124 research outputs found

    Unique arrangement of bone matrix orthogonal to osteoblast alignment controlled by Tspan11-mediated focal adhesion assembly

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    During tissue construction, cells coordinate extracellular matrix (ECM)assembly depending on the cellular arrangement. The traditional understanding of the relationship between the ECM and cells is limited to the orientation-matched interaction between them. Indeed, it is commonly accepted that the bone matrix (collagen/apatite)is formed along osteoblast orientation. Nonetheless, our recent findings are contrary to the above theory; osteoblasts on nanogrooves organize formation of the bone matrix perpendicular to cell orientation. However, the precise molecular mechanisms underlying the orthogonal organization of bone matrix are still unknown. Here, we show that mature fibrillar focal adhesions (FAs)facilitate the perpendicular arrangement between cells and bone matrix. The osteoblasts aligned along nanogrooves expressed highly mature fibrillar FAs mediated by integrin clustering. Microarray analysis revealed that Tspan11, a member of the transmembrane tetraspanin protein family, was upregulated in cells on the nanogrooved surface compared with that in cells on isotropic, flat, or rough surfaces. Tspan11 silencing significantly disrupted osteoblast alignment and further construction of aligned bone matrix orthogonal to cell orientation. Our results demonstrate that the unique bone matrix formation orthogonal to cell alignment is facilitated by FA maturation. To the best of our knowledge, this report is the first to show that FA assembly mediated by Tspan11 determines the direction of bone matrix organization.Nakanishi Y., Matsugaki A., Kawahara K., et al. Unique arrangement of bone matrix orthogonal to osteoblast alignment controlled by Tspan11-mediated focal adhesion assembly. Biomaterials, 209, 103. https://doi.org/10.1016/j.biomaterials.2019.04.016

    肝線維化におけるペリオスチンの役割 : レニン・アンギオテンシン系とクロストーク

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    Periostin is a 90‑kDa extracellular matrix protein, which is secreted primarily from fibroblasts and is expressed in the lungs, kidneys and heart valves. Angiotensin II (AT‑II) serves pivotal roles in the pathogenesis of several diseases with accompanying fibrosis, including chronic liver diseases. AT‑II induces periostin expression by regulating transforming growth factor‑β1 (TGF‑β1)/Smad signaling during cardiac fibrosis. The aim of the present study was to investigate the interaction between AT‑II and periostin during liver fibrosis development. Fischer 344 rats were fed a choline‑deficient L‑amino‑acid (CDAA)‑defined diet for 12 weeks to simulate the development of steatohepatitis with liver fibrosis. Losartan, an AT‑II type I receptor blocker, was administered to inhibit the effect of AT‑II. The therapeutic effect of losartan on hepatic fibrosis development and on periostin expression was then evaluated. Several in vitro experiments were performed to examine the mechanisms underlying the interaction between AT‑II and periostin in activated hepatic stellate cells (Ac‑HSCs). Treatment with losartan suppressed the development of liver fibrosis induced by the CDAA diet, and reduced hepatic periostin expression. In addition, losartan treatment suppressed hepatic Ac‑HSC expansion and hepatic TGF‑β1 expression. In vitro analysis using LX2 HSC cells indicated that AT‑II can augment TGF‑β1 and collagen type I α1 mRNA expression via periostin expression, suggesting that the interaction between AT‑II and periostin may serve a role in liver fibrosis development. In conclusion, blockade of AT‑II‑induced periostin may suppress the progression of liver fibrosis development.博士(医学)・乙第1413号・平成30年3月15日Copyright: © Takeda et al. This is an open access article distributed under the terms of Creative Commons Attribution License(CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/

    OpenPLC based control system testbed for PLC whitelisting system

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    This paper proposes a security testbed system for industrial control systems. In control systems, controllers are final fortresses to continue the operation of field systems. Then, we need countermeasures of controllers. The whitelisting function is efficient in controller security. The whitelisting function registers normal operations in a list and detects unregistered operations as abnormal. We need a testbed system to check whether the whitelist function does not affect other functions of the controller. The industrial controller and its engineering tool are relatively expensive, and are customized with respect to controller vendors. To enhance the whitelist development, this study proposes a testbed system using OpenPLC which is an open-source software. This system is independent of controller vendors and is applicable for controller programming languages. We implement a whitelist based anomaly detection method for the testbed system and validate that the anomaly detection method operates correctly

    フルクトースの経口投与はラット脂肪性肝炎モデルにおいて腸管透過性亢進作用を介して肝線維化および肝発癌を悪化させる

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    Recent reports have revealed the impact of a western diet containing large amounts of fructose on the pathogenesis of non-alcoholic steatohepatitis (NASH). Fructose exacerbates hepatic inflammation in NASH by inducing increasing intestinal permeability. However, it is not clear whether fructose contributes to the progression of liver fibrosis and hepatocarcinogenesis in NASH. The aim of this study was to investigate the effect of fructose intake on NASH in a rat model. A choline-deficient/L-amino acid diet was fed to F344 rats to induce NASH. Fructose was administrated to one group in the drinking water. The development of liver fibrosis and hepatocarcinogenesis were evaluated histologically. Oral fructose administration exacerbated liver fibrosis and increased the number of preneoplastic lesions positive for glutathione S-transferase placental form. Fructose-treated rats had significantly higher expression of hepatic genes related to toll-like receptor-signaling, suggesting that fructose consumption increased signaling in this pathway, leading to the progression of NASH. We confirmed that intestinal permeability was significantly higher in fructose-treated rats, as evidenced by a loss of intestinal tight junction proteins. Fructose exacerbated both liver fibrosis and hepatocarcinogenesis by increasing intestinal permeability. This observation strongly supports the role of endotoxin in the progression of NASH.博士(医学)・乙第1432号・令和元年9月27日Copyright © 2018 Impact Journals, LLCCopyright © Seki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0 https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    Spatiotemporal Control of Ice Crystallization in Supercooled Water via an Ultrashort Laser Impulse

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    Takahashi H., Kono T., Sawada K., et al. Spatiotemporal Control of Ice Crystallization in Supercooled Water via an Ultrashort Laser Impulse. Journal of Physical Chemistry Letters, 14(19), 4394-4402, 18 May 2023: © 2023 American Chemical Society. DOI: 10.1021/acs.jpclett.3c00414.Focused irradiation with ultrashort laser pulses realized the fine spatiotemporal control of ice crystallization in supercooled water. An effective multiphoton excitation at the laser focus generated shockwaves and bubbles, which acted as an impulse for inducing ice crystal nucleation. The impulse that was localized close to the laser focus and accompanied by a small temperature elevation allowed the precise position control of ice crystallization and its observation with spatiotemporal resolution of micrometers and microseconds using a microscope. To verify the versatility of this laser method, we also applied it using various aqueous systems (e.g., plant extracts). The systematic study of crystallization probability revealed that laser-induced cavitation bubbles play a crucial role in inducing ice crystal nucleation. This method can be used as a tool for studying ice crystallization dynamics in various natural and biological phenomena

    Functional 1,3a,6a-triazapentalene scaffold : Design of fluorescent probes for kinesin spindle protein (KSP)

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    1,3a,6a-Triazapentalene is a compact fluorescent chromophore. In this study, triazapentalene was used to modify a series of biphenyl-type inhibitors of kinesin spindle protein (KSP) to develop fluorescent probes for the intracellular visualization of this protein. Microscopic studies demonstrated that these novel triazapentalene-labeled compounds exhibited inhibitory activity towards KSP in cultured cells and provided important information concerning the intracellular distribution

    Theranostic Agent Combining Fullerene Nanocrystals and Gold Nanoparticles for Photoacoustic Imaging and Photothermal Therapy

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    Developing photoactivatable theranostic platforms with integrated functionalities of biocompatibility, targeting, imaging contrast, and therapy is a promising approach for cancer diagnosis and therapy. Here, we report a theranostic agent based on a hybrid nanoparticle comprising fullerene nanocrystals and gold nanoparticles (FGNPs) for photoacoustic imaging and photothermal therapy. Compared to gold nanoparticles and fullerene crystals, FGNPs exhibited stronger photoacoustic signals and photothermal heating characteristics by irradiating light with an optimal wavelength. Our studies demonstrated that FGNPs could kill cancer cells due to their photothermal heating characteristics in vitro. Moreover, FGNPs that are accumulated in tumor tissue via the enhanced permeation and retention effect can visualize tumor tissue due to their photoacoustic signal in tumor xenograft model mice. The theranostic agent with FGNPs shows promise for cancer therapy
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