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https://www.readbyqxmd.com/read/29329594/modelling-the-structure-of-a-cerna-theoretical-bipartite-microrna-mrna-interaction-network-regulating-intestinal-epithelial-cellular-pathways-using-r-programming
#1
J M Robinson, W A Henderson
OBJECTIVE: We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors...
January 12, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29314498/design-of-aminobenzothiazole-inhibitors-of-rho-kinases-1-and-2-utilizing-pka-as-a-structure-surrogate
#2
Russell Judge, Victoria Scott, Gricelda Simler, Steve Pratt, Marian Namovic, Brent Putman, Ana Aguirre, Vincent Stoll, Mulugeta Mamo, Steve Swann, Adrian D Hobson
We describe the design, synthesis and SAR of a series of 2-aminobenzothiazole inhibitors of Rho Kinase (ROCK) 1 and 2 which were optimized to low nanomolar potencies using structure-based design. Protein Kinase A was used as a surrogate protein structure to guide compound design. A subset of these molecules also showed robust activity in a myosin phosphatase cell based assay and in a mechanical hyperalgesia in vivo pain model.
January 4, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29310804/the-cytoskeletal-network-regulates-expression-of-the-profibrotic-genes-pai-1-and-ctgf-in-vascular-smooth-muscle-cells
#3
Rohan Samarakoon, Paul J Higgins
Vascular smooth muscle cells (VSMCs) are subject to changing hemodynamic stimuli that alter cytoskeletal dynamics, cellular architecture, and structure-associated signal transduction. Tensional stress, force application, and structural perturbations are sensed by VSMCs and impact the physiological as well as pathophysiological responses of the vasculature. Microtubule-targeting drugs provide useful tools to analyze cytoskeletal-associated signaling pathways and their linkages to pathological outcomes. Architecture-based controls on a subset of profibrotic genes commonly expressed in vascular disease are highlighted by their frequent induction in mechanically manipulated cells and with associated changes in cytoskeletal dynamics...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29306925/calcium-sensitization-mechanisms-in-detrusor-smooth-muscles
#4
REVIEW
Irfan Anjum
The contraction of detrusor smooth muscles depends on the increase in intracellular calcium. The influx of calcium from the plasma membrane calcium channels and calcium release from the sarcoplasmic reticulum give rise to intracellular calcium. Under the pathophysiological conditions, the increased sensitivity of regulatory and contractile proteins to calcium also plays an important role in maintaining the spontaneous detrusor smooth muscle activity. Many proteins have been identified to play a role in calcium sensitization...
January 8, 2018: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29305605/role-of-the-autotaxin-lpa-pathway-in-dexamethasone-induced-fibrotic-responses-and-extracellular-matrix-production-in-human-trabecular-meshwork-cells
#5
Megumi Honjo, Nozomi Igarashi, Junko Nishida, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Kuniyuki Kano, Junken Aoki, Makoto Aihara
Purpose: Dexamethasone (Dex) regulates aqueous humor outflow by inducing reorganization of the cytoskeleton and extracellular matrix (ECM) production. Rho kinase (ROCK) has an important role in this process, but the upstream pathway leading to its activation remains elusive. The purpose of the study was to determine the role of autotaxin (ATX), an enzyme involved in the generation of lysophosphatidic acid (LPA), in the Dex-induced fibrotic response and ECM production in human trabecular meshwork (HTM) cells...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29288243/rho-rock-pathway-regulates-migration-and-invasion-of-esophageal-squamous-cell-carcinoma-by-regulating-caveolin-1
#6
Zhaohui Liu, Jing Yu, Ruinuan Wu, Shengxin Tang, Xiaoman Cai, Guanghua Guo, Suzuan Chen
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. Caveolin-1 (Cav1) and Rho/ROCK pathway play important roles in tumor metastasis, separately. However, less research was focused on the relationship between Cav1 and Rho/ROCK in ECSS metastasis. Therefore, we investigated the relationship between Cav1 and Rho/ROCK pathway in ESCC metastasis. MATERIAL AND METHODS Cav1 and phosphorylated Cav1 (PY14Cav1) were examined in ESCC and in adjacent and non-tumorous tissues from ESCC patients by immunohistochemistry (IHC)...
December 30, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29285182/effects-of-caszi-on-bronchopulmonary-development-of-neonatal-rats
#7
Liping Xu, Ruifang Tong, Xiangnan Li, Lihong Liang, Han Huang
The effect of CASZI on bronchopulmonary development in neonatal rats was investigated. Forty SD rats were randomly divided into the control group (n=20) and the experimental group (n=20) using a random number table. The experimental group was treated with hyperoxia to establish the bronchopulmonary dysplasia (BPD) model, while the control group received no treatment. At 14 days of experiment, rats in each group were treated, and lung tissues were taken for hematoxylin and eosin (H&E) staining. Radial alveolar count (RAC) and morphological changes in lung tissues were observed under a microscope, and the thickness of respiratory membrane was detected via IPP6 image...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29283979/inhibition-of-rho-kinase-by-fasudil-attenuates-ischemic-lung-injury-after-cardiac-arrest-in-rats
#8
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
#9
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/29259896/involvement-of-rho-associated-coiled-coil-kinase-signaling-inhibition-in-tgf-%C3%AE-1-smad2-3-signal-transduction-in-vitro
#10
Zhao-Hui Feng, Xiao-Hui Zhang, Jia-Qi Zhao, Jun-Ze Ma
AIM: To research the effect of Y-27632, a selective Rho-associated coiled-coil kinase (ROCK) inhibitor, on TGF-β1/Smad2, 3 signal transduction in ocular Tenon's capsule fibroblasts (OTFs). METHODS: Primary ocular Tenon's capsule fibroblasts had been cultured in vitro. The effect of Y27632 on proliferation of OTF stimulated by lysophosphatidic acid (LPA) was evaluated by MTT colorimetric assay so as to sift out the proper concentrations range of Y-27632 for the next experiment...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29249463/derivation-of-human-trophoblast-stem-cells
#11
Hiroaki Okae, Hidehiro Toh, Tetsuya Sato, Hitoshi Hiura, Sota Takahashi, Kenjiro Shirane, Yuka Kabayama, Mikita Suyama, Hiroyuki Sasaki, Takahiro Arima
Trophoblast cells play an essential role in the interactions between the fetus and mother. Mouse trophoblast stem (TS) cells have been derived and used as the best in vitro model for molecular and functional analysis of mouse trophoblast lineages, but attempts to derive human TS cells have so far been unsuccessful. Here we show that activation of Wingless/Integrated (Wnt) and EGF and inhibition of TGF-β, histone deacetylase (HDAC), and Rho-associated protein kinase (ROCK) enable long-term culture of human villous cytotrophoblast (CT) cells...
November 30, 2017: Cell Stem Cell
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
#12
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/29246246/rho-gtpases-as-therapeutic-targets-in-alzheimer-s-disease
#13
REVIEW
Byron J Aguilar, Yi Zhu, Qun Lu
The progress we have made in understanding Alzheimer's disease (AD) pathogenesis has led to the identification of several novel pathways and potential therapeutic targets. Rho GTPases have been implicated as critical components in AD pathogenesis, but their various functions and interactions make understanding their complex signaling challenging to study. Recent advancements in both the field of AD and Rho GTPase drug development provide novel tools for the elucidation of Rho GTPases as a viable target for AD...
December 15, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29231515/-reviews-on-acupuncture-for-cellular-signal-transduction-in-spinal-cord-injury
#14
REVIEW
Jisheng Liu, Hong Zhang, Guilan Huang, Ming Xu, Jian Zhang, Xiuting Yin
Investigating the influence of acupuncture on cellular signal transduction is an efficient pathway to reveal the action mechanism of acupuncture on spinal cord injury (SCI). In this study, the experiment research literature regarding acupuncture for SCI during past 10 years was reviewed and analyzed. As a result, it was found that acupuncture could regulate the expression of the first intercellular messenger as well as the second signal molecules including cyclic adenosine monophosphate, cyclic guanosine monophosphate, Ca2+, nitric oxide to intervene the apoptotic signaling pathway, Rho/Rock signaling pathway, Wnt signaling pathway, MAPK signaling pathway, Notch signaling pathway, etc...
June 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29228716/sox2-modulates-motility-and-enhances-progression-of-colorectal-cancer-via-the-rho-rock-signaling-pathway
#15
Junheng Zheng, Lixiao Xu, Yubin Pan, Shuyi Yu, Hongbo Wang, Derek Kennedy, Yan Zhang
Sox2 (Sry-box2) is essential for a variety of stem cells and is also expressed in colorectal cancer (CRC). However, the underlying mechanism by which Sox2 enhances CRC progression remains unclear. In the present study, we show that elevated Sox2 expression is significantly correlated with poor clinical prognosis. CRC is phenotypically heterogeneous, and harbors several subtypes of cancer cells. Elevated Sox2 expression was always detected in rounded-shape cells, which co-located to poorly differentiated regions, the invasive frontier and metastatic lesions...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221121/tropomyosin-isoform-tpm2-1-regulates-collective-and-amoeboid-cell-migration-and-cell-aggregation-in-breast-epithelial-cells
#16
HyeRim Shin, Dayoung Kim, David M Helfman
Metastasis dissemination is the result of various processes including cell migration and cell aggregation. These processes involve alterations in the expression and organization of cytoskeletal and adhesion proteins in tumor cells. Alterations in actin filaments and their binding partners are known to be key players in metastasis. Downregulation of specific tropomyosin (Tpm) isoforms is a common characteristic of transformed cells. In this study, we examined the role of Tpm2.1 in non-transformed MCF10A breast epithelial cells in cell migration and cell aggregation, because this isoform is downregulated in primary and metastatic breast cancer as well as various breast cancer cell lines...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220720/induction-of-thymic-stromal-lymphopoietin-by-a-steroid-alkaloid-derivative-in-mouse-keratinocytes
#17
Yan Weng, Natsumi Mizuno, Jiangxu Dong, Ryosuke Segawa, Takayuki Yonezawa, Byung Yoon Cha, Je-Tae Woo, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and exacerbating allergic diseases. Chemical compounds that induce TSLP production can enhance sensitization to antigens and exacerbate allergic inflammation. Hence, identifying such chemicals will be important to prevent an increase in allergic diseases. In the present study, we found, for the first time, that a steroid alkaloid derivative, code no. 02F04, concentration and time dependently induced mRNA expression and production of TSLP in a mouse keratinocyte cell line, PAM212...
December 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29219181/exercise-increases-rho-kinase-activity-and-insulin-signaling-in-skeletal-muscle
#18
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/29217659/rock-dependent-phosphorylation-of-nup62-regulates-p63-nuclear-transport-and-squamous-cell-carcinoma-proliferation
#19
Masaharu Hazawa, De-Chen Lin, Akiko Kobayashi, Yan-Yi Jiang, Liang Xu, Firli Rahmah Primula Dewi, Mahmoud Shaaban Mohamed, Hartono, Mitsutoshi Nakada, Makiko Meguro-Horike, Shin-Ichi Horike, H Phillip Koeffler, Richard W Wong
p63, more specifically its ΔNp63α isoform, plays essential roles in squamous cell carcinomas (SCCs), yet the mechanisms controlling its nuclear transport remain unknown. Nucleoporins (NUPs) are a family of proteins building nuclear pore complexes (NPC) and mediating nuclear transport across the nuclear envelope. Recent evidence suggests a cell type-specific function for certain NUPs; however, the significance of NUPs in SCC biology remains unknown. In this study, we show that nucleoporin 62 (NUP62) is highly expressed in stratified squamous epithelia and is further elevated in SCCs...
December 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29214163/protective-effects-of-pyridoxamine-supplementation-in-the-early-stages-of-diet-induced-kidney-dysfunction
#20
F Chiazza, A S Cento, D Collotta, D Nigro, G Rosa, F Baratta, V Bitonto, J C Cutrin, M Aragno, R Mastrocola, M Collino
Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative effects, has been proposed as supplementary approach in patients with initial diabetic nephropathy. However, the molecular mechanism(s) underlying its protective role has been so far slightly examined. C57Bl/6J mice were fed with a standard diet (SD) or a diet enriched in fat and fructose (HD) for 12 weeks. After 3 weeks, two subgroups of SD and HD mice started pyridoxamine supplementation (150 mg/kg/day) in the drinking water. HD fed mice showed increased body weight and impaired glucose tolerance, whereas pyridoxamine administration significantly improved insulin sensitivity, but not body weight, and reduced diet-induced increase in serum creatinine and urine albumin...
2017: BioMed Research International
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