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Apoptosis was demonstrated to be a major mode of intestinal epithelial cell death caused by intestinal ischemia/reperfusion (II/R). Ceramide has been proposed as a messenger for apoptosis. The present study was aimed to investigate the effect of Ginkgo biloba extract 761 (EGb 761) pretreatment on II/R-induced intestinal mucosal epithelial apoptosis in rats and the mechanism related to ceramide. The rat model of II/R injury was produced by clamping superior mesenteric artery for 60 min followed by reperfusion for 180 min. Twenty four rats were randomly allocated into Sham, II/R and EGb + II/R groups. In EGb + II/R group, EGb 761 (100 mg/kg per day) was administered intragastrically for 7 days before the surgery. Animals in II/R and sham groups were treated with equal volume of normal saline solution. Intestinal mucosal epithelial apoptosis was detected via electron microscopy and TUNEL method. Lipid peroxidation in intestinal mucosa was determined by detecting the malondialdehyde level and the activities of superoxide dismutase and peroxidase glutathione. The ceramide generation and sphingomyelinase (SMase) mRNA expression in intestinal mucosa were determined by high performance, thin layer chromatography, and RT-PCR, respectively. II/R caused intestinal mucosal epithelial apoptosis and over-production of the ceramide accompanied by up-regulation of SMase mRNA expression and increases of lipid peroxidation. EGb 761 pretreatment significantly decreased apoptosis index, and concurrently reduced the ceramide generation accompanied by down-regulation of SMase expression and inhibition of lipid peroxidation. The findings indicate that EGb 761 pretreatment attenuates II/R-induced intestinal epithelial apoptosis, which might be attributable to its antioxidant action of mediating ceramide pathway.

Colorectal cancers are the third most common type of cancer. They originate from intestinal crypts, glands that descend from the intestinal lumen into the underlying connective tissue. Normal crypts are thought to exist in a dynamic equilibrium where the rate of cell production at the base of a crypt is matched by that of loss at the top. Understanding how genetic alterations accumulate and proceed to disrupt this dynamic equilibrium is fundamental to understanding the origins of colorectal cancer. Colorectal cancer emerges from the interaction of biological processes that span several spatial scales, from mutations that cause inappropriate intracellular responses to changes at the cell/tissue level, such as uncontrolled proliferation and altered motility and adhesion. Multiscale mathematical modelling can provide insight into the spatiotemporal organisation of such a complex, highly regulated and dynamic system. Moreover, the aforementioned challenges are inherent to the multiscale modelling of biological tissue more generally. In this review we describe the mathematical approaches that have been applied to investigate multiscale aspects of crypt behavior, highlighting a number of model predictions that have since been validated experimentally. We also discuss some of the key mathematical and computational challenges associated with the multiscale modelling approach. We conclude by discussing recent efforts to derive coarse-grained descriptions of such models, which may offer one way of reducing the computational cost of simulation by leveraging well-established tools of mathematical analysis to address key problems in multiscale modelling.

The hydrodynamic dispersion of a solute in peristaltic flow of a reactive incompressible micropolar biofluid is studied as a model of chyme transport in the human intestinal system with wall effects. The long wavelength approximation, Taylor's limiting condition and dynamic boundary conditions at the flexible walls are used to obtain the average effective dispersion coefficient in the presence of combined homogeneous and heterogeneous chemical reactions. The effects of various pertinent parameters on the effective dispersion coefficient are discussed. It is observed that average effective dispersion coefficient increases with amplitude ratio which implies that dispersion is enhanced in the presence of peristalsis. Furthermore, average effective dispersion coefficient is also elevated with the micropolar rheological and wall parameters. Conversely dispersion is found to decrease with cross viscosity coefficient, homogeneous and heterogeneous chemical reaction rates. The present simulations provide an important benchmark for future chemo-fluid-structure interaction (FSI) computational models.

Multiphoton microscopy (MPM), based on two-photon excited fluorescence and second harmonic generation, enables direct noninvasive visualization of tissue architecture and cell morphology in live tissues without the administration of exogenous contrast agents. In this paper, we used MPM to image the microstructures of the mucosa in fresh, unfixed, and unstained intestinal tissue of mouse. The morphology and distribution of the main components in mucosa layer such as columnar cells, goblet cells, intestinal glands, and a little collagen fibers were clearly observed in MPM images, and then compared with standard H&E images from paired specimens. Our results indicate that MPM combined with endoscopy and miniaturization probes has the potential application in the clinical diagnosis and in vivo monitoring of early intestinal cancer.

Tissue engineering is an innovative field of research applied to treat intestinal diseases. Engineered smooth muscle requires dense smooth muscle tissue and robust vascularization to support contraction. The purpose of this study was to use heparan sulfate (HS) and collagen coatings to increase the attachment of smooth muscle cells (SMCs) to scaffolds and improve their survival after implantation. SMCs grown on biologically coated scaffolds were evaluated for maturity and cell numbers after 2, 4 and 6 weeks in vitro and both 2 and 6 weeks in vivo. Implants were also assessed for vascularization. Collagen-coated scaffolds increased attachment, growth and maturity of SMCs in culture. HS-coated implants increased angiogenesis after 2 weeks, contributing to an increase in SMC survival and growth compared to HS-coated scaffolds grown in vitro. The angiogenic effects of HS may be useful for engineering intestinal smooth muscle.

Of the three human arylamine N-acetyltransferase (NAT) genes, (HUMAN)NAT1 and (HUMAN)NAT2 code for functional enzymes, namely (HUMAN)NAT1 and (HUMAN)NAT2. (HUMAN)NAT1 is expressed early during development and is ubiquitously expressed during adulthood, whereas (HUMAN)NAT2 expression and enzyme activity is primarily restricted to adult liver and intestine. A similar temporal and spatial distribution of the corresponding orthologues has been found in rodent models regularly used to investigate their expression and endogenous function, and to understand their role in the metabolism of aromatic amines (AAs). While NAT1 is considered to have an additional endogenous role, NATs are defined as xenobiotic-phase II conjugating enzymes, which N- or O-acetylate AAs, heterocyclic aromatic amines (HAAs) and their N-oxidised metabolites using acetyl-CoA as a co-substrate. The substrates are mainly environmental chemicals, including carcinogens. While both human NATs deactivate their substrates, especially AAs, through N-acetylation, (HUMAN)NAT2 appears to be extremely important also in the activation of carcinogenic compounds. Their presence and activity in the organs involved in uptake of arylamines (skin, respiratory tract, gastro-intestinal tract), influences AA and HAA loads and their fates, thereby allowing their distribution throughout the body (blood), metabolism (liver), excretion (bladder, intestine), but also provoking tumour formation in specific organs, particularly in the case of carcinogenic AAs and HAAs.

Many fundamental questions remain regarding the cellular and molecular mechanisms of lipid metabolism. One major impediment to answering important questions in the field has been the lack of a tractable and sufficiently complex model system. Until recently, most studies of lipid metabolism have been performed in vitro or in the mouse, yet each approach possesses certain limitations. The zebrafish (Danio rerio) offers an excellent model system with which to study lipid metabolism in vivo due to its small size, genetic tractability and optical clarity. We have exploited the unique advantages of the zebrafish to visualize digestive processes in vivo by using a number of fluorescent tools, including fluorescent reporters of lipase and protease activity, fluorescent lipid analogs, and fluorescent microspheres. Using these tools with the zebrafish model system enables one to generate visible readouts of digestive physiology and organ function in real time. Additionally, the zebrafish system is amenable to high-throughput approaches to identify small molecules that influence lipid metabolism and new pharmaceuticals for the treatment of human lipid disorders. In this chapter we present recent advances in visualizing lipid metabolism in live larval zebrafish with a focus on fatty acid metabolism.