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https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-beta-promotes-liver-tumorigenesis-in-mice-via-upregulation-of-snail
#1
Hyuk Moon, Hye-Lim Ju, Sook In Chung, Kyung Joo Cho, Jung Woo Eun, Suk Woo Nam, Kwang-Hyub Han, Diego F Calvisi, Simon Weonsang Ro
BACKGROUND & AIMS: Transforming growth factor beta (TGFB) suppresses early stages of tumorigenesis, but also contributes to migration and metastasis of cancer cells. A large number of human tumors contain mutations that inactivate its receptors, or downstream proteins such as Smad transcription factors, indicating that the TGFB signaling pathway prevents tumor growth. We investigated the effects of TGFB inhibition on liver tumorigenesis in mice. METHODS: C57BL/6 mice received hydrodynamic tail injections of transposons encoding HRAS(G12V) and a short hairpin RNA (shRNA) to downregulate p53, or those encoding HRAS(G12V) and MYC, or those encoding HRAS(G12V) and TAZ(S89), to induce liver tumor formation; mice were also given injections of transposons encoding SMAD7 or shRNA against SMAD2, SMAD3, SMAD4, or SNAI1 (Snail), with or without ectopic expression of Snail...
July 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28733897/alleviation-of-neuropathology-by-inhibition-of-monoacylglycerol-lipase-in-app-transgenic-mice-lacking-cb2-receptors
#2
Jian Zhang, Chu Chen
Inhibition of monoacylglycerol lipase (MAGL), the primary enzyme that hydrolyzes the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain, produces profound anti-inflammatory and neuroprotective effects and improves synaptic and cognitive functions in animal models of Alzheimer's disease (AD). However, the molecular mechanisms underlying the beneficial effects produced by inhibition of 2-AG metabolism are still not clear. The cannabinoid receptor type 2 (CB2R) has been thought to be a therapeutic target for AD...
July 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#3
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733471/helicobacter-species-are-potent-drivers-of-colonic-t-cell-responses-in-homeostasis-and-inflammation
#4
Jiani N Chai, Yangqing Peng, Sunaina Rengarajan, Benjamin D Solomon, Teresa L Ai, Zeli Shen, Justin S A Perry, Kathryn A Knoop, Takeshi Tanoue, Seiko Narushima, Kenya Honda, Charles O Elson, Rodney D Newberry, Thaddeus S Stappenbeck, Andrew L Kau, Daniel A Peterson, James G Fox, Chyi-Song Hsieh
Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cell responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. We addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg cell responses during homeostasis and Teff cell responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28733446/how-does-pressure-overload-cause-cardiac-hypertrophy-and-dysfunction-high-ouabain-affinity-cardiac-na-pumps-are-crucial
#5
Mordecai P Blaustein
Left ventricular hypertrophy is frequently observed in hypertensive patients, and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically-engineered Na(+) pumps, however, demonstrate that cardiac ouabain-sensitive α2 Na(+) pumps play a key role in the pathogenesis of trans-aortic constriction (TAC)-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α2 Na(+) pumps and in mice with cardiac-selective knockout (KO) or transgenic overexpression (TG) of α2 Na(+) pumps...
July 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28733313/granzyme-a-deficiency-breaks-immune-tolerance-and-promotes-autoimmune-diabetes-through-a-type-i-interferon-dependent-pathway
#6
Zia Ua Mollah, Hong Sheng Quah, Kate L Graham, Gaurang Jhala, Balasubramanian Krishnamurthy, Joanna Francisca M Dharma, Jonathan Chee, Prerak M Trivedi, Evan G Pappas, Leanne Mackin, Edward Pf Chu, Satoru Akazawa, Stacey Fynch, Charlotte Hodson, Andrew J Deans, Joseph A Trapani, Mark Mw Chong, Phillip I Bird, Thomas C Brodnicki, Helen E Thomas, Thomas Wh Kay
Granzyme A is a protease implicated in the degradation of intracellular DNA. Nucleotide complexes are known triggers of systemic autoimmunity, but a role in organ-specific autoimmune disease has not been demonstrated. To investigate whether such a mechanism could be an endogenous trigger for autoimmunity, we examined the impact of granzyme A deficiency in the NOD mouse model of autoimmune diabetes. Granzyme A deficiency resulted in an increased incidence in diabetes associated with accumulation of single stranded DNA in immune cells and induction of an interferon response in pancreatic islets...
July 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28732359/resveratrol-inhibits-age-dependent-spontaneous-tumorigenesis-by-sirt1-mediated-post-translational-modulations-in-the-annual-fish-nothobranchius-guentheri
#7
Tingting Liu, Long Ma, Zhaodi Zheng, Fenglin Li, Shan Liu, Yingbo Xie, Guorong Li
Resveratrol, SIRT1 activator, inhibits carcinogenesis predominantly performed in transgenic animal models, orthotopic cancers of nude mice or different cancer cell lines, but its effects during process of spontaneous tumors using vertebrate models remain untested. Spontaneous liver neoplasm is an age-related disease and is inhibited by resveratrol in the annual fish Nothobranchius guentheri, which indicates that the fish can act as an excellent model to study spontaneous tumorigenesis. Totally, 175 fish were fed with resveratrol and another 175 fish for controls...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732240/constitutive-transgene-expression-of-stem-cell-antigen-1-in-the-hair-follicle-alters-the-sensitivity-to-tumor-formation-and-progression
#8
Rikke Christensen, David M Owens, Annette C Füchtbauer, Anders Gunnarsson, Mette Ramsing, Ernst-Martin Füchtbauer, Uffe Birk Jensen
The cell surface protein Stem Cell Antigen-1 (Sca-1) marks stem or progenitor cells in several murine tissues and is normally upregulated during cancer development. Although the specific function of Sca-1 remains unknown, Sca-1 seems to play a role in proliferation, differentiation and cell migration in a number of tissues. In the skin epithelium, Sca-1 is highly expressed in the interfollicular epidermis but is absent in most compartments of the hair follicle; however, the function of Sca-1 in the skin has not been investigated...
July 8, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28732181/irf6-and-spry4-signaling-interact-in-periderm-development
#9
Y A Kousa, R Roushangar, N Patel, A Walter, P Marangoni, R Krumlauf, O D Klein, B C Schutte
Rare mutations in IRF6 and GRHL3 cause Van der Woude syndrome, an autosomal dominant orofacial clefting disorder. Common variants in IRF6 and GRHL3 also contribute risk for isolated orofacial clefting. Similarly, variants within genes that encode receptor tyrosine kinase (RTK) signaling components, including members of the FGF pathway, EPHA3 and SPRY2, also contribute risk for isolated orofacial clefting. In the mouse, loss of Irf6 or perturbation of Fgf signaling leads to abnormal oral epithelial adhesions and cleft palate...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28732092/dietary-oleic-acid-regulates-hepatic-lipogenesis-through-a-liver-x-receptor-dependent-signaling
#10
Simon Ducheix, Alexandra Montagner, Arnaud Polizzi, Frédéric Lasserre, Marion Régnier, Alice Marmugi, Fadila Benhamed, Justine Bertrand-Michel, Laila Mselli-Lakhal, Nicolas Loiseau, Pascal G Martin, Jean-Marc Lobaccaro, Laurent Ferrier, Catherine Postic, Hervé Guillou
Olive oil consumption is beneficial for health as it is associated with a decreased prevalence of cancer and cardiovascular diseases. Oleic acid is, by far, the most abundant component of olive oil. Since it can be made through de novo synthesis in animals, it is not an essential fatty acid. While it has become clear that dietary oleic acid regulates many biological processes, the signaling pathway involved in these regulations remains poorly defined. In this work we tested the impact of an oleic acid-rich diet on hepatic gene expression...
2017: PloS One
https://www.readbyqxmd.com/read/28731445/colivelin-ameliorates-impairments-in%C3%A2-cognitive-behaviors-and-synaptic-plasticity-in-app-ps1-transgenic-mice
#11
Meina Wu, Hui Shi, Yexin He, Li Yuan, Xuesong Qu, Jun Zhang, Zhaojun Wang, Hongyan Cai, Jinshun Qi
Alzheimer's disease (AD) is the most common cause of dementia, and effective therapeutics are lacking. Colivelin (CLN), a novel, strong humanin derivative, is effective in vitro in preventing cell death induced by AD-causative genes and amyloid-β protein (Aβ) even at a low concentration. We recently demonstrated that intrahippocampal injection of CLN prevents Aβ25-35-induced deficits in spatial memory and synaptic plasticity in normal rats. Here, we further observed the effects of chronically intranasally (i...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731433/the-effects-of-cardiotrophin-1-on-early-synaptic-mitochondrial-dysfunction-and-synaptic-pathology-in-appswe-ps1de9-mice
#12
Dongmei Wang, Xiaozhuan Liu, Yumei Liu, Sanqiang Li, Chenying Wang
The coexistence of neuronal mitochondrial pathology and synaptic dysfunction is an early pathological feature of Alzheimer's disease (AD). Cardiotrophin-1 (CT-1) has been shown to exhibit impressive neuroprotective effects. Previous studies have shown positive effects of CT-1 on brain glucose metabolism and cognition in APPswe/PS1dE9 transgenic mice; however, little is known about the effects of CT-1 on early synaptic mitochondrial dysfunction and resultant synaptic pathology in the brain. In this study, 4-month-old transgenic mice with brain tissue-specific CT-1 expression were used alone or in combination with APPswe/PS1dE9 transgenic mice to evaluate the effect of CT-1 on synaptic mitochondrial dysfunction and resultant synaptic pathology, and cryptic memory deficits in the APPswe/PS1dE9 transgenic mice...
July 19, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28731378/experimental-infection-of-cattle-with-a-novel-prion-derived-from-atypical-h-type-bovine-spongiform-encephalopathy
#13
Hiroyuki Okada, Kentaro Masujin, Kohtaro Miyazawa, Yoshihumi Iwamaru, Morikazu Imamura, Yuichi Matsuura, Shozo Arai, Shigeo Fukuda, Yuichi Murayama, Takashi Yokoyama
H-type bovine spongiform encephalopathy (H-BSE) is an atypical form of BSE in cattle. During passaging of H-BSE in transgenic bovinized (TgBoPrP) mice, a novel phenotype of BSE, termed BSE-SW emerged and was characterized by a short incubation time and host weight loss. To investigate the biological and biochemical properties of the BSE-SW prion, a transmission study was conducted in cattle, which were inoculated intracerebrally with brain homogenate from BSE-SW-infected TgBoPrP mice. The disease incubation period was approximately 15 months...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28729694/paracrine-cyclooxygenase-2-activity-by-macrophages-drives-colorectal-adenoma-progression-in-the-apc-min-mouse-model-of-intestinal-tumorigenesis
#14
Mark A Hull, Richard J Cuthbert, C W Stanley Ko, Daniel J Scott, Elizabeth J Cartwright, Gillian Hawcroft, Sarah L Perry, Nicola Ingram, Ian M Carr, Alexander F Markham, Constanze Bonifer, P Louise Coletta
Genetic deletion or pharmacological inhibition of cyclooxygenase (COX)-2 abrogates intestinal adenoma development at early stages of colorectal carcinogenesis. COX-2 is localised to stromal cells (predominantly macrophages) in human and mouse intestinal adenomas. Therefore, we tested the hypothesis that paracrine Cox-2-mediated signalling from macrophages drives adenoma growth and progression in vivo in the Apc (Min/+) mouse model of intestinal tumorigenesis. Using a transgenic C57Bl/6 mouse model of Cox-2 over-expression driven by the chicken lysozyme locus (cLys-Cox-2), which directs integration site-independent, copy number-dependent transgene expression restricted to macrophages, we demonstrated that stromal macrophage Cox-2 in colorectal (but not small intestinal) adenomas from cLys-Cox-2 x Apc (Min/+) mice was associated with significantly increased tumour size (P = 0...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729622/three-dimensional-visualization-of-intrauterine-conceptus-through-the-uterine-wall-by-tissue-clearing-method
#15
Kyosuke Kagami, Yohei Shinmyo, Masanori Ono, Hiroshi Kawasaki, Hiroshi Fujiwara
Visualization of specific cells in the three-dimensional organ architecture is one of the key steps to develop our knowledge about pathophysiological mechanisms in various organs. In this study, we successfully obtained stereoscopic whole images of the intrauterine murine embryo and placenta through the uterus using a modified tissue clearing CUBIC method. By this procedure, we can recognize the three-dimensional relationships among various tissues within the pregnant uterus and analyze free-angle images of cross-sections with single-cell resolution using a computer system...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729247/adaptive-regulation-of-pancreatic-acinar-mitochondrial-thiamin-pyrophosphate-uptake-process-possible-involvement-of-epigenetic-mechanism-s
#16
Subrata Sabui, Veedamali S Subramanian, Rubina Kapadia, Hamid M Said
The essentiality of thiamin stems from its roles as a co-factor (mainly in the form of thiamin pyrophosphate, TPP) in critical metabolic reactions including oxidative energy metabolism and reduction of cellular oxidative stress. Like other mammalian cells, pancreatic acinar cells (PAC) obtain thiamin from their surroundings and convert it to TPP; mitochondria then take up TPP by a carrier-mediated process that involves the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the MTPP uptake process, but little is known about its possible adaptive-regulation...
July 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28729192/butyrylcholinesterase-knockout-reduces-fibrillar-%C3%AE-amyloid-and-conserves-18-fdg-retention-in-5xfad-mouse-model-of-alzheimer-s-disease
#17
D R DeBay, G A Reid, I R Macdonald, G Mawko, S Burrell, E Martin, C V Bowen, S Darvesh
Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia. One hallmark of the AD brain is the deposition of β-amyloid (Aβ) plaques. AD is also a state of cholinergic dysfunction and butyrylcholinesterase (BChE) associates with Aβ pathology. A transgenic mouse (5XFAD) is an aggressive amyloidosis model, producing Aβ plaques of which BChE also associates. A derived strain (5XFAD/BChE-KO), with the BChE gene knocked out, has significantly lower fibrillar Aβ than 5XFAD mice at the same age...
July 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28727987/associations-of-autoimmunity-immunodeficiency-lymphomagenesis-and-gut-microbiota-in-mice-with-knockins-for-a-pathogenic-autoantibody
#18
Shweta Jain, Jerrold M Ward, Dong-Mi Shin, Hongsheng Wang, Zohreh Naghashfar, Alexander L Kovalchuk, Herbert C Morse
A number of mouse strains transgenic for B-cell receptors specific for nucleic acids or other autoantigens have been generated to understand how autoreactive B cells are regulated in normal and autoimmune mice. Previous studies of nonautoimmune C57BL/6 mice heterozygous for both the IgH and IgL knockins of the polyreactive autoantibody, 564, produced high levels of autoantibodies in a largely Toll-like receptor 7-dependent manner. Herein, we describe studies of mice homozygous for the knockins that also expressed high levels of autoantibodies but, unlike the heterozygotes, exhibited a high incidence of mature B-cell lymphomas and enhanced susceptibility to bacterial infections...
July 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28727907/novel-role-of-surfactant-protein-a-in-bacterial-sinusitis
#19
George T Noutsios, Amanda L Willis, Julie G Ledford, Eugene H Chang
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disorder of the upper airway characterized by chronic inflammation and significant sinonasal remodeling. CRS is comprised of 2 major subgroups, based on whether polyps are present or absent. In some cases, it is characterized by colonization with opportunistic pathogens such as Pseudomonas aeruginosa (PA), Staphylococcus aureus, and other bacteria. The innate immune system of the sinonasal epithelium is the first line of defense against inhaled pathogens...
July 20, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28727179/overexpression-of-g%C3%AE-s-in-murine-osteoblasts-in-vivo-leads-to-increased-bone-mass-and-decreased-bone-quality
#20
Lucia Zhang, Kim S Sugamori, Colin Claridge, Ariana Dela Cruz, Marc D Grynpas, Jane Mitchell
GαS is a heterotrimeric G protein that transduces signals from activated G protein-coupled receptors on the cell surface to stimulate adenylyl cyclase/cyclic AMP signaling. GαS plays a central role in mediating numerous growth and maintenance processes including osteogenesis and bone turnover. Decreased GαS expression or activating mutations in GαS both affect bone suggesting that modulating GαS protein levels may be important for bone health and development. To examine the effects of increased osteoblastic GαS expression on bone development in vivo, we generated transgenic mice with GαS over-expression in osteoblasts (HOM-Gs mice) driven by the 3...
July 20, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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