Systemic Sclerosis Dermal Fibroblasts Induce Cutaneous Fibrosis Through Lysyl Oxidase–like 4: New Evidence From Three‐Dimensional Skin‐like Tissues

2020 ◽  
Vol 72 (5) ◽  
pp. 791-801 ◽  
Author(s):  
Mengqi Huang ◽  
Guoshuai Cai ◽  
Lauren M. Baugh ◽  
Zhiyi Liu ◽  
Avi Smith ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lysyl Oxidase ◽  
Three Dimensional ◽  
Dermal Fibroblasts ◽  
New Evidence ◽  
Cutaneous Fibrosis

scholarly journals P149 The intracellular chloride channel 4 (CLIC4) plays an important role in systemic sclerosis fibroblast activation

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Christopher Wasson ◽  
Rebecca Ross ◽  
Ruth Morton ◽  
Jamel Mankouri ◽  
Francesco Del Galdo
Keyword(s):  
Systemic Sclerosis ◽  
Ion Channel ◽  
Smooth Muscle Actin ◽  
Chloride Ion ◽  
Dermal Fibroblasts ◽  
Cancer Associated Fibroblasts ◽  
Alpha Smooth Muscle Actin ◽  
Direct Role ◽  
Fibroblast Activation ◽  
Intracellular Chloride

Abstract Background/Aims  The intracellular chloride ion channel CLIC4 mediates the activation of cancer associated fibroblasts. Interestingly, systemic sclerosis (SSc) fibroblasts display a number of similar properties to cancer associated fibroblasts. Tissue fibrosis in SSc is driven by active fibroblasts (myofibroblasts). Therefore in this study we investigated the role of CLIC4 in SSc fibroblast activation. Methods  Dermal fibroblasts were obtained from full thickness skin biopsies from SSc patients (early-diffuse). RNA and protein were collected from the fibroblasts and CLIC4 transcript and protein levels were assessed by qPCR and western blot. SSc patient fibroblasts were treated with the chloride ion channel inhibitors NPPB and IAA-94. Results  CLIC4 was found to be expressed at significantly higher levels in SSc patients fibroblasts compared to healthy controls, at both the transcript (3.7 fold) and protein (1.7 fold) levels. Inhibition of the TGF-β signalling pathway led to reduced CLIC4 expression in SSc fibroblasts, confirming this pathway as the main driver of CLIC4 expression. Finally, treatment of SSc fibroblasts with small molecule inhibitors that target the channel led to reduced expression of the myofibroblast markers collagen type 1 and alpha-smooth muscle actin, suggesting a direct role for CLIC4 in SSc associated skin fibrosis. Conclusion  We have identified a novel role for CLIC4 in SSc myofibroblast activation, which further strengthen the similarities between SSc fibroblasts and cancer associated fibroblasts. Furthermore this study highlights this channel as a novel target for therapeutic intervention. Disclosure  C. Wasson: None. R. Ross: None. R. Morton: None. J. Mankouri: None. F. Del Galdo: None.

scholarly journals NEW EVIDENCE OF DISCRETE SCALE INVARIANCE IN THE ENERGY DISSIPATION OF THREE-DIMENSIONAL TURBULENCE: CORRELATION APPROACH AND DIRECT SPECTRAL DETECTION

2003 ◽  
Vol 14 (04) ◽  
pp. 459-470 ◽  
Author(s):  
WEI-XING ZHOU ◽  
DIDIER SORNETTE ◽  
VLADILEN PISARENKO
Keyword(s):  
Energy Dissipation ◽  
Three Dimensional ◽  
Energy Dissipation Rate ◽  
Corrections To Scaling ◽  
Developed Turbulence ◽  
Pairwise Correlations ◽  
Spectral Detection ◽  
Simple Variant ◽  
High Reynolds ◽  
New Evidence

We extend the analysis of Ref. 16 showing statistically significant log-periodic corrections to scaling in the moments of the energy dissipation rate in experiments at high Reynolds number (≈ 2500) of three-dimensional fully developed turbulence. First, we develop a simple variant of the canonical averaging method using a rephasing scheme between different samples based on pairwise correlations that confirms Zhou and Sornette's previous results. The second analysis uses a simpler local spectral approach and then performs averages over many local spectra. This yields stronger evidence of the existence of underlying log-periodic undulations, with the detection of more than 20 harmonics of a fundamental logarithmic frequency f = 1.434 ± 0.007 corresponding to the preferred scaling ratio γ = 2.008 ± 0.006.

AB0141 Lysyl oxidase is correlated with fibrosis in systemic sclerosis

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A828.3-A828
Author(s):  
D. Rimar ◽  
I. Rosner ◽  
G. Slobodin ◽  
M. Rozenbaum ◽  
T. haj ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Lysyl Oxidase

scholarly journals Cytotoxicity of three-dimensional paper-based models from a three-dimensional paper-based printer

NEMESIS ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. 15 ◽  
Author(s):  
Marcin Kozakiewicz ◽  
Piotr Szymor ◽  
Raphael Olszewski
Keyword(s):  
Operating Room ◽  
Dermal Fibroblast ◽  
Statistical Significance ◽  
Three Dimensional ◽  
Dermal Fibroblasts ◽  
Tissue Adhesive ◽  
Biological Behaviour ◽  
Sterilization Method ◽  
Significant Difference ◽  
Before And After

Objective: Our study aimed to determine the possibility of using models created with a low-cost, paper based 3D printer in an operating room. Therefore influence of different methods of sterilization on models was tested and cytotoxicity of generated models was determined. Material and methods: 30 cuboids divided into three groups were used for verification of shape stability after sterilization. Each group was sterilized either with: Ethylene oxide in temperature 55˚C, Hydrogen peroxide gas plasma in temperature 60˚C or Gamma irradiation at 21˚C, 25kGy. Each cuboid was measured using calliper three times before and three times after sterilization. Results were analysed statistically in Statgraphics Plus. Statistical significance was determined as p< 0.05. Sixty cylinders divided into six groups were used for cytotoxicity tests. Three of those groups were covered before sterilization with 2-octyl-cyanoacrylate. Each group was sterilized with one of the previously described methods. Cytotoxicity was tested by Nanostructural and Molecular Biophysics Laboratory in Technopark Lodz using normal adult human dermal fibroblasts. Survival of cells was tested using spectrophotometry with XTT and was defined as ratio of absorbency of tested probe to absorbency of control probe. Calcein/Ethidium dyeing test was performed according to LIVE/DEAD Viability/Cytotoxicity Kit protocol. Observation was done under Olympus GX71 fluorescence microscope. Results: There was no statistically significant difference for established statistical significance p=0.05 in cuboids dimensions before and after sterilization regardless of sterilization method. In XTT analysis all samples showed higher cytotoxicity against normal, human, adult dermal fibroblast culture when compared to positive control. ANOVA statistical analysis confirmed that 2-octyl cyanoacrylate coating of paper model improved biological behaviour of the material. It decreased cytotoxicity of the model independently of sterilization method. In calcein/ethidium dyeing test due to the high fluorescence of the background caused by cylinders of analysed substance it was impossible to perform the exact analysis of the number of marked cells. Conclusions: Acquired results allow to conclude that Mcor Technology Matrix 300 3D paper-based models can be used in operating room only if covered with cyanoacrylate tissue adhesive. Nemesis relevance: We found no statistically significant difference in cuboids dimensions before and after sterilization regardless of sterilization method. Three-dimensional paper-based models present with high cytotoxicity without coating.

Quantum Spectra and Classical Orbits in Nano-Microstructure

2010 ◽  
Vol 160-162 ◽  
pp. 625-629 ◽  
Author(s):  
Jun Lu ◽  
Xue Mei Wang
Keyword(s):  
Closed Orbit ◽  
Three Dimensional ◽  
Spectrum Function ◽  
Molecular Reaction ◽  
Classical Quantum ◽  
Orbit Theory ◽  
Quantum Correspondence ◽  
New Evidence ◽  
Quantum Spectrum ◽  
Classical Orbits

A kind of new classical-quantum correspondence principle is proposed using the idea of closed-orbit theory. The quantum spectrum function is introduced by means of the eigenvalues and the eigenfunctions in the system of one-dimensional nano-microstructure. The Fourier transformation of the quantum spectrum function is found corresponding with the classical orbits in the system. These results give new evidence about the classical-quantum correspondence. All the methods and results can be used in a lot of other systems, including some two-dimensional and three-dimensional systems. The researches about these systems are very important in the field of applied science, for example, molecular reaction dynamics and quantum information.

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