Bicellular tight junctions (TJs) are intercellular junctions comprised of a variety of transmembrane proteins including occludin, claudins, and junctional adhesion molecules (JAMs) as well as intracellular scaffold proteins such as zonula occludens (ZOs). TJs are functional, intercellular structures that form a barrier between adjacent cells, which constantly seals and unseals to control the paracellular passage of molecules. They are primarily present in the epithelial and endothelial cells of all tissues and organs. In addition to their well-recognized roles in maintaining cell polarity and barrier functions, TJs are important regulators of signal transduction, which modulates cell proliferation, migration, and differentiation, as well as some components of the immune response and homeostasis. A vast breadth of research data is available on TJs, but little has been done to decipher their specific roles in wound healing, despite their primary distribution in epithelial and endothelial cells, which are essential contributors to the wound healing process. Some data exists to indicate that a better understanding of the functions and significance of TJs in healing wounds may prove crucial for future improvements in wound healing research and therapy. Specifically, recent studies demonstrate that occludin and claudin-1, which are two TJ component proteins, are present in migrating epithelial cells at the wound edge but are absent in chronic wounds. This indicates that functional TJs may be critical for effective wound healing. A tremendous amount of work is needed to investigate their roles in barrier function, re-epithelialization, angiogenesis, scar formation, and in the interactions between epithelial cells, endothelial cells, and immune cells both in the acute wound healing process and in non-healing wounds. A more thorough understanding of TJs in wound healing may shed new light on potential research targets and reveal novel strategies to enhance tissue regeneration and improve wound repair.
Bicellular tight junctions are multiprotein complexes that are required for maintenance of barrier function and fence function in epithelial tissues. Wound healing in the oral cavity leads to minimal scar formation compared to the skin, and the precise mechanisms for this regenerative response remain to be elucidated. We hypothesized that oral and skin tissues express a different tight junction repertoire both at baseline and during the wound healing response, and that these molecules may be critical to the differential repair between the two tissues. We re-analyzed a mouse skin and palate epithelium microarray dataset to identify the tight junction repertoire of these tissue types. We then re-analyzed a skin and tongue wound healing microarray dataset to see how expression levels of tight junction genes change over time in response to injury. We performed in vitro scratch assays on human oral and skin keratinocyte cell lines to assay for tight junction expression over time, tight junction expression in response to lipopolysaccharide and histamine treatment, and the effects of siRNA knockdown of claudin 1 or occludin on migration and proliferation. Our data showed that oral and skin epithelium expressed different tight junction genes at baseline and during the wound healing response. Knockdown of claudin 1 or occludin led to changes in proliferation and migration in human skin keratinocytes but not oral keratinocytes. Furthermore, we also showed that skin keratinocytes were more permeable than oral keratinocytes upon histamine treatment. In conclusion, this study highlights a specific subset of functional tight junction genes that are differentially expressed between the oral and skin tissues, which may contribute to the mechanisms leading to distinct healing phenotypes in response to injury in the two tissues.
Several studies have focused on the antimicrobial effects of cerium oxide nanoparticles (CeO 2-NP) but few have focused on their effects on bacteria under initial biofilm formation conditions. Streptococcus mutans is a prolific biofilm former contributing to dental caries in the presence of fermentable carbohydrates and is a recognized target for therapeutic intervention. CeO 2-NP derived solely from Ce(IV) salt hydrolysis were found to reduce adherent bacteria by approximately 40% while commercial dispersions of "bare" CeO 2-NP (e.g., 3 nm, 10-20 nm, 30 nm diameter) and Ce(NO 3) 3 •6H 2 O were either inactive or observed to slightly increase biofilm formation under similar in vitro conditions. Planktonic growth and dispersal assays support a nonbactericidal mode of biofilm inhibition active in the initial phases of S. mutans biofilm production. Human cell proliferation assays suggest only minor effects of hydrolyzed Ce(IV) salts on cellular metabolism at concentrations up to 1 mM Ce, with less observed toxicity compared to equimolar concentrations of AgNO 3. The results presented herein have implications in clinical dentistry.
Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, exacerbate the deterioration of renal function and increase the risk of cardiovascular events in chronic kidney disease (CKD) patients. The effects of microbiota-driven therapy (probiotics, prebiotics or synbiotics) on decreasing circulating IS and PCS concentrations are controversial; thus, we performed the present systematic review and meta-analysis to assess the effects of microbiota-driven therapy on the circulating IS and PCS concentrations in CKD patients. PubMed, EMBASE, and Cochrane Library databases were systematically searched from inception to July 22, 2021, and randomized controlled trials (RCTs) investigating the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients were included. In all, 14 RCTs with 513 participants were eligible for the meta-analysis. The effects of microbiota-driven therapy on the circulating IS and PCS concentrations were evaluated with weighted mean differences (WMDs) measured by a fixed-effects model or a random-effects model. Compared with placebo, the microbiota-driven therapy had no statistically significant effect on the circulating IS concentration (WMD: –1.64 mg/L; 95% CI: –3.46, 0.18 mg/L; P = 0.077) but it decreased the circulating PCS concentration (WMD: –2.44 mg/L; 95% CI: –3.82, –1.05 mg/L; P = 0.001). In the subgroup analyses, prebiotic (n = 5) and synbiotic (n = 3) supplementation significantly decreased the circulating PCS concentration, while probiotic (n = 4) supplementation did not. Meta-regression showed that the effects of microbiota-driven therapy were not associated with the supplementation time or the year of publication. Moreover, there was no significant evidence of publication bias. This review found that microbiota-driven therapy decreased the circulating PCS concentration in CKD patients. Additional large, well-designed, randomized controlled trials with improved methodology and reporting are necessary to assess the effects of microbiota-driven therapy on the circulating IS and PCS concentrations in the long term. Significance: The findings of clinical studies investigating the effects of microbiota-driven therapy on the reduction of IS and PCS concentrations in CKD patients are controversial. To the best of our knowledge, this is the first study to systematically assesses the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients.
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