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https://www.readbyqxmd.com/read/28314593/25-hydroxycholesterol-protects-host-against-zika-virus-infection-and-its-associated-microcephaly-in-a-mouse-model
#1
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28151409/helicobacter-pylori-induced-gastric-pathology-insights-from-in-vivo-and-ex-vivo-models
#2
REVIEW
Michael D Burkitt, Carrie A Duckworth, Jonathan M Williams, D Mark Pritchard
Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H...
February 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28132835/recent-zika-virus-isolates-induce-premature-differentiation-of-neural-progenitors-in-human-brain-organoids
#3
Elke Gabriel, Anand Ramani, Ulrike Karow, Marco Gottardo, Karthick Natarajan, Li Ming Gooi, Gladiola Goranci-Buzhala, Oleg Krut, Franziska Peters, Milos Nikolic, Suvi Kuivanen, Essi Korhonen, Teemu Smura, Olli Vapalahti, Argyris Papantonis, Jonas Schmidt-Chanasit, Maria Riparbelli, Giuliano Callaini, Martin Krönke, Olaf Utermöhlen, Jay Gopalakrishnan
The recent Zika virus (ZIKV) epidemic is associated with microcephaly in newborns. Although the connection between ZIKV and neurodevelopmental defects is widely recognized, the underlying mechanisms are poorly understood. Here we show that two recently isolated strains of ZIKV, an American strain from an infected fetal brain (FB-GWUH-2016) and a closely-related Asian strain (H/PF/2013), productively infect human iPSC-derived brain organoids. Both of these strains readily target to and replicate in proliferating ventricular zone (VZ) apical progenitors...
January 23, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28124153/gastric-organoids-an-emerging-model-system-to-study-helicobacter-pylori-pathogenesis
#4
Malvika Pompaiah, Sina Bartfeld
Helicobacter research classically uses fixed human tissue, animal models or cancer cell lines. Each of these study objects has its advantages and has brought central insights into the infection process. Nevertheless, in model systems for basic and medical research, there is a gap between two-dimensional and most often transformed cell cultures and three-dimensional, highly organized tissues. In recent years, stem cell research has provided the means to fill this gap. The identification of the niche factors that support growth, expansion and differentiation of stem cells in vitro has allowed the development of three-dimensional culture systems called organoids...
2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28041895/induction-of-expansion-and-folding-in-human-cerebral-organoids
#5
Yun Li, Julien Muffat, Attya Omer, Irene Bosch, Madeline A Lancaster, Mriganka Sur, Lee Gehrke, Juergen A Knoblich, Rudolf Jaenisch
An expansion of the cerebral neocortex is thought to be the foundation for the unique intellectual abilities of humans. It has been suggested that an increase in the proliferative potential of neural progenitors (NPs) underlies the expansion of the cortex and its convoluted appearance. Here we show that increasing NP proliferation induces expansion and folding in an in vitro model of human corticogenesis. Deletion of PTEN stimulates proliferation and generates significantly larger and substantially folded cerebral organoids...
December 20, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28005068/immuno-engineered-organoids-for-regulating-the-kinetics-of-b-cell-development-and-antibody-production
#6
Alberto Purwada, Ankur Singh
Induction of B-cell immunity against infection depends on the initiation of the germinal center (GC) reaction in secondary lymphoid organs. Ex vivo recapitulation of the GC reaction in 2D cultures results in transient cell growth, with poor yield and short-term survival. Furthermore, no reported 2D ex vivo system can modulate the kinetics of a GC-like phenotype or the rate of antibody class switching. This protocol describes a methodology for developing immune organoids that partially mimic the B-cell zone of a lymphoid tissue, for efficient and rapid generation of B cells with a GC-like phenotype from naive murine B cells...
January 2017: Nature Protocols
https://www.readbyqxmd.com/read/27990460/the-development-of-spasmolytic-polypeptide-tff2-expressing-metaplasia-spem-during-gastric-repair-is-absent-in-the-aged-stomach
#7
Amy C Engevik, Rui Feng, Eunyoung Choi, Shana White, Nina Bertaux-Skeirik, Jing Li, Maxime M Mahe, Eitaro Aihara, Li Yang, Betsy DiPasquale, Sunghee Oh, Kristen A Engevik, Andrew S Giraud, Marshall H Montrose, Mario Medvedovic, Michael A Helmrath, James R Goldenring, Yana Zavros
BACKGROUND & AIMS: During aging, physiological changes in the stomach result in more tenuous gastric tissue that is less capable of repairing injury, leading to increased susceptibility to chronic ulceration. Spasmolytic polypeptide/trefoil factor 2-expressing metaplasia (SPEM) is known to emerge after parietal cell loss and during Helicobacter pylori infection, however, its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27912091/genetic-ablation-of-axl-does-not-protect-human-neural-progenitor-cells-and-cerebral-organoids-from-zika-virus-infection
#8
Michael F Wells, Max R Salick, Ole Wiskow, Daniel J Ho, Kathleen A Worringer, Robert J Ihry, Sravya Kommineni, Bilada Bilican, Joseph R Klim, Ellen J Hill, Liam T Kane, Chaoyang Ye, Ajamete Kaykas, Kevin Eggan
Zika virus (ZIKV) can cross the placental barrier, resulting in infection of the fetal brain and neurological defects including microcephaly. The cellular tropism of ZIKV and the identity of attachment factors used by the virus to gain access to key cell types involved in pathogenesis are under intense investigation. Initial studies suggested that ZIKV preferentially targets neural progenitor cells (NPCs), providing an explanation for the developmental phenotypes observed in some pregnancies. The AXL protein has been nominated as a key attachment factor for ZIKV in several cell types including NPCs...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27912090/advances-in-zika-virus-research-stem-cell-models-challenges-and-opportunities
#9
REVIEW
Guo-Li Ming, Hengli Tang, Hongjun Song
The re-emergence of Zika virus (ZIKV) and its suspected link with various disorders in newborns and adults led the World Health Organization to declare a global health emergency. In response, the stem cell field quickly established platforms for modeling ZIKV exposure using human pluripotent stem cell-derived neural progenitors and brain organoids, fetal tissues, and animal models. These efforts provided significant insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection as well as platforms for drug testing...
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27680706/frizzled-proteins-are-colonic-epithelial-receptors-for-c-difficile-toxin-b
#10
Liang Tao, Jie Zhang, Paul Meraner, Alessio Tovaglieri, Xiaoqian Wu, Ralf Gerhard, Xinjun Zhang, William B Stallcup, Ji Miao, Xi He, Julian G Hurdle, David T Breault, Abraham L Brass, Min Dong
Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium...
October 20, 2016: Nature
https://www.readbyqxmd.com/read/27640087/modeling-infectious-diseases-and-host-microbe-interactions-in-gastrointestinal-organoids
#11
REVIEW
Sina Bartfeld
Advances in stem cell research have allowed the development of 3-dimensional (3D) primary cell cultures termed organoid cultures, as they closely mimic the in vivo organization of different cell lineages. Bridging the gap between 2-dimensional (2D) monotypic cancer cell lines and whole organisms, organoids are now widely applied to model development and disease. Organoids hold immense promise for addressing novel questions in host-microbe interactions, infectious diseases and the resulting inflammatory conditions...
December 15, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27633294/mammalian-cell-cultures-as-models-for-mycobacterium-tuberculosis-human-immunodeficiency-virus-hiv-interaction-studies-a-review
#12
REVIEW
Walter Chingwaru, Richard H Glashoff, Jerneja Vidmar, Petrina Kapewangolo, Samantha L Sampson
Mycobacterium tuberculosis and human immunodeficiency virus (HIV) co-infections have remained a major public health concern worldwide, particularly in Southern Africa. Yet our understanding of the molecular interactions between the pathogens has remained poor due to lack of suitable preclinical models for such studies. We reviewed the use, this far, of mammalian cell culture models in HIV-MTB interaction studies. Studies have described the use of primary human cell cultures, including (1) monocyte-derived macrophage (MDM) fractions of peripheral blood mononuclear cell (PBMC), alveolar macrophages (AM), (2) cell lines such as the monocyte-derived macrophage cell line (U937), T lymphocyte cell lines (CEMx174, ESAT-6-specific CD4(+) T-cells) and an alveolar epithelial cell line (A549) and (3) special models such as stem cells, three dimensional (3D) or organoid cell models (including a blood-brain barrier cell model) in HIV-MTB interaction studies...
September 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27576565/derivation-of-intestinal-organoids-from-human-induced-pluripotent-stem-cells-for-use-as-an-infection-system
#13
Jessica L Forbester, Nicholas Hannan, Ludovic Vallier, Gordon Dougan
Intestinal human organoids (iHOs) provide an effective system for studying the intestinal epithelium and its interaction with various stimuli. By using combinations of different signaling factors, human induced pluripotent stem cells (hIPSCs) can be driven to differentiate down the intestinal lineage. Here, we describe the process for this differentiation, including the derivation of hindgut from hIPSCs, embedding hindgut into a pro-intestinal culture system and passaging the resulting iHOs. We then describe how to carry out microinjections to introduce bacteria to the apical side of the intestinal epithelial cells (IECs)...
August 31, 2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27571349/identification-of-small-molecule-inhibitors-of-zika-virus-infection-and-induced-neural-cell-death-via-a-drug-repurposing-screen
#14
Miao Xu, Emily M Lee, Zhexing Wen, Yichen Cheng, Wei-Kai Huang, Xuyu Qian, Julia Tcw, Jennifer Kouznetsova, Sarah C Ogden, Christy Hammack, Fadi Jacob, Ha Nam Nguyen, Misha Itkin, Catherine Hanna, Paul Shinn, Chase Allen, Samuel G Michael, Anton Simeonov, Wenwei Huang, Kimberly M Christian, Alison Goate, Kristen J Brennand, Ruili Huang, Menghang Xia, Guo-Li Ming, Wei Zheng, Hongjun Song, Hengli Tang
In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of ∼6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds; we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and three-dimensional organoid cultures...
October 2016: Nature Medicine
https://www.readbyqxmd.com/read/27566565/epithelial-mesenchymal-transition-and-nuclear-%C3%AE-catenin-induced-by-conditional-intestinal-disruption-of-cdh1-with-apc-is-e-cadherin-ec1-domain-dependent
#15
Julia Matheson, Claudia Bühnemann, Emma J Carter, David Barnes, Hans-Jürgen Hoppe, Jennifer Hughes, Stephen Cobbold, James Harper, Hans Morreau, Mirvat Surakhy, A Bassim Hassan
Two important protein-protein interactions establish E-cadherin (Cdh1) in the adhesion complex; homophilic binding via the extra-cellular (EC1) domain and cytoplasmic tail binding to β-catenin. Here, we evaluate whether E-cadherin binding can inhibit β-catenin when there is loss of Adenomatous polyposis coli (APC) from the β-catenin destruction complex. Combined conditional loss of Cdh1 and Apc were generated in the intestine, intestinal adenoma and adenoma organoids. Combined intestinal disruption (Cdh1fl/flApcfl/flVil-CreERT2) resulted in lethality, breakdown of the intestinal barrier, increased Wnt target gene expression and increased nuclear β-catenin localization, suggesting that E-cadherin inhibits β-catenin...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27539461/study-bacteria-host-interactions-using-intestinal-organoids
#16
Yong-Guo Zhang, Jun Sun
The intestinal epithelial cells function to gain nutrients, retain water and electrolytes, and form an efficient barrier against foreign microbes and antigens. Researchers employed cell culture lines derived from human or animal cancer cells as experimental models in vitro for understanding of intestinal infections. However, most in vitro models used to investigate interactions between bacteria and intestinal epithelial cells fail to recreate the differentiated tissue components and structure observed in the normal intestine...
August 19, 2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27529056/restoration-of-thymus-function-with-bioengineered-thymus-organoids
#17
Asako Tajima, Isha Pradhan, Massimo Trucco, Yong Fan
The thymus is the primary site for the generation of a diverse repertoire of T-cells that are essential to the efficient function of adaptive immunity. Numerous factors varying from aging, chemotherapy, radiation exposure, virus infection and inflammation contribute to thymus involution, a phenomenon manifested as loss of thymus cellularity, increased stromal fibrosis and diminished naïve T-cell output. Rejuvenating thymus function is a challenging task since it has limited regenerative capability and we still do not know how to successfully propagate thymic epithelial cells (TECs), the predominant population of the thymic stromal cells making up the thymic microenvironment...
June 2016: Current Stem Cell Reports
https://www.readbyqxmd.com/read/27525286/neuropathology-of-zika-virus-infection
#18
Isaac H Solomon, Danny A Milner, Rebecca D Folkerth
Zika virus (ZIKV) is a member of the Flaviviridae family that had been associated only with mild disease prior to the 2015 outbreak in Brazil. A dramatic increase in reported cases of microcephaly and Guillain-Barré syndrome during this time prompted significant research into possible associations with ZIKV and its neurotropic properties. Infection of neural progenitor cells and organoids have been shown to induce apoptosis and dysregulation of growth, and mouse studies have demonstrated viral replication in brain tissue in adults, as well as vertical transmission resulting in embryonic brain abnormalities...
June 2016: Journal of Neuroinfectious Diseases
https://www.readbyqxmd.com/read/27468950/mycophenolic-acid-potently-inhibits-rotavirus-infection-with-a-high-barrier-to-resistance-development
#19
Yuebang Yin, Yijin Wang, Wen Dang, Lei Xu, Junhong Su, Xinying Zhou, Wenshi Wang, Krzysztof Felczak, Luc J W van der Laan, Krzysztof W Pankiewicz, Annemiek A van der Eijk, Marcel Bijvelds, Dave Sprengers, Hugo de Jonge, Marion P G Koopmans, Herold J Metselaar, Maikel P Peppelenbosch, Qiuwei Pan
Rotavirus infection has emerged as an important cause of complications in organ transplantation recipients. Immunosuppressants used to prevent alloreactivity can also interfere with virus infection, but the direct effects of the specific type of immunosuppressants on rotavirus infection are still unclear. Here we profiled the effects of different immunosuppressants on rotavirus using a 2D culture model of Caco2 human intestinal cell line and a 3D model of human primary intestinal organoids inoculated with laboratory and patient-derived rotavirus strains...
September 2016: Antiviral Research
https://www.readbyqxmd.com/read/27322618/influenza-virus-infects-epithelial-stem-progenitor-cells-of-the-distal-lung-impact-on-fgfr2b-driven-epithelial-repair
#20
Jennifer Quantius, Carole Schmoldt, Ana I Vazquez-Armendariz, Christin Becker, Elie El Agha, Jochen Wilhelm, Rory E Morty, István Vadász, Konstantin Mayer, Stefan Gattenloehner, Ludger Fink, Mikhail Matrosovich, Xiaokun Li, Werner Seeger, Juergen Lohmeyer, Saverio Bellusci, Susanne Herold
Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high...
June 2016: PLoS Pathogens
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