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https://www.readbyqxmd.com/read/29028806/a-novel-immunotoxin-reveals-a-new-role-for-cd321-in-endothelial-cells
#1
Takeshi Fukuhara, Jia Kim, Shintaro Hokaiwado, Makiko Nawa, Hayato Okamoto, Tomohiko Kogiso, Tetsuro Watabe, Nobutaka Hattori
There are currently several antibody therapies that directly target tumors, and antibody-drug conjugates represent a novel moiety as next generation therapeutics. Here, we used a unique screening probe, DT3C, to identify functional antibodies that recognized surface molecules and functional epitopes, and which provided toxin delivery capability. Accordingly, we generated the 90G4 antibody, which induced DT3C-dependent cytotoxicity in endothelial cells. Molecular analysis revealed that 90G4 recognized CD321, a protein localized at tight junctions...
2017: PloS One
https://www.readbyqxmd.com/read/29027376/adenosine-a2a-receptor-agonist-ameliorates-eae-and-correlates-with-th1-cytokine-induced-blood-brain-barrier-dysfunction-via-suppression-of-mlck-signaling-pathway
#2
Ying Liu, Marwan Alahiri, Bianca Ulloa, Boxun Xie, Saud A Sadiq
INTRODUCTION: Multiple sclerosis (MS) disease activity is associated with blood-brain barrier (BBB) disruption, which is mediated by inflammatory cytokines released by CD4+ lymphocytes. To assess the effects of adenosine A2A receptors on BBB permeability in vitro and in vivo. METHODS: A2A receptor expression was detected by immunostaining in experimental autoimmune encephalomyelitis (EAE) C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 , and human MS brain...
October 12, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29026006/potential-contribution-of-alveolar-epithelial-type-i-cells-to-pulmonary-fibrosis
#3
Michael Kasper, Kathrin Barth
Pulmonary fibrosis is characterized by inflammation and fibrosis of the interstitium and destruction of alveolar histoarchitecture ultimately leading to a fatal impairment of lung function. Different concepts describe either a dominant role of inflammatory pathways or a disturbed remodeling of resident cells of the lung parenchyma during fibrogenesis. Further, a combination of both mechanisms has been postulated. The present review emphasizes the particular involvement of alveolar epithelial type I cells in all of these processes, their contribution to innate immune/inflammatory functions and maintenance of proper alveolar barrier functions...
October 12, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29025734/dietary-copper-fructose-interactions-alter-gut-microbial-activity-in-male-rats
#4
Ming Song, Xiaohong Li, Xiang Zhang, Hongxue Shi, Miriam B Vos, Xiaoli Wei, Yuhua Wang, Hong Gao, Eric C Rouchka, Xinmin Yin, Zhanxiang Zhou, Russell A Prough, Matthew C Cave, Craig J McClain
Dietary copper-fructose interactions contribute to the development of nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in the pathogenesis of NAFLD. The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbiome. Male weanling Sprague-Dawley rats were fed diets with adequate copper (6 ppm, CuA), marginal copper (1.5 ppm, CuM) (low-copper) or supplemented copper (20 ppm, CuS) (high-copper) for 4 weeks...
October 12, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29023813/dual-catenin-loss-in-murine-liver-causes-tight-junctional-deregulation-and-progressive-intrahepatic-cholestasis
#5
Tirthadipa Pradhan-Sundd, Lili Zhou, Ravi Vats, An Jiang, Laura Molina, Sucha Singh, Minakshi Poddar, Jacquelyn M Russell, Donna B Stolz, Michael Oertel, Udayan Apte, Simon Watkins, Sarangarajan Ranganathan, Kari N Nejak-Bowen, Prithu Sundd, Satdarshan Pal Monga
β-Catenin, the downstream effector of the Wnt signaling, plays important roles in hepatic development, regeneration and tumorigenesis. However, its role at hepatocyte adherens junctions (AJ) is relatively poorly understood, chiefly due to spontaneous compensation by γ-catenin. Here, we simultaneously ablate β- and γ-catenin expression in mouse liver by interbreeding β-catenin-γ-catenin double-floxed mice and albumin-cre transgenic mice. Double knockout mice (DKO) show failure to thrive, impaired hepatocyte differentiation, cholemia, ductular reaction, progressive cholestasis, inflammation, fibrosis and tumorigenesis, which was associated with deregulation of tight junctions (TJ) and bile acid transporters, leading to early morbidity and mortality, a phenotype reminiscent of Progressive Familial Intrahepatic Cholestasis (PFIC)...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29022894/adiponectin-controls-the-apoptosis-and-the-expression-of-tight-junction-proteins-in-brain-endothelial-cells-through-adipor1-under-beta-amyloid-toxicity
#6
Juhyun Song, Seong-Min Choi, Daniel J Whitcomb, Byeong C Kim
Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by excessive beta amyloid (Aβ) deposition in brain, leading to blood-brain barrier (BBB) disruption. The mechanisms of BBB disruption in AD are still unclear, despite considerable research. The adipokine adiponectin is known to regulate various metabolic functions and reduce inflammation. Though adiponectin receptors have been reported in the brain, its role in the central nervous system has not been fully characterized. In the present study, we investigate whether adiponectin contributes to the tight junction integrity and cell death of brain endothelial cells under Aβ-induced toxicity conditions...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29021401/rnaseq-analysis-of-differentiated-keratinocytes-reveals-a-massive-response-to-late-events-during-human-papillomavirus-type-16-infection-including-loss-of-epithelial-barrier-function
#7
T Klymenko, Q Gu, I Herbert, A Stevenson, V Iliev, G Watkins, C Pollock, R Bhatia, K Cuschieri, P Herzyk, D Gatherer, S V Graham
The human papillomavirus (HPV) replication cycle is tightly linked to epithelial cell differentiation. To examine HPV-associated changes in the keratinocyte transcriptome, RNAs isolated from undifferentiated and differentiated cell populations of normal, spontaneously immortalised, keratinocytes (NIKS), and NIKS stably transfected with HPV16 episomal genomes (NIKS16), were compared using RNASeq. HPV16 infection altered expression of 2862 cellular genes. Next, to elucidate the role of keratinocyte gene expression in late events during the viral life cycle, RNASeq was carried out on triplicate differentiated populations of NIKS (uninfected) and NIKS16 (infected)...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29020011/a-microfluidic-renal-proximal-tubule-with-active-reabsorptive-function
#8
Else M Vedula, José Luis Alonso, M Amin Arnaout, Joseph L Charest
In the kidney, the renal proximal tubule (PT) reabsorbs solutes into the peritubular capillaries through active transport. Here, we replicate this reabsorptive function in vitro by engineering a microfluidic PT. The microfluidic PT architecture comprises a porous membrane with user-defined submicron surface topography separating two microchannels representing a PT filtrate lumen and a peritubular capillary lumen. Human PT epithelial cells and microvascular endothelial cells in respective microchannels created a PT-like reabsorptive barrier...
2017: PloS One
https://www.readbyqxmd.com/read/29018933/from-osteoimmunology-to-osteomicrobiology-how-the-microbiota-and-the-immune-system-regulate-bone
#9
REVIEW
Emory Hsu, Roberto Pacifici
Osteomicrobiology refers to the role of microbiota in bone health and the mechanisms by which the microbiota regulates post-natal skeletal development, bone aging, and pathologic bone loss. Here, we review recent reports linking gut microbiota to changes in bone phenotype. A pro-inflammatory cytokine milieu drives bone resorption in conditions such as sex steroid hormone deficiency. The response of the immune system to activation by the microbiome results in increased circulating osteoclastogenic cytokines in a T cell-dependent mechanism...
October 10, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29018453/inulin-type-fructans-modulates-pancreatic-gut-innate-immune-responses-and-gut-barrier-integrity-during-experimental-acute-pancreatitis-in-a-chain-length-dependent-manner
#10
Yue He, Chengfei Wu, Jiahong Li, Hongli Li, Zhenghua Sun, Hao Zhang, Paul de Vos, Li-Long Pan, Jia Sun
Acute pancreatitis (AP) is a common abdominal inflammatory disorder and one of the leading causes of hospital admission for gastrointestinal disorders. No specific pharmacological or nutritional therapy is available but highly needed. Inulin-type fructans (ITFs) are capable of modifying gut immune and barrier homeostasis in a chemistry-dependent manner and hence potentially applicable for managing AP, but their efficacy in AP has not been demonstrated yet. The current study aimed to examine and compare modulatory effects of ITFs with different degrees of fermentability on pancreatic-gut immunity and barrier function during experimentally induced AP in mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29018435/lactobacillus-plantarum-bsgp201683-isolated-from-giant-panda-feces-attenuated-inflammation-and-improved-gut-microflora-in-mice-challenged-with-enterotoxigenic-escherichia-coli
#11
Qian Liu, Xueqin Ni, Qiang Wang, Zhirong Peng, Lili Niu, Hengsong Wang, Yi Zhou, Hao Sun, Kangcheng Pan, Bo Jing, Dong Zeng
In this work, we searched for an effective probiotic that can help control intestinal infection, particularly enterotoxigenic Escherichia coli K88 (ETEC) invasion, in giant panda (Ailuropoda melanoleuca). As a potential probiotic strain, Lactobacillus plantarum BSGP201683 (L. plantarum G83) was isolated from the feces of giant panda and proven beneficial in vitro. This study was aimed to evaluate the protective effect of L. plantarum G83 in mice challenged with ETEC. The mice were orally administered with 0...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29018347/mechanisms-of-the-testis-toxicity-induced-by-chronic-exposure-to-mequindox
#12
Qianying Liu, Zhixin Lei, Anxiong Huang, Qirong Lu, Xu Wang, Saeed Ahmed, Ihsan Awais, Zonghui Yuan
Mequindox (MEQ) is a synthetic antimicrobial agent widely used in China since the 1980s. Although the toxicity of MEQ is well recognized, its testis toxicity has not been adequately investigated. In the present study, we provide evidence that MEQ triggers oxidative stress, mitochondrion dysfunction and spermatogenesis deficiency in mice after exposure to MEQ (0, 25, 55, and 110 mg/kg in the diet) for up to 18 months. The genotoxicity and adrenal toxicity may contribute to sperm abnormalities caused by MEQ. Moreover, using LC/MS-IT-TOF analysis, two metabolites, 3-methyl-2-(1-hydroxyethyl) quinoxaline-N4-monoxide (M4) and 3-methyl-2-(1-hydroxyethyl) quinoxaline-N1-monoxide (M8), were detected in the serum of mice, which directly confirms the relationship between the N→O group reduction metabolism of MEQ and oxidative stress...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29017935/physiological-implications-of-dheas-induced-non-classical-steroid-hormone-signaling
#13
Dimitrios Papadopoulos, Mazen Shihan, Georgios Scheiner-Bobis
In the spermatogenic cell line GC-2, dehydroepiandrosterone sulfate (DHEAS), activates the Src/Ras/c-Raf/Erk1/2/CREB(ATF-1) signaling cascade. Since DHEAS is present in the gonads, and since spermatogenesis and maturation of spermatogonia to haploid spermatozoa requires activation of Erk1/2, the triggering of these signaling events by DHEAS might have physiological relevance. In the Sertoli cell line TM4, DHEAS-induces activation of Erk1/2, CREB, and ATF-1, stimulates expression of claudin-3 and claudin-5 and augments transepithelial resistance, indicating the formation of tight junctions between adjacent Sertoli cells...
October 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29017810/redox-mediated-regulation-of-connexin-proteins-focus-on-nitric-oxide
#14
REVIEW
Isaac E García, Helmuth A Sánchez, Agustín D Martínez, Mauricio A Retamal
Connexins are membrane proteins that form hemichannels and gap junction channels at the plasma membrane. Through these channels connexins participate in autocrine and paracrine intercellular communication. Connexin-based channels are tightly regulated by membrane potential, phosphorylation, pH, redox potential, and divalent cations, among others, and the imbalance of this regulation have been linked to many acquired and genetic diseases. Concerning the redox potential regulation, the nitric oxide (NO) has been described as a modulator of the hemichannels and gap junction channels properties...
October 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29016922/morphologic-mechanisms-of-increased-vascular-permeability-of-triolein-emulsion-to-the-blood-brain-barrier
#15
Yuri Sol, Seon Hee Choi, Hak Jin Kim, Yong-Woo Kim, Byung Mann Cho, Hyung Soo Han, Ki J Choi
Triolein emulsion has been known to increase vascular permeability in the brain when it is infused into the carotid artery. The purpose of this study was to identify the morphologic mechanism of increased vascular permeability in brain induced by infusion of emulsified triolein into the carotid artery by transmission electron microscopy (TEM). Triolein emulsion was infused into the carotid artery of rats. TEM using lanthanum tracer was used to evaluate morphologic changes in endothelium with a focus on transcytotic vesicles and tight junction opening...
October 1, 2017: Microscopy
https://www.readbyqxmd.com/read/29016860/primary-angle-closure-glaucoma-pacg-susceptibility-gene-plekha7-encodes-a-novel-rac1-cdc42-gap-that-modulates-cell-migration-and-blood-aqueous-barrier-function
#16
Mei-Chin Lee, William Shei, Anita S Chan, Boon-Tin Chua, Shuang-Ru Goh, Yaan-Fun Chong, Maryam H Hilmy, Monisha E Nongpiur, Mani Baskaran, Chiea-Chuen Khor, Tin Aung, Walter Hunziker, Eranga N Vithana
PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28994773/improved-method-for-the-establishment-of-an-in-vitro-blood-brain-barrier-model-based-on-porcine-brain-endothelial-cells
#17
Simone S E Nielsen, Piotr Siupka, Ana Georgian, Jane E Preston, Andrea E Tóth, Siti R Yusof, N Joan Abbott, Morten S Nielsen
The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation...
September 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28994126/staphylococcus-aureus-v8-protease-disrupts-the-integrity-of-the-airway-epithelial-barrier-and-impairs-il-6-production-in-vitro
#18
Jae Murphy, Mahnaz Ramezanpour, Natalia Stach, Grzegorz Dubin, Alkis James Psaltis, Peter-John Wormald, Sarah Vreugde
OBJECTIVE: Staphylococcus aureus (S. aureus) infection is known to contribute to the severity and recalcitrance of chronic rhinosinusitis (CRS), and its secreted products have been shown to alter the airway barrier. Extracellular proteases secreted by S. aureus are thought to be important in epithelial infection and immune evasion; however, their effect on airway mucosal barrier function is not known. METHODS: To investigate the impact of extracellular proteases on airway epithelial integrity, the purified S...
October 10, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28993815/membrane-pore-spacing-can-modulate-endothelial-cell-substrate-and-cell-cell-interactions
#19
Stephanie M Casillo, Ana P Peredo, Spencer J Perry, Henry H Chung, Thomas R Gaborski
Mechanical cues and substrate interaction affect the manner in which cells adhere, spread, migrate and form tissues. With increased interest in tissue-on-a-chip and co-culture systems utilizing porous membranes, it is important to understand the role of disrupted surfaces on cellular behavior. Using a transparent glass membrane with defined pore geometries, we investigated endothelial fibronectin fibrillogenesis and formation of focal adhesions as well as development of intercellular junctions. Cells formed fewer focal adhesions and had shorter fibronectin fibrils on porous membranes compared to non-porous controls, which was similar to cell behavior on continuous soft substrates with Young's moduli seven orders of magnitude lower than glass...
2017: ACS Biomaterials Science & Engineering
https://www.readbyqxmd.com/read/28993710/dose-dependent-expression-of-claudin-5-is-a-modifying-factor-in-schizophrenia
#20
C Greene, J Kealy, M M Humphries, Y Gong, J Hou, N Hudson, L M Cassidy, R Martiniano, V Shashi, S R Hooper, G A Grant, P F Kenna, K Norris, C K Callaghan, M dN Islam, S M O'Mara, Z Najda, S G Campbell, J S Pachter, J Thomas, N M Williams, P Humphries, K C Murphy, M Campbell
Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells...
October 10, 2017: Molecular Psychiatry
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