Vocal Fold Tissue Failure: Preliminary Data and Constitutive Modeling†

2004 ◽  
Vol 126 (4) ◽  
pp. 466-474 ◽  
Author(s):  
Roger W. Chan
Keyword(s):  
Preliminary Data ◽  
Vocal Fold ◽  
Large Strain ◽  
Deformation And Failure ◽  
Rate Dependent ◽  
Nonlinear Stress ◽  
Tissue Specimens ◽  
Dependent Failure ◽  
Tissue Stresses

In human voice production (phonation), linear small-amplitude vocal fold oscillation occurs only under restricted conditions. Physiologically, phonation more often involves large-amplitude oscillation associated with tissue stresses and strains beyond their linear viscoelastic limits, particularly in the lamina propria extracellular matrix (ECM). This study reports some preliminary measurements of tissue deformation and failure response of the vocal fold ECM under large-strain shear. The primary goal was to formulate and test a novel constitutive model for vocal fold tissue failure, based on a standard-linear cohesive-zone (SL-CZ) approach. Tissue specimens of the sheep vocal fold mucosa were subjected to torsional deformation in vitro, at constant strain rates corresponding to twist rates of 0.01, 0.1, and 1.0 rad/s. The vocal fold ECM demonstrated nonlinear stress-strain and rate-dependent failure response with a failure strain as low as 0.40 rad. A finite-element implementation of the SL-CZ model was capable of capturing the rate dependence in these preliminary data, demonstrating the model’s potential for describing tissue failure. Further studies with additional tissue specimens and model improvements are needed to better understand vocal fold tissue failure.

Structural Constitutive Characterization of the Vocal Fold: Modeling the Fibrous and the Interstitial Matrix Proteins

2004 ◽  
Author(s):  
Roger W. Chan ◽  
Thomas H. Siegmund ◽  
Kai Zhang ◽  
Neeraj Tirunagari ◽  
Min Fu
Keyword(s):  
Vocal Fold ◽  
Sound Production ◽  
Large Strain ◽  
Stress Strain ◽  
Strain Behavior ◽  
Nonlinear Viscoelastic ◽  
Nonlinear Stress ◽  
Deep Layers ◽  
Biomechanical Stimuli

The extracellular matrix (ECM) of the human vocal fold is a highly specialized soft connective tissue with a layered microstructure that is optimally tuned for vibration and sound production in response to a unique set of biomechanical stimuli in vivo, including oscillation at amplitudes up to 3–4 mm at magnitudes of acceleration > 200g and at high frequencies (> 100Hz). The vocal fold ECM, commonly called the lamina propria or mucosa, consists of biomacromolecules of two major classes distributed in different densities: (1) fibrous proteins including collagen and elastin fibers that are denser in the deep layers of the ECM, and (2) interstitial proteins like glycosaminoglycans and structural glycoproteins that are scattered throughout the entire ECM [1,2]. Nonlinear viscoelastic response of the vocal fold ECM under different loading conditions has been reported, including strain rate-dependence and hysteresis of tensile stress-strain curves, and nonlinear stress-strain behavior under large-strain shear [3,4].

Analytical Solutions for Circular Bars Subjected to Large Strain Plastic Torsion

1990 ◽  
Vol 57 (2) ◽  
pp. 298-306 ◽  
Author(s):  
K. W. Neale ◽  
S. C. Shrivastava
Keyword(s):  
Closed Form ◽  
Analytical Solutions ◽  
Large Strain ◽  
Kinematic Hardening ◽  
Flow Theory ◽  
Constitutive Laws ◽  
Isotropic Hardening ◽  
Large Strains ◽  
Inelastic Behavior ◽  
Rate Dependent

The inelastic behavior of solid circular bars twisted to arbitrarily large strains is considered. Various phenomenological constitutive laws currently employed to model finite strain inelastic behavior are shown to lead to closed-form analytical solutions for torsion. These include rate-independent elastic-plastic isotropic hardening J2 flow theory of plasticity, various kinematic hardening models of flow theory, and both hypoelastic and hyperelastic formulations of J2 deformation theory. Certain rate-dependent inelastic laws, including creep and strain-rate sensitivity models, also permit the development of closed-form solutions. The derivation of these solutions is presented as well as numerous applications to a wide variety of time-independent and rate-dependent plastic constitutive laws.

scholarly journals Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryosuke Nakamura ◽  
Nao Hiwatashi ◽  
Renjie Bing ◽  
Carina P. Doyle ◽  
Ryan C. Branski
Keyword(s):  
Vocal Fold ◽  
Vocal Folds ◽  
Nuclear Accumulation ◽  
Smad Pathway ◽  
Surgical Interventions ◽  
Smad Signaling ◽  
Iatrogenic Damage ◽  
Tgf Β1

AbstractVocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.

Continuum Description of the Time- and Strain-Dependent Poisson’s Ratio of Ligament Under Finite Deformation

2013 ◽  
Author(s):  
Aaron M. Swedberg ◽  
Shawn P. Reese ◽  
Steve A. Maas ◽  
Benjamin J. Ellis ◽  
Jeffrey A. Weiss
Keyword(s):  
Large Scale ◽  
Mechanical Response ◽  
Tensile Deformation ◽  
Large Strain ◽  
Fiber Direction ◽  
Strain Behavior ◽  
Nonlinear Stress ◽  
Poisson's Ratios ◽  
Poisson’S Ratios ◽  
Strain Dependent

Ligament volumetric behavior controls fluid and thus nutrient movement as well as the mechanical response of the tissue to applied loads. The reported Poisson’s ratios for tendon and ligament subjected to tensile deformation loading along the fiber direction are large, ranging from 0.8 ± 0.3 in rat tail tendon fascicles [1] to 2.98 ± 2.59 in bovine flexor tendon [2]. These Poisson’s ratios are indicative of volume loss and thus fluid exudation [3,4]. We have developed micromechanical finite element models that can reproduce both the characteristic nonlinear stress-strain behavior and large, strain-dependent Poisson’s ratios seen in tendons and ligaments [5], but these models are computationally expensive and unfeasible for large scale, whole joint models. The objectives of this research were to develop an anisotropic, continuum based constitutive model for ligaments and tendons that can describe strain-dependent Poisson’s ratios much larger than the isotropic limit of 0.5. Further, we sought to demonstrate the ability of the model to describe experimental data, and to show that the model can be combined with biphasic theory to describe the rate- and time-dependent behavior of ligament and tendon.

scholarly journals Properties of precise firing synchrony between synaptically coupled cortical interneurons depend on their mode of coupling

2015 ◽  
Vol 114 (1) ◽  
pp. 624-637 ◽  
Author(s):  
Hang Hu ◽  
Ariel Agmon
Keyword(s):  
Firing Rate ◽  
Electrical Coupling ◽  
Gamma Oscillations ◽  
Inhibitory Synapses ◽  
Data Set ◽  
Temporal Precision ◽  
Gamma Frequency ◽  
Rate Dependent ◽  
Cortical Interneurons

Precise spike synchrony has been widely reported in the central nervous system, but its functional role in encoding, processing, and transmitting information is yet unresolved. Of particular interest is firing synchrony between inhibitory cortical interneurons, thought to drive various cortical rhythms such as gamma oscillations, the hallmark of cognitive states. Precise synchrony can arise between two interneurons connected electrically, through gap junctions, chemically, through fast inhibitory synapses, or dually, through both types of connections, but the properties of synchrony generated by these different modes of connectivity have never been compared in the same data set. In the present study we recorded in vitro from 152 homotypic pairs of two major subtypes of mouse neocortical interneurons: parvalbumin-containing, fast-spiking (FS) interneurons and somatostatin-containing (SOM) interneurons. We tested firing synchrony when the two neurons were driven to fire by long, depolarizing current steps and used a novel synchrony index to quantify the strength of synchrony, its temporal precision, and its dependence on firing rate. We found that SOM-SOM synchrony, driven solely by electrical coupling, was less precise than FS-FS synchrony, driven by inhibitory or dual coupling. Unlike SOM-SOM synchrony, FS-FS synchrony was strongly firing rate dependent and was not evident at the prototypical 40-Hz gamma frequency. Computer simulations reproduced these differences in synchrony without assuming any differences in intrinsic properties, suggesting that the mode of coupling is more important than the interneuron subtype. Our results provide novel insights into the mechanisms and properties of interneuron synchrony and point out important caveats in current models of cortical oscillations.

scholarly journals Expression of PRDX6 Correlates with Migration and Invasiveness of Colorectal Cancer Cells

2018 ◽  
Vol 51 (6) ◽  
pp. 2616-2630 ◽  
Author(s):  
Wen-Shih Huang ◽  
Cheng-Yi Huang ◽  
Meng-Chiao Hsieh ◽  
Yi-Hung Kuo ◽  
Shui-Yi Tung ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transcriptional Activation ◽  
Colorectal Adenomas ◽  
Tissue Array ◽  
Boyden Chamber ◽  
Node Positive ◽  
Proliferation Capacity ◽  
Twist 1 ◽  
Tissue Specimens

Background/Aims: Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related deaths worldwide. PRDXs are antioxidant enzymes that play an important role in cell differentiation, proliferation and apoptosis and have diverse functions in malignancy development. However, the mechanism of aberrant overexpression of PRDX6 in CRC remains unclear. Methods: Boyden chamber assay, flow cytometry and a lentiviral shRNA targeting PRDX6 and transient transfection with pCMV-6-PRDX6 plasmid were used to examine the role of PRDX6 in the proliferation capacity and invasiveness of CRC cells. Immunohistochemistry (IHC) with tissue array containing 40 paraffin- embedded CRC tissue specimens and Western blot assays were used to detect target proteins. Results: PRDX6 was significantly up-expressed in different comparisons of metastasis of colorectal adenomas in node-positive CRC (P = 0.03). In in vitro HCT-116, PRDX6 silencing markedly suppressed CRC cell migration and invasiveness while also inducing cell cycle arrest as well as the generation of reactive oxygen species (ROS); specific overexpression of PRDX6 had the opposite effect. Mechanistically, the PRDX6 inactivation displayed decreased levels of PRDX6, N-cadherin, β-catenin, Vimentin, Slug, Snail and Twist-1 through the activation of the PI3K/ AKT/p38/p50 pathways, but they were also significantly inhibited by PRDX6 transfectants. There was also increased transcriptional activation of dimethylation of histone H3 lysine 4 (H3K4me3) of PRDX6 promoter via the activation of the PI3K/Akt/NFkB pathways. Conclusion: Our findings demonstrated that PRDX6 expression plays a characteristic growth-promoting role in CRC metastasis. This study suggests that PRDX6 may serve as a biomarker of node-positive status and may have a role as an important endogenous regulator of cancer cell tumorigenicity in CRC. PRDX6 may also be an effective therapeutic target.

Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

2011 ◽  
Vol 300 (2) ◽  
pp. H565-H573 ◽  
Author(s):  
Masahide Harada ◽  
Yukiomi Tsuji ◽  
Yuko S. Ishiguro ◽  
Hiroki Takanari ◽  
Yusuke Okuno ◽  
...  
Keyword(s):  
Action Potential ◽  
High Frequency ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
High Frequency Stimulation ◽  
Electrophysiological Properties ◽  
Rate Dependent ◽  
Frequency Stimulation ◽  
And Control

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF ( n = 18) and control ( n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

scholarly journals LncRNA PVT1 Knockdown Ameliorates Myocardial Ischemia Reperfusion Damage via Suppressing Gasdermin D-Mediated Pyroptosis in Cardiomyocytes

2021 ◽  
Vol 8 ◽  
Author(s):  
Cuizhi Li ◽  
Huafeng Song ◽  
Chunlin Chen ◽  
Shaoxian Chen ◽  
Qiyu Zhang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cell Viability ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
H9c2 Cells ◽  
Myocardial Ischemia Reperfusion ◽  
Tissue Specimens ◽  
Masson Staining

Objective: Myocardial ischemia reperfusion (I/R) damage is a life-threatening vascular emergency after myocardial infarction. Here, we observed the cardioprotective effect of long non-coding RNA (lncRNA) PVT1 knockdown against myocardial I/R damage.Methods: This study constructed a myocardial I/R-induced mouse model and a hypoxia/reoxygenation (H/R)-treated H9C2 cells. PVT1 expression was examined via RT-qPCR. After silencing PVT1 via shRNA against PVT1, H&amp;E, and Masson staining was performed to observe myocardial I/R damage. Indicators of myocardial injury including cTnI, LDH, BNP, and CK-MB were examined by ELISA. Inflammatory factors (TNF-α, IL-1β, and IL-6), Gasdermin D (GSDMD), and Caspase1 were detected via RT-qPCR, western blot, immunohistochemistry, or immunofluorescence. Furthermore, CCK-8 and flow cytometry were presented for detecting cell viability and apoptosis.Results: LncRNA PVT1 was markedly up-regulated in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Silencing PVT1 significantly lowered serum levels of cTnI, LDH, BNP, and CK-MB in myocardial I/R mice. H&amp;E and Masson staining showed that silencing PVT1 alleviated myocardial I/R injury. PVT1 knockdown significantly lowered the production and release of inflammatory factors as well as inhibited the expression of GSDMD-N and Caspase1 in myocardial I/R tissue specimens as well as H/R-induced H9C2 cells. Moreover, silencing PVT1 facilitated cell viability and induced apoptosis of H/R-treated H9C2 cells.Conclusion: Our findings demonstrated that silencing PVT1 could alleviate myocardial I/R damage through suppressing GSDMD-mediated pyroptosis in vivo and in vitro. Thus, PVT1 knockdown may offer an alternative therapeutic strategy against myocardial I/R damage.

scholarly journals Association of CD44−/CD24− Breast Cancer Cells with Late Stage Tumor Recurrence

2020 ◽  
Author(s):  
Xinbo Qiao ◽  
Yixiao Zhang ◽  
Lisha Sun ◽  
Qingtian Ma ◽  
Jie Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Tumor Metastasis ◽  
Cancer Prognosis ◽  
Molecular Events ◽  
Cell Conversion ◽  
Tissue Specimens ◽  
Distant Tumor

AbstractTumor metastasis remains the main cause of breast cancer-related deaths, especially the later breast cancer distant metastasis. This study assessed CD44−/CD24− tumor cells in 576 tissue specimens for associations with clinicopathological features and metastasis and then investigated the underlying molecular events. The data showed that level of CD44−/CD24− cells was associated with later postoperative distant tumor metastasis. Furthermore, CD44−/CD24− triple negative cells could spontaneously convert into CD44+/CD24− cancer stem cells (CSCs) with properties similar to CD44+/CD24− CSCs from parental MDA-MB-231 cells in terms of gene expression, tumor cell xenograft formation, and lung metastasis in vitro and in vivo. Single-cell RNA sequencing identified RHBDL2 as a regulator that enhanced spontaneous CD44+/CD24− CSC conversion, whereas knockdown of RHBDL2 expression inhibited YAP/NF-κB signaling and blocked spontaneous CD44−/CD24− cell conversion to CSCs. These data suggested that the level of CD44−/CD24− tumor cells could predict breast cancer prognosis, metastasis, and response to adjuvant therapy.

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