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61.
Shoubin Dong Zetao Huang Xiaoyang Zhang Yongrou Zhang Yi Jiang 《Computer methods in biomechanics and biomedical engineering》2017,20(9):991-1003
The extracellular matrix (ECM) provides structural and biochemical support to cells and tissues, which is a critical factor for modulating cell dynamic behavior and intercellular communication. In order to further understand the mechanisms of the interactive relationship between cell and the ECM, we developed a three-dimensional (3D) collagen-fiber network model to simulate the micro structure and mechanical behaviors of the ECM and studied the stress–strain relationship as well as the deformation of the ECM under tension. In the model, the collagen-fiber network consists of abundant random distributed collagen fibers and some crosslinks, in which each fiber is modeled as an elastic beam and a crosslink is modeled as a linear spring with tensile limit, it means crosslinks will fail while the tensile forces exceed the limit of spring. With the given parameters of the beam and the spring, the simulated tensile stress–strain relation of the ECM highly matches the experimental results including damaged and failed behaviors. Moreover, by applying the maximal inscribed sphere method, we measured the size distribution of pores in the fiber network and learned the variation of the distribution with deformation. We also defined the alignment of the collagen-fibers to depict the orientation of fibers in the ECM quantitatively. By the study of changes of the alignment and the damaged crosslinks against the tensile strain, this paper reveals the comprehensive mechanisms of four stages of ‘toe’, ‘linear’, ‘damage’ and ‘failure’ in the tensile stress–strain relation of the ECM which can provide further insight in the study of cell-ECM interaction. 相似文献
62.
63.
Homeostasis and wound healing rely on stem cells (SCs) whose activity and directed migration are often governed by Wnt signaling. In dissecting how this pathway integrates with the necessary downstream cytoskeletal dynamics, we discovered that GSK3β, a kinase inhibited by Wnt signaling, directly phosphorylates ACF7, a > 500 kDa microtubule-actin crosslinking protein abundant in hair follicle stem cells (HF-SCs). We map ACF7's GSK3β sites to the microtubule-binding domain and show that phosphorylation uncouples ACF7 from microtubules. Phosphorylation-refractile ACF7 rescues overall microtubule architecture, but phosphorylation-constitutive mutants do not. Neither mutant rescues polarized movement, revealing that phospho-regulation must be dynamic. This circuitry is physiologically relevant and depends upon polarized GSK3β inhibition at the migrating front of SCs/progeny streaming from HFs during wound repair. Moreover, only ACF7 and not GSKβ-refractile-ACF7 restore polarized microtubule-growth and SC-migration to ACF7 null skin. Our findings provide insights into how this conserved spectraplakin integrates signaling, cytoskeletal dynamics, and polarized locomotion of somatic SCs. 相似文献
64.
Min Fei Na Li Yuguan Ze Jie Liu Xiaolan Gong Yanmei Duan Xiaoyang Zhao Han Wang Fashui Hong 《Biological trace element research》2011,139(1):72-80
In order to study the mechanisms underlying the effects of lanthanoid (Ln) on the liver, ICR mice were injected with LaCl3, CeCl3, and NdCl3 at a dose of 20 mg/kg BW into the abdominal cavity daily for 14 days. We then examined oxidative stress-mediated responses
in the liver. The increase of lipid peroxide in the liver produced by Ln suggested an oxidative attack that was activated
by a reduction of antioxidative defense mechanisms as measured by analyzing the activities of superoxide dismutase, catalase,
and ascorbate peroxidase, as well as antioxidant levels such as glutathione and ascorbic acid, which were greatest in Ce3+ treatment, medium in Nd3+, and least in La3+. Our results also implied that the oxidative stress in the liver caused by Ln likely is Ce3+ > Nd3+ >La3+, but the mechanisms need to be further studied in future. 相似文献
65.
Bannister JP Thomas-Gatewood CM Neeb ZP Adebiyi A Cheng X Jaggar JH 《The Journal of biological chemistry》2011,286(17):15058-15066
Voltage-dependent Ca(2+) (Ca(V)1.2) channels are the primary Ca(2+) influx pathway in arterial smooth muscle cells and are essential for contractility regulation by a variety of stimuli, including intravascular pressure. Arterial smooth muscle cell Ca(V)1.2 mRNA is alternatively spliced at exon 1 (e1), generating e1b or e1c variants, with e1c exhibiting relatively smooth muscle-specific expression in the cardiovascular system. Here, we examined physiological functions of Ca(V)1.2e1 variants and tested the hypothesis that targeting Ca(V)1.2e1 modulates resistance size cerebral artery contractility. Custom antibodies that selectively recognize Ca(V)1.2 channel proteins containing sequences encoded by either e1b (Ca(V)1.2e1b) or e1c (Ca(V)1.2e1c) both detected Ca(V)1.2 in rat and human cerebral arteries. shRNA targeting e1b or e1c reduced expression of that Ca(V)1.2 variant, induced compensatory up-regulation of the other variant, decreased total Ca(V)1.2, and reduced intravascular pressure- and depolarization-induced vasoconstriction. Ca(V)1.2e1b and Ca(V)1.2e1c knockdown reduced whole cell Ca(V)1.2 currents, with Ca(V)1.2e1c knockdown most effectively reducing total Ca(V)1.2 and inducing the largest vasodilation. Knockdown of α(2)δ-1, a Ca(V)1.2 auxiliary subunit, reduced surface expression of both Ca(V)1.2e1 variants, inhibiting Ca(V)1.2e1c more than Ca(V)1.2e1b. e1b or e1c overexpression reduced Ca(V)1.2 surface expression and whole cell currents, leading to vasodilation, with e1c overexpression inducing the largest effect. In summary, data indicate that arterial smooth muscle cells express Ca(V)1.2 channels containing e1b or e1c-encoded N termini that contribute to Ca(V)1.2 surface expression, α(2)δ-1 preferentially traffics the Ca(V)1.2e1c variant to the plasma membrane, and targeting of Ca(V)1.2e1 message or the Ca(V)1.2 channel proximal N terminus induces vasodilation. 相似文献
66.
Endovascular aneurysm repair (EVAR) is considered as a promising alternative technique for the treatment of aortic aneurysm. However, complications often occur after EVAR. In this paper, the influence of the physiological factors on the biomechanical behaviors of stented and non-stented thoracic aortic aneurysm (TAA) were presented. Representative TAA models with different intraluminal thrombus (ILT) volume before and after stent-graft (SG) implantation were built. Fluid-structure interaction effect was taken into account. The relative sliding between the SG wall and the aortic wall was allowed. Results showed that the cardiac cycle and ILT volume should be given much more consideration than previously thought in future investigations on TAA compliance. The time-averaged longitudinal displacement of SG necks were not uniformly distributed along circumferential direction of the aortic wall. Drag force increased with the increase of the cardiac cycle and decreased with the decrease of ILT volume. Computational results of TAA wall stress, sac and lumen pressure indicated that patient with faster heart rate might be at great risk of aneurysm rupture. The stress absorption effect of the SG was influenced by both ILT and cardiac cycle, which was also found to have strong impact on flow pattern. We believe that this study will bring new insights into further researches on the relevant issues and provide mechanics-based implications for clinical management of EVAR for TAA patient. 相似文献
67.
Xiaojing Chang Xiaoyang Xu Jinguo Ma Xiaoying Xue Zhenhua Li Peng Deng Shuanglong Zhang Yu Zhi Jing Chen Dongqiu Dai 《Molecular biology reports》2014,41(9):6215-6223
N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1–NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer. 相似文献
68.
该研究以麻疯树种子实生苗的小芽和芽条为接穗,以带有胚根的实生苗下胚轴为砧木进行无菌微嫁接,试图建立新的有效微嫁接方法,解决农杆菌介导的麻疯树遗传转化体系中再生的转化不定芽难以顺利发育成完整植株的问题。结果表明:(1)抗生素对嫁接苗的生长有显著的抑制作用。(2)进行微嫁接所用砧木的苗龄以5d为宜。(3)进行微嫁接时适宜采用的砧木类型为带有部分胚根的下胚轴。(4)嫁接苗在0.3mg/L IBA+2mg/L谷氨酰胺+1/2MS培养基上的生长效果最好。(5)嫁接苗的移栽成活率最高可达76.40%。(6)以小芽或芽条为接穗的嫁接苗均可正常生长。该研究建立的麻疯树微嫁接体系,为解决麻疯树转化不定芽或芽条生长发育困难的问题提供了一条新的途径。 相似文献
69.
Scott?A?Yuzwa Xiaoyang?Shan Bryan?A?Jones Gang?Zhao Melissa?L?Woodward Xiaojing?Li Yanping?Zhu Ernest?J?McEachern Michael?A?Silverman Neil?V?Watson Cheng-Xin?Gong David?J?VocadloEmail author 《Molecular neurodegeneration》2014,9(1):42
Background
Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer’s disease (AD). Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. It remains unknown, however, if O-GlcNAc can influence the formation of amyloid plaques in the presence of tau pathology.Results
We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques.Conclusions
This study indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology. The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease.70.