Tissue Barriers最新文献

The bicellular tight junction molecule cingulin (CGN) binds to microtubules in centrosomes. Furthermore, CGN contributes to the tricellular tight junction (tTJ) proteins lipolysis-stimulated lipoprotein receptor (LSR) and tricellulin (TRIC). CGN as well as LSR decreased during the malignancy of endometrioid endometrial cancer (EEC). Although tTJ protein LSR is involved in the malignancy of some cancers, including EEC, the role of CGN is unknown. In this study, we investigated the roles of CGN with tTJ proteins in human EEC cells by using the CGN-overexpressing EEC cell line Sawano. In 2D cultures, CGN was colocalized with LSR and TRIC at tTJ or at γ-tubulin-positive centrosomes. In immunoprecipitation with CGN antibodies, CGN directly bound to LSR, TRIC, and β-tubulin. Knockdown of CGN by the siRNA decreased the epithelial barrier and enhanced cell proliferation, migration and invasion, as well as knockdown of LSR. In the Sawano cells cocultured with normal human endometrial stromal cells, knockdown of CGN decreased expression of LSR and TRIC via MAPK and AMPK pathways. In 2.5D cultures, knockdown of CGN induced the formation of abnormal cysts and increased the permeability of FD-4 to the lumen. In 2D and 2.5D cultures, treatment with β-estradiol with or without EGF or TGF-β decreased CGN expression and the epithelial permeability barrier and enhanced cell migration, and pretreatment with EW7197+AG1478, U0126 or an anti-IL-6 antibody prevented this. In conclusion, CGN, with tTJ proteins might suppress the malignancy of human EEC and its complex proteins are sensitive to estrogen and growth factors derived from stromal cells.

Ciliopathies are a group of diseases caused by defects in cilia, hair-like organelles that can have many functions ranging from regulating extracellular fluid flow to sensing mechanical or chemical stimuli. Multiciliated cells (MCCs) with motile cilia are found in locations that include the central nervous system, where they are critical for homeostasis. Specifically, ependymal MCCs line the brain ventricles and central canal of the spinal cord, while other specialized MCCs occupy highly vascularized structures known as the choroid plexuses (ChPs) and produce cerebrospinal fluid (CSF). Now, a recent study has shown that murine ChP MCCs develop nodal-like cilia. Interestingly, ChP cilia were found to undergo resorption during early postnatal stages in part through axoneme regression, and this phenomenon was mirrored in human postmortem ChP samples. Taken together, these findings reveal important new insights about the ultrastructure of MCCs that comprise the mammalian ChP, and may have ramifications for other MCC populations in health and disease states.

Ginseng, a well-known herbal supplement, is widely recognized for its pharmacological properties, including anti-inflammatory, antioxidant, and immune-modulatory effects. This review explores the potential therapeutic benefits of ginseng, particularly its active compounds, ginsenosides, in promoting nasal mucosa health. The nasal mucosa plays a crucial role in respiratory defense, acting as a barrier to pathogens and particulate matter, while also orchestrating immune responses. Ginseng's bioactive compounds have shown promise in modulating inflammation, reducing oxidative stress, and enhancing immune functions, which could be beneficial in conditions such as allergic rhinitis, chronic rhinosinusitis, and viral infections. Histological studies highlight the impact of ginseng on nasal mucosal cells, particularly in regulating immune responses and promoting tissue resilience. Research demonstrates that ginseng can reduce inflammation in the nasal passages by inhibiting pro-inflammatory cytokines and pathways like NF-κB, while enhancing the activity of immune cells such as natural killer cells and macrophages. Furthermore, ginseng's antioxidant properties help protect nasal tissue from oxidative damage, which is common in chronic nasal conditions. Although promising, the evidence base is still developing, with many studies limited by small sample sizes and variations in ginseng preparations. Further clinical trials are needed to substantiate ginseng's efficacy, optimal dosage, and delivery methods for treating nasal conditions. This review provides insights into the potential of ginseng as a complementary therapeutic approach for enhancing nasal mucosa health and improving respiratory outcomes.

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.

Arrestins and integrin-linked kinase (ILK) are important scaffold proteins that regulate myriad cell functions in metazoans. β-arrestins, first identified as critical components in G-protein-coupled receptor (GPCR) signaling pathways, participate in inflammatory, immunomodulatory and tissue repair processes in GPCR-dependent and -independent manners. ILK is a central mediator of signaling cascades elicited by activation of integrins, regulating cell motility, proliferation, and mechanotransduction. In the epidermis, ILK is essential for maintenance of barrier function, hair follicle development, melanocyte colonization and regeneration after injury. In this tissue, β-arrestin 2 mitigates inflammatory processes and development of allergic dermatitis, which also is associated with loss of epidermal barrier function. However, the functional role of β-arrestin 1 in epidermal cells is poorly understood. We now report that β-arrestin 1 directly binds ILK, forming hitherto unidentified protein complexes in epidermal keratinocytes. In the absence of exogenous GPCR ligand stimulation, β-arrestin 1 and ILK are found throughout the cytoplasm in epidermal keratinocytes, and also co-localize to plasma membrane regions associated with cell protrusions. Inactivation of the genes that encode both β-arrestin 1 and 2 attenuates forward cell migration, whereas expression of ILK together with β-arrestin 1 restores cell motility. The cooperative effect of ILK and β-arrestin 1 in promoting directional cell migration may have important implications for epidermal regeneration and reestablishment of barrier function after injury.

Recent years have heralded many exciting advancements in our knowledge about kidney development. In particular, there has been tremendous progress in identifying genes and signaling pathways that pattern renal functional units - a process known as nephron segmentation. An intriguing potential regulator of this process, 17β-estradiol (E2), was implicated previously by a high-throughput screen that examined the effects of known bioactive molecules on nephrogenesis. Now, a detailed study has shown that exogenous E2 or exposure to several xenoestrogens has significant effects on nephron distal tubule establishment during development of the zebrafish pronephros, or embryonic kidney. Attenuation of estrogen receptor 2b (Esr2b) activity by pharmacological antagonism or genetic knockdown revealed that E2/Esr2b signaling is necessary for normal distal segment pattern by regulating the expression of Iroquois transcription factors. These findings demonstrate that estrogen signaling influences renal stem cell development during the process of vertebrate nephron segmentation and may have important ramifications for understanding congenital birth defects and kidney diseases.

Somatostatin is expressed in various tissues - including the hypothalamus - and strongly suppresses Growth Hormone levels to maintain homeostasis. Synthetic somatostatin analogs are currently used in clinics to treat neuroendocrine tumors and acromegaly. An emerging body of evidence suggests that those synthetic peptides exert anti-inflammatory activities. The present study examines the effect of Lanreotide (LAN) on Lipopolysaccharide (LPS)-triggered injury in endothelial cells and mice. Our findings indicate that LAN effectively mitigates LPS-induced endothelial hyperpermeability, inflammation, and reactive oxygen species (ROS) generation in bovine pulmonary artery endothelial cells (BPAEC) and human lung microvascular endothelial cells (HULEC-5a). A murine model of LPS-induced acute lung injury was also utilized, to examine the effects of LAN in lung edema and inflammation. Our observations suggest that LAN suppresses LPS-induced myosin light chain 2 (MLC2), Cofilin, extracellular signal-regulated kinase 1/2 (ERK1/2), STAT1, STAT3, P38 activation; and lung edema. In conclusion, and based on the aforementioned observations, it is suggested that LAN counteracts experimental LPS-induced injury in endothelial cells and mice.

Diabetic retinopathy is the most prevalent microvascular consequences of diabetes mellitus that can result in vision loss. Nanotechnology has been widely used in the treatment of ophthalmic diseases. Selenium is a naturally occurring compound that has antioxidant and anti-inflammatory effects. This study aimed at comparing the possible ameliorating effect of selenium versus Nano-selenium on streptozotocin-induced diabetic retinopathy in rats. Sixty adult male albino-Wister rats were divided randomly into six groups; control, Selenium+ve, Nanoselenium+ve, diabetic, DR-Se treated group, and DR-NS treated group. Animals were anesthetized and sacrificed at the end of study. Eyes were removed and prepared for biochemical, histological, and immunohistochemical studies. The results showed that the diabetic group had an apparent decrease in retinal thickness, loss of photoreceptors, dilated congested blood vessels in retinal layers. Additionally, a significant increase in malondialdehyde and significant decrease in Total Antioxidant Capacity were detected. Significant increase in surface area fraction of vascular endothelial growth factor, nuclear factor kappa B, Glial fibrillary acidic protein immune stained cells were noticed, and significant decrease in connexin 43 expression was also detected. Improvement in all mentioned parameters in DR-Se and DR-NS groups was noticed. Our study suggested that Selenium, whether in its regular or nano form, holds promise for alleviating diabetic retinopathy in rats on biochemical, histological, and immunohistochemical basis.

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.

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.