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Tight junction

Li Wen, Tanveer A Javed, Dean Yimlamai, Amitava Mukherjee, Xiangwei Xiao, Sohail Z Husain
BACKGROUND AND AIMS: Pancreatitis following endoscopic retrograde cholangiopancreatography (PEP) is thought to be provoked by pancreatic ductal hypertension, via unknown mechanisms. We investigated the effects of hydrostatic pressures on the development of pancreatitis in mice. METHODS: We performed studies with Swiss Webster mice, B6129 mice (controls), and B6129 mice with disruption of the protein phosphatase 3, catalytic subunit, beta isoform gene (Cnab-/- mice)...
June 18, 2018: Gastroenterology
Justyna S Grothaus, Guillermo Ares, Carrie Y Yuan, Douglas R Wood, Catherine J Hunter
Necrotizing enterocolitis (NEC) is a deadly disease that occurs in 5-10% of neonates. Although NEC has been extensively studied, no single therapeutic target has been identified. Rho kinase is a serine/ threonine kinase that affects multiple cellular processes including tight junction function, cellular permeability, and apoptosis. We hypothesized that ROCK inhibition would decrease cellular permeability, stabilize tight junction (TJ) proteins (occludin), and decrease the severity of NEC. To test this hypothesis, human colon epithelial cells (Caco-2) and human endothelial cells (HUVEC) were studied...
June 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Irina Zurina, Anastasia Shpichka, Irina Saburina, Nastasia V Kosheleva, Anastasiya Gorkun, Ekaterina A Grebenik, Daria Kuznetsova, Deying Zhang, Yury Rochev, Denis Butnaru, Tatyana Zharikova, Elena Victorovna Istranova, Yuanyuan Zhang, Leonid Prokofievich Istranov, Peter S Timashev
Maintaining the epithelial status of cells in vitro and fabrication of a multilayered epithelial lining is one of the key problems in the therapy using cell technologies. When cultured in a monolayer, epithelial cells change their phenotype from epithelial to epithelial-mesenchymal or mesenchymal that makes it difficult to obtain a sufficient number of cells in a 2D culture and to use them in tissue engineering. Here, using buccal epithelial cells from the oral mucosa, we developed a novel approach to recover and maintain the stable cell phenotype and form a multilayered epithelial lining in vitro via the 2D/3D cell self-assembling...
June 21, 2018: Biomedical Materials
Wen-di Luo, Jia-Wei Min, Wen-Xian Huang, Xin Wang, Yuan-Yuan Peng, Song Han, Jun Yin, Wan-Hong Liu, Xiao-Hua He, Bi-Wen Peng
BACKGROUND: Neonatal hypoxic-ischemic brain damage, characterized by tissue loss and neurologic dysfunction, is a leading cause of mortality and a devastating disease of the central nervous system. We have previously shown that vitexin has been attributed various medicinal properties and has been demonstrated to have neuroprotective roles in neonatal brain injury models. In the present study, we continued to reinforce and validate the basic understanding of vitexin (45 mg/kg) as a potential treatment for epilepsy and explored its possible underlying mechanisms...
June 20, 2018: Journal of Neuroinflammation
Michelle L Wright, Christina Fournier, Madelyn C Houser, Malú Tansey, Jonathan Glass, Vicki Stover Hertzberg
Amyotrophic lateral sclerosis (ALS) etiology and pathophysiology are not well understood. Recent data suggest that dysbiosis of gut microbiota may contribute to ALS etiology and progression. This review aims to explore evidence of associations between gut microbiota and ALS etiology and pathophysiology. Databases were searched for publications relevant to the gut microbiome in ALS. Three publications provided primary evidence of changes in microbiome profiles in ALS. An ALS mouse model revealed damaged tight junction structure and increased permeability in the intestine versus controls along with a shifted microbiome profile, including decreased levels of butyrate-producing bacteria...
January 1, 2018: Biological Research for Nursing
Annita Louloupi, Evgenia Ntini, Thomas Conrad, Ulf Andersson Vang Ørom
Splicing efficiency varies among transcripts, and tight control of splicing kinetics is crucial for coordinated gene expression. N-6-methyladenosine (m6A) is the most abundant RNA modification and is involved in regulation of RNA biogenesis and function. The impact of m6A on regulation of RNA splicing kinetics is unknown. Here, we provide a time-resolved high-resolution assessment of m6A on nascent RNA transcripts and unveil its importance for the control of RNA splicing kinetics. We find that early co-transcriptional m6A deposition near splice junctions promotes fast splicing, while m6A modifications in introns are associated with long, slowly processed introns and alternative splicing events...
June 19, 2018: Cell Reports
Tatjana Zake, Sandra Skuja, Ieva Kalere, Ilze Konrade, Valerija Groma
Th17 cells together with their hallmark cytokine interleukin (IL)-17 were identified as crucial contributing factors in the pathogenesis of thyroid autoimmunity. The cytokine-regulated tight junction (Tj) disruption is thought to be essential in the initiation and/or development of several diseases. Still, the role of IL-17 maintaining Tj integrity in autoimmune thyroid diseases (AITDs) has not yet been evaluated. We aimed to investigate integrity of the thyroid follicle by studying immunoexpression of cellular Tj - zonula occludens (ZO)-1 and claudin-1 proteins coupled to IL-17A and CD68 detection in AITD patients compared with controls...
June 2018: Medicine (Baltimore)
Kai Wang, Qinqin Yang, Quanxin Ma, Bei Wang, Zhengrui Wan, Minli Chen, Liming Wu
Salvianolic acid A (SAA) is an active phenolic acid derived from Salvia miltiorrhiza Bunge (Danshen). To explore whether SAA has a therapeutic effect against inflammatory bowel disease (IBD), an acute colitis model was induced in rats by administering 3% dextran sodium sulphate (DSS) for one week. SAA in doses of 4 and 8 mg/kg/day was given by tail vein injection during DSS administration. Both dosages of SAA ameliorated the colitis symptoms, with decreases observed in the disease activity index. A high dosage of SAA (8 mg/kg/day) promoted a longer colon length and an improved colonic tissue structure, compared with the DSS-treated rats not receiving SAA...
June 19, 2018: Nutrients
Annabelle M Watts, Nicholas P West, Allan W Cripps, Pete K Smith, Amanda J Cox
BACKGROUND: Investigations of gene expression in allergic rhinitis (AR) typically rely on invasive nasal biopsies (site of inflammation) or blood samples (systemic immunity) to obtain sufficient genetic material for analysis. New methodologies to circumvent the need for invasive sample collection offer promise to further the understanding of local immune mechanisms relevant in AR. METHODS: A within-subject design was employed to compare immune gene expression profiles obtained from nasal washing/brushing and whole blood samples collected during peak pollen season...
June 19, 2018: International Archives of Allergy and Immunology
Frédéric H Login, Helene H Jensen, Gitte A Pedersen, Manuel R Amieva, Lene N Nejsum
Enteropathogenic Escherichia coli (EPEC) causes watery diarrhea when colonizing the surface of enterocytes. The translocated intimin receptor (Tir):intimin receptor complex facilitates tight adherence to epithelial cells and formation of actin pedestals beneath EPEC. We found that the host cell adherens junction protein E-cadherin (Ecad) was recruited to EPEC microcolonies. Live-cell and confocal imaging revealed that Ecad recruitment depends on, and occurs after, formation of the Tir:intimin complex. Combinatorial binding experiments using wild-type EPEC, isogenic mutants lacking Tir or intimin, and E...
June 19, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers
The N-terminal domain (NTD) of nuclear human uracil DNA glycosylase (hUNG2) assists in targeting hUNG2 to replication forks through specific interactions with replication protein A (RPA). Here, we explored hUNG2 activity in the presence and absence of RPA using substrates with ssDNA-dsDNA junctions that mimic structural features of the replication fork and transcriptional R-loops. We find that when RPA is tightly bound to the ssDNA overhang of junction DNA substrates, base excision by hUNG2 is strongly biased toward uracils located 21 bp or less from the ssDNA-dsDNA junction...
June 18, 2018: Nucleic Acids Research
Priyanka Samanta, Yitang Wang, Shadi Fuladi, Jinjing Zou, Ye Li, Le Shen, Christopher Weber, Fatemeh Khalili-Araghi
Tight junctions are macromolecular structures that traverse the space between adjacent cells in epithelia and endothelia. Members of the claudin family are known to determine tight junction permeability in a charge- and size-selective manner. Here, we use molecular dynamics simulations to build and refine an atomic model of claudin-15 channels and study its transport properties. Our simulations indicate that claudin-15 forms well-defined channels for ions and molecules and otherwise "seals" the paracellular space through hydrophobic interactions...
June 18, 2018: Journal of General Physiology
Elisabeth Hansson
Nociceptive and neuropathic pain signals are known to result from noxious stimuli, which are converted into electrical impulses within tissue nociceptors. There is a complex equilibrium of pain-signalling and pain-relieving pathways connecting PNS and CNS. Drugs against long-term pain are today directed against increased neuronal excitability, mostly with less success. An injury often starts with acute physiological pain, which becomes inflammatory, nociceptive, or neuropathic, and may be transferred into long-term pain...
December 29, 2017: Scandinavian Journal of Pain
Chaoling Dong, E Scott Helton, Ping Zhou, Xuan Ouyang, Xavier d'Anglemont de Tassigny, Alberto Pascual, José López-Barneo, Eroboghene E Ubogu
There is emerging evidence that glial-derived neurotrophic factor (GDNF) is a potent inducer of restrictive barrier function in tight junction-forming microvascular endothelium and epithelium, including the human blood-nerve barrier (BNB) in vitro. We sought to determine the role of GDNF in restoring BNB function in vivo by evaluating sciatic nerve horseradish peroxidase (HRP) permeability in tamoxifen-inducible GDNF conditional knockout (CKO) adult mice following non-transecting crush injury via electron microscopy, with appropriate wildtype (WT) and heterozygous (HET) littermate controls...
June 18, 2018: Tissue Barriers
Aekkacha Moonwiriyakit, Panisara Wattanaphichet, Varanuj Chatsudthipong, Chatchai Muanprasat
Tight junctions play key roles in the regulation of airway epithelial barrier function and promotion of tight junction integrity is beneficial to lung health. G-protein coupled receptor (GPR) 40 has been identified as a receptor of polyunsaturated fatty acids. This study aimed to investigate the function of GPR40 in regulating tight junction assembly in human airway epithelial cells (Calu-3 cells) using GW9508, a GPR40 agonist. Immunoblotting and immunofluorescence analyses showed that Calu-3 cells expressed both types of polyunsaturated fatty acid receptors including GPR40 and GPR120...
June 18, 2018: Tissue Barriers
Kang Qi, Xiangdong Li, Yongjian Geng, Hehe Cui, Chen Jin, Peihe Wang, Yue Li, Yuejin Yang
OBJECTIVE: Endothelial barrier function in the onset and Tongxinluo (TXL) protection of myocardial ischemia/reperfusion (I/R) injury, and TXL can induce the secretion of Angiopoietin-like 4 (Angptl4) in human cardiac microvascular endothelial cells during hypoxia/reoxygenation. We intend to demonstrate whether TXL can attenuate myocardial I/R injury in diabetes, characterized with microvascular endothelial barrier disruption, by induction of Angptl4-mediated protection of endothelial barrier integrity...
2018: PloS One
Amy L Creekmore, Shuangsong Hong, Shengtao Zhu, Jing Xue, John W Wiley
In humans, chronic psychological stress is associated with increased intestinal paracellular permeability and visceral hyperalgesia, which is recapitulated in the chronic intermittent water avoidance stress (WAS) rat model. However, it is unknown whether enhanced visceral pain and permeability are intrinsically linked and correlate. Treatment of rats with lubiprostone during WAS significantly reduced WAS-induced changes in intestinal epithelial paracellular permeability and visceral hyperalgesia in a subpopulation of rats...
April 30, 2018: Pain
Pradeep K Shukla, Avtar S Meena, Bhargavi Manda, Maria Gomes-Solecki, Paula Dietrich, Ioannis Dragatsis, RadhaKrishna Rao
Pathogenesis of alcohol-related diseases such as alcoholic hepatitis involves gut barrier dysfunction, endotoxemia, and toxin-mediated cellular injury. Here we show that Lactobacillus plantarum not only blocks but also mitigates ethanol (EtOH)-induced gut and liver damage in mice. L. plantarum blocks EtOH-induced protein thiol oxidation, and down-regulation of antioxidant gene expression in colon L. plantarum also blocks EtOH-induced expression of TNF-α, IL-1β, IL-6, monocyte chemotactic protein 1 ( MCP1), C-X-C motif chemokine ligand ( CXCL)1, and CXCL2 genes in colon...
June 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Natalya A Zimbovskaya
We report results of theoretical studies of thermoelectric efficiency of single-molecule junctions with long molecular linkers. The linker is simulated by a chain of identical sites described using a tight-binding model. It is shown that thermoelectric figure of merit ZT strongly depends on the bridge length, being controlled by the lineshape of electron transmission function within the tunnel energy range corresponding to HOMO/LUMO transport channel. Using the adopted model we demonstrate that ZT may significantly increase as the linker lengthens, and that gateway states on the bridge (if any) may noticeably affect the length-dependent ZT...
June 18, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
Ke Wang, Haili Wang, Wenjuan Lou, Longhuan Ma, Yunchuan Li, Nan Zhang, Chong Wang, Fang Li, Muhammad Awais, Shengbo Cao, Ruiping She, Zhen F Fu, Min Cui
Japanese encephalitis is a neuropathological disorder caused by Japanese encephalitis virus (JEV), which is characterized by severe pathological neuroinflammation and damage to the blood-brain barrier (BBB). Inflammatory cytokines/chemokines can regulate the expression of tight junction (TJ) proteins and are believed to be a leading cause of BBB disruption, but the specific mechanisms remain unclear. IP-10 is the most abundant chemokine produced in the early stage of JEV infection, but its role in BBB disruption is unknown...
2018: Frontiers in Immunology
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