Protection of Tight Junctional Complexes between hCMEC/D3 Cells by Deep-Sea Fibrinolytic Compound FGFC1.

Tight junctional complexes (TJCs) between cerebral microvascular endothelial cells (CMECs) are essential parts of the blood-brain barrier (BBB), whose regulation closely correlates to the BBB's integrity and function. hCMEC/D3 is the typical cell line used to imitate and investigate the barrier function of the BBB via the construction of an in vitro model. This study aims to investigate the protective effect of the deep-sea-derived fibrinolytic compound FGFC1 against H2O2-induced dysfunction of TJCs and to elucidate the underlying mechanism. The barrier function was shown to decline following exposure to 1 mM H2O2 in an in vitro model of hCMEC/D3 cells, with a decreasing temperature-corrected transendothelial electrical resistance (tcTEER) value. The decrease in the tcTEER value was significantly inhibited by 80 or 100 µM FGFC1, which suggested it efficiently protected the barrier integrity, allowing it to maintain its function against the H2O2-induced dysfunction. According to immunofluorescence microscopy (IFM) and quantitative real-time polymerase chain reaction (qRT-PCR), compared to the H2O2-treated group, 80~100 µM FGFC1 enhanced the expression of claudin-5 (CLDN-5) and VE-cadherin (VE-cad). And this enhancement was indicated to be mainly achieved by both up-regulation of CLDN-5 and inhibition of the down-regulation by H2O2 of VE-cad at the transcriptional level. Supported by FGFC1's molecular docking to these proteins with reasonable binding energy, FGFC1 was proved to exert a positive effect on TJCs' barrier function in hCMEC/D3 cells via targeting CLDN-5 and VE-cad. This is the first report on the protection against H2O2-induced barrier dysfunction by FGFC1 in addition to its thrombolytic effect. With CLDN-5 and VE-cad as the potential target proteins of FGFC1, this study provides evidence at the cellular and molecular levels for FGFC1's reducing the risk of bleeding transformation following its application in thrombolytic therapy for cerebral thrombosis.

The Rare Marine Bioactive Compounds in Neurological Disorders and Diseases: Is the Blood-Brain Barrier an Obstacle or a Target?

The blood-brain barrier (BBB) is a dynamic barrier separating neurocytes and brain tissues from blood that is extremely sealed and strictly regulated by transporters such as aquaporin-4 (AQP-4), glucose transporter (GLUT), and specialized tight junctional complexes (TJCs) including tight junctions (TJs), adherens junctions (AJs), and Zonulae occludens (ZOs). With specifically selective transcellular and paracellular permeability, the BBB maintains a homeostatic microenvironment to protect the central nervous system (CNS). In recent years, increasing attention has been paied to the importance of BBB disruption and dysfunction in the pathology of neurological disorders and diseases, such as Alzheimer's diseases (AD), Parkinson diseases (PD), stroke and cerebral edema. However, the further research on how the integral structure and function of BBB are altered under the physiological or pathological conditions is still needed. Focusing on the ultrastructural features of the BBB and combining the latest research on associated proteins and transporters, physiological regulation and pathological change of the BBB were elucidated. By summarizing the protective effects of known bioactive compounds derived from marine life on the BBB, this review aims to highlight the BBB as a key to the treatment of several major neurological diseases instead of a normally described obstacle to drug absorption and transport. Overall, the BBB's morphological characteristics and physiological function and their regulation provide the theoretical basis for the study on the BBB and inspire the diagnosis of and therapy for neurological diseases.

Metabolites Produced by a New Lactiplantibacillus plantarum Strain BF1-13 Isolated from Deep Seawater of Izu-Akazawa Protect the Intestinal Epithelial Barrier from the Dysfunction Induced by Hydrogen Peroxide.

This study aimed to investigate the protective effect of the metabolites produced by a new Lactiplantibacillus plantarum strain BF1-13, isolated from deep seawater (DSW), on the intestinal epithelial barrier against the dysfunction induced by hydrogen peroxide (H2O2) and to elucidate the mechanism underlying the effect. Protective effect of the metabolites by strain BF1-13 on the barrier function of the intestinal epithelial model treated with H2O2 was investigated by the transepithelial electrical resistance (TEER). The metabolites enhanced the Claudin-4 (CLDN-4) expression, including at the transcription level, indicated by immunofluorescence staining and quantitative RT-PCR. The metabolites also showed a suppression of aquaporin3 (AQP3) expression. Lactic acid (LA) produced by this strain of homofermentative lactic acid bacteria (LAB) had a similar enhancement on CLDN-4 expression. The metabolites of L. plantarum strain BF1-13 alleviated the dysfunction of intestinal epithelial barrier owing to its enhancement on the tight junctions (TJs) by LA, along with its suppression on AQP3-facilitating H2O2 intracellular invasion into Caco-2 cells. This is the first report on the enhancement of TJs by LA produced by LAB.