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https://www.readbyqxmd.com/read/28193209/secretion-of-biologically-active-pancreatitis-associated-protein-i-pap-by-genetically-modified-dairy-lactococcus-lactis-nz9000-in-the-prevention-of-intestinal-mucositis
#1
Rodrigo D Carvalho, Natalia Breyner, Zelia Menezes-Garcia, Nubia M Rodrigues, Luisa Lemos, Tatiane U Maioli, Danielle da Gloria Souza, Denise Carmona, Ana M C de Faria, Philippe Langella, Jean-Marc Chatel, Luis G Bermúdez-Humarán, Henrique C P Figueiredo, Vasco Azevedo, Marcela S de Azevedo
BACKGROUND: Mucositis is one of the most relevant gastrointestinal inflammatory conditions in humans, generated by the use of chemotherapy drugs, such as 5-fluoracil (5-FU). 5-FU-induced mucositis affects 80% of patients undergoing oncological treatment causing mucosal gut dysfunctions and great discomfort. As current therapy drugs presents limitations in alleviating mucositis symptoms, alternative strategies are being pursued. Recent studies have shown that the antimicrobial pancreatitis-associated protein (PAP) has a protective role in intestinal inflammatory processes...
February 13, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28174748/requirement-of-g%C3%AE-q-g%C3%AE-11-signaling-in-the-preservation-of-mouse-intestinal-epithelial-homeostasis
#2
Noboru Watanabe, Hirosato Mashima, Kouichi Miura, Takashi Goto, Makoto Yoshida, Akiteru Goto, Hirohide Ohnishi
BACKGROUND & AIMS: Proliferation, differentiation, and morphogenesis of the intestinal epithelium are tightly regulated by a number of molecular pathways. Coordinated action of intestine is achieved by gastrointestinal hormones, most of which exert these actions through G-protein-coupled receptors. We herein investigated the role of Gαq/11-mediated signaling in intestinal homeostasis. METHODS: Intestinal tissues from control (Gnaq(flox/flox)Gna11(+/+) ), Int-Gq knock-out (KO) (VilCre(+/-)Gnaq(flox/flox)Gna11(+/+) ), G11 KO (Gnaq(flox/flox)Gna11(-/-) ), and Int-Gq/G11 double knock-out (DKO) (VilCre(+/-)Gnaq(flox/flox)Gna11(-/-) ) mice were examined by microscopy, transmission electron microscopy, and immunohistochemistry...
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174744/intestinal-gpcrs-control-paneth-cell-maturation-and-susceptibility-to-experimental-colitis
#3
EDITORIAL
Xiao Zhang, Nan Gao
No abstract text is available yet for this article.
November 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174721/znt2-mediated-zinc-import-into-paneth-cell-granules-is-necessary-for-coordinated-secretion-and-paneth-cell-function%C3%A2-in%C3%A2-mice
#4
Abigail B Podany, Justin Wright, Regina Lamendella, David I Soybel, Shannon L Kelleher
BACKGROUND & AIMS: Defects in Paneth cell (PC) function are associated with microbial dysbiosis and intestinal inflammation. PC granules contain antimicrobial peptides, cytokines, and substantial stores of zinc (Zn). We hypothesized that Zn, transported into the granule through the Zn transporter (ZnT)2, is critical for signature PC functions. METHODS: ZnT2 was localized to PC granules using immunofluorescence and sucrose gradient fractionation in wild-type (wt) mice, and consequences of ZnT2 loss were characterized in ZnT2 knockout (ZnT2ko) mice...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174718/the-paneth-cell-a-guardian-of-gut-health
#5
EDITORIAL
Mark Manary
No abstract text is available yet for this article.
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28147355/improvement-of-a-leaky-intestinal-barrier
#6
REVIEW
Eduard F Stange
In Crohn's disease, the mucus layer appears to be defective in terms of low defensin levels and lack of antibacterial activity. These deficiencies actually explain the Montreal phenotypes and the stable localization of disease in the terminal ileum with low α-defensins from Paneth cells and/or low β-defensins in colonic disease, respectively. Conversely, in ulcerative colitis (UC) the defensin production is normal or even induced, but the mucus layer is thinner and patchy, more in the liquid form and also chemically altered so that antibacterial peptides are not retained and lost into the luminal bacterial bulk...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28130498/myeloid-atg16l1-facilitates-host-bacteria-interactions-in-maintaining-intestinal-homeostasis
#7
Hong Zhang, Libo Zheng, Dermot P B McGovern, Ariel M Hamill, Ryan Ichikawa, Yoshitake Kanazawa, Justin Luu, Kotaro Kumagai, Marianne Cilluffo, Masayuki Fukata, Stephan R Targan, David M Underhill, Xiaolan Zhang, David Q Shih
Intact ATG16L1 plays an essential role in Paneth cell function and intestinal homeostasis. However, the functional consequences of ATG16L1 deficiency in myeloid cells, particularly macrophages, are not fully characterized. We generated mice with Atg16l1 deficiency in myeloid and dendritic cells and showed that mice with myeloid Atg16l1 deficiency had exacerbated colitis in two acute and one chronic model of colitis with increased proinflammatory to anti-inflammatory macrophage ratios, production of proinflammatory cytokines, and numbers of IgA-coated intestinal microbes...
January 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28129947/target-intestinal-microbiota-to-alleviate-disease-progression-in-amyotrophic-lateral-sclerosis
#8
Yong-Guo Zhang, Shaoping Wu, Jianxun Yi, Yinglin Xia, Dapeng Jin, Jingsong Zhou, Jun Sun
PURPOSE: Emerging evidence has demonstrated that gut microbiome plays essential roles in the pathogenesis of human diseases in distal organs. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Treatment with the only drug approved by the US Food and Drug Administration for use in ALS, riluzole, extends a patient׳s life span by only a few months. Thus, there is an urgent need to develop novel interventions that for alleviate disease progression and improve quality of life in patients with ALS...
January 24, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28125357/mucosal-ecological-network-of-epithelium-and-immune-cells-for-gut-homeostasis-and-tissue-healing
#9
Yosuke Kurashima, Hiroshi Kiyono
The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well as other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. The intestinal mucosa is covered by mucin, which contains antimicrobial peptides and secretory IgA and prevents luminal bacteria, fungi, and viruses from stimulating intestinal immune responses. Conversely, the transport of luminal microorganisms-mediated by M, dendritic, and goblet cells-into intestinal tissues facilitates the harmonization of active and quiescent mucosal immune responses...
January 11, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28122499/uridine-stimulate-laxative-effect-in-the-loperamide-induced-constipation-of-sd-rats-through-regulation-of-the-machrs-signaling-pathway-and-mucin-secretion
#10
Ji Eun Kim, Jun Go, Ji Eun Sung, Hyun Ah Lee, Woo Bin Yun, Jin Tae Hong, Dae Youn Hwang
BACKGROUND: Uridine (Urd), which has been reported as a major component of RNA, plays an important role in various biological process including neuroprotection, biochemical modulation and glycolysis, although its role in constipation has yet to be established. Therefore, in this study, we investigated the laxative effects of Urd on chronic constipation. METHODS: The constipation phenotypes and their related mechanisms were investigated in the transverse colons of SD rats with loperamide (Lop)-induced constipation after treatment with 100 mg/kg of Urd...
January 26, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28114549/underperforming-big-ideas-in-biomedical-research-reply
#11
LETTER
Michael J Joyner, Nigel Paneth, John P A Ioannidis
No abstract text is available yet for this article.
17, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28102757/dysbiosis-in-crohn-s-disease-joint-action-of-stochastic-injuries-and-focal-inflammation-in-the-gut
#12
Ludovica F Buttó, Dirk Haller
Gut homeostasis involves interrelated biological networks that include the immune system, specialized cells of the epithelium, such as Paneth and goblet cells, as well as triggers derived from the microbiota. Disruption of these homeostatic interactions may lead to the pathogenesis of inflammatory bowel diseases (IBD). To develop more targeted and individual treatments in Crohn's disease and ulcerative colitis, it becomes more and more important to link key mechanisms of the disease pathogenesis to distinct IBD subsets...
January 19, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28097227/a-xenogeneic-free-system-generating-functional-human-gut-organoids-from-pluripotent-stem-cells
#13
Hajime Uchida, Masakazu Machida, Takumi Miura, Tomoyuki Kawasaki, Takuya Okazaki, Kengo Sasaki, Seisuke Sakamoto, Noriaki Ohuchi, Mureo Kasahara, Akihiro Umezawa, Hidenori Akutsu
Functional intestines are composed of cell types from all 3 primary germ layers and are generated through a highly orchestrated and serial developmental process. Directed differentiation of human pluripotent stem cells (hPSCs) has been shown to yield gut-specific cell types; however, these structures do not reproduce critical functional interactions between cell types of different germ layers. Here, we developed a simple protocol for the generation of mature functional intestinal organoids from hPSCs under xenogeneic-free conditions...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28070680/a-disturbance-of-intestinal-epithelial-cell-population-and-kinetics-in-apc1638t-mice
#14
Tuya Wang, Takanori Onouchi, Nami O Yamada, Shuji Matsuda, Takao Senda
The adenomatous polyposis coli (APC) is a multifunctional protein as well as a tumor suppressor. To determine the functions of the C-terminal domain of APC, we explored APC (1638T/1638T) (APC1638T) mice that express a truncated APC lacking the C-terminal domain. The APC1638T mice were tumor free and exhibited growth retardation. In the present study, we compared small intestinal crypt-villus cells homeostasis in APC (+/+) (WT) mice and APC1638T mice. The body weight of APC1638T mice was significantly smaller than that of WT mice at all ages...
January 9, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28067516/elucidating-the-bacterial-membrane-disruption-mechanism-of-human-%C3%AE-defensin-5-a-theoretical-study
#15
Sang Won Jung, Juho Lee, Art E Cho
Human α-defensin 5 (HD5) is a broad-spectrum antibacterial peptide produced by small intestinal Paneth cells. Despite considerable experimental evidence for the correlation between bacterial membrane destruction and the antibacterial activity of HD5, its membrane disruption mechanism remains unclear. Using all-atom molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area analysis, we demonstrate the membrane disruption mechanism of HD5 based on the intrinsic binding of HD5 to Gram-negative (GN) bacterial inner membrane...
January 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28002460/metformin-improves-ileal-epithelial-barrier-function-in-interleukin-10-deficient-mice
#16
Yansong Xue, Hanying Zhang, Xiaofei Sun, Mei-Jun Zhu
BACKGROUND AND AIMS: The impairment of intestinal epithelial barrier is the main etiologic factor of inflammatory bowel disease. The proper intestinal epithelial proliferation and differentiation is crucial for maintaining intestinal integrity. Metformin is a common anti-diabetic drug. The objective is to evaluate the protective effects of metformin on ileal epithelial barrier integrity using interleukin-10 deficient (IL10KO) mice. METHODS: Wild-type and IL10KO mice were fed with/without metformin for 6 weeks and then ileum was collected for analyses...
2016: PloS One
https://www.readbyqxmd.com/read/27939219/induced-quiescence-of-lgr5-stem-cells-in-intestinal-organoids-enables-differentiation-of-hormone-producing-enteroendocrine-cells
#17
Onur Basak, Joep Beumer, Kay Wiebrands, Hiroshi Seno, Alexander van Oudenaarden, Hans Clevers
Lgr5+ adult intestinal stem cells are highly proliferative throughout life. Single Lgr5+ stem cells can be cultured into three-dimensional organoids containing all intestinal epithelial cell types at near-normal ratios. Conditions to generate the main cell types (enterocyte, goblet cells, Paneth cells, and M cells) are well established, but signals to induce the spectrum of hormone-producing enteroendocrine cells (EECs) have remained elusive. Here, we induce Lgr5+ stem cell quiescence in vitro by blocking epidermal growth factor receptor (EGFR) or mitogen-associated protein kinase (MAPK) signaling pathways in organoids and show that their quiescent state is readily reverted...
February 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/27935584/ketogenesis-contributes-to-intestinal-cell-differentiation
#18
Qingding Wang, Yuning Zhou, Piotr Rychahou, Teresa W-M Fan, Andrew N Lane, Heidi L Weiss, B Mark Evers
The intestinal epithelium undergoes a continual process of proliferation, differentiation and apoptosis. Previously, we have shown that the PI3K/Akt/mTOR pathway has a critical role in intestinal homeostasis. However, the downstream targets mediating the effects of mTOR in intestinal cells are not known. Here, we show that the ketone body β-hydroxybutyrate (βHB), an endogenous inhibitor of histone deacetylases (HDACs) induces intestinal cell differentiation as noted by the increased expression of differentiation markers (Mucin2 (MUC2), lysozyme, IAP, sucrase-isomaltase, KRT20, villin, Caudal-related homeobox transcription factor 2 (CDX2) and p21(Waf1))...
December 9, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27930931/deficiency-in-duox2-activity-alleviates-ileitis-in-gpx1-and-gpx2-knockout-mice-without-affecting-apoptosis-incidence-in-the-crypt-epithelium
#19
Fong-Fong Chu, R Steven Esworthy, James H Doroshow, Helmut Grasberger, Agnes Donko, Thomas L Leto, Qiang Gao, Binghui Shen
Mice deficient in glutathione peroxidase (GPx)-1 and -2 (GPx1(-/-)GPx2(-/-) double knockout or DKO mice) develop very-early-onset (VEO) ileocolitis, suggesting that lack of defense against reactive oxygen species (ROS) renders susceptibility to intestinal inflammation. Two members of ROS-generating NADPH oxidase family, NOX1 and DUOX2, are highly inducible in the intestinal epithelium. Previously, we reported that Nox1 deficiency ameliorated the pathology in DKO mice (Nox1-TKO). The role of Duox2 in ileocolitis of the DKO mice is evaluated here in Duoxa-TKO mice by breeding DKO mice with Duoxa(-/-) mice (Duoxa-TKO), which do not have Duox2 activity...
November 22, 2016: Redox Biology
https://www.readbyqxmd.com/read/27895587/vitamin-d-signaling-through-induction-of-paneth-cell-defensins-maintains-gut-microbiota-and-improves-metabolic-disorders-and-hepatic-steatosis-in-animal-models
#20
Danmei Su, Yuanyang Nie, Airu Zhu, Zishuo Chen, Pengfei Wu, Li Zhang, Mei Luo, Qun Sun, Linbi Cai, Yuchen Lai, Zhixiong Xiao, Zhongping Duan, Sujun Zheng, Guihui Wu, Richard Hu, Hidekazu Tsukamoto, Aurelia Lugea, Zhenqui Liu, Stephen J Pandol, Yuan-Ping Han
Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis...
2016: Frontiers in Physiology
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