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https://www.readbyqxmd.com/read/28820907/positive-regulatory-interactions-between-yap-and-hedgehog-signalling-in-skin-homeostasis-and-bcc-development-in-mouse-skin-in-vivo
#1
Bassem Akladios, Veronica Mendoza Reinoso, Jason E Cain, Taopeng Wang, Duncan L Lambie, D Neil Watkins, Annemiek Beverdam
Skin is a highly plastic tissue that undergoes tissue turnover throughout life, but also in response to injury. YAP and Hedgehog signalling play a central role in the control of epidermal stem/progenitor cells in the skin during embryonic development, in postnatal tissue homeostasis and in skin carcinogenesis. However, the genetic contexts in which they act to control tissue homeostasis remain mostly unresolved. We provide compelling evidence that epidermal YAP and Hedgehog/GLI2 signalling undergo positive regulatory interactions in the control of normal epidermal homeostasis and in basal cell carcinoma (BCC) development, which in the large majority of cases is caused by aberrant Hedgehog signalling activity...
2017: PloS One
https://www.readbyqxmd.com/read/28820136/protective-effect-of-val129-prp-against-bovine-spongiform-encephalopathy-but-not-variant-creutzfeldt-jakob-disease
#2
Natalia Fernández-Borges, Juan Carlos Espinosa, Alba Marín-Moreno, Patricia Aguilar-Calvo, Emmanuel A Asante, Tetsuyuki Kitamoto, Shirou Mohri, Olivier Andréoletti, Juan María Torres
Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met129) or valine (Val129) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met129 Hu-PrP...
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28819903/inhibition-of-pten-attenuates-endoplasmic-reticulum-stress-and-apoptosis-via-activation-of-pi3k-akt-pathway-in-alzheimer-s-disease
#3
Weigang Cui, Songtao Wang, Zhongping Wang, Zhiyong Wang, Chunli Sun, Yinghua Zhang
Amyloid plaques and neurofibrillary tangles are pathologic hallmarks of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been implicated in the loss of neurons in AD. The phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in regulating neuronal survival processes. However, the direct effects of the PTEN on ER stress and apoptosis in AD have not been elucidated. In this study, we demonstrate that the expression of PTEN and ER stress related proteins, GRP78 and CHOP, increased in APP/PS1 transgenic AD mice compared with WT mice...
August 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28819706/generation-of-a-functional-humanized-delta-like-ligand-4-transgenic-mouse-model
#4
John Wiseman, Pernilla Gregersson, Johan Johansson, Kerstin Magnell, Fernanda Pilataxi, Chris Morehouse, Philip Brohawn, Nicholas Holoweckyj, Patrick Strout, Song Cho
Humanized mouse models are important tools in many areas of biological drug development including, within oncology research, the development of antagonistic antibodies that have the potential to block tumor growth by controlling vascularization and are key to the generation of in vivo proof-of-concept efficacy data. However, due to cross reactivity between human antibodies and mouse target such studies regularly require mouse models expressing only the human version of the target molecule. Such humanized knock-in/knock-out, KIKO, models are dependent upon the generation of homozygous mice expressing only the human molecule, compensating for loss of the mouse form...
August 17, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28819375/bone-marrow-derived-mesenchymal-stem-cells-involve-in-the-lymphangiogenesis-of-lung-cancer-and-jinfukang-inhibits-the-involvement-in-vivo
#5
Xian-Mei Zhou, Dan Wang, Hai-Lang He, Jie Tang, Jing Wu, Ling Xu, Jian-Xin Li
Lymphangiogenesis plays an important role in cancer metastasis. Bone marrow-derived mesenchymal stem cells (BMMSCs) migrate to the site of tumorigenesis and in turn promote the metastasis. However, whether BMMSCs involve in the lymphangiogenesis of lung cancer is unclear. Jinfukang has clinically been used for the treatment of non small cell lung cancer (NSCLC) in China. In this study, to investigate the involvement of BMMSCs in lymphangiogenesis in lung cancer, and evaluate the inhibitory effect of Jinfukang on the lymphangiogenesis, chimeric mice were prepared by transplanting bone marrow from green fluorescent protein (GFP) transgenic mice (C57BL/6-EGFP) into irradiated C57BL/6 mice...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818856/deletion-of-nf-%C3%AE%C2%BAb-rela-in-angiotensin-ii-sensitive-mesenchymal-cells-blocks-aortic-vascular-inflammation-and-abdominal-aortic-aneurysm-formation
#6
Talha Ijaz, Hong Sun, Irina V Pinchuk, Dianna M Milewicz, Ronald G Tilton, Allan R Brasier
OBJECTIVE: Infusion of angiotensin II (Ang II) induces extracellular matrix remodeling and inflammation resulting in abdominal aortic aneurysms (AAAs) in normolipidemic mice. Although Ang II activates mesenchymal cells in the media and adventitia to become fibrogenic, the sentinel role of this mesenchymal population in modulating the inflammatory response and aneurysms is not known. We test the hypothesis that these fibrogenic mesenchymal cells play a critical role in Ang II-induced aortic wall vascular inflammation and AAA formation...
August 17, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28818566/a-synthetic-human-cytomegalovirus-pp65-ie1-fusion-antigen-efficiently-induces-and-expands-virus-specific-t-cells
#7
Ellen K Link, Christine Brandmüller, Yasemin Suezer, Stefanie Ameres, Asisa Volz, Andreas Moosmann, Gerd Sutter, Michael H Lehmann
Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA...
August 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28817668/titanium-biomaterials-with-complex-surfaces-induced-aberrant-peripheral-circadian-rhythms-in-bone-marrow-mesenchymal-stromal-cells
#8
Nathaniel Hassan, Kirstin McCarville, Kenzo Morinaga, Cristiane M Mengatto, Peter Langfelder, Akishige Hokugo, Yu Tahara, Christopher S Colwell, Ichiro Nishimura
Circadian rhythms maintain a high level of homeostasis through internal feed-forward and -backward regulation by core molecules. In this study, we report the highly unusual peripheral circadian rhythm of bone marrow mesenchymal stromal cells (BMSCs) induced by titanium-based biomaterials with complex surface modifications (Ti biomaterial) commonly used for dental and orthopedic implants. When cultured on Ti biomaterials, human BMSCs suppressed circadian PER1 expression patterns, while NPAS2 was uniquely upregulated...
2017: PloS One
https://www.readbyqxmd.com/read/28816082/zeaxanthin-dipalmitate-alleviates-hepatic-injury-induced-by-superimposed-chronic-hepatitis-b-and-non-alcoholic-steatohepatitis-in-non-obese-mice
#9
Jing-Jing Li, Hao Gao, Yi Lv, Mian-Huan Li, Chao-Ran Ren, Kwok-Fai So, Jia Xiao
A hepatitis B virus (HBV) transgenic mice model was used to establish the fatty liver superimposed model by feeding the methionine choline-deficient (MCD) diet for 8 weeks, with or without the gavage of 2 mg/kg zeaxanthin dipalmitate (ZD) three times per week. Both wild-type and HBV transgenic mice, with MCD diet, gained typical non-obese non-alcoholic steatohepatitis (NASH) and HBV symptoms. Coadministration with ZD exhibited evident therapeutic effects through alleviating those pathological events. Moreover, long-term vehicle-ZD treatment was found to be safe...
September 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28815933/an-%C3%AE-iib-%C3%AE-3-antagonist-prevents-thrombosis-without-causing-fc%C3%AE-riia-mediated-thrombocytopenia
#10
Yu-Ju Kuo, Ying-Ru Chen, Chun-Chieh Hsu, Hui-Chin Peng, Tur-Fu Huang
BACKGROUND: Thrombocytopenia, a common side effect of Arg-Gly-Asp (RGD)-mimetic antiplatelet drugs, is associated with drug-dependent antibodies (DDAbs) that recognize conformation-altered integrin αIIb β3 . OBJECTIVE: To explore the correlation between αIIb β3 binding epitopes and induction of DDAb binding to conformation-altered αIIb β3 , we examined whether two purified disintegrins TMV-2 and TMV-7 with distinct binding motifs that have different effects on induction of αIIb β3 conformational change and platelet aggregation in the presence of AP2, an IgG1 inhibitory monoclonal antibody (mAb) raised against αIIb β3 ...
August 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28815695/a-distinctive-histidine-residue-is-essential-for-in-vivo-glycation-inactivation-of-human-cd59-transgenically-expressed-in-mice-erythrocytes-implications-for-human-diabetes-complications
#11
Rupam Sahoo, Pamela Ghosh, Michael Chorev, Jose A Halperin
Clinical and experimental evidences support a link between the complement system and the pathogenesis of diabetes complications. CD59, an extracellular cell membrane-anchored protein, inhibits formation of the membrane attack complex (MAC), the main effector of complement-mediated tissue damage. This complement regulatory activity of human CD59 (hCD59) is inhibited by hyperglycemia-induced ε-amino glycation of Lys(41) . Biochemical and structural analyses of glycated proteins with known three-dimensional structure revealed that glycation of ε-amino lysyl residues occurs predominantly at "glycation motives" that include lysyl/lysyl pairs or proximity of a histidyl residue, in which the imidazolyl moiety is ≈ 5Å from the ε-amino group...
August 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28815470/alterations-in-scai-expression-during-cell-plasticity-fibrosis-and-cancer
#12
Ákos Gasparics, Gábor Kökény, Attila Fintha, Rita Bencs, Miklós M Mózes, Emese Irma Ágoston, Anna Buday, Zoltán Ivics, Péter Hamar, Balázs Győrffy, László Rosivall, Attila Sebe
Suppressor of cancer cell invasion (SCAI) has been originally characterized as a tumor suppressor inhibiting metastasis in different human cancer cells, and it has been suggested that SCAI expression declines in tumors. The expression patterns and role of SCAI during physiological and pathophysiological processes is still poorly understood. Earlier we demonstrated that SCAI is regulating the epithelial-mesenchymal transition of proximal tubular epithelial cells, it is downregulated during renal fibrosis and it is overexpressed in Wilms' tumors...
August 16, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28814671/antifibrotic-role-of-vascular-endothelial-growth-factor-in-pulmonary-fibrosis
#13
Lynne A Murray, David M Habiel, Miriam Hohmann, Ana Camelo, Huilan Shang, Yang Zhou, Ana Lucia Coelho, Xueyan Peng, Mridu Gulati, Bruno Crestani, Matthew A Sleeman, Tomas Mustelin, Meagan W Moore, Changwan Ryu, Awo D Osafo-Addo, Jack A Elias, Chun G Lee, Buqu Hu, Jose D Herazo-Maya, Darryl A Knight, Cory M Hogaboam, Erica L Herzog
The chronic progressive decline in lung function observed in idiopathic pulmonary fibrosis (IPF) appears to result from persistent nonresolving injury to the epithelium, impaired restitution of the epithelial barrier in the lung, and enhanced fibroblast activation. Thus, understanding these key mechanisms and pathways modulating both is essential to greater understanding of IPF pathogenesis. We examined the association of VEGF with the IPF disease state and preclinical models in vivo and in vitro. Tissue and circulating levels of VEGF were significantly reduced in patients with IPF, particularly in those with a rapidly progressive phenotype, compared with healthy controls...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814429/nintedanib-macrophage-activation-and-ameliorates-vascular-and-fibrotic-manifestations-in-the-fra2-mouse-model-of-systemic-sclerosis
#14
Jingang Huang, Christiane Maier, Yun Zhang, Alina Soare, Clara Dees, Christian Beyer, Ulrike Harre, Chih-Wei Chen, Oliver Distler, Georg Schett, Lutz Wollin, Jörg H W Distler
BACKGROUND: Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to analyse the effects of nintedanib in the fos-related antigen-2 (Fra2) mouse model of systemic sclerosis (SSc). METHODS: The effects of nintedanib on pulmonary arterial hypertension with proliferation of pulmonary vascular smooth muscle cells (PVSMCs) and luminal occlusion, on microvascular disease with apoptosis of microvascular endothelial cells (MVECs) and on fibroblast activation with myofibroblast differentiation and accumulation of extracellular matrix were analysed...
August 16, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28814342/septal-contributions-to-olfactory-bulb-interneuron-diversity-in-the-embryonic-mouse-telencephalon-role-of-the-homeobox-gene-gsx2
#15
Shenyue Qin, Stephanie M Ware, Ronald R Waclaw, Kenneth Campbell
BACKGROUND: Olfactory bulb (OB) interneurons are known to represent diverse neuronal subtypes, which are thought to originate from a number of telencephalic regions including the embryonic dorsal lateral ganglionic eminence (dLGE) and septum. These cells migrate rostrally toward the OB, where they then radially migrate to populate different OB layers including the granule cell layer (GCL) and the outer glomerular layer (GL). Although previous studies have attempted to investigate regional contributions to OB interneuron diversity, few genetic tools have been used to address this question at embryonic time points when the earliest populations are specified...
August 16, 2017: Neural Development
https://www.readbyqxmd.com/read/28814066/mice-expressing-human-erap1-variants-associated-with-ankylosing-spondylitis-have-altered-t-cell-repertoires-and-nk-cell-functions-as-well-as-increased-in-utero-and-perinatal-mortality
#16
David P W Rastall, Fadel S Alyaquob, Patrick O'Connell, Yuliya Pepelyayeva, Douglas Peters, Sarah Godbehere-Roosa, Cristiane Pereira-Hicks, Yasser A Aldhamen, Andrea Amalfitano
Specific variants of endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) identified by genome-wide association study modify the risk for developing ankylosing spondylitis. We previously confirmed that disease-associated ERAP1 variants have altered enzymatic abilities that can impact upon the production of pro-inflammatory cytokines from cells expressing the same ERAP1 variants. To determine if these ERAP1 variants also impacted immune responses in vivo, we generated two strains of transgenic mice expressing human ERAP1 genes containing non-synonymous single-nucleotide polymorphisms associated with an increased (ERAP1-High) or decreased (ERAP1-Low) risk for developing autoimmune disease...
June 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28813718/transgenic-mice-over-expressing-rbp4-have-rbp4-dependent-and-light-independent-retinal-degeneration
#17
Mei Du, Eric Phelps, Michael J Balangue, Aaron Dockins, Gennadiy Moiseyev, Younghwa Shin, Shelley Kane, Laura Otalora, Jian-Xing Ma, Rafal Farjo, Krysten M Farjo
Purpose: Transgenic mice overexpressing serum retinol-binding protein (RBP4-Tg) develop progressive retinal degeneration, characterized by microglia activation, yet the precise mechanisms underlying retinal degeneration are unclear. Previous studies showed RBP4-Tg mice have normal ocular retinoid levels, suggesting that degeneration is independent of the retinoid visual cycle or light exposure. The present study addresses whether retinal degeneration is light-dependent and RBP4-dependent by testing the effects of dark-rearing and pharmacological lowering of serum RBP4 levels, respectively...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28812046/extra-virgin-olive-oil-ameliorates-cognition-and-neuropathology-of-the-3xtg-mice-role-of-autophagy
#18
Elisabetta Lauretti, Luigi Iuliano, Domenico Praticò
OBJECTIVE: Consumption of extra virgin olive oil (EVOO), a major component of the Mediterranean diet, has been associated with reduced incidence of Alzheimer's disease (AD). However, the mechanisms involved in this protective action remain to be fully elucidated. METHODS: Herein, we investigated the effect of daily consumption of EVOO on the AD-like phenotype of a mouse mode of the disease with plaques and tangles. RESULTS: Triple transgenic mice (3xTg) received either regular chow or a chow diet supplemented with EVOO starting at 6 months of age for 6 months, then assessed for the effect of the diet on the AD-like neuropathology and behavioral changes...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28811745/inhibition-of-inflammation-mediated-through-the-tumor-necrosis-factor-%C3%AE-biochemical-pathway-can-lead-to-favorable-outcomes-in-alzheimer-disease
#19
REVIEW
Daniah Shamim, Michael Laskowski
Tumor necrosis factor α (TNF-α) inhibitors have long been used as disease-modifying agents in immune disorders. Recently, research has shown a role of chronic neuroinflammation in the pathophysiology of neurodegenerative diseases such as Alzheimer disease, and interest has been generated in the use of anti-TNF agents and TNF-modulating agents for prevention and treatment. This article extensively reviewed literature on animal studies testing these agents. The results showed a role for direct and indirect TNF-α inhibition through agents such as thalidomide, 3,6-dithiothalidomide, etanercept, infliximab, exendin-4, sodium hydrosulfide, minocycline, imipramine, and atorvastatin...
2017: Journal of Central Nervous System Disease
https://www.readbyqxmd.com/read/28811640/a-reciprocal-interaction-between-%C3%AE-catenin-and-osterix-in-cementogenesis
#20
Hwajung Choi, Tak-Heun Kim, Siqin Yang, Jeong-Chae Lee, Hyung-Keun You, Eui-Sic Cho
Although accumulating evidence indicates that both β-catenin and osterix (Osx) are essential for bone and tooth development, few studies have investigated the interaction of these two key proteins in the context of cementogenesis. In this study, we used transgenic mice with constitutively active β-catenin and inactive Osx in the dental mesenchyme to address this question. We found that cementoblasts with constitutively active β-catenin require Osx to produce excessive cellular cementum, and that ablation of Osx prevents this abnormal accumulation...
August 15, 2017: Scientific Reports
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