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https://www.readbyqxmd.com/read/28925883/novel-therapeutics-in-glaucoma-management
#1
Claudio Bucolo, Chiara Bianca Maria Platania, Filippo Drago, Michele Reibaldi, Vincenza Bonfiglio, Teresio Avitabile, Maurizio Uva
Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell death and alterations of visual field. Elevated intraocular pressure (IOP) is considered the main risk factor of glaucoma, even though other factors cannot be ruled out, such as epigenetic mechanisms. An overview of the ultimate promising experimental drugs to manage glaucoma has been provided. In particular, we have focused on purinergic ligands, KATP channel activators, gases (nitric oxide, carbon monoxide and hydrogen sulfide), non-glucocorticoid steroidal compounds, neurotrophic factors, PI3K/Akt activators, citicoline, histone deacetylase inhibitors, cannabinoids, dopamine and serotonin receptors ligands, small interference RNA, and Rho kinase inhibitors...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28924490/the-lauric-acid-activated-signaling-prompts-apoptosis-in-cancer-cells
#2
Rosamaria Lappano, Anna Sebastiani, Francesca Cirillo, Damiano Cosimo Rigiracciolo, Giulia Raffaella Galli, Rosita Curcio, Roberta Malaguarnera, Antonino Belfiore, Anna Rita Cappello, Marcello Maggiolini
The saturated medium-chain fatty-acid lauric acid (LA) has been associated to certain health-promoting benefits of coconut oil intake, including the improvement of the quality of life in breast cancer patients during chemotherapy. As it concerns the potential to hamper tumor growth, LA was shown to elicit inhibitory effects only in colon cancer cells. Here, we provide novel insights regarding the molecular mechanisms through which LA triggers antiproliferative and pro-apoptotic effects in both breast and endometrial cancer cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28923399/up-regulation-of-rho-associated-kinase-1-2-by-glucocorticoids-promotes-migration-invasion-and-metastasis-of-melanoma
#3
Gao-Xiang Huang, Yan Wang, Jie Su, Peng Zhou, Bo Li, Li-Juan Yin, Jian Lu
Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2)...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28921504/g%C3%AE-12-facilitates-carbachol-induced-shortening-in-human-airway-smooth-muscle-by-modulating-phosphoinositide-3-kinase-mediated-activation-in-a-rhoa-dependent-manner
#4
Edwin J Yoo, Gaoyuan Cao, Cynthia J Koziol-White, Christie A Ojiaku, Krishna Sunder, Joseph A Jude, James V Michael, Hong Lam, Ivan Pushkarsky, Robert Damoiseaux, Dino Di Carlo, Kwangmi Ahn, Steven S An, Raymond B Penn, Reynold A Panettieri
BACKGROUND AND PURPOSE: Phosphoinositide 3-kinase (PI3K)-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The upstream mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given the capacity of G12 family proteins to activate ROCK pathways in other cell types (Riobo and Manning, 2005), the role of G12 proteins in modulating M3 muscarinic acetylcholine receptor (M3R)-stimulated PI3K/ROCK activation and HASMC contraction was examined...
September 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28920944/the-dosage-dependent-effect-exerted-by-the-nm23-h1-h2-homolog-ndk-1-on-distal-tip-cell-migration-in-c-elegans
#5
Zsolt Farkas, Luca Fancsalszky, Éva Saskői, Alexandra Gráf, Krisztián Tárnok, Anil Mehta, Krisztina Takács-Vellai
Abnormal regulation of cell migration and altered rearrangement of the cytoskeleton are fundamental properties of metastatic cells. The first identified metastasis suppressor NM23-H1, which displays nucleoside-diphosphate kinase (NDPK) activity is involved in these processes. NM23-H1 inhibits the migratory and invasive potential of some cancer cells. Correspondingly, numerous invasive cancer cell lines (eg, breast, colon, oral, hepatocellular carcinoma, and melanoma) display low endogenous NM23 levels. In this review, we summarize mechanisms, which are linked to the anti-metastatic activity of NM23...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28920922/g%C3%AE-13-ablation-reprograms-myofibers-to-oxidative-phenotype-and-enhances-whole-body-metabolism
#6
Ja Hyun Koo, Tae Hyun Kim, Shi-Young Park, Min Sung Joo, Chang Yeob Han, Cheol Soo Choi, Sang Geon Kim
Skeletal muscle is a key organ in energy homeostasis owing to its high requirement for nutrients. Heterotrimeric G proteins converge signals from cell-surface receptors to potentiate or blunt responses against environmental changes. Here, we show that muscle-specific ablation of Gα13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, Gα13 and its downstream effector RhoA suppressed nuclear factor of activated T cells 1 (NFATc1), a chief regulator of myofiber conversion, by increasing Rho-associated kinase 2-mediated (Rock2-mediated) phosphorylation at Ser243...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28916556/cell-scientist-to-watch-paul-timpson
#7
(no author information available yet)
Paul Timpson received his bachelor's degree from the University of Strathclyde, UK and completed his PhD under the supervision of Margaret Frame at the Beatson Institute for Cancer Research and the University of Glasgow in 2002, working on Src kinases and Rho family GTPases in cancer cell invasion. He then moved to the Garvan Institute of Medical Research in Sydney, Australia to work with Roger Daly on the actin-binding protein cortactin in several cancer models. Paul returned to the Beatson Institute in 2007 with the aid of an AstraZeneca postdoctoral research fellowship...
September 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28916261/differential-involvement-of-l-and-t-type-ca-2-channels-store-operated-calcium-channel-trpc-and-rho-kinase-signaling-pathway-s-in-pgf2%C3%AE-induced-contractions-in-myometrium-of-non-pregnant-and-pregnant-buffaloes-bubalus-bubalis
#8
Abhishek Sharma, Udayraj P Nakade, Pooja Jaitley, Vipin Sharma, Soumen Choudhury, Satish Kumar Garg
This study unravels the differential involvement of calcium signaling pathway(s) in PGF2α-induced contractions in myometrium of non-pregnant and pregnant buffaloes. Compared to the myometrium of pregnant animals, myometrium of non-pregnant buffaloes was more sensitive to PGF2α-induced contractile effect as manifested by the changes in mean integral tension (MIT) and tonicity. However, phasic contraction was significantly more in myometrium of pregnant animals. The uterotonic effect of PGF2α was dependent on extracellular Ca(2+) and its influx through nifedipine-sensitive L-type Ca(2+) channels both in non-pregnant and pregnant animals, but T-type Ca(2+) channels play an additional role during pregnancy...
September 12, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28916199/erk-and-rock-functionally-interact-in-a-signaling-network-that-is-compensationally-upregulated-in-spinal-muscular-atrophy
#9
Niko Hensel, Svetlana Baskal, Lisa Marie Walter, Hella Brinkmann, Manuela Gernert, Peter Claus
Spinal Muscular Atrophy (SMA) is a motoneuron disease caused by low levels of functional survival of motoneuron protein (SMN). Molecular disease mechanisms downstream of functional SMN loss are still largely unknown. Previous studies suggested an involvement of Rho kinase (ROCK) as well as the extracellular signal-regulated kinases (ERK) pathways in the pathomechanism. Both pathways are bi-directionally linked and inhibit each other. Thus, we hypothesize that both pathways regulate SMA pathophysiology in vivo in a combined manner rather than acting separately...
September 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28915620/prpf-overexpression-induces-drug-resistance-through-actin-cytoskeleton-rearrangement-and-epithelial-mesenchymal-transition
#10
Salman Ul Islam, Adeeb Shehzad, Jong Kyung Sonn, Young Sup Lee
Pre-mRNA processing factor (PRPF) 4B kinase belongs to the CDK-like kinase family, and is involved in pre-mRNA splicing, and in signal transduction. In this study, we observed that PRPF overexpression decreased the intracellular levels of reactive oxygen species, and inhibited resveratrol-induced apoptosis by activating the cell survival signaling proteins NFκB, ERK, and c-MYC in HCT116 human colon cancer cells. PRPF overexpression altered cellular morphology, and rearranged the actin cytoskeleton, by regulating the activity of Rho family proteins...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914001/comparative-study-of-the-effects-of-trabecular-meshwork-outflow-drugs-on-the-permeability-and-nitric-oxide-production-in-trabecular-meshwork-cells
#11
Jae Woo Kim
PURPOSE: To compare the effects of the barrier function in human trabecular meshwork (TM) cells monolayer and the production of nitric oxide (NO) between trabecular outflow drugs, Rho-associated kinase (ROCK) inhibitors, adenosine, and statin. METHODS: Primary cultured TM cells were exposed to 10 or 25 μM Y-27632, 0.1 or 1 μM N6-cyclohexyladenosine (CHA), or 15 or 30 μM simvastatin for 24 hours. NO production and expression of endothelial nitric oxide synthase mRNA were measured by Griess assay and reverse transcription polymerase chain reaction, respectively...
July 25, 2017: Korean Journal of Ophthalmology: KJO
https://www.readbyqxmd.com/read/28912272/the-transcription-factor-hoxb7-regulates-erk-kinase-activity-and-thereby-stimulates-the-motility-and-invasiveness-of-pancreatic-cancer-cells
#12
Makiko Tsuboi, Keisuke Taniuchi, Takahiro Shimizu, Motoaki Saito, Toshiji Saibara
HOX genes encode transcription factors that function as sequence-specific transcription factors that are involved in cellular proliferation, differentiation, and death. The aim of this study was to investigate the role of a HOX family protein, HOXB7, in the motility and invasiveness of pancreatic cancer cells. We previously identified a HOXB7 transcript that is one of a number of transcripts that are preferentially translated in membrane protrusions in pancreatic cancer cells. Immunocytochemistry showed that HOXB7 was localized to the cell protrusions of migrating pancreatic cancer cells...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28903319/loss-of-giant-obscurins-alters-breast-epithelial-cell-mechanosensing-of-matrix-stiffness
#13
Kimberly M Stroka, Bin Sheng Wong, Marey Shriver, Jude M Phillip, Denis Wirtz, Aikaterini Kontrogianni-Konstantopoulos, Konstantinos Konstantopoulos
Obscurins are a family of RhoGEF-containing proteins with tumor and metastasis suppressing roles in breast epithelium. Downregulation of giant obscurins in normal breast epithelial cells leads to reduced levels of active RhoA and of its downstream effectors. Herein, we elucidate how depletion of giant obscurins affects the response of breast epithelial cells to changes in the mechanical properties of the microenvironment. We find that knockdown of obscurins increases cell morphodynamics, migration speed, and diffusivity on polyacrylamide gels of ≥ 1 kPa, presumably by decreasing focal adhesion area and density as well as cell traction forces...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901478/microrna%C3%A2-195-inhibits-cell-proliferation-migration-and-invasion-in-laryngeal-squamous-cell-carcinoma-by-targeting-rock1
#14
Yang Liu, Jixiang Liu, Lin Wang, Xiangli Yang, Xiang Liu
Laryngeal carcinoma is the second most common malignancy of the head and neck cancers. The most common type of laryngeal carcinoma comprises laryngeal squamous cell carcinoma (LSCC), which accounts for ~95% of laryngeal carcinoma cases. Despite great progress in diagnostic and therapeutic techniques over the last few decades, the prognosis for patients with LSCC remains poor. A number of studies reported that various miRNAs are dysregulated in LSCC and serve critical roles in LSCC tumorigenesis and tumor development...
September 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28899515/the-water-extract-of-liuwei-dihuang-possesses-multi-protective-properties-on-neurons-and-muscle-tissue-against-deficiency-of-survival-motor-neuron-protein
#15
Yu-Ting Tseng, Yuh-Jyh Jong, Wei-Fang Liang, Fang-Rong Chang, Yi-Ching Lo
BACKGROUND: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28894005/varicose-and-cheerio-collaborate-with-pebble-to-mediate-semaphorin-1a-reverse-signaling-in-drosophila
#16
Sangyun Jeong, Da-Som Yang, Young Gi Hong, Sarah P Mitchell, Matthew P Brown, Alex L Kolodkin
The transmembrane semaphorin Sema-1a acts as both a ligand and a receptor to regulate axon-axon repulsion during neural development. Pebble (Pbl), a Rho guanine nucleotide exchange factor, mediates Sema-1a reverse signaling through association with the N-terminal region of the Sema-1a intracellular domain (ICD), resulting in cytoskeletal reorganization. Here, we uncover two additional Sema-1a interacting proteins, varicose (Vari) and cheerio (Cher), each with neuronal functions required for motor axon pathfinding...
September 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28893556/the-ilk-mmp9-mrtf-axis-is-crucial-for-endmt-differentiation-of-endothelial-cells-in-a-tumor-microenvironment
#17
Wojciech M Ciszewski, Katarzyna Sobierajska, Marta E Wawro, Wanda Klopocka, Natasza Chefczyńska, Angelika Muzyczuk, Kamil Siekacz, Agata Wujkowska, Jolanta Niewiarowska
Increasing evidence indicates that the tumor microenvironment is a critical factor supporting cancer progression, chemoresistance and metastasis. Recently, cancer-associated fibroblasts (CAFs) have been recognized as a crucial tumor stromal component promoting cancer growth and invasiveness via modulation of the extracellular matrix (ECM) structure, tumor metabolism and immune reprogramming. One of the main sources of CAFs are endothelial cells undergoing the endothelial-mesenchymal transition (EndMT). EndMT is mainly promoted by the Transforming Growth Factor-β (TGF-β) family secreted by tumor cells, though the role of particular members in EndMT regulation remains poorly understood...
September 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28893104/ripasudil-hydrochloride-hydrate-targeting-rho-kinase-in-the-treatment-of-glaucoma
#18
Toshihiro Inoue, Hidenobu Tanihara
Among the intraocular pressure (IOP)-lowering drugs used in a clinical setting, Rho kinase (ROCK) inhibitors lower IOP by a unique mechanism, namely the depolymerization of intracellular actin in the conventional outflow tissues: the trabecular meshwork (TM) and Schlemm's canal (SC). Furthermore, ROCK inhibitors suppress the production of extracellular matrix by TM cells, which represents a potential alternative method of lowering IOP. Considering that conventional outflow is a dominant pathway in humans, IOP-lowering ROCK inhibitors, delivered in conjunction with other drugs, may be able to treat the glaucomatous eye...
September 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28892560/mutations-of-kif14-cause-primary-microcephaly-by-impairing-cytokinesis
#19
Abubakar Moawia, Ranad Shaheen, Sajida Rasool, Syeda Seema Waseem, Nour Ewida, Birgit Budde, Amit Kawalia, Susanne Motameny, Kamal Khan, Ambrin Fatima, Muhammad Jameel, Farid Ullah, Talia Akram, Zafar Ali, Uzma Abdullah, Saba Irshad, Wolfgang Höhne, Angelika Anna Noegel, Mohammed Al-Owain, Konstanze Hörtnagel, Petra Stöbe, Shahid Mahmood Baig, Peter Nürnberg, Fowzan Sami Alkuraya, Andreas Hahn, Muhammad Sajid Hussain
OBJECTIVE: Autosomal recessive primary microcephaly (MCPH) is a rare condition characterized by a reduced cerebral cortex accompanied with intellectual disability. Mutations in 17 genes have been shown to cause this phenotype. Recently, mutations in CIT, encoding CRIK (Citron Rho-interacting kinase) - a component of the central spindle matrix, were added. We aimed at identifying novel MCPH-associated genes and exploring their functional role in pathogenesis. METHODS: Linkage analysis and whole-exome sequencing were performed in consanguineous and nonconsanguineous MCPH families to identify disease-causing variants...
September 11, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28892071/a-novel-rare-variant-r292h-in-rtn4r-affects-growth-cone-formation-and-possibly-contributes-to-schizophrenia-susceptibility
#20
H Kimura, Y Fujita, T Kawabata, K Ishizuka, C Wang, Y Iwayama, Y Okahisa, I Kushima, M Morikawa, Y Uno, T Okada, M Ikeda, T Inada, A Branko, D Mori, T Yoshikawa, N Iwata, H Nakamura, T Yamashita, N Ozaki
Reticulon 4 receptor (RTN4R) plays an essential role in regulating axonal regeneration and plasticity in the central nervous system through the activation of rho kinase, and is located within chromosome 22q11.2, a region that is known to be a hotspot for schizophrenia (SCZ) and autism spectrum disorder (ASD). Recently, rare variants such as copy-number variants and single-nucleotide variants have been a focus of research because of their large effect size associated with increased susceptibility to SCZ and ASD and the possibility of elucidating the pathophysiology of mental disorder through functional analysis of the discovered rare variants...
August 22, 2017: Translational Psychiatry
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