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Tight Junction and Its Proteins
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Biography
Updated time: 24 Mar 2021
Submitted by: Jun Young Heo
Abstract: The blood-brain barrier (BBB) is a selectively permeable barrier that divides the central nervous system (CNS) from the peripheral circulation, preventing infectious substances and immune cells from entering the CNS.
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Topic review
Updated time: 27 Apr 2021
Submitted by: Ahmad Joshkon
Definition: CD146 is a cell adhesion molecule expressed on all the vascular tree and belongs to the immunoglobulin superfamily. Two isoforms of CD146 exists, a long isoform expressed at the cell junction and a short isoform located at the apical membrane of the cells. CD146 appears to be critical in regulating vascular permeability, cell-cell cohesion, leukocyte transmigration, and angiogenesis. As a consequence, CD146 is involved in the pathogenesis of various diseases including autoimmune diseases and cancers. Also, CD146 exists in a soluble form generated via the action of matrix metalloproteinases and referred to as soluble CD146 (sCD146). The concentration of sCD146 is quantifiable in the sera and cerebrospinal fluid of healthy individuals. Indeed, any variation in its physiological concentration is associated with certain diseases making it an excellent biomarker for diagnostic purposes.
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Topic review
Updated time: 18 Jun 2021
Submitted by: Xiangru Wang
Definition: Brain microvascular endothelial cells (BMECs) constitute the structural and functional basis for the blood–brain barrier (BBB) and play essential roles in bacterial meningitis. Electrical cell-substrate impedance sensing (ECIS) measurement and Western blot assay demonstrated lncRSPH9-4 overexpression in hBMECs mediated the BBB integrity disruption.
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Topic review
Updated time: 13 Jul 2021
Submitted by: Norihisa Nishimura
Definition: An alteration of gut microbiota and their products, particularly endotoxins may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, the so-called “leaky gut.” Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases. The decreased diversity of gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of posttransplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor–alpha, interleukin (IL)–6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is also a major receptor activated by the binding of endotoxins in hepatic stellate cells, which play a crucial role in liver fibrogenesis that could develop into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression.
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Topic review
Updated time: 01 Jun 2021
Submitted by: Melvin Hayden
Definition: The triad of obesity, metabolic syndrome (MetS), Type 2 diabetes mellitus (T2DM) and advancing age are currently global societal problems that are expected to grow over the coming decades. This triad is associated with multiple end-organ complications of diabetic vasculopathy (maco-microvessel disease), neuropathy, retinopathy, nephropathy, cardiomyopathy, cognopathy encephalopathy and/or late-onset Alzheimer’s disease.
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Others
Updated time: 20 Jul 2021
Submitted by: Lara Rocha
Abstract: The myotendinous junction (MTJ) is the muscle-tendon interface and constitutes an integrated mechanical unit to force transmission. Joint immobilization promotes muscle atrophy via disuse, while physical exercise can be used as an adaptative stimulus. In this study, we aimed to investigate the components of the MTJ and their adaptations and the associated elements triggered with aquatic training after joint immobilization. Forty-four male Wistar rats were divided into sedentary (SD), aquatic training (AT), immobilization (IM), and immobilization/aquatic training (IMAT) groups. The samples were processed to measure fiber area, nuclear fractal dimension, MTJ nuclear density, identification of telocytes, sarcomeres, and MTJ perimeter length. In the AT group, the maintenance of ultrastructure and elements in the MTJ region were observed; the IM group presented muscle atrophy effects with reduced MTJ perimeter; the IMAT group demonstrated that aquatic training after joint immobilization promotes benefits in the muscle fiber area and fractal dimension, in the MTJ region shows longer sarcomeres and MTJ perimeter. We identified the presence of telocytes in the MTJ region in all experimental groups. We concluded that aquatic training is an effective rehabilitation method after joint immobilization due to reduced muscle atrophy and regeneration effects on MTJ in rats.
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Topic review
Updated time: 05 Nov 2020
Submitted by: Joen-Rong Sheu
Definition: Osteoarthritis (OA) is a most common type of arthritis occur in the aged population. It affects any joint in the body and degenerates the articular cartilage and subchondral bone. Despite the pathophysiology of OA is different, still cartilage resorption is a symbol of osteoarthritis. Matrix metalloproteinases (MMPs) are important proteolytic enzymes that degrade extra-cellular matrix proteins (ECM) in the body. MMPs contribute to the turnover of cartilage and its break down; their levels have increased in the joint tissues of OA patients. Application of chondroprotective drugs neutralize the activities of MMPs. Natural products derived from herbs and plants developed as traditional medicine have paid much attention due to their potential biological effects. Therapeutic value of natural products in OA has increased reputation by presenting clinical impact with insignificant side effects. Several MMPs inhibitor have been used as therapeutic drugs for long time. Recently, different types of compounds have been reviewed for their biological activities. In this review, we summarize numerous natural products for the development as MMPs inhibitors in arthritic diseases and describe the major signaling targets that involved for the treatments of these destructive joint diseases.
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Topic review
Updated time: 30 Oct 2020
Submitted by: Markus Gräler
Definition: The breakdown of the endothelial cell (EC) barrier contributes significantly to sepsis mortality. Sphingosine 1-phosphate (S1P) is one of the most effective EC barrier-stabilizing signaling molecules. Stabilization is mainly transduced via the S1P receptor type 1 (S1PR1). Here, we demonstrate that S1P was autonomously produced by ECs. S1P secretion was significantly higher in primary human umbilical vein endothelial cells (HUVEC) compared to the endothelial cell line EA.hy926. Constitutive barrier stability of HUVEC, but not EA.hy926, was significantly compromised by the S1PR1 antagonist W146 and by the anti-S1P antibody Sphingomab. HUVEC and EA.hy926 differed in the expression of the S1P-transporter Spns2, which allowed HUVEC, but not EA.hy926, to secrete S1P into the extracellular space. Spns2 deficient mice showed increased serum albumin leakage in bronchoalveolar lavage fluid (BALF). Lung ECs isolated from Spns2 deficient mice revealed increased leakage of fluorescein isothiocyanate (FITC) labeled dextran and decreased resistance in electric cell-substrate impedance sensing (ECIS) measurements. Spns2 was down-regulated in HUVEC after stimulation with pro-inflammatory cytokines and lipopolysaccharides (LPS), which contributed to destabilization of the EC barrier. Our work suggests a new mechanism for barrier integrity maintenance. Secretion of S1P by EC via Spns2 contributed to constitutive EC barrier maintenance, which was disrupted under inflammatory conditions via the down-regulation of the S1P-transporter Spns2.
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