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https://www.readbyqxmd.com/read/29351449/personalized-medicine-in-cf-from-modulator-development-to-therapy-for-cystic-fibrosis-patients-with-rare-cftr-mutations
#1
Misak Harutyunyan, Yunjie Huang, Kyu-Shik Mun, Fanmuyi Yang, Kavisha Arora, Anjaparavanda P Naren
Cystic fibrosis (CF) is the most common life-shortening genetic disease affecting approximately 1 in 3500 of the Caucasian population. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. To date, over 2000 CFTR mutations have been identified and produce a wide range of phenotypes. The CFTR protein, a chloride channel, is normally expressed on epithelial cells lining the lung, gut, and exocrine glands. Mutations in CFTR have led to pleiotropic effects in CF patients and have resulted in early morbidity and mortality...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351448/extracellular-oxidation-in-cystic-fibrosis-airway-epithelium-causes-enhanced-egfr-adam17-activity
#2
Marta Stolarczyk, Guido Veit, Andrea Schnur, Mieke Veltman, Gergely L Lukacs, Bob J Scholte
The EGFR/ADAM17 signaling pathway mediates the shedding of growth factors and secretion of cytokines, and is involved in chronic inflammation and tissue remodeling. Since these are hallmarks of cystic fibrosis (CF) lung disease, we hypothesized that CFTR deficiency enhances EGFR/ADAM17 activity in human bronchial epithelial cells. In CFBE41o- cells lacking functional CFTR (iCFTR-) cultured at air-liquid interface (ALI) we found enhanced ADAM17-mediated shedding of the EGFR ligand amphiregulin (AREG) compared to genetically identical cells with induced CFTR expression (iCFTR+)...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351447/cigarette-smoke-dampens-anti-viral-signaling-in-small-airway-epithelial-cells-by-disrupting-tlr3-cleavage
#3
Parker F Duffney, Claire E McCarthy, Aitor Nogales, Thomas H Thatcher, Luis Martinez-Sobrido, Richard P Phipps, Patricia J Sime
Cigarette smokers and people exposed to secondhand smoke are at an increased risk for pulmonary viral infections, yet the mechanism responsible for this heightened susceptibility is not understood. To understand the effect of cigarette smoke on susceptibility to viral infection we used an air-liquid interface culture system, and exposed primary human small airway epithelial cells (SAEC) to whole cigarette smoke followed by treatment with the viral mimetic polyinosinic polycytidylic acid (poly I:C) or influenza A virus (IAV)...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351441/vx-809-vx-770-treatment-reduces-inflammatory-response-to-pseudomonas-aeruginosa-in-primary-differentiated-cystic-fibrosis-bronchial-epithelial-cells
#4
Manon Ruffin, Lucie Roussel, Émilie Maillé, Simon Rousseau, Emmanuelle Brochiero
Cystic fibrosis patients exhibit chronic P. aeruginosa respiratory infections and sustained pro-inflammatory state favoring lung tissue damage and remodeling, ultimately leading to respiratory failure. Loss of CFTR function is associated with MAPK hyper-activation and increased cytokines expression, such as the interleukin 8 (CXCL8). Recently, new therapeutic strategies directly targeting the basic CFTR defect have been developed and ORKAMBI (Vx-809/Vx-770 combination) is the only FDA-approved treatment for CF patients homozygous for the F508del mutation...
December 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351436/therapeutic-attenuation-of-the-epithelial-sodium-channel-with-a-splunc1-derived-peptide-in-airway-diseases
#5
James F Collawn, Rafal Bartoszewski, Ahmad Lazrak, Sadis Matalon
The airway surface liquid (ASL) coats the lining of the airways and allows for efficient cilial movement and therefore effective mucociliary transport. Cell surface channels regulate the hydration status of the ASL and the two critical channels in the process are the cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channel (ENaC). In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) there is loss of CFTR function or compromised CFTR function in chronic bronchitis, respectively...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351430/dynamic-changes-in-nitric-oxide-synthase-expression-are-involved-in-seawater-acclimation-of-rainbow-trout-oncorhynchus-mykiss
#6
Lucie Gerber, Frank B Jensen, Steffen S Madsen
Recent research has shown that nitric oxide (NO) produced by nitric oxide synthases (Nos) is an inhibitor of ion transporter activity and a modulator of epithelial ion transport in fish but little is known on changes in the Nos/NO system during osmotic stress. We hypothesized that the Nos/NO system responds to salinity changes as an integrated part of the acclimation process. Expression and localization of nos1/Nos1 and nos2/Nos2 were investigated in gill, kidney and intestine of FW- and SW-transferred trout using qPCR, Western blotting and immunohistochemistry, along with expressional changes of major ion transporters in the gill...
December 20, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29351414/the-murine-choroid-plexus-epithelium-expresses-the-2cl-h-exchanger-clc-7-and-na-h-exchanger-nhe6-in-the-luminal-membrane-domain
#7
Helle H Damkier, Henriette L Christensen, Inga B Christensen, Qi Wu, Robert A Fenton, Jeppe Praetorius
The choroid plexus epithelium within the brain ventricles secretes the majority of the cerebrospinal fluid (CSF). The luminal Na+,K+-ATPase acts in concert with a host of other transport proteins to mediate efficient fluid secretion across the epithelium. The CSF contains little protein buffer, but the pH value seems nonetheless maintained within narrow limits, even when faced with acid/base challenges. The involvement of choroid plexus acid/base transporters in CSF pH regulation is highlighted by the expression of several acid/base transporters in the epithelium...
December 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351411/disruption-of-the-lens-circulation-causes-calcium-accumulation-and-precipitates-in-connexin-mutant-mice
#8
Junyuan Gao, Peter J Minogue, Eric C Beyer, Richard T Mathias, Viviana M Berthoud
The lens is an avascular organ whose function and survival depend on an internal circulation system. Cx46fs380 mice model a human autosomal dominant cataract caused by a mutant lens connexin. In these mice, fiber cell connexin levels and gap junction coupling are severely decreased. The present studies were conducted to examine components of the lens circulation system that might be altered and contribute to the pathogenesis of cataracts. Lenses from wild type mice and Cx46fs380 heterozygotes and homozygotes were studied at 2 months of age...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351408/choroid-plexus-epithelial-cells-express-the-adhesion-protein-p-cadherin-at-cell-cell-contacts-and-syntaxin-4-in-the-luminal-membrane-domain
#9
Inga Baasch Christensen, Esben Nees Mogensen, Helle Hasager Damkier, Jeppe Praetorius
The choroid plexus epithelial cells (CPECs) belong to a small group of polarized cells, where the Na+,K+-ATPase is expressed in the luminal membrane. The basic polarity of the cells is, therefore, still debated. We investigated the subcellular distribution of an array of proteins known to play fundamental roles in either in establishing and maintaining basic cell polarity or the polarized delivery and recycling of plasma membrane proteins. Immunofluorescence histochemical analysis was applied to determine the subcellular localization of apical and basolateral membrane determinants...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351391/the-bile-acids-deoxycholic-acid-and-ursodeoxycholic-acid-regulate-colonic-epithelial-wound-healing
#10
Magdalena S Mroz, Natalia K Lajczak, Bridie J Goggins, Simon Keely, Stephen Joseph Keely
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although, bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on epithelial restitution. Wound healing in T84 cell monolayers grown on transparent, permeable, supports was assessed over 48 hrs {plus minus} bile acids...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351356/epha2-ephrin-a1-mediate-corneal-epithelial-cell-compartmentalization-via-adam10-regulation-of-egfr-signaling
#11
Nihal Kaplan, Rosa Ventrella, Han Peng, Sonali Pal-Ghosh, Constadina Arvanitis, Joshua Z Rappoport, Brian J Mitchell, Mary Ann Stepp, Robert M Lavker, Spiro Getsios
Purpose: Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29351209/the-prognostic-significance-of-histone-demethylase-utx-in-esophageal-squamous-cell-carcinoma
#12
Shau-Hsuan Li, Hung-I Lu, Wan-Ting Huang, Wan-Yu Tien, Ya-Chun Lan, Wei-Che Lin, Hsin-Ting Tsai, Chang-Han Chen
The dysregulation of the ubiquitously transcribed TPR gene on the X chromosome (UTX) has been reported to be involved in the oncogenesis of several types of cancers. However, the expression and significance of UTX in esophageal squamous cell carcinoma (ESCC) remains largely undetermined. Immunohistochemistry was performed in 106 ESCC patients, and correlated with clinicopathological features and survival. The functional role of UTX in ESCC cells was determined by UTX-mediated siRNA. Univariate analyses showed that high UTX expression was associated with superior overall survival (OS, p = 0...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350973/epithelial-progenitor-cells-take-center-stage-in-lung-transplantation
#13
Natalia F Smirnova, Oliver Eickelberg
No abstract text is available yet for this article.
January 19, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29350877/effects-of-human-rhinovirus-on-epithelial-barrier-integrity-and-function-in-children-with-asthma
#14
Kevin Looi, Alysia G Buckley, Paul J Rigby, Luke W Garratt, Thomas Iosifidis, Graeme R Zosky, Alexander N Larcombe, Francis J Lannigan, Kak-Ming Ling, Kelly M Martinovich, Elizabeth Kicic-Starcevich, Nicole C Shaw, Erika N Sutanto, Darryl A Knight, Anthony Kicic, Stephen M Stick
BACKGROUND: Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma. OBJECTIVES: To investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AEC) of children with and without asthma...
January 19, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29350680/effects-of-microrna-135a-on-the-epithelial-mesenchymal-transition-migration-and-invasion-of-bladder-cancer-cells-by-targeting-gsk3%C3%AE-through-the-wnt-%C3%AE-catenin-signaling-pathway
#15
Xia-Wa Mao, Jia-Quan Xiao, Zhong-Yi Li, Yi-Chun Zheng, Nan Zhang
This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3β (GSK3β) on the epithelial-mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/β-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3β, β-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3β or miR-135a inhibitors+siRNA-GSK3β groups...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29350614/lipg-signaling-promotes-tumor-initiation-and-metastasis-of-human-basal-like-triple-negative-breast-cancer
#16
Pang-Kuo Lo, Yuan Yao, Ji Shin Lee, Yongshu Zhang, Weiliang Huang, Maureen A Kane, Qun Zhou
Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC...
January 19, 2018: ELife
https://www.readbyqxmd.com/read/29350477/pharmacokinetic-evaluation-and-safety-of-topical-1-morphine-sulfate-application-on-the-healthy-equine-eye
#17
Emma Gordon, Bernadette V Stang, Jerry Heidel, Keith P Poulsen, Christopher K Cebra, John W Schlipf
OBJECTIVE: To determine if corneal epithelial cell integrity is detrimentally affected by short-term administration of 1.0% morphine sulfate. Additionally, we sought to determine if topical 1.0% morphine applied to the equine cornea would result in ocular or systemic absorption. ANIMAL STUDIED: Six healthy horses. PROCEDURE: Morphine sulfate (1.0%) was applied topically to one eye every four hours for 72 h before horses were euthanized. Serum samples were collected at varying time points during the study and aqueous and vitreous humor were collected immediately after euthanasia...
January 19, 2018: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/29350451/morphological-specializations-of-the-epidermis-of-an-angler-catfish-chaca-chaca-siluriformes-chacidae-in-relation-to-its-ecological-niche-a-scanning-electron-microscopic-investigation
#18
Arup Mistri, Usha Kumari, Swati Mittal, Ajay Kumar Mittal
The present work was undertaken with the aim to deduce morphological adaptations in skin of an angler catfish Chaca chaca by means of scanning electron microscopy. The fish is nocturnal, bottom dwelling, sluggish, ambush predator, lives in sand, mud, or soft substrates often buried and camouflaged for protection and to feed. The surface of the epidermis is covered with polygonal epithelial cells, each having surface relief of microridges forming intricate patterns. In between epithelial cells irregularly distributed mucous cell openings, randomly distributed epidermal specialized structures, taste buds, and neuromasts are discernible...
January 19, 2018: Microscopy Research and Technique
https://www.readbyqxmd.com/read/29350444/four-cases-of-iridociliary-tumors-in-domestic-rabbits-oryctolagus-cuniculus
#19
Samantha D Swisher, Heidi Klein, Angela M Lennox, Drury R Reavill, Leandro B C Teixeira, Gillian C Shaw
Spontaneously occurring ocular neoplasia is rarely reported in rabbits. This case series presents four cases of rabbits diagnosed with iridociliary tumors, which have not been previously reported in this species. Major pathological findings include epithelial tumors affecting the anterior uvea with variable pigmentation and basement membrane formation. Follow-up information was only available for two cases, but neither showed evidence of metastasis, suggesting that the prognosis for these tumors in rabbits, as in other species, may be very good...
January 19, 2018: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/29350377/melatonin-exhibits-supportive-effects-on-oxidants-and-anastomotic-healing-during-intestinal-ischemia-reperfusion-injury
#20
Namık Özkan, Ömer Faik Ersoy, Zeki Özsoy, Ebru Çakır
BACKGROUND: The aim of this study was to investigate the effects of melatonin on intestinal anastomosis after intestinal ischemia/ reperfusion injury (IRI). METHODS: Thirty Wistar albino rats of both sexes were divided into 3 groups: sham, control, and treatment. IRI was performed by clamping the superior mesenteric artery (SMA) for 30 minutes, followed by reperfusion. The sham rats received only manipulation of the SMA. Melatonin (10 mg/kg) was administered to the treatment group, and the control group was given a vehicle injection...
January 2018: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
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