Biology subjects

Rashidi, M.

Publications and source records attributed to Rashidi, M..

4 recordsLinked to original sources

bioRxiv2025

A Novel Method for the Mechanical Testing of Human Cerebrovascular Tissue: A Validation Study

This study describes and validates a novel mechanical testing apparatus capable of generating a viscoelastic response from which the time-dependent behavior of human cerebrovascular tissue can be derived to inform vessel wall failure prediction and therapeutic device design. Testing involved vascular specimen cannulation, pressurization, and recording dynamic changes in vessel diameter using a three-axis laser micrometer. Device validity and versatility were evaluated via two synthetic microvessel specimen experiments: (I) comparison to an Instron stress-relaxation protocol, and (II) vessel segment length parametric analysis. A standard linear solid (SLS) model was chosen to fit the experimental results, from which the model coefficients (E1, E2, and ) and equilibrium modulus (Ge) were computed. Ge comparisons were made using Bland-Altman analysis and Welchs F-test for experiment I and II, respectively. Device feasibility was evaluated through testing human cadaveric cerebrovascular tissue. The SLS model provided accurate experimental data fits, with overall mean R2 value of 0.99 (SD= 2.4E-3). Ge for inflation-creep and Instron stress-relaxation experiments were statistically comparable, with Bland-Altman mean bias of 1.9% (95% CI: -0.9% - 4.6%, p=.18). Holistically, the vessel segment length parametric analysis revealed inconsistent values for Ge across the complete range of testing lengths, where ad hoc family-wise comparison indicated that the 0.5 cm length cohort was the singular outlier (p < .05). Our device successfully recorded a viscoelastic response from human cadaveric middle cerebral artery tissue (n=12). This study demonstrated that our novel device was both versatile and capable of eliciting an accurate viscoelastic response.

bioengineering↗

bioRxiv2025

Fluid-structure Interaction Simulation of the Cerebrovascular Circulation: Immersed Boundary versus Arbitrary Lagrangian Eulerian Mesh Formulations

PurposePatient-specific fluid-structure interaction (FSI) simulations allow for the in silico modeling of vascular pathology. Though existing attempts to model the cerebrovasculature confirm the potential of FSI as a future diagnostic tool, standard simulation methods and modeling parameters remain undefined. The purpose of this investigation was to compare immersed boundary (IB) and arbitrary Lagrangian Eulerian (ALE) formulations to discern whether the increased modeling complexity offered by ALE is necessary for the modeling of smaller-caliber vessels, given increased computational load. MethodsDirect comparisons of Fluent and Mechanical behavior were conducted between IB and ALE methods of FSI simulation. Simulations utilized an internal carotid artery geometry conduit with optimized mesh. Boundary constraints were derived from previous investigation of vascular tissue and fit to a Prony series. Both qualitative profile comparisons and quantitative parametric analyses of variance were conducted to assess differences in simulation output. ResultsIn this study, we report deviations in Fluent and Mechanical output between IB and ALE cases of FSI simulation. More specifically, ALE-method simulations boast higher stress, lower wall shear stress, and lower strain. These differences persist across the vessel geometry and increase with high strain. Additionally, inconsistencies between solving methods are exacerbated in areas of more complex mesh geometry (i.e. vessel bifurcation). ConclusionSubstantial alterations in intraluminal stress, shear stress, and strain suggest that ALE formulation is necessary for modeling blood vessels of the cerebrovasculature. Our findings highlight the importance of accurately modeling the dynamic interactions that occur between the fluid and material domains of simulation.

bioengineering↗

bioRxiv2023

Divergent roles for caspase-8 and MLKL in high-fat diet induced obesity and NAFLD in mice

Cell death frequently occurs in the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD). However, the exact contribution of core cell death machinery to disease manifestations remains ill-defined. Here, we show via the direct comparison of mice genetically deficient in apoptotic caspase-8 in myeloid cells, or the essential necroptotic regulators, Receptor-interacting protein kinase-3 (RIPK3) and Mixed lineage kinase domain-like (MLKL), that RIPK3-caspase-8 signaling regulates macrophage inflammatory responses and drives adipose tissue inflammation and NAFLD upon high-fat diet feeding. In contrast, MLKL, divergent to RIPK3, contributes to both obesity and NAFLD in a manner largely independent of inflammation. We also uncover that MLKL regulates the expression of molecules involved in lipid uptake, transport and metabolism and, congruent with this, we discover a shift in the hepatic lipidome upon MLKL deletion. Collectively, these findings highlight MLKL as an attractive therapeutic target to combat the growing obesity pandemic and metabolic disease.

immunology↗

bioRxiv2021

The inflammasome-activated cytokine IL-1 is targeted for ubiquitylation and proteasomal degradation to limit its inflammatory potential

Interleukin-1{beta} (IL-1{beta}) is activated by inflammasome-associated caspase-1 in rare autoinflammatory conditions and in wide-spread diseases. Therefore, IL-1{beta} activity must be fine-tuned to enable antimicrobial responses whilst limiting collateral damage. Here we report that precursor IL-1{beta} is rapidly turned over by the proteasome and this correlates with its decoration by K11-, K63- and K48-linked ubiquitin chains. The ubiquitylation of IL-1{beta} is not just a degradation signal triggered by inflammasome priming and activating stimuli, but also limits IL-1{beta} cleavage by caspase-1. We further demonstrate that IL-1{beta} K133 is modified by ubiquitin and forms a salt bridge with IL-1{beta} D129. Loss of IL-1{beta} K133 ubiquitylation, or disruption of the K133:D129 electrostatic interaction, stabilizes IL-1{beta}. Accordingly, IL-1{beta}K133R/K133R mice display increased precursor IL-1{beta} upon inflammasome priming and increased bioactive IL-1{beta}, both in vitro and following LPS injection in vivo. These findings reveal new mechanisms for limiting IL-1{beta} activity and safeguarding against damaging inflammation.

immunology↗