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https://www.readbyqxmd.com/read/29338098/increase-in-motility-and-invasiveness-of-mcf7-cancer-cells-induced-by-nicotine-is-abolished-by-melatonin-through-inhibition-of-erk-phosphorylation
#1
Sara Proietti, Angela Catizone, Maria Grazia Masiello, Simona Dinicola, Gianmarco Fabrizi, Mirko Minini, Giulia Ricci, Roberto Verna, Russel J Reiter, Alessandra Cucina, Mariano Bizzarri
Through activation of the ERK pathway nicotine, in both normal MCF-10A and low malignant breast cancer cells (MCF7), promotes increased motility and invasiveness. Melatonin antagonizes both these effects by inhibiting almost completely ERK phosphorylation. As melatonin has no effect on not-stimulated cells, it is likely that melatonin can counteract ERK-activation only downstream of nicotine-induced activation. This finding suggests that melatonin hampers ERK phosphorylation presumably by targeting a still unknown intermediate factor that connects nicotine stimulation to ERK phosphorylation...
January 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29337059/fpps-mediates-tgf-%C3%AE-1-induced-non-small-cell-lung-cancer-cell-invasion-and-the-emt-process-via-the-rhoa-rock1-pathway
#2
Lin Lin, Ming Li, Lei Lin, Xiaolin Xu, Gening Jiang, Liang Wu
Farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway, was recently shown to play a role in cancer progression. However, its role in non-small cell lung cancer (NSCLC) metastasis and the underlying mechanism remain unclear. In this study, FPPS expression was significantly correlated with TNM stage, and metastasis. Inhibition or knockdown of FPPS blocked TGF-β1-induced cell invasion and epithelial-to-mesenchymal transition (EMT) process. FPPS expression of FPPS was induced by TGF-β1 and FPPS promoted cell invasion and EMT via the RhoA/Rock1 pathway...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29328417/microrna-129-5p-suppresses-cell-proliferation-migration-and-invasion-via-targeting-rock1-in-osteosarcoma
#3
Chaofan Han, Wenbo Wang
Osteosarcoma (OS) is the most common primary malignancy of the bone in teenagers and accounts for 20‑35% of all malignant primary bone tumors. Increasing evidence shows that microRNAs (miRNAs) are abnormally expressed in several types of human cancer. miRNAs are necessary to maintain the malignant phenotype of cancer cells and can function as either tumor suppressors or oncogenes. The present study aimed to measure the expression of miRNA‑129‑5p (miR‑129‑5p) in OS, determine the effects of miR‑129‑5p on the malignant behaviors of OS cells, and elucidate the molecular mechanism underlying the oncogenesis and progression of OS...
January 4, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29324316/microrna-145-alleviates-high-glucose-induced-proliferation-and-migration-of-vascular-smooth-muscle-cells-through-targeting-rock1
#4
Mantian Chen, Yi Zhang, Wei Li, Jieying Yang
The excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are important steps in atherosclerosis. The present study aimed to investigate whether the high glucose-induced changes of VSCMs are mediated by miR-145 and the potential molecular mechanism involved. We found that loss of miR-145 accompanied with increased proliferation and migration was observed in cultured human VSMCs exposed to high glucose. Exogenous overexpression of miR-145 effectively suppressed the high glucose-induced excessive proliferation and migration of VSMCs...
January 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29319354/inhibition-of-the-rhoa-rho-associated-coiled-coil-containing-protein-kinase-1-pathway-is-involved-in-the-therapeutic-effects-of-simvastatin-on-pulmonary-arterial-hypertension
#5
Wei-Hua Liu, Xiao-Hong Xu, Qin Luo, Hong-Liang Zhang, Yong Wang, Qun-Ying Xi, Zhi-Hui Zhao, Zhi-Hong Liu
BACKGROUND: Recent research has shown that statins improve pulmonary arterial hypertension (PAH), but their mechanisms of action are not fully understood. This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. METHODS: For in vivo experiments, rats (N = 40) were randomly assigned to four groups: control, simvastatin, monocrotaline (MCT), and MCT + simvastatin. The MCT group and MCT + simvastatin groups received proline dithiocarbamate (50 mg/kg, i...
January 10, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29283979/inhibition-of-rho-kinase-by-fasudil-attenuates-ischemic-lung-injury-after-cardiac-arrest-in-rats
#6
Jian Wei, Peng Wang, Yi Li, Qingli Dou, Jiali Lin, Wuyuan Tao, Jinle Lin, Xuan Fu, Zitong Huang, Wenwu Zhang
Lung injury is a common complication after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), and Rho kinase (ROCK) may be involved in the process of this injury. In this study, we aimed to study the effects of ROCK inhibition by fasudil on lung injury induced by asphyxial CA and CPR in rats. A total of 130 rats were randomized into three groups: Sham, Control, and Fasudil intervention group. Animals in the Fasudil intervention group were intraperitoneally administered with 10 mg/kg of the drug, 1 h before inducing CA...
December 27, 2017: Shock
https://www.readbyqxmd.com/read/29280463/cavernous-nerve-injury-by-radiation-therapy-may-potentiate-erectile-dysfunction-in-rats
#7
Javed Mahmood, Caroline Q Connors, Allen A Alexander, Radmila Pavlovic, Santanu Samanta, Sandrine Soman, Hotaka Matsui, Nikolai A Sopko, Trinity J Bivalacqua, Daniel Weinreich, Cheng-Ying Ho, John Eley, Amit Sawant, Isabel L Jackson, Zeljko Vujaskovic
PURPOSE/OBJECTIVES: Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT lead to RiED; however, the precise role of RT-induced neurogenic injury in RiED has not been fully established...
November 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29275176/cxcl16-rock1-signaling-pathway-exacerbates-acute-kidney-injury-induced-by-ischemia-reperfusion
#8
Hua Liang, Meijuan Liao, Weicheng Zhao, Xueqin Zheng, Feng Xu, Hanbing Wang, Jian Huang
Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) resulting in an abrupt deterioration of kidney function. CXC chemokine ligand 16 (CXCL16) contributes significantly to the pathogenesis of renal injury. However, the signaling pathway mechanisms of CXCL16 in IRI-induced AKI remains obscured. In this study, we examined the role of the CXCL16/ Rho Associated Coiled-Coil Containing Protein Kinase-1 (ROCK1) signaling pathway in AKI induced by IRI. In vivo, CXCL16 was induced markedly after IRI...
December 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29251334/niclosamide-acts-as-a-new-inhibitor-of-vasculogenic-mimicry-in-oral-cancer-through-upregulation-of-mir-124-and-downregulation-of-stat3
#9
Xiaoxu Li, Zhicheng Yang, Zewen Han, Yanhui Wen, Zeyun Ma, Yixiang Wang
Tumors require nutrients and oxygen for growth and metastasis. Vasculogenic mimicry (VM) has been found as a new manner of blood supply, which is characterized as the formation of tumor cell-lined vessels instead of endothelial vessels. This is why angiogenesis agents targeted to endothelial cells show a limited efficacy. Up to this point, there is no effective drug reported for inhibiting VM formation. Niclosamide is an oral anti-helminthic drug used to treat human tapeworms. Recent studies have indicated that niclosamide has broad applications for cancer and other diseases...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29246448/common-variants-of-rocks-and-the-risk-of-hypertension-and-stroke-two-case-control-studies-and-a-follow-up-study-in-chinese-han-population
#10
Song Yang, Yanping Zhao, Yuanrui Tian, Yanchun Chen, Xianghai Zhao, Ying Li, Hailong Zhao, Xiaotian Chen, Lijun Zhu, Zhengmei Fang, YingShui Yao, Zhibing Hu, Chong Shen
The Rho kinases (ROCKs) are recognized as a critical regulator of vascular functions in cardiovascular disorders. It is crucial to illustrate the association of ROCKs genetic variation and hypertension and/or stroke events. Herein we aimed at investigating the association of ROCK1 and ROCK2 with hypertension and stroke in Chinese Han population. Seven tagSNPs at ROCK1 and ROCK2 were genotyped in a community-based case-control study consisting of 2012 hypertension cases and 2210 nomotensive controls and 4128 subjects were further followed up...
December 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29219181/exercise-increases-rho-kinase-activity-and-insulin-signaling-in-skeletal-muscle
#11
Vitor Rosetto Muñoz, Rafael Calais Gaspar, Gabriel Keine Kuga, Alisson Luiz da Rocha, Barbara Moreira Crisol, José Diego Botezelli, Igor Luchini Baptista, Rania A Mekary, Adelino Sanchez Ramos da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Eduardo Rochete Ropelle, José Rodrigo Pauli
The effects of physical exercise on insulin signaling and glycemic homeostasis are not yet fully understood. Recent findings elucidated the positive role of Rho-kinase (Rock) in increasing the glucose uptake through insulin receptor substrate-1 (IRS1) phosphorylation in the skeletal muscle. Here, we explored the effects of short-term exercise on Rock activity and insulin signaling. Fischer 344 rats (3 months old) were subjected to a short-term swimming exercise for 2 h per day for 5 days, with an overload corresponding to 1...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29211497/the-rho-kinase-isoforms-rock1-and-rock2-each-contribute-to-the-development-of-experimental-pulmonary-fibrosis
#12
Rachel S Knipe, Clemens K Probst, David Lagares, Alicia Franklin, Jillian J Spinney, Patricia L Brazee, Paula Grasberger, Linlin Zhang, Katharine E Black, Norihiko Sakai, Barry S Shea, James K Liao, Benjamin D Medoff, Andrew M Tager
Pulmonary fibrosis is thought to result from dysregulated wound repair after repetitive lung injury. Many cellular responses to injury involve rearrangements of the actin cytoskeleton mediated by the two isoforms of the Rho-associated coiled coil forming protein kinase, ROCK1 and ROCK2. Additionally, profibrotic mediators such as transforming growth factor-beta (TGF-β), thrombin and lysophosphatidic acid (LPA) act through receptors that activate ROCK. Inhibition of ROCK activation may be a potent therapeutic strategy for human pulmonary fibrosis...
December 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29201230/inhibition-of-penile-tunica-albuginea-myofibroblasts-activity-by-adipose-derived-stem-cells
#13
Hesong Jiang, Qingqiang Gao, Xiaoyan Che, Leilei Zhu, Zheng Zhang, Yun Chen, Yutian Dai
The activation of tunica albuginea myofibroblasts (MFs) serves an essential role in Peyronie's disease (PD). Increasing evidence has reported that adipose tissue-derived stem cells (ADSCs) have been demonstrated to attenuate the symptoms of PD in animal models. However, the mechanisms of the antifibrotic effects of ADSCs in PD remain to be fully elucidated. In the present study, the inhibitory effects and possible mechanism of ADSCs on the activation of MFs derived from rat penile tunica albuginea were investigated...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29156422/syndecan-1-in-mechanosensing-of-nanotopological-cues-in-engineered-materials
#14
Victoria Le, Jason Lee, Somali Chaterji, Adrianne Spencer, Yen-Liang Liu, Peter Kim, Hsin-Chih Yeh, Deok-Ho Kim, Aaron B Baker
The cells of the vascular system are highly sensitive to biophysical cues from their local cellular microenvironment. To engineer improved materials for vascular devices and delivery of cell therapies, a key challenge is to understand the mechanisms that cells use to sense biophysical cues from their environment. Syndecans are heparan sulfate proteoglycans (HSPGs) that consist of a protein core modified with heparan sulfate glycosaminoglycan chains. Due to their presence on the cell surface and their interaction with cytoskeletal and focal adhesion associated molecules, cell surface proteoglycans are well poised to serve as mechanosensors of the cellular microenvironment...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29142175/macrophage-differentiation-induced-by-pma-is-mediated-by-activation-of-rhoa-rock-signaling
#15
Lifeng Yang, Fan Dai, Lian Tang, Yulan Le, Wenjuan Yao
In order to investigate the effects of RhoA/ROCK signaling in macrophage differentiation, we used 100 ng/mL PMA to induce macrophage differentiation from U937 cells in vitro. The observation of cell morphology and the expression of CD68 and SR-A were performed to confirm the differentiation induced by PMA. Western blot analysis showed that the expression of ROCK1 and ROCK2 and the phosphorylation of MYPT1 were significantly increased after PMA treatment. Pulldown assay showed that the activation of RhoA was obviously enhanced when U937 cells were treated with PMA...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29130345/mir-199a-targeting-rock1-to-affect-kidney-cell-proliferation-invasion-and-apoptosis
#16
Zhigang Qin, Xin Wei, Ning Jin, Yao Wang, Rui Zhao, Yangqing Hu, Weijian Yan, Junke Li, Qiaoling Zhou
Renal cell carcinoma (RCC) is one of the three most common cancers of urinary tract cancer, accounting for 2-3% of all systemic cancers. Recent studies have found that miR-199a is lowly expressed in RCC, may act as a tumour suppressor gene to induce the occurrence of kidney cancer. In the present study, we investigated the role of miR-199a in the progression and metastasis of RCC. The results showed that miR-199a significantly downregulated in RCC and cell lines. Overexpression of miR-199a in RCC cell lines significantly inhibited cell proliferation, migration and invasion...
November 13, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29123196/identification-of-selection-signals-by-large-scale-whole-genome-resequencing-of-cashmere-goats
#17
Xiaokai Li, Rui Su, Wenting Wan, Wenguang Zhang, Huaizhi Jiang, Xian Qiao, Yixing Fan, Yanjun Zhang, Ruijun Wang, Zhihong Liu, Zhiying Wang, Bin Liu, Yuehui Ma, Hongping Zhang, Qianjun Zhao, Tao Zhong, Ran Di, Yu Jiang, Wei Chen, Wen Wang, Yang Dong, Jinquan Li
Inner Mongolia and Liaoning cashmere goats are two outstanding Chinese multipurpose breeds that adapt well to the semi-arid temperate grassland. These two breeds are characterized by their soft cashmere fibers, thus making them great models to identify genomic regions that are associated with cashmere fiber traits. Whole-genome sequencing of 70 cashmere goats produced more than 5.52 million single-nucleotide polymorphisms and 710,600 short insertions and deletions. Further analysis of these genetic variants showed some population-specific molecular markers for the two cashmere goat breeds that are otherwise phenotypically similar...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115372/inhibition-of-rho-kinase-protects-against-colitis-in-mice-by-attenuating-intestinal-epithelial-barrier-dysfunction-via-mlc-and-the-nf-%C3%AE%C2%BAb-pathway
#18
Yanting Zou, Lili Ma, Yuan Zhao, Shuncai Zhang, Chaohui Zhou, Yu Cai
The aim of the present study was to investigate the role of Rho kinase (also known as ROCK) inhibitor in 2,4,6-trinitrobenzene sulfonic acid induced mouse colitis; and to elucidate the underlying mechanism of ROCK1/ROCK2 inhibition in enhancing intestinal epithelial barrier (IEB) function. A specific inhibitor of ROCK, Y-27632, was used to examine the role of ROCK in mouse colitis models. ROCK1 and ROCK2 were silenced respectively using RNA interference in Caco-2 cells. The expression of tight junction proteins and the downstream molecules of ROCK were assessed...
October 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29096333/distinct-ephb4-mediated-mechanisms-of-apoptotic-and-resistance-to-dasatinib-in-human-chronic-myeloid-leukemia-and-k562-cell-lines
#19
Wei-Hong Zhao, Bin-Tao Huang, Jian-Yu Zhang, Qing-Chun Zeng
OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29070696/structural-determinants-influencing-the-potency-and-selectivity-of-indazole-paroxetine-hybrid-g-protein-coupled-receptor-kinase-2-inhibitors
#20
Renee Bouley, Helen V Waldschmidt, M Claire Cato, Alessandro Cannavo, Jianliang Song, Joseph Y Cheung, Xin-Qiu Yao, Walter J Koch, Scott D Larsen, John J G Tesmer
G protein-coupled receptor kinases (GRKs) phosphorylate activated receptors to promote arrestin binding, decoupling from heterotrimeric G proteins, and internalization. GRK2 and GRK5 are overexpressed in the failing heart and thus have become therapeutic targets. Previously, we discovered two classes of GRK2-selective inhibitors, one stemming from GSK180736A, a Rho-associated coiled-coil containing kinase 1 (ROCK1) inhibitor, the other from paroxetine, a selective serotonin-reuptake inhibitor. These two classes of compounds bind to the GRK2 active site in a similar configuration but contain different hinge-binding "warheads": indazole and benzodioxole, respectively...
December 2017: Molecular Pharmacology
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