforts identified a dihydrothieno[3,2-d]-pyrimidin-4(1H)-one scaffold having a heteroaromatic hinge-binding moiety...
February 16, 2017: Bioorganic & Medicinal Chemistry
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
#19
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
#20
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
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