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Tao Wei, Lei Liu, Xiaoying Zhou
Airway smooth muscle (ASM) is a prominent effecter in maintaining bronchial muscle contraction and responsible for airway hyper-responsiveness (AHR); the phenotype change and over-proliferation of airway smooth muscle cells (ASMCs) play key roles in the pathogenesis of asthma. The aim of this study was to investigate the anti-proliferation effects of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDE) on ASMCs and the possible underline mechanisms. Cell proliferation rates were determined by MTT assay; matrix metalloproteinases-2 (MMP-2) activity was examined by gelatin zymography; cell proliferation and migration were appraised by in-vitro cell-gap closure assessment; protein expressions of p38, Bcl-2 and FAK of ASMCs were evaluated by western blotting and Ca2+ influx of cells was measured by confocal laser microscope...
March 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
He Wang, Jianjia Li, Xiaoyi Zhang, Tingting Ning, Dandan Ma, Yihong Ge, Shuaimei Xu, Yilin Hao, Buling Wu
To seek a potential target for periodontal tissue regeneration, this study aimed to explore the role of Integrin alpha 5 (ITGA5) in human periodontal ligament stem cells (PDLSCs). Transwell assay, Cell Counting Kit 8 (CCK8) assay, cell cycle assay, alkaline phosphatase (ALP) activity, alizarin red staining, and western blot were used to investigate the effects of ITGA5 on PDLSC migration, proliferation and osteogenic differentiation. The in vivo effect was investigated by nude mice subcutaneous transplantation with cell and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) complex...
March 12, 2018: Journal of Proteomics
Peng Song, Yang Hai, Xin Wang, Longhe Zhao, Baoqiang Chen, Peng Cui, Qinjian Xie, Lan Yu, Yang Li, Zhengrong Wu, Hongyu Li
Realgar (As4 S4 ), as an arsenic sulfide mineral drug, has a good therapeutic reputation for anticancer in Traditional Chinese Medicine, and has recently been reported to inhibit angiogenesis in tumor growth. However, considering the poor solubility and low bioavailability of realgar, large dose of realgar and long period of treatment are necessary for achieving the effective blood medicine concentration. In present study, we resolved the crucial problem of poor solubility of realgar by using intrinsic biotransformation in microorganism, and investigated underlying mechanisms of realgar transforming solution (RTS) for antiangiogenesis...
March 15, 2018: Archives of Pharmacal Research
Carmen Ruggiero, Mauro Grossi, Giorgia Fragassi, Antonella Di Campli, Carmine Di Ilio, Alberto Luini, Michele Sallese
Membrane trafficking via the Golgi-localised KDEL receptor activates signalling cascades that coordinate both trafficking and other cellular functions, including autophagy and extracellular matrix degradation. In this study, we provide evidence that membrane trafficking activates KDEL receptor and the Src family kinases at focal adhesions of HeLa cells, where this phosphorylates ADP-ribosylation factor GTPase-activating protein with SH3 domain, ankyrin repeat and PH domain (ASAP)1 and focal adhesion kinase (FAK)...
February 13, 2018: Oncotarget
Cui Zhang, Liang Li, Yuanda Jiang, Cuicui Wang, Baoming Geng, Yanqiu Wang, Jianling Chen, Fei Liu, Peng Qiu, Guangjie Zhai, Ping Chen, Renfu Quan, Jinfu Wang
Bone formation is linked with osteogenic differentiation of mesenchymal stem cells (MSCs) in the bone marrow. Microgravity in spaceflight is known to reduce bone formation. In this study, we used a real microgravity environment of the SJ-10 Recoverable Scientific Satellite to examine the effects of space microgravity on the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs). hMSCs were induced toward osteogenic differentiation for 2 and 7 d in a cell culture device mounted on the SJ-10 Satellite...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sawana Singkhorn, Mayuree H Tantisira, Supita Tanasawet, Pilaiwanwadee Hutamekalin, Tulaporn Wongtawatchai, Wanida Sukketsiri
Centella asiatica is widely considered the most important medicinal plant for treating and relieving skin diseases. Recently developed standardized extract of Centella asiatica ECa 233 has demonstrated positive effects on wound healing of incision and burn wound in rats. However, knowledge associated with wound healing mechanism of ECa 233 was scare. Therefore, this study aimed to investigate the effect and underlying molecular mechanisms of ECa 233 on the migration of a human keratinocyte cell line (HaCaT) using scratch wound healing assay...
March 13, 2018: Phytotherapy Research: PTR
Yeming Xie, Koon Hee Han, Nathan Grainger, Wen Li, Robert D Corrigan, Brian A Perrino
Smooth muscle contraction involves regulating myosin light chain phosphorylation and dephosphorylation by myosin light chain kinase and myosin light chain phosphatase. CPI-17 and MYPT1 are crucial for regulating gastrointestinal smooth muscle contraction by inhibiting myosin light chain phosphatase. Integrin signalling involves the dynamic recruitment of several proteins, including FAK, to focal adhesions. FAK tyrosine kinase activation is involved in cell adhesion to the extracellular matrix via integrin signalling...
March 12, 2018: Journal of Physiology
Min Jiang, Qiang Lyu, Yun-Gang Bai, Huan Liu, Jing Yang, Jiu-Hua Cheng, Ming Zheng, Jin Ma
Recent studies have suggested that microgravity-induced arterial remodelling contributes to post-flight orthostatic intolerance and that multiple mechanisms are involved in arterial remodelling. However, the initial mechanism by which haemodynamic changes induce arterial remodelling is unknown. Focal adhesions (FAs) are dynamic protein complexes that have mechanotransduction properties. This study aimed to investigate the role of FAs in simulated microgravity-induced basilar and femoral arterial remodelling...
March 11, 2018: Canadian Journal of Physiology and Pharmacology
Zhiqiang Wu, Ting Wang, Meng Fang, Wending Huang, Zhengwang Sun, Jianru Xiao, Wangjun Yan
Breast cancer accounts for about 30% of all cancers in women, while approximately 70% breast cancer patients developed bone metastases throughout the course of their disease, highlighting the importance of exploring new therapeutic targets. Microfibrillar-associated protein 5 (MFAP5) is a component of extracellular elastic microfibril which has been confirmed to function in tissue development and cancer progression. But the role of MFAP5 in breast cancer remains unclear. The present study demonstrated that MFAP5 was up-regulated in breast cancers compared with that in normal breast tissues, and further increased in breast cancer bone metastasis...
March 8, 2018: Biochemical and Biophysical Research Communications
Yixi Chen, Jianping Cao, Qihui Zhao, Haiyong Luo, Yiguang Wang, Wenjian Dai
Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content...
March 2018: Korean Journal of Physiology & Pharmacology
Hyun-Kyung Kim, Purevjargal Naidansuren, Seung Woo Lee, Rae-Kwon Kim, Su-Jae Lee, Suk Keun Lee, Yong-Kil Hong, Young Ae Joe
The recombinant kringle domain of urokinase (UK1) has been shown to inhibit angiogenesis and brain tumor growth in vivo . To avoid limitations in application due to mass production of recombinant protein, we attempted to develop a novel peptide inhibitor from UK1 sequence consisting of 83 amino acids that contains α-helices, loops and β-sheets. We dissected UK1 sequence to seven peptides based on structure and amino acid characteristics, and examined the anti-angiogenic activities for the constructed peptides...
February 9, 2018: Oncotarget
Yan Cheng, Xing-Hua Gao, Xian-Jing Li, Qiu-Hua Cao, Dan-Dan Zhao, Jin-Rong Zhou, Hong-Xi Wu, Yun Wang, Lin-Jun You, Hong-Bao Yang, Yun-Long He, Yong-Ren Li, Jin-Song Bian, Qing-Yi Zhu, Lutz Birnbaumer, Yong Yang
Depression drives cancer progression and induces poor clinical outcome. However, the mechanisms underlying depression and cancer outcomes are unclear. In this work, we investigated 98 prostate cancer patients and found that patients with high score of psychological depression were correlated with tumor invasion and metastasis. We found focal adhesion kinase (FAK) was increased in cancer patients with metastatic features and high score of depression. FAK knockdown completely blocked depression-promoted tumor invasion in orthotopic transplantation tumors...
March 8, 2018: Oncogene
Yan Liang, Xuedan Chen, Yuanyuan Wu, Juan Li, Shixin Zhang, Kai Wang, Xingying Guan, Kang Yang, Yun Bai
Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Long noncoding RNAs (lncRNAs) are thought to play a critical role in cancer development. Recently, lncRNA CASC9 was shown to be dysregulated in many cancer types, but the mechanisms whereby this occurs remain largely unknown. In this study, we found that CASC9 was significantly upregulated in ESCC tissues, with further analysis revealing that elevated CASC9 expression was associated with ESCC prognosis and metastasis. Furthermore, we found that CASC9 knockdown significantly repressed ESCC migration and invasion in vitro and metastasis in nude mice in vivo...
March 6, 2018: Cell Death and Differentiation
Deepesh Kumar Gupta, Jian Du, Siamak A Kamranvar, Staffan Johansson
Previous studies have shown that cytokinetic abscission at the end of mitosis is executed by the ESCRT machinery in mammalian cells, and that the process is dependent on adhesion-induced integrin signalling via a FAK-PLK1-CEP55-TSG101/Alix-CHMP4B pathway. The present study identified an alternative abscission mechanism driven by mechanical force. In the absence of integrin signals (non-adherent conditions), cytokinesis in non-transformed human fibroblasts proceeds to CEP55 accumulation at the midbody, but after prolonged time (>3 hours) the major midbody components Aurora B, MKLP1 and CEP55 were no longer detected in the area...
February 6, 2018: Oncotarget
Dongliang Li, Yongjian Zhang, He Zhang, Chao Zhan, Xin Li, Tu Ba, Zini Qiu, Fang E, Guixiang Lv, Chendan Zou, Chuxuan Wang, Lining Si, Chaoxia Zou, Qiang Li, Xu Gao
BACKGROUND: Cell adhesion molecules (CADMs) comprise of a protein family whose functions include maintenance of cell polarity and tumor suppression. Hypo-expression of CADM2 gene expression has been observed in several cancers including hepatocellular carcinoma (HCC). However, the role and mechanisms of CADM2 in HCC remain unclear. METHODS: The expression of CADM2 and miRNA-10b (miR-10b) in HCC tissues and cell lines were detected using real-time PCR and Western blotting...
March 5, 2018: Journal of Experimental & Clinical Cancer Research: CR
Jian Song, Bin Ye, Hanghang Liu, Ruiye Bi, Nian Zhang, Jing Hu, En Luo
OBJECTIVES: To investigate the mechanism of mechanical stimulation in bone formation and regeneration during distraction osteogenesis. MATERIALS AND METHODS: In this study, microarray technology was used to investigate the time course of bone-related molecular changes in distraction osteogenesis in rats. Real-time PCR and Western-blot analyses were used to confirm the expression of genes identified in microarrays. Meanwhile, we used a lentivirus vector to inhibit Fak expression, in order to identify the osteogenic effect of Fak and Fak-Mapk pathway during distraction osteogenesis...
March 5, 2018: Cell Proliferation
Ceren Yarar-Fisher, Keith Fl Polston, Mualla Eraslan, Kathryn Y Henley, Gizem I Kinikli, C Scott Bickel, Samuel T Windham, Amie B McLain, Robert A Oster, Marcas M Bamman
This study compares the effects of an 8-week iso-caloric high protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and non-paralytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-week interventions. A total of 11 participants (C5-T12 levels, 21...
March 1, 2018: Journal of Applied Physiology
Xin Tan, Aizhang Xu, Tuo Zhao, Qin Zhao, Jun Zhang, Cuihong Fan, Yulin Deng, Andrew Freywald, Harald Genth, Jim Xiang
Simulated microgravity (SMG) was reported to affect tumor cell proliferation and metastasis. However, the underlying mechanism is elusive. In this study, we demonstrate that clinostat-modelled SMG reduces BL6-10 melanoma cell proliferation, adhesion and invasiveness in vitro and decreases tumor lung metastasis in vivo. It down-regulates metastasis-related integrin α6β4, MMP9 and Met72 molecules. SMG significantly reduces formation of focal adhesions and activation of focal adhesion kinase (FAK) and Rho family proteins (RhoA, Rac1 and Cdc42) and of mTORC1 kinase, but activates AMPK and ULK1 kinases...
February 28, 2018: Scientific Reports
Meiyu Sun, Guangfan Chi, Juanjuan Xu, Ye Tan, Jiayi Xu, Shuang Lv, Ziran Xu, Yuhan Xia, Lisha Li, Yulin Li
BACKGROUND: Human mesenchymal stem cell (hMSC) differentiation into osteoblasts has important clinical significance in treating bone injury, and the stiffness of the extracellular matrix (ECM) has been shown to be an important regulatory factor for hMSC differentiation. The aim of this study was to further delineate how matrix stiffness affects intracellular signaling through integrin α5/β1, FAK, and Wnt signaling, subsequently regulating the osteogenic phenotype of hMSCs. METHODS: hMSCs were cultured on tunable polyacrylamide hydrogels coated with fibronectin with stiffness corresponding to a Young's modulus of 13-16 kPa and 62-68 kPa...
March 1, 2018: Stem Cell Research & Therapy
Hongchi Yu, Min Gao, Yunlong Ma, Lijuan Wang, Yang Shen, Xiaoheng Liu
angiogenesis plays an important role in the development and progression of tumors, and it involves a series of signaling pathways contributing to the migration of endothelial cells for vascularization and to the invasion of cancer cells for secondary tumor formation. Among these pathways, the focal adhesion kinase (FAK) signaling cascade has been implicated in a variety of human cancers in connection with cell adhesion and migration events leading to tumor angiogenesis, metastasis and invasion. Therefore, the inhibition of FAK in endothelial and/or cancer cells is a potential target for anti‑angiogenic therapy...
February 23, 2018: International Journal of Molecular Medicine
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