Annals of biomedical engineering
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One critical step in tumor metastasis is tumor cell adhesion to the endothelium forming the microvessel wall. Understanding this step may lead to new therapeutic concepts for tumor metastasis. Vascular endothelium forming the microvessel wall and the glycocalyx layer at its surface are the principal barriers to, and regulators of the material exchange between circulating blood and body tissues. ⋯ Thus the first part of the review introduced the mathematical models for water and solutes transport through the interendothelial cleft. These models, combined with the experimental results from in vivo animal studies and electron microscopic observations, are used to evaluate the role of the endothelial surface glycocalyx, the junction strand geometry in the interendothelial cleft, and the surrounding extracellular matrix and tissue cells, as the determinants of microvascular transport. The second part of the review demonstrated how the microvascular permeability, hydrodynamic factors, microvascular geometry and cell adhesion molecules affect tumor cell adhesion in the microcirculation.
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Sepsis accounts annually for nearly 10% of total U. S. deaths, costing nearly $17 billion/year. Sepsis is a manifestation of disordered systemic inflammation. ⋯ Based on a decade of systems and computational approaches to deciphering acute inflammation, along with translationally-motivated experimental studies in both small and large animals, we propose that MODS evolves due to the feed-forward cycle of inflammation → damage → inflammation. We hypothesize that inflammation proceeds at a given, "nested" level or scale until positive feedback exceeds a "tipping point." Below this tipping point, inflammation is contained and manageable; when this threshold is crossed, inflammation becomes disordered, and dysfunction propagates to a higher biological scale (e.g., progressing from cellular, to tissue/organ, to multiple organs, to the organism). Finally, we suggest that a combination of computational biology approaches involving data-driven and mechanistic mathematical modeling, in close association with studies in clinically relevant paradigms of sepsis/MODS, are necessary in order to define scale-specific "tipping points" and to suggest novel therapies for sepsis.