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https://www.readbyqxmd.com/read/28648364/differentiation-of-human-pluripotent-stem-cells-into-colonic-organoids-via-transient-activation-of-bmp-signaling
#1
Jorge O Múnera, Nambirajan Sundaram, Scott A Rankin, David Hill, Carey Watson, Maxime Mahe, Jefferson E Vallance, Noah F Shroyer, Katie L Sinagoga, Adrian Zarzoso-Lacoste, Jonathan R Hudson, Jonathan C Howell, Praneet Chatuvedi, Jason R Spence, John M Shannon, Aaron M Zorn, Michael A Helmrath, James M Wells
Gastric and small intestinal organoids differentiated from human pluripotent stem cells (hPSCs) have revolutionized the study of gastrointestinal development and disease. Distal gut tissues such as cecum and colon, however, have proved considerably more challenging to derive in vitro. Here we report the differentiation of human colonic organoids (HCOs) from hPSCs. We found that BMP signaling is required to establish a posterior SATB2+ domain in developing and postnatal intestinal epithelium. Brief activation of BMP signaling is sufficient to activate a posterior HOX code and direct hPSC-derived gut tube cultures into HCOs...
June 20, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28625828/precision-monitoring-of-immunotherapies-in-solid-organ-and-hematopoietic-stem-cell-transplantation
#2
Rose Diloreto, Kiran Khush, Iwijn De Vlaminck
Pharmacological immunotherapies are a key component of post-transplant therapy in solid-organ and hematopoietic stem cell transplantation. In current clinical practice, immunotherapies largely follow a one-size fits all approach, leaving a large portion of transplant recipients either over- or under-immunosuppressed, and consequently at risk of infections or immune-mediated complications. Our goal here is to review recent and rapid advances in precision and genomic medicine approaches to monitoring of post-transplant immunotherapies...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28624056/evaluating-the-efficacy-of-different-types-of-stem-cells-in-preserving-gut-barrier-function-in-necrotizing-enterocolitis
#3
Christopher J McCulloh, Jacob K Olson, Yijie Wang, Jennifer Vu, Sarah Gartner, Gail E Besner
BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. Increased intestinal permeability is central to NEC development. We have shown that stem cells (SCs) can reduce the incidence and severity of NEC. Our current goal was to investigate the efficacy of four different types of SC in preservation of gut barrier function during NEC. MATERIALS AND METHODS: We compared (1) amniotic fluid-derived mesenchymal SC, (2) bone marrow-derived mesenchymal SC, (3) amniotic fluid-derived neural SC, and (4) enteric neural SC...
June 15, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28621429/the-sumo-targeted-ubiquitin-ligase-dgrn-is-essential-for-drosophila-innate-immunity
#4
Bella Koltun, Eliza Shackelford, François Bonnay, Nicolas Matt, Jean Marc Reichhart, Amir Orian
The ability of metazoans to combat pathogenic infection involves both systemic and local responses to the invading pathogens. Ubiquitin and SUMO pathways molecularly regulate the response to infection, immune signaling and gene expression. Here, we report that Degringolade (Dgrn, CG10981), a SUMO-targeted ubiquitin ligase connecting the two pathways, is essential for the innate immunity response in Drosophila. dgrn(DK) null and heterozygous mutant adult flies are severely immune-compromised and succumb rapidly to both pathogenic bacteria and fungi infections...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28618973/from-clinical-uncertainties-to-precision-medicine-the-emerging-role-of-the-gut-barrier-and-microbiome-in-small-bowel-functional-diseases
#5
Wojciech Marlicz, Diana Yung, Karolina Skonieczna-Żydecka, Igor Loniewski, Saskia van Hemert, Beata Loniewska, Anastasios Koulaouzidis
Over the last decade, remarkable progress has been made in the understanding of disease pathophysiology. Many new theories expound on the importance of emerging factors such as microbiome influences, genomics/omics, stem cells, innate intestinal immunity or mucosal barrier complexities. This has introduced a further dimension of uncertainty into clinical decision-making, but equally, may shed some light on less well-understood and difficult to manage conditions. Areas covered: Comprehensive review of the literature on gut barrier and microbiome relevant to small bowel pathology...
June 16, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28615312/stem-cells-in-repair-of-gastrointestinal-epithelia
#6
REVIEW
Amanda Andersson-Rolf, Matthias Zilbauer, Bon-Kyoung Koo, Hans Clevers
Among the endodermal tissues of adult mammals, the gastrointestinal (GI) epithelium exhibits the highest turnover rate. As the ingested food moves along the GI tract, gastric acid, digestive enzymes, and gut resident microbes aid digestion as well as nutrient and mineral absorption. Due to the harsh luminal environment, replenishment of new epithelial cells is essential to maintain organ structure and function during routine turnover and injury repair. Tissue-specific adult stem cells in the GI tract serve as a continuous source for this immense regenerative activity...
July 2017: Physiology
https://www.readbyqxmd.com/read/28611768/innate-immunity-and-breast-milk
#7
REVIEW
Nicole Theresa Cacho, Robert M Lawrence
Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28598238/nlrc3-regulates-cellular-proliferation-and-apoptosis-to-attenuate-the-development-of-colorectal-cancer
#8
Rajendra Karki, R K Subbarao Malireddi, Qifan Zhu, Thirumala-Devi Kanneganti
Nucleotide-binding domain, leucine-rich-repeat-containing proteins (NLRs) are intracellular innate immune sensors of pathogen-associated and damage-associated molecular patterns. NLRs regulate diverse biological processes such as inflammatory responses, cell proliferation and death, and gut microbiota to attenuate tumorigenesis. In a recent publication in Nature, we identified NLRC3 as a negative regulator of PI3K-mTOR signaling and characterized its potential tumor suppressor function. Enterocytes lacking NLRC3 cannot control cellular proliferation because they are unable to suppress activation of PI3K-mTOR signaling pathways...
June 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28592766/fecal-microbiota-transplantation-for-acute-graft-versus-host-disease-of-the-gut
#9
Kazuhiko Kakihana
Advances in microbial analysis have provided new insights into the complex interactions between the host and gut microbiota. An imbalance in the gut microbiota (dysbiosis) is associated with various disorders and their pathogenesis. Furthermore, in allogeneic stem cell transplantation, increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (GVHD) and transplant outcomes, suggesting that its manipulation could be a new treatment strategy for this acute condition...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28588586/the-research-progress-on-intestinal-stem-cells-and-its-relationship-with-intestinal-microbiota
#10
REVIEW
Qihang Hou, Lulu Ye, Lulu Huang, Qinghua Yu
The intestine is home to trillions of microorganisms, and the vast diversity within this gut microbiota exists in a balanced state to protect the intestinal mucosal barrier. Research into the association of the intestinal microbiota with health and disease (including diet, nutrition, obesity, inflammatory bowel disease, and cancer) continues to expand, with the field advancing at a rapid rate. Intestinal stem cells (ISCs) are the fundamental component of the mucosal barrier; they undergo continuous proliferation to replace the epithelium, which is also intimately involved in intestinal diseases...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28581463/the-burden-of-chemotherapy-induced-nausea-and-vomiting-in-children-receiving-hematopoietic-stem-cell-transplantation-conditioning-a-prospective-study
#11
J Flank, J Sparavalo, H Vol, L Hagen, R Stuhler, D Chong, S Courtney, J J Doyle, A Gassas, T Schechter, L L Dupuis
This prospective study describes chemotherapy-induced nausea and vomiting (CINV) in children (4-18 years) receiving their first hematopoietic stem cell transplant. Emetic episodes, nausea severity (assessed using a validated, self-report nausea severity assessment tool) and antiemetic administration were documented from the start of conditioning until 24 h after the last conditioning agent was administered (acute) and for a further 7 days (delayed). Relationships between CINV control and parenteral nutrition (PN) use and acute gut GvHD (aGvHD) were explored...
June 5, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28576788/pigs-%C3%A2-unlike-mice-have-two-distinct-colonic-stem-cell-populations-similar-to-humans-that-respond-to-high-calorie-diet-prior-to-insulin-resistance
#12
Venkata Charepalli, Lavanya Reddivari, Sridhar Radhakrishnan, Elisabeth Eriksson, Xia Xiao, Sung Woo Kim, Frank Shen, Vijay Kumar Matam, Qunhua Li, Vadiraja B Bhat, Rob Knight, Jairam K P Vanamala
Basal colonic crypt stem cells are long lived and play a role in colon homeostasis. Previous evidence has shown that high-calorie diet (HCD) enhances colonic stem cell numbers and expansion of the proliferative zone, an important biomarker for colon cancer. However, it is not clear how HCD drives dysregulation of colon stem cell/colonocyte proliferative kinetics. We used a human-relevant pig model and developed an immunofluorescence technique to detect and quantify colonic stem cells. Pigs (n = 8/group) were provided either standard diet (SD; 5 % fat) or HCD (25 % fat) for 13 weeks...
June 2, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28576475/gut-microbiota-and-acute-graft-versus-host-disease
#13
REVIEW
Kosuke Yoshioka, Kazuhiko Kakihana, Noriko Doki, Kazuteru Ohashi
Although allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for various hematological diseases, acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality, and its management is clinically important. Advances in biological techniques have led to great progress in understanding the complex interactions between the host and the gut microbiota. The gut microbiota clearly modulates the immune response and is associated with the pathogenesis of various disorders...
May 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28561738/oxidative-stress-induces-stem-cell-proliferation-via-trpa1-ryr-mediated-ca-2-signaling-in-the-drosophila-midgut
#14
Chiwei Xu, Junjie Luo, Li He, Craig Montell, Norbert Perrimon
Precise regulation of stem cell activity is crucial for tissue homeostasis and necessary to prevent overproliferation. In the Drosophila adult gut, high levels of reactive oxygen species (ROS) has been detected with different types of tissue damage, and oxidative stress has been shown to be both necessary and sufficient to trigger intestinal stem cell (ISC) proliferation. However, the connection between oxidative stress and mitogenic signals remains obscure. In a screen for genes required for ISC proliferation in response to oxidative stress, we identified two regulators of cytosolic Ca(2+) levels, transient receptor potential A1 (TRPA1) and ryanodine receptor (RyR)...
May 31, 2017: ELife
https://www.readbyqxmd.com/read/28553289/major-cd4-t-cell-depletion-and-immune-senescence-in-a-patient-with-chronic-granulomatous-disease
#15
Adriana S Albuquerque, Susana M Fernandes, Rita Tendeiro, Rémi Cheynier, Margarida Lucas, Susana L Silva, Rui M M Victorino, Ana E Sousa
Chronic granulomatous disease (CGD) results from primary defects in phagocytic reactive oxygen species (ROS) production. T-cell evaluation is usually neglected during patients' follow-up, although T-cell depletion has been reported in CGD through unknown mechanisms. We describe here a 36-year-old patient with X-linked CGD with severe CD4 T-cell depletion <200 CD4 T-cells/μl, providing insights into the mechanisms that underlie T-cell loss in the context of oxidative burst defects. In addition to the typical infections, the patient featured a progressive T-cell loss associated with persistent lymphocyte activation, expansion of interleukin (IL)-17-producing CD4 T-cells, and impaired thymic activity, leading to a reduced replenishment of the T-cell pool...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28550196/il-6-signaling-regulates-small-intestinal-crypt-homeostasis
#16
Victoria Jeffery, Andrew J Goldson, Jack R Dainty, Marcello Chieppa, Anastasia Sobolewski
Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28536321/-disruption-of-gut-immune-system-caused-by-damage-of-intestinal-stem-cells-and-their-niche-in-graft-versus-host-disease-after-allogeneic-hematopoietic-stem-cell-transplantation
#17
Eiko Hayase, Takanori Teshima
Allogeneic hematopoietic stem cell transplantation(allo-SCT)is curative therapy for various hematological diseases. Graft-versus-host disease(GVHD)and infection remain the main problems in allo-SCT. Gastrointestinal tract is targeted by GVHD. In intestinal GVHD, intestinal stem cells and Paneth cells reside at the base of crypts are damaged by donor T cells. These damage leads to disruption of intestinal mucosal barrier and intestinal dysbiosis, resulting in more exaggerated GVHD. Recently, we and others have reported that R-Spondin1 and interleukin-22 as factors regenerated intestinal tissue homeostasis in murine model of bone marrow transplantation...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28505005/gastric-cancer-with-primitive-enterocyte-phenotype-an-aggressive-subgroup-of-intestinal-type-adenocarcinoma
#18
Sho Yamazawa, Tetsuo Ushiku, Aya Shinozaki-Ushiku, Akimasa Hayashi, Akiko Iwasaki, Hiroyuki Abe, Amane Tagashira, Hiroharu Yamashita, Yasuyuki Seto, Hiroyuki Aburatani, Masashi Fukayama
A primitive cell-like gene expression signature is associated with aggressive phenotypes of various cancers. We assessed the expression of phenotypic markers characterizing primitive cells and its correlation with clinicopathologic and molecular characteristics in gastric cancer. Immunohistochemical analysis of a panel of primitive phenotypic markers, including embryonic stem cell markers (OCT4, NANOG, SALL4, CLDN6, and LIN28) and known oncofetal proteins (AFP and GPC3), was performed using tissue microarray on 386 gastric cancers...
May 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28492284/inhibition-of-corticotropin-releasing-hormone-receptor-1-and-activation-of-receptor-2-protect-against-colonic-injury-and-promote-epithelium-repair
#19
Bo Li, Carol Lee, Tali Filler, Alison Hock, Richard You Wu, Qi Li, Shigang Chen, Yuhki Koike, Wan Ip, Lijun Chi, Elke Zani-Ruttenstock, Pekka Määttänen, Tanja Gonska, Paul Delgado-Olguin, Augusto Zani, Philip M Sherman, Agostino Pierro
Maternal separation (MS) in neonates can lead to intestinal injury. MS in neonatal mice disrupts mucosal morphology, induces colonic inflammation and increases trans-cellular permeability. Several studies indicate that intestinal epithelial stem cells are capable of initiating gut repair in a variety of injury models but have not been reported in MS. The pathophysiology of MS-induced gut injury and subsequent repair remains unclear, but communication between the brain and gut contribute to MS-induced colonic injury...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28485389/egfr-dependent-tor-independent-endocycles-support-drosophila-gut-epithelial-regeneration
#20
Jinyi Xiang, Jennifer Bandura, Peng Zhang, Yinhua Jin, Hanna Reuter, Bruce A Edgar
Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors...
May 9, 2017: Nature Communications
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