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https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#1
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28591806/quantitative-proteomics-of-intestinal-mucosa-from-male-mice-lacking-intestinal-epithelial-insulin-receptors
#2
Stina Rikke Jensen, Erwin M Schoof, Sarah E Wheeler, Henning Hvid, Jonas Ahnfelt-Rønne, Bo Falck Hansen, Erica Nishimura, Grith Skytte Olsen, Thomas Kislinger, Patricia L Brubaker
The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was applied to jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon...
June 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28583864/the-gut-bacterium-and-pathobiont-bacteroides-vulgatus-activates-nf-%C3%AE%C2%BAb-in-a-human-gut-epithelial-cell-line-in-a-strain-and-growth-phase-dependent-manner
#3
Páraic Ó Cuív, Tomas de Wouters, Rabina Giri, Stanislas Mondot, Wendy J Smith, Hervé M Blottière, Jakob Begun, Mark Morrison
The gut microbiota is increasingly implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) although the identity of the bacteria that underpin these diseases has remained elusive. The pathobiont Bacteroides vulgatus has been associated with both diseases although relatively little is known about how its growth and functional activity might drive the host inflammatory response. We identified an ATP Binding Cassette (ABC) export system and lipoprotein in B. vulgatus ATCC 8482 and B...
June 2, 2017: Anaerobe
https://www.readbyqxmd.com/read/28572005/reelin-protects-from-colon-pathology-by-maintaining-the-intestinal-barrier-integrity-and-repressing-tumorigenic-genes
#4
Ana E Carvajal, José M Serrano-Morales, María D Vázquez-Carretero, Pablo García-Miranda, María L Calonge, María J Peral, Anunciación A Ilundain
We previously reported that reelin, an extracellular matrix protein first known for its key role in neuronal migration, reduces the susceptibility to dextran sulphate sodium (DSS)-colitis. The aim of the study was to determine whether reelin protects from colorectal cancer and how reelin defends from colon pathology. In the colon of wild-type and of mice lacking reelin (reeler mice) we have analyzed the: i) epithelium cell renewal processes, ii) morphology, iii) Sox9, Cdx2, Smad5, Cyclin D1, IL-6 and IFNγ mRNA abundance in DSS-treated and untreated mice, and iv) development of azoxymethane/DSS-induced colorectal cancer, using histological and real time-PCR methodologies...
May 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28554134/lactobacillus-rhamnosus-atcc-7469-exopolysaccharides-synergizes-with-low-level-ionizing-radiation-to-modulate-signaling-molecular-targets-in-colorectal-carcinogenesis-in-rats
#5
Walid E Zahran, Sawsan M Elsonbaty, Fatma S M Moawed
Combination therapy that targets cellular signaling pathway represents an alternative therapy for the treatment of colon cancer (CRC). The present study was therefore aimed to investigate the probable interaction of Lactobacillus rhamnosus ATCC 7469 exopolysaccharides (EPS) with low level ionizing γ radiation (γ-R) exposure against dimethylhydrazine (DMH)- induced colorectal carcinogenesis in rats. Colon cancer was induced with 20mg DMH/kg BW. Rats received daily by gastric gavage 100mg EPS/Kg BW concomitant with 1Gy γ-R over two months...
May 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28550342/influence-of-dietary-avocado-on-gut-health-in-rats
#6
Gunaranjan Paturi, Christine A Butts, Kerry L Bentley-Hewitt
This study investigated the impact of diets containing various levels of avocado (5, 10 and 15%) on gut health in rats fed for six weeks. Avocado-fed rats had significantly higher food intakes while their body weights remained similar to the control diet-fed rats. No significant changes in intestinal bacterial populations (ileum, cecum and colon) were found in rats fed avocado diets compared to the control diet. Ileum and colon tissues of rats fed avocado diets showed significantly higher expression of genes (β-defensin 1, mucin 3 or mucin 4) and a greater number of mucin-producing goblet cells in the colon...
May 26, 2017: Plant Foods for Human Nutrition
https://www.readbyqxmd.com/read/28538804/transitional-metaplasia-in-intestinal-epithelium-of-rats-submitted-to-intestinal-cystoplasty-and-treatment-with-l-lysine
#7
Alessandra Marques Dos Santos, Joao Paulo Ferreira Coelho, Camila de Carvalho Juanes, Rafael Barbosa de Azevedo, Clara Araujo Diniz, Francisco Vagnaldo Fechine Jamacaru, Conceição Aparecida Dornelas
Purpose: To evaluated the effects of L-lysine on the intestinal and urothelial epithelia in cystoplasty in rats. Methods: Twenty-eight 9-week-old rats were assigned to 4 groups: Group A (n=8) cystoplasty followed by administration of L-lysine (150 mg/kg body weight by gavage) for 30 weeks; Group B (n=8) cystoplasty + water for 30 weeks; Group C (n=6) L-lysine for 30 weeks; Group D (n=6) water for 30 weeks. Results: On histopathology with hematoxylin and eosin, mild to moderate hyperplasia transitional was observed in at the site of anastomosis in all animals submitted to cystoplasty (Groups A and B), but "transitional metaplasia" of the intestinal glandular epithelium was more accentuated in Group A (p=0...
April 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28532656/the-il-33-st2-axis-is-crucial-in-type-2-airway-responses-induced-by-the-staphylococcus-aureus-protease-spld
#8
Andrea R Teufelberger, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriele Holtappels, Clara O'Brien, Sharen Provoost, Hamida Hammad, Amanda Gonçalves, Rudi Beyaert, Wim Declercq, Peter Vandenabeele, Dmitri V Krysko, Barbara M Bröker, Claus Bachert, Olga Krysko
BACKGROUND: Chronic airway inflammatory diseases such as chronic rhinosinusitis with nasal polyps and asthma showed increased nasal Staphylococcus aureus (S. aureus) colonization. Serine protease like protein D (SplD) and other closely related proteases secreted by S. aureus have recently been identified as inducers of allergic asthma in humans and mice but their mechanism of action is largely unknown. OBJECTIVE: We investigated the role of recombinant SplD in driving Th2-biased responses and IgE formation in a murine model of allergic asthma...
May 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28525602/aloin-a-component-of-the-aloe-vera-plant-leaf-induces-pathological-changes-and-modulates-the-composition-of-microbiota-in-the-large-intestine-of-f344-n-male-rats
#9
Mary D Boudreau, Greg R Olson, Volodymyr P Tryndyak, Matthew S Bryant, Robert P Felton, Frederick A Beland
In a previous study, the oral administration of an Aloe vera whole leaf extract induced dose-related mucosal and goblet cell hyperplasia in the rat colon after 13-weeks and colon cancer after two years. The primary goal of this study was to determine whether or not the administration of aloin, a component of the Aloe vera plant leaf, would replicate the pathophysiological effects that were observed in rats in the previous study with an Aloe vera whole leaf extract. Groups of 10 male F344/N rats were administered aloin at 0, 6...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28524086/dietary-green-pea-protects-against-dss-induced-colitis-in-mice-challenged-with-high-fat-diet
#10
Shima Bibi, Luís Fernando de Sousa Moraes, Noelle Lebow, Mei-Jun Zhu
Obesity is a risk factor for developing inflammatory bowel disease. Pea is unique with its high content of dietary fiber, polyphenolics, and glycoproteins, all of which are known to be health beneficial. We aimed to investigate the impact of green pea (GP) supplementation on the susceptibility of high-fat diet (HFD)-fed mice to dextran sulfate sodium (DSS)-induced colitis. Six-week-old C57BL/6J female mice were fed a 45% HFD or HFD supplemented with 10% GP. After 7-week dietary supplementation, colitis was induced by adding 2...
May 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28495755/intestinal-microbiota-contributes-to-colonic-epithelial-changes-in-simulated-microgravity-mouse-model
#11
Junxiu Shi, Yifan Wang, Jian He, Pingping Li, Rong Jin, Ke Wang, Xi Xu, Jie Hao, Yan Zhang, Hongju Liu, Xiaoping Chen, Hounan Wu, Qing Ge
Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28493993/mechanism-of-down-regulation-of-na-h-exchanger-2-in-experimental-colitis
#12
Amal Ali Soleiman, Farook Thameem, Islam Khan
BACKGROUND: The Na-H exchanger [NHE] performs an electroneutral uptake of NaCl and water from the lumen of the gastrointestinal tract. There are several distinct NHE isoforms, some of which show an altered expression in the inflammatory bowel diseases (IBD). In this study, we examined a role of NHE-2 in experimental colitis. METHODS: Colitis was induced in male Sprague-Dawley rats by intra-rectal administration of trinitrobenzenesulphonic acid (TNBS). On day 6 post-TNBS, the animals were sacrificed, colonic and ileal segments were taken out, cleaned with phosphate buffered saline and used in this study...
2017: PloS One
https://www.readbyqxmd.com/read/28487604/overexpression-of-fibrinogen-like-protein-2-protects-against-t-cell-induced-colitis
#13
Agata Bartczak, Jianhua Zhang, Oyedele Adeyi, Achiya Amir, David Grant, Reginald Gorczynski, Nazia Selzner, Andrzej Chruscinski, Gary A Levy
AIM: To determine the effect of overexpression of fibrinogen-like protein 2 (FGL2) on regulatory T cell (Treg) and effector T (Teff) cell function on T cell-induced colitis in Rag1(-/-) mice. METHODS: Treg and Teff cells from fgl2(-/-), fgl2(+/+), and fgl2(Tg) mice were purified by FACS. They were studied in vitro for immunosuppressive activity and cell proliferation and in vivo for their effects on the development and prevention of T cell-induced colitis in Rag1(-/-) mice...
April 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28475172/keratins-regulate-colonic-epithelial-cell-differentiation-through-the-notch1-signalling-pathway
#14
Iris A K Lähdeniemi, Julia O Misiorek, Christian J M Antila, Sebastian K-J Landor, Carl-Gustaf A Stenvall, Lina E Fortelius, Linda K Bergström, Cecilia Sahlgren, Diana M Toivola
Keratins (K) are intermediate filament proteins important in stress protection and mechanical support of epithelial tissues. K8, K18 and K19 are the main colonic keratins, and K8-knockout (K8(-/-)) mice display a keratin dose-dependent hyperproliferation of colonic crypts and a colitis-phenotype. However, the impact of the loss of K8 on intestinal cell differentiation has so far been unknown. Here we show that K8 regulates Notch1 signalling activity and differentiation in the epithelium of the large intestine...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28416688/knockout-of-the-lrrc26-subunit-reveals-a-primary-role-of-lrrc26-containing-bk-channels-in-secretory-epithelial-cells
#15
Chengtao Yang, Vivian Gonzalez-Perez, Taro Mukaibo, James E Melvin, Xiao-Ming Xia, Christopher J Lingle
Leucine-rich-repeat-containing protein 26 (LRRC26) is the regulatory γ1 subunit of Ca(2+)- and voltage-dependent BK-type K(+) channels. BK channels that contain LRRC26 subunits are active near normal resting potentials even without Ca(2+), suggesting they play unique physiological roles, likely limited to very specific cell types and cellular functions. By using Lrrc26 KO mice with a β-gal reporter, Lrrc26 promoter activity is found in secretory epithelial cells, especially acinar epithelial cells in lacrimal and salivary glands, and also goblet and Paneth cells in intestine and colon, although absent from neurons...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28375676/tyrosine-phosphorylation-of-an-actin-binding-protein-girdin-specifically-marks-tuft-cells-in-human-and-mouse-gut
#16
Daisuke Kuga, Kaori Ushida, Shinji Mii, Atsushi Enomoto, Naoya Asai, Masato Nagino, Masahide Takahashi, Masato Asai
Tuft cells (TCs) are minor components of gastrointestinal epithelia, characterized by apical tufts and spool-shaped somas. The lack of reliable TC-markers has hindered the elucidation of its role. We developed site-specific and phosphorylation-status-specific antibodies against Girdin at tyrosine-1798 (pY1798) and found pY1798 immunostaining of mouse jejunum clearly depicted epithelial cells closely resembling TCs. This study aimed to validate pY1798 as a TC-marker. Double-fluorescence staining of intestines was performed with pY1798 and known TC-markers, for example, hematopoietic-prostaglandin-D-synthase (HPGDS), or doublecortin-like kinase 1 (DCLK1)...
June 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28361356/-pathophysiology-of-atopic-blepharokeratoconjunctivitis
#17
T Lapp, P Maier, T Jakob, T Reinhard
Atopic dermatitis (AD) is a systemic inflammatory disease, which is characterized by pronounced eczema and pruritus. In addition to the involvement of the entire integument, the periocular lid skin and the surface of the eye are frequently involved. Ocular involvement may occur solely without dermatitis of facial or body skin. Pathophysiologically, besides a dysregulated immune response, genetic changes can occur in various dermal structural proteins which will lead to a disturbed skin barrier. Furthermore, there is a regular colonization with bacterial pathogens and an increased susceptibility for viral skin infections...
March 30, 2017: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/28359759/a-vesicle-trafficking-protein-%C3%AE-snap-regulates-paneth-cell-differentiation-in%C3%A2-vivo
#18
Susana Lechuga, Nayden G Naydenov, Alex Feygin, Antonio J Jimenez, Andrei I Ivanov
A soluble N-ethylmaleimide-sensitive factor-attachment protein alpha (αSNAP) is a multifunctional scaffolding protein that regulates intracellular vesicle trafficking and signaling. In cultured intestinal epithelial cells, αSNAP has been shown to be essential for cell survival, motility, and adhesion; however, its physiologic functions in the intestinal mucosa remain unknown. In the present study, we used a mouse with a spontaneous hydrocephalus with hop gait (hyh) mutation of αSNAP to examine the roles of this trafficking protein in regulating intestinal epithelial homeostasis in vivo...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342610/intentionally-induced-intestinal-barrier-dysfunction-causes-inflammation-affects-metabolism-and-reduces-productivity-in-lactating-holstein-cows
#19
S K Kvidera, M J Dickson, M Abuajamieh, D B Snider, M V Sanz Fernandez, J S Johnson, A F Keating, P J Gorden, H B Green, K M Schoenberg, L H Baumgard
Study objectives were to evaluate the effects of intentionally reduced intestinal barrier function on productivity, metabolism, and inflammatory indices in otherwise healthy dairy cows. Fourteen lactating Holstein cows (parity 2.6 ± 0.3; 117 ± 18 d in milk) were enrolled in 2 experimental periods. Period 1 (5 d) served as the baseline for period 2 (7 d), during which cows received 1 of 2 i.v. treatments twice per day: sterile saline or a gamma-secretase inhibitor (GSI; 1.5 mg/kg of body weight). Gamma-secretase inhibitors reduce intestinal barrier function by inhibiting crypt cell differentiation into absorptive enterocytes...
May 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28314262/the-histogenesis-of-the-third-pathway-of-colonic-carcinogenesis-in-rats
#20
Carlos A Rubio
BACKGROUND/AIM: Conventional (tubular or villous) adenomas, and the more recently described serrated adenomas, are non-invasive neoplasias that precede colon carcinomas in carcinogen-treated rats. In contrast, the histological steps antedating carcinomas in gut-associated lymphoid tissue (GALT) in rats, i.e. the third pathway of colonic carcinogenesis, remain unidentified. Aim of the study was to investigate the histological changes preceding colonic GALT carcinomas in Sprague-Dawley (SD) rats...
March 2017: Anticancer Research
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