China
Africa
Explore chapters and articles related to this topic
Microengineered Models of Human Gastrointestinal Diseases
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Woojung Shin, Landon A. Hackley, Hyun Jung Kim
To recapitulate the pathophysiological microenvironment of GI diseases, essential components of illness should be considered in a defined 3D structure. The intestinal epithelium is the most critical component to build an intestinal mucosal microenvironment, where an intact epithelial barrier forms two compartments: a luminal and an abluminal (i.e., lamina propria, capillaries, or mesenchyme) side. Because the GI tract is continuously exposed to the external environment, a physical barrier is necessary to protect the body from foreign invaders (Peterson and Artis 2014). Since barrier dysfunction prevalently occurs in most GI diseases (Turner 2009), demonstrating the integrity of the epithelial barrier function in a model is the first and foremost prerequisite for mimicking a GI disease. Both innate and adaptive immune cells are necessary components for inducing immune responses that are involved in GI diseases (Mowat and Agace 2014). An imbalanced population of the commensal gut microbes (i.e., dysbiosis) plays a crucial role in the initiation and pathogenesis of GI diseases (Round and Mazmanian 2009). Dysbiosis is remarkably implicated in IBD (Tamboli et al. 2004) and colorectal cancer (Sobhani et al. 2011). Furthermore, specific bacteria are known to be involved in the pathogenesis of certain GI diseases, such as Helicobacter pylori in gastric cancer (Uemura et al. 2001) and Fusobacterium nucleatum in CRC (Mima et al. 2016). Thus, human microbiome must be taken into account to accurately model GI diseases.
Fundamentals of Nanotechnology
Published in C. Anandharamakrishnan, S. Parthasarathi, Food Nanotechnology, 2019
S. Parthasarathi, C. Anandharamakrishnan
The intestinal tract is highly absorptive and is composed of villi with a total absorptive surface area of 300–400 m2 (Schenk and Mueller, 2008). Gastrointestinal (GI) transit time is an important factor that determines oral absorption, as most of the bioactive compounds are absorbed from the upper part of the small intestine, i.e. duodenum and jejunum (Abuhelwa et al., 2017). Nanoparticle absorption in the GI tract can be well explained through various microscopic routes. Two transepithelial routes allow the passage of substances from the lumen to the basolateral side: transcellular transport (i.e. through an epithelial cell) or paracellular transport (i.e. between adjacent epithelial cells) (Bellmann et al., 2015). Most of the orally administered bioactive compounds are not retained in the GI tract, but undergo direct transit. Nanoparticles have an improved residence time in the GI tract due to its mucoadhesive ability. To protect the intestinal epithelium, mucus is continuously secreted to remove pathogens as well as lubricate the epithelial surface. Mucus is composed of proteins, carbohydrates, lipids, salts, antibodies, bacteria, and cellular debris. The main protein present in mucus is mucin, and there are at least 20 proteins encoded in the MUC gene family (Ensign et al., 2012). Mucus production in an adult human is approximately 1 kg/day, 10–200 µm thick (Lundquist and Artursson, 2016).
Preparation, characterization, and in vitro drug release behavior of thiolated alginate nanoparticles loaded budesonide as a potential drug delivery system toward inflammatory bowel diseases
Published in Journal of Biomaterials Science, Polymer Edition, 2020
Muhammad Arif, Zhe Chi, Yong-Jun Liu, Chen-Guang Liu
Mucins formed by goblet cells in the intestinal epithelium are a highly glycosylated polymer that is the primary component of mucus. Assessing the mucoadhesion of Alg-Cys nanoparticles using the mucin adsorption assay showed that Alg-Cys exhibited increased mucin adsorption compared to Alg particles (Figure 8), suggesting that thiolation improved intestinal mucoadhesion [29]. Figure 8 shows that the adsorption rate of mucin on nanoparticles with the same degree of substitution at pH = 7.4 is significantly higher than that at pH = 2, which is related to the tendency of sulfhydryl groups at different pH values. It has been pointed out that in solutions with pH less than 4, sulfhydryl groups tend to exist in the form of reductions, i.e. free sulfhydryl groups, while at pH greater than 4, they tend to exist in the form of oxidation. In the same way, when pH = 2, it is difficult to form disulfide bond between mucin and Alg-Cys nanoparticles, so the adsorption rate of mucin decreases, while at pH = 7.4 it is the opposite [34].
The perinatal period, the developing intestinal microbiome and inflammatory bowel diseases: What links early life events with later life disease?
Published in Journal of the Royal Society of New Zealand, 2020
Fathalla Ali, Kei Lui, Alex Wang, Andrew S. Day, Steven T. Leach
The development and maintenance of this homeostatic relationship in the gut is initially achieved at two different levels of stratification and compartmentalisation of the gut microbiota (Hooper et al. 2012). Stratification is the minimisation of the direct contact between the gut bacteria and the epithelial cell surface. In this mechanism, the immune effectors act together to stratify luminal bacteria and decrease bacterial-epithelial contact (Hooper et al. 2012). For example, the mucin glycoprotein that is secreted by intestinal goblet cells is assembled into a thick viscous coating layer (∼150 μm) at the intestinal epithelial cell surface (Johansson et al. 2008). In the colon, where there is the greatest bacterial load, this mucus layer is composed of two structurally distinct layers: a 50-μm thick firmly-adherent inner layer attached to the epithelial cells and a 100-μm thick non-attached outer layer. The inner part of these two mucus layer is an efficient bacterial barrier (Johansson et al. 2008). In contrast in the small intestine, where the bacterial load is much reduced compared to the colon, this mucus layer is discontinuous and less defined (Johansson et al. 2011).
Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Susan S. Schiffman, Elizabeth H. Scholl, Terrence S. Furey, H. Troy Nagle
The assessment of transepithelial electrical resistance (TEER) and permeability in human transverse colon epithelium in the current in vitro study found that sucralose-6-acetate and sucralose both disrupt gastrointestinal epithelial tight junctions and mucosal barrier function at mM concentrations in the absence of bacteria. A significant collapse of TEER occurred after a single 24-hr exposure to 40 mM sucralose which is only 6.7-fold greater than the concentration of sucralose currently approved by the European Union (2004) for use in a single syrup-type food supplement at 2400 mg/kg (6 mM). Integrity of the intestinal epithelial barrier is dependent upon tight junctions, the specialized complexes which connect adjacent cells and provide a physical and functional barrier that limits or regulates passive diffusion of ions, solutes, macromolecules, and cells from the lumen through the paracellular space. Sucralose-6-acetate and sucralose reduced the transepithelial resistance and enabled ions and macromolecules to pass from the apical (luminal) to the basolateral side of intestinal epithelium through the paracellular pathways. Enhanced intestinal permeability (leaky gut) that enables passage of microorganisms and metabolites into the body plays a major role in IBD (Lee 2015; Welcker et al. 2004), chronic liver disease (Mohandas and Vairappan 2017), as well as pathogenesis of colorectal cancer (Sánchez-Alcoholado et al. 2020). Further, elevated intestinal permeability in conjunction with repeated ingestion and retention of colonic contents over days may increase intraluminal concentration, absorption, and systemic exposure to sucralose and sucralose-6-acetate resulting long-term in bioaccumulation and toxicity.