Tissue Barriers最新文献

Crohn's disease is a form of inflammation that affects the gastrointestinal (GI) tract. It is characterized by persistent inflammation in the gut, which can lead to the formation of abnormal connections called fistulas. These fistulas can occur between the GI tract and the abdominal cavity, adjacent organs, or the skin. The most prevalent type of fistula in Crohn's disease patients is the perianal fistula, which forms between the rectum and the skin near the anus. Although the exact cause of fistula formation is not fully understood, research suggests that factors such as epithelial to mesenchymal transition, matrix metalloproteinase, immune system dysregulation, and microbiota may contribute to their development. There is currently no definitive treatment for fistula closure, but options include surgery, endoscopic procedures, antibiotics, biologic agents, and immunosuppressive drugs. These treatments can be used alone or in combination. However, recurrence is a significant challenge that needs to be addressed in the case of fistula treatment. This review provides an overview of the common types of fistulas, their characteristics, the main factors and mechanisms of fistula formation, and available therapeutic options.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the result of an exaggerated inflammatory response triggered by a variety of pulmonary and systemic insults. The lung tissues are comprised of a variety of cell types, including alveolar epithelial cells, pulmonary vascular endothelial cells, macrophages, neutrophils, and others. There is mounting evidence that these diverse cell populations within the lung interact to regulate lung inflammation in response to both direct and indirect stimuli. The aim of this review is to provide a summary and discussion of recent advances in the understanding of the importance of cell-cell crosstalk in the pathogenesis of ALI/ARDS, with a specific focus on the cell-cell interactions that may offer prospective therapeutic avenues for ALI/ARDS.

The immunohistochemical expression of various members of the claudin family has already been studied in pathological affections of the vulva whether to differentiate precancerous lesions from vulvar squamous cell carcinoma or in inflammatory conditions such as lichen sclerosus. From an oncological perspective, however, immunohistochemical analysis of claudin 18.2 protein expression has become increasingly clinically relevant nowadays since the impressive therapeutic benefits of the claudin 18.2 antibody zolbetuximab have been widely recognized. Systematic studies evaluating its expression, including in vulvar cancer, are needed to understand whether such treatment strategies may eventually benefit patients with vulvar neoplasia.

Lipolysis-stimulated lipoprotein receptor (LSR), a lipid metabolism-related factor localized in tricellular tight junctions (tTJs), plays an important role in maintaining the epithelial homeostasis. LSR is highly expressed in well-differentiated cancers, and its expression decreases during malignancy. The LSR antibody inhibits cell growth and promotes apoptosis in some cancers. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors promote differentiation and prevent cell proliferation and migration in cancers. HDAC inhibitors together with TNFα also induce apoptosis via TNFα-related apoptosis-inducing ligand (TRAIL) in some cancers. In this study, we investigated the apoptosis signaling induced by an anti-LSR antibody in human salivary duct adenocarcinoma (SDC) cell line A253, compared to TRAIL-induced apoptosis. A253 cells were treated with human recombinant TNFα with or without HDAC inhibitor trichostatin A (TSA) and quisinostat (JNJ-26481585). Treatment using TNFα with HDAC inhibitors markedly induced apoptosis in A253 cells and the anti-TNFα antibody prevented the induced apoptosis. A253 cells were treated with an antibody against the extracellular N-terminal domain of human LSR (LSR-N-ab) with or without HDAC inhibitors. Treatment with HDAC inhibitors induced LSR expression in the membranes of A253 cells. Treatment using LSR-N-ab with HDAC inhibitors markedly promoted apoptosis in A253 cells. The tricellular signaling pathway JNK inhibitor SP600125 and Hippo pathway MST1/2 inhibitor XMU-MP-1 prevented the apoptosis induced by treatment using TNFα or LSR-N-ab with HDAC inhibitors. Our findings indicated that treatment with TNFα or LSR-N-ab with HDAC inhibitors might be useful in the therapy for human SDC by enhancing apoptosis.

The development of efficient targeted therapies to ameliorate endothelial disorders is of the utmost need, as evident by the devastating outcomes of the recent pandemic. Recent findings suggest that unfolded protein response (UPR) modulates barrier function. In the current study, we reveal that the aforementioned highly conservative mechanism is involved in the protective effects of growth hormone-releasing hormone antagonists (GHRHAnt) in lung injury, both in vivo and in vitro. In bovine pulmonary artery endothelial cells, UPR suppression counteracted the protective effects of GHRHAnt in lipopolysaccharide (LPS)-induced endothelial hyperpermeability. In mouse lungs, UPR activation enhanced the beneficial effects of GHRHAnt against LPS-induced acute lung injury. Our observations - which are focused on lung endothelial cells and tissues - enhance our knowledge on the mechanisms mediating the barrier function and contribute to the development of novel therapies toward sepsis, direct and indirect lung injury. The effects of UPR modulation on the effects of GHRHAnt in other tissues are unknown, and they are the subject of future investigations.

This review investigates the pathogenic processes through which Streptococcus pneumoniae crosses the blood-brain barrier (BBB) to cause meningitis, with a focus on the interaction with host receptors in the central nervous system (CNS). S. pneumoniae a primary cause of bacterial meningitis, utilizes unique receptor-mediated pathways to infiltrate the BBB. The bacterial interaction with the platelet-activating factor receptor (PAFR) and the polymeric immunoglobulin receptor (pIgR) is looked at in this study. The goal is to understand how this interaction helps the bacterium move across the BBB and cause infection in the CNS. We examine the functions of cellular and molecular participants at the endothelium level, such as cytokines, chemokines, and matrix metalloproteinases (MMP), which have a role in the development of the disease. This study consolidates data from multiple studies, providing a thorough summary of the interactions between S. pneumoniae and the BBB. It also explores potential treatment targets that could reduce the significant illness and death rates associated with pneumococcal meningitis.

Background: Fatty acids (FAs) play pivotal roles in modulating inflammatory pathways in celiac disease (CD). The present study explored the relationship between serum FAs levels and the expression of both pro- and anti-inflammatory cytokines in adult and pediatric patients with CD.

Methods: Serum FA levels in 20 treated CD patients (11 children, 9 adults) and 20 healthy controls (10 children, 10 adults) were analyzed using gas chromatography. Cytokine gene expression (IL-6, TNF-α, IL-10, IL-12, TGFβ, NF-κB) was assessed through quantitative real-time PCR.

Results: Myristoleic acid levels decreased in children with CD (p = 0.03) but increased in adults (p = 0.04). Elevated IL-6 mRNA expression was found in both pediatric (p = 0.01) and adult (p = 0.04) groups. TNF-α expression was significantly higher in adults (p = 0.01). In children, IL-10 mRNA levels positively correlated with palmitic acid (p = 0.01, r = 0.73), and TGF-β correlated with myristoleic acid (p = 0.03, r = 0.63). In adults, IL-10 positively correlated with dihomo-gamma-linolenic acid (p = 0.04, r = 0.68) and negatively with linoleic acid (p = 0.02, r = -0.72). These age-related differences may reflect variations in disease duration, metabolic and developmental factors, dietary intake, and gut microbiota composition.

Conclusion: These findings suggest that FAs could be therapeutic targets for improving CD management across different age groups.

Mechanobiological forces play a pivotal role in the processes of skin homeostasis, wound healing and regeneration. Changes in tissue stiffness are linked to various skin diseases. Using atomic force microscopy, we analyzed the elastic modulus, representing mechanical stiffness, of different skin layers in a group of six participants, including 2 males and 4 females, aged between 1 and 70 years. The skin layers, ranked from highest to lowest elastic modulus, are the epidermis, papillary dermis, upper reticular dermis, lower reticular dermis, sebaceous gland, and subcutaneous tissue. This study contributes to more understanding of the physical properties of the skin, offering a reference for further research on skin physiology or pathology.

Numerous signaling pathways are activated during hypoxia to facilitate angiogenesis, promoting interactions among endothelial cells and initiating downstream signaling cascades. Although the pivotal role of the nitric oxide (NO) response pathway is well-established, the involvement of arginine-specific metabolism and bioactive lipid mechanisms in 3D flow-activated in vitro models remains less understood. In this study, we explored the levels of arginine-specific metabolites and bioactive lipids in human coronary artery endothelial cells (HCAECs) under both transient and persistent hypoxia. We compared targeted metabolite levels between a 2D static culture model and a 3D microvessels-on-chip model. Notably, we observed robust regulation of NO metabolites in both transient and persistent hypoxic conditions. In the 2D model under transient hypoxia, metabolic readouts of bioactive lipids revealed increased oxidative stress markers, a phenomenon not observed in the 3D microvessels. Furthermore, we made a novel discovery that the responses of bioactive lipids were regulated by hypoxia inducible factor-1α (HIF-1α) in the 2D cell culture model and partially by HIF-1α and flow-induced shear stress in the 3D microvessels. Immunostaining confirmed the HIF-1α-induced regulation under both hypoxic conditions. Real-time oxygen measurements in the 3D microvessels using an oxygen probe validated that oxygen levels were maintained in the 3D model. Overall, our findings underscore the critical regulatory roles of HIF-1α and shear stress in NO metabolites and bioactive lipids in both 2D and 3D cell culture models.