Human dihydroorotate dehydrogenase (DHODH) is a flavin-dependent mitochondrial enzyme catalyzing the fourth step in the de novo pyrimidine synthesis pathway. It is originally a target for the treatment of the non-neoplastic diseases involving in rheumatoid arthritis and multiple sclerosis, and is re-emerging as a validated therapeutic target for cancer therapy. In this review, we mainly unravel the biological function of DHODH in tumor progression, including its crucial role in de novo pyrimidine synthesis and mitochondrial respiratory chain in cancer cells. Moreover, various DHODH inhibitors developing in the past decades are also been displayed, and the specific mechanism between DHODH and its additional effects are illustrated. Collectively, we detailly discuss the association between DHODH and tumors in recent years here, and believe it will provide significant evidences and potential strategies for utilizing DHODH as a potential target in preclinical and clinical cancer therapies.
We consider three different compressible versions of the conventional incompressible neo-Hookean material model. The different versions are not new and have been used in various model studies. They each give neo-Hookean behavior in an appropriate incompressible limit. The three versions each show some basic differences with respect to each other as regards the qualitative nature of the approach to the neo-Hookean limit. The purpose of this study is to exhibit these differences.
Angioedema, the rapid swelling of under-skin tissue, is typically triggered by complex biochemical processes that disrupt an original steady state filtration of liquid through the tissue. Swelling stabilizes once a new steady state is achieved in which the tissue has significantly increased liquid content. These processes are controlled by events at the molecular to the cellular length scale. For describing consequences at organ level length scales it is useful to invoke consolidated continuum mechanics treatments within a generalized hyperelastic framework. We describe the challenges associated with such modeling and demonstrate their use in the context of tracheal angioedema. The trachea is modeled as a two layered cylindrical tube. The inner layer and outer layer represent the soft mucosal tissue and the stiffer cartilaginous tissue respectively. Axially oriented fibers contribute anisotropy to the inner layer, and the swelling is largely confined to this layer. A boundary value problem is formulated; existence and uniqueness is verified. Numerical solutions track airway constriction as a function of mucosal swelling.
During pregnancy, the cervix experiences significant mechanical property change due to tissue swelling, and to ongoing changes in the collagen content. In this paper, we model how these two effects contribute to cervical deformation as the pressure load on top of the cervix increases. The cervix and its surrounding supporting ligaments are taken into consideration in the resulting mechanical analysis. The cervix itself is treated as a multilayered tube-like structure, with layer-specific collagen orientation. The cervical tissue in each layer is treated in terms of a collagen constituent that remodels with time within a ground substance matrix that experiences swelling. The load and swelling are taken to change sufficiently slowly so that the collagen properties at any instant can be regarded as being in a state of homeostasis. Among other things, the simulations show how the luminal cross-sectional area varies along its length as a function of pressure and swelling. In general, an increase in pressure causes an overall shortening of the lumen while an increase in swelling has the opposite effect.
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