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https://www.readbyqxmd.com/read/29150092/generation-of-integration-free-induced-pluripotent-stem-cell-lines-derived-from-two-patients-with-x-linked-alport-syndrome-xlas
#1
Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, Angel Raya
Skin biopsies were obtained from two male patients with X-linked Alport syndrome (XLAS) with hemizygous COL4A5 mutations in exon 41 or exon 46. Dermal fibroblasts were extracted and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53 shRNA. The generated induced Pluripotent Stem Cell (iPSC) lines AS-FiPS2-Ep6F-28 and AS-FiPS3-Ep6F-9 were free of genomically integrated reprogramming genes, had the specific mutations, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro...
September 9, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29149760/patterns-of-relapse-in-poor-prognosis-germ-cell-tumours-in-the-getug-13-trial-implications-for-assessment-of-brain-metastases
#2
Y Loriot, L Pagliaro, A Fléchon, J Mardiak, L Geoffrois, P Kerbrat, C Chevreau, R Delva, F Rolland, C Theodore, G Roubaud, G Gravis, J C Eymard, J P Malhaire, C Linassier, M Habibian, A L Martin, F Journeau, M Reckova, C Logothetis, A Laplanche, G Le Teuff, S Culine, K Fizazi
BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain...
November 14, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29142409/reversible-testicular-toxicity-of-piperine-on-male-albino-rats
#3
Gopichand Chinta, Mohane Selvaraj Coumar, Latha Periyasamy
Background: Piperine was widely used in traditional medicine for inducing sterility and abortion. Objective: To evaluate the effect of the piperine on testis of male albino rats. Materials and Methods: Adult male rats were divided into four groups (n = 12). Group I (control): Rats were given vehicle p.o. i.e. 0.5% carboxymethyl cellulose in normal saline daily for 60 days, Group II (ED): Rats received piperine at a dose of 10 mg/kg body weight (b...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142301/alteration-of-the-intestinal-microbiome-characterizes-preclinical-inflammatory-arthritis-in-mice-and-its-modulation-attenuates-established-arthritis
#4
Rebecca Rogier, Heather Evans-Marin, Julia Manasson, Peter M van der Kraan, Birgitte Walgreen, Monique M Helsen, Liduine A van den Bersselaar, Fons A van de Loo, Peter L van Lent, Steven B Abramson, Wim B van den Berg, Marije I Koenders, Jose U Scher, Shahla Abdollahi-Roodsaz
Perturbations of the intestinal microbiome have been observed in patients with new-onset and chronic autoimmune inflammatory arthritis. However, it is currently unknown whether these alterations precede the development of arthritis or are rather a consequence of disease. Modulation of intestinal microbiota by oral antibiotics or germ-free condition can prevent arthritis in mice. Yet, the therapeutic potential of modulation of the microbiota after the onset of arthritis is not well characterized. We here show that the intestinal microbial community undergoes marked changes in the preclinical phase of collagen induced arthritis (CIA)...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142211/the-microbiota-protects-against-respiratory-infection-via-gm-csf-signaling
#5
Rebecca L Brown, Richard P Sequeira, Thomas B Clarke
The microbiota promotes resistance to respiratory infection, but the mechanistic basis for this is poorly defined. Here, we identify members of the microbiota that protect against respiratory infection by the major human pathogens Streptococcus pneumoniae and Klebsiella pneumoniae. We show that the microbiota enhances respiratory defenses via granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which stimulates pathogen killing and clearance by alveolar macrophages through extracellular signal-regulated kinase signaling...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29140422/multidisciplinary-clinic-approach-improves-overall-survival-outcomes-of-patients-with-metastatic-germ-cell-tumors
#6
C Albany, N Adra, A C Snavely, C Cary, T A Masterson, R S Foster, K Kesler, T M Ulbright, L Cheng, M Chovanec, F Taza, K Ku, M J Brames, N H Hanna, L H Einhorn
Background: To report our experience utilizing a multidisciplinary clinic (MDC) at Indiana University (IU) since the publication of the International Germ Cell Cancer Collaborative Group (IGCCCG), and to compare our overall survival to that of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. Patients and Methods: We conducted a retrospective analysis of all patients with metastatic germ cell tumor (GCT) seen at IU from 1998-2014...
November 10, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29136563/generation-of-human-ipsc-line-from-a-patient-with-laterality-defects-and-associated-congenital-heart-anomalies-carrying-a-dand5-missense-alteration
#7
Fernando Cristo, José M Inácio, Graça Rosas, Isabel Marques Carreira, Joana Barbosa Melo, Luís Pereira de Almeida, Patrícia Mendes, Duarte Saraiva Martins, José Maio, Rui Anjos, José A Belo
A human iPSC line was generated from exfoliated renal epithelial (ERE) cells of a patient affected with Congenital Heart Disease (CHD) and Laterality Defects carrying tshe variant p.R152H in the DAND5 gene. The transgene-free iPSCs were generated with the human OSKM transcription factor using the Sendai-virus reprogramming system. The established iPSC line had the specific heterozygous alteration, a stable karyotype, expressed pluripotency markers and generated embryoid bodies that can differentiate towards the three germ layers in vitro...
October 31, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29133078/enteric-delivery-of-regenerating-family-member-3-alpha-alters-the-intestinal-microbiota-and-controls-inflammation-in-mice-with-colitis
#8
Marion Darnaud, Alexandre Dos Santos, Patrick Gonzalez, Sandrine Augui, Claire Lacoste, Christophe Desterke, Gert De Hertogh, Emma Valentino, Emilie Braun, Jinzi Zheng, Raphael Boisgard, Christel Neut, Laurent Dubuquoy, Franck Chiappini, Didier Samuel, Patricia Lepage, Francesca Guerrieri, Joel Doré, Christian Bréchot, Nicolas Moniaux, Jamila Faivre
BACKGROUND & AIMS: Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic expression of the human regenerating family member 3 alpha gene (REG3A) alters the fecal microbiota and affects development of colitis in mice. METHODS: We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter...
November 10, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29131106/gut-microbiota-dependent-modulation-of-energy-metabolism
#9
Christina N Heiss, Louise E Olofsson
The gut microbiota has emerged as an environmental factor that modulates the host's energy balance. It increases the host's ability to harvest energy from the digested food, and produces metabolites and microbial products such as short-chain fatty acids, secondary bile acids, and lipopolysaccharides. These metabolites and microbial products act as signaling molecules that modulate appetite, gut motility, energy uptake and storage, and energy expenditure. Several findings suggest that the gut microbiota can affect the development of obesity...
November 8, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29127271/whole-grain-consumption-and-risk-of-ischemic-stroke-results-from-2-prospective-cohort-studies
#10
Juan Juan, Gang Liu, Walter C Willett, Frank B Hu, Kathryn M Rexrode, Qi Sun
BACKGROUND AND PURPOSE: Higher intake of whole grains may exert cardiometabolic benefits, although findings on stroke risk are inconclusive. The potentially differential effects of individual whole grain foods on ischemic stroke have not been examined. METHODS: We analyzed whole grain consumption in relation to ischemic stroke among 71 750 women from the Nurses' Health Study and 42 823 men from the Health Professionals Follow-up Study who were free of cardiovascular disease, diabetes mellitus, and cancer at baseline (1984 and 1986, respectively) through 2010 using a Cox proportional hazards model...
November 10, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29118745/biofilm-structures-in-a-mono-associated-mouse-model-of-clostridium-difficile-infection
#11
Anna P Soavelomandroso, Françoise Gaudin, Sandra Hoys, Valérie Nicolas, Gayatri Vedantam, Claire Janoir, Sylvie Bouttier
Clostridium difficile infection (CDI) is a major healthcare-associated disease with high recurrence rates. Host colonization is critical for the infectious process, both in first episodes and in recurrent disease, with biofilm formation playing a key role. The ability of C. difficile to form a biofilm on abiotic surfaces is established, but has not yet been confirmed in the intestinal tract. Here, four different isolates of C. difficile, which are in vitro biofilm producers, were studied for their ability to colonize germ-free mice...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29115387/generation-of-human-induced-pluripotent-stem-cells-from-burn-patient-derived-skin-fibroblasts-using-a-non-integrative-method
#12
Shangfeng Fu, Jianwu Ding, Dewu Liu, Heping Huang, Min Li, Yang Liu, Longxiang Tu, Deming Liu
Patient specific induced pluripotent stem cells (iPSCs) have been recognized as a possible source of cells for skin tissue engineering. They have the potential to greatly benefit patients with large areas of burned skin or skin defects. However, the integration virus-based reprogramming method is associated with a high risk of genetic mutation and mouse embryonic fibroblast feeder-cells may be a pollutant. In the present study, human skin fibroblasts (HSFs) were successfully harvested from patients with burns and patient-specific iPSCs were generated using a non-integration method with a feeder-free approach...
October 23, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29113135/nonalcoholic-fatty-liver-disease-is-exacerbated-in-high-fat-diet-fed-gnotobiotic-mice-by-colonization-with-the-gut-microbiota-from-patients-with-nonalcoholic-steatohepatitis
#13
Chien-Chao Chiu, Yung-Hao Ching, Yen-Peng Li, Ju-Yun Liu, Yen-Te Huang, Yi-Wen Huang, Sien-Sing Yang, Wen-Ching Huang, Hsiao-Li Chuang
Nonalcoholic fatty liver disease (NAFLD) is a serious liver disorder associated with the accumulation of fat and inflammation. The objective of this study was to determine the gut microbiota composition that might influence the progression of NAFLD. Germ-free mice were inoculated with feces from patients with nonalcoholic steatohepatitis (NASH) or from healthy persons (HL) and then fed a standard diet (STD) or high-fat diet (HFD). We found that the epididymal fat weight, hepatic steatosis, multifocal necrosis, and inflammatory cell infiltration significantly increased in the NASH-HFD group...
November 6, 2017: Nutrients
https://www.readbyqxmd.com/read/29109476/the-major-targets-of-acute-norovirus-infection-are-immune-cells-in-the-gut-associated-lymphoid-tissue
#14
Katrina R Grau, Alexa N Roth, Shu Zhu, Abel Hernandez, Natacha Colliou, Bayli B DiVita, Drake T Philip, Cara Riffe, Benoit Giasson, Shannon M Wallet, Mansour Mohamadzadeh, Stephanie M Karst
Noroviruses are the leading cause of food-borne gastroenteritis outbreaks and childhood diarrhoea globally, estimated to be responsible for 200,000 deaths in children each year (1-4) . Thus, reducing norovirus-associated disease is a critical priority. Development of vaccines and therapeutics has been hindered by the limited understanding of basic norovirus pathogenesis and cell tropism. While macrophages, dendritic cells, B cells and stem-cell-derived enteroids can all support infection of certain noroviruses in vitro (5-7) , efforts to define in vivo norovirus cell tropism have generated conflicting results...
November 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29107285/host-microbiota-interaction-induces-bi-phasic-inflammation-and-glucose-intolerance-in-mice
#15
Antonio Molinaro, Robert Caesar, Louise Mannerås Holm, Valentina Tremaroli, Patrice D Cani, Fredrik Bäckhed
OBJECTIVE: Gut microbiota modulates adiposity and glucose metabolism in humans and mice. Here we investigated how colonization of germ-free (GF) mice affects kinetics of adiposity and glucose metabolism. METHODS: Adiposity and glucose metabolism were evaluated at different time points in ex-GF and antibiotic treated mice after colonization with gut microbiota from a conventionally raised (CONV-R) mouse. Mouse physiology, microbiome configuration, serum cytokine levels, and gene expression for inflammatory markers were performed in different tissues...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29097494/gut-microbiome-influences-efficacy-of-pd-1-based-immunotherapy-against-epithelial-tumors
#16
Bertrand Routy, Emmanuelle Le Chatelier, Lisa Derosa, Connie P M Duong, Maryam Tidjani Alou, Romain Daillère, Aurélie Fluckiger, Meriem Messaoudene, Conrad Rauber, Maria P Roberti, Marine Fidelle, Caroline Flament, Vichnou Poirier-Colame, Paule Opolon, Christophe Klein, Kristina Iribarren, Laura Mondragón, Nicolas Jacquelot, Bo Qu, Gladys Ferrere, Céline Clémenson, Laura Mezquita, Jordi Remon Masip, Charles Naltet, Solenn Brosseau, Coureche Kaderbhai, Corentin Richard, Hira Rizvi, Florence Levenez, Nathalie Galleron, Benoit Quinquis, Nicolas Pons, Bernhard Ryffel, Véronique Minard-Colin, Patrick Gonin, Jean-Charles Soria, Eric Deutsch, Yohann Loriot, François Ghiringhelli, Gérard Zalcman, François Goldwasser, Bernard Escudier, Matthew D Hellmann, Alexander Eggermont, Didier Raoult, Laurence Albiges, Guido Kroemer, Laurence Zitvogel
Immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizeable minority of cancer patients. Here, we show that primary resistance to ICI can be due to abnormal gut microbiome composition. Antibiotics (ATB) inhibited the clinical benefit of ICI in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICI (but not from non-responding patients) into germ-free or ATB-treated mice ameliorated the antitumor effects of PD-1 blockade...
November 2, 2017: Science
https://www.readbyqxmd.com/read/29097493/gut-microbiome-modulates-response-to-anti-pd-1-immunotherapy-in-melanoma-patients
#17
V Gopalakrishnan, C N Spencer, L Nezi, A Reuben, M C Andrews, T V Karpinets, P A Prieto, D Vicente, K Hoffman, S C Wei, A P Cogdill, L Zhao, C W Hudgens, D S Hutchinson, T Manzo, M Petaccia de Macedo, T Cotechini, T Kumar, W S Chen, S M Reddy, R Szczepaniak Sloane, J Galloway-Pena, H Jiang, P L Chen, E J Shpall, K Rezvani, A M Alousi, R F Chemaly, S Shelburne, L M Vence, P C Okhuysen, V B Jensen, A G Swennes, F McAllister, E Marcelo Riquelme Sanchez, Y Zhang, E Le Chatelier, L Zitvogel, N Pons, J L Austin-Breneman, L E Haydu, E M Burton, J M Gardner, E Sirmans, J Hu, A J Lazar, T Tsujikawa, A Diab, H Tawbi, I C Glitza, W J Hwu, S P Patel, S E Woodman, R N Amaria, M A Davies, J E Gershenwald, P Hwu, J E Lee, J Zhang, L M Coussens, Z A Cooper, P A Futreal, C R Daniel, N J Ajami, J F Petrosino, M T Tetzlaff, P Sharma, J P Allison, R R Jenq, J A Wargo
Pre-clinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-PD-1 immunotherapy (n=112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders (R) versus non-responders (NR). Analysis of patient fecal microbiome samples (n=43, 30R, 13NR) showed significantly higher alpha diversity (p<0...
November 2, 2017: Science
https://www.readbyqxmd.com/read/29079994/osteomicrobiology-a-new-cross-disciplinary-research-field
#18
REVIEW
Claes Ohlsson, Klara Sjögren
The mutualistic interaction between the gut microbiota (GM) and its host profoundly shapes many aspects of our physiology. The composition and activity of the gut microbiota is modulated by environmental factors such as dietary habits and antibiotic treatments. In rodents, studies demonstrate that the GM is a crucial regulator of bone metabolism and that modulation of the GM composition by probiotic interventions can prevent castration-induced bone loss. Short-term colonization of germ-free mice with GM results in an activation of CD4+T cells, resulting in increased levels of pro-inflammatory cytokines in bone and thereby activation of osteoclastic bone resorption...
October 27, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29079701/mutational-signatures-of-non-homologous-and-polymerase-theta-mediated-end-joining-in-embryonic-stem-cells
#19
Joost Schimmel, Hanneke Kool, Robin van Schendel, Marcel Tijsterman
Cells employ potentially mutagenic DNA repair mechanisms to avoid the detrimental effects of chromosome breaks on cell survival. While classical non-homologous end-joining (cNHEJ) is largely error-free, alternative end-joining pathways have been described that are intrinsically mutagenic. Which end-joining mechanisms operate in germ and embryonic cells and thus contribute to heritable mutations found in congenital diseases is, however, still largely elusive. Here, we determined the genetic requirements for the repair of CRISPR/Cas9-induced chromosomal breaks of different configurations, and establish the mutational consequences...
October 27, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29069103/the-yeast-form-of-the-fungus-candida-albicans-promotes-persistence-in-the-gut-of-gnotobiotic-mice
#20
Lena Böhm, Sanda Torsin, Su Hlaing Tint, Marie Therese Eckstein, Tobias Ludwig, J Christian Pérez
Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice...
October 2017: PLoS Pathogens
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