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https://www.readbyqxmd.com/read/28918467/anisodamine-inhibits-endoplasmic-reticulum-stress-associated-txnip-nlrp3-inflammasome-activation-in-rhabdomyolysis-induced-acute-kidney-injury
#1
Xiaopeng Yuan, Yitao Zheng, Chuanbao Chen, Changxi Wang
Anisodamine protects against free radical-induced cellular damage. This study aimed to investigate the protective effect of anisodamine on rhabdomyolysis-induced acute kidney injury (RIAKI). C57BL/6 J mice, TXNIP(-/-) and NLRP3 (-/-) (both were C57BL/6 J background) mice were used to construct RIAKI model. Anisodamine administration was performed on RIAKI mice only. Mice were divided into control, TXNIP-KD (knock down), LNPR3-KD, and anisodamine group (n = 15 in each group). The renal injury, renal function, renal tubular cells apoptosis and expression of Caspase-1, ASC, endoplasmic reticulum (ER) stress markers IRE-1α, CHOP, and ATF4, and interleukin (IL-1α, IL-1β, and IL-18) were detected...
September 16, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28917158/quantitative-trait-locus-mapping-in-mice-identifies-phospholipase-pla2g12a-as-novel-atherosclerosis-modifier
#2
Alexandros Nicolaou, Bernd H Northoff, Kristina Sass, Jana Ernst, Alexander Kohlmaier, Knut Krohn, Christian Wolfrum, Daniel Teupser, Lesca M Holdt
BACKGROUND AND AIMS: In a previous work, a female-specific atherosclerosis risk locus on chromosome (Chr) 3 was identified in an intercross of atherosclerosis-resistant FVB and atherosclerosis-susceptible C57BL/6 (B6) mice on the LDL-receptor deficient (Ldlr(-/-)) background. It was the aim of the current study to identify causative genes at this locus. METHODS: We established a congenic mouse model, where FVB.Chr3(B6/B6) mice carried an 80 Mb interval of distal Chr3 on an otherwise FVB...
September 4, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28915221/metformin-exerts-beneficial-effects-in-hemorrhagic-shock-in-an-ampk%C3%AE-1-independent-manner
#3
Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Patrick Lahni, Basilia Zingarelli
Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified, with α1 subunit largely expressed in major organs. Here, we hypothesized that genetic deficiency of AMPKα1 worsens hemorrhage-induced multiple organ failure. We also investigated whether treatment with metformin, a clinically used drug for metabolic homeostasis, affords beneficial effects...
September 14, 2017: Shock
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#4
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28912160/dopamine-d2-receptors-modulate-pyramidal-neurons-in-mouse-medial-prefrontal-cortex-through-a-stimulatory-g-protein-pathway
#5
Sarah E Robinson, Vikaas S Sohal
Dopaminergic modulation of prefrontal cortex is believed to play key roles in many cognitive functions and to be disrupted in pathological conditions such as schizophrenia. We have previously described a phenomenon whereby dopamine D2 receptor (D2R) activation elicits afterdepolarizations (ADPs) in subcortically-projecting (SC) pyramidal neurons within L5 of the prefrontal cortex. These D2R-induced ADPs only occur following synaptic input which activates NMDA receptors (NMDARs) even when the delay between the synaptic input and afterdepolarizations is relatively long, e...
September 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28911214/growth-regulation-by-estrogen-in-breast-cancer-1-greb1-is-a-novel-progesterone-responsive-gene-required-for-human-endometrial-stromal-decidualization
#6
Alison J Camden, Maria M Szwarc, Sangappa B Chadchan, Francesco J DeMayo, Bert W O'Malley, John P Lydon, Ramakrishna Kommagani
STUDY QUESTION: Is Growth Regulation by Estrogen in Breast Cancer 1 (GREB1) required for progesterone-driven endometrial stromal cell decidualization? SUMMARY ANSWER: GREB1 is a novel progesterone-responsive gene required for progesterone-driven human endometrial stromal cell (HESC) decidualization. WHAT IS KNOWN ALREADY: Successful establishment of pregnancy requires HESCs to transform from fibroblastic to epithelioid cells in a process called decidualization...
September 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28903780/stat-6-signaling-pathway-and-not-interleukin-1-mediates-multi-walled-carbon-nanotube-induced-lung-fibrosis-in-mice-insights-from-an-adverse-outcome-pathway-framework
#7
Jake Nikota, Allyson Banville, Laura Rose Goodwin, Dongmei Wu, Andrew Williams, Carole Lynn Yauk, Håkan Wallin, Ulla Vogel, Sabina Halappanavar
BACKGROUND: The accumulation of MWCNTs in the lung environment leads to inflammation and the development of disease similar to pulmonary fibrosis in rodents. Adverse Outcome Pathways (AOPs) are a framework for defining and organizing the key events that comprise the biological changes leading to undesirable events. A putative AOP has been developed describing MWCNT-induced pulmonary fibrosis; inflammation and the subsequent healing response induced by inflammatory mechanisms have been implicated in disease progression...
September 13, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28902427/nlrp3-inflammasome-driven-liver-injury-and-fibrosis-roles-of-il-17-and-tnf
#8
Alexander Wree, Matthew D McGeough, Maria Eugenia Inzaugarat, Akiko Eguchi, Susanne Schuster, Casey D Johnson, Carla A Peña, Lukas J Geisler, Bettina G Papouchado, Hal M Hoffman, Ariel E Feldstein
The NLRP3 inflammasome, a caspase-1 activation platform plays a key role in the modulation of liver inflammation and fibrosis. Here, we tested the hypothesis that interleukin 17 (IL-17) and tumor necrosis factor (TNF) are key cytokines involved in amplifying and perpetuating the liver damage and fibrosis resulting from NLRP3 activation. To address this hypothesis gain of function Nlrp3(A350V) knock-in mice were bred onto il17a and Tnf knockout backgrounds allowing for constitutive Nlrp3 activation in myeloid derived cells in mice deficient in IL-17 or TNF...
September 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28901722/%C3%AE-6-subunit-containing-nicotinic-receptors-mediate-low-dose-ethanol-effects-on-ventral-tegmental-area-neurons-and-ethanol-reward
#9
Scott C Steffensen, Samuel I Shin, Ashley C Nelson, Stephanie S Pistorius, Stephanie B Williams, Taylor J Woodward, Hyun Jung Park, Lindsey Friend, Ming Gao, Fenfei Gao, Devin H Taylor, M Foster Olive, Jeffrey G Edwards, Sterling N Sudweeks, Lori M Buhlman, J Michael McIntosh, Jie Wu
Dopamine (DA) neuron excitability is regulated by inhibitory GABAergic synaptic transmission and modulated by nicotinic acetylcholine receptors (nAChRs). The aim of this study was to evaluate the role of α6 subunit-containing nAChRs (α6*-nAChRs) in acute ethanol effects on ventral tegmental area (VTA) GABA and DA neurons. α6*-nAChRs were visualized on GABA terminals on VTA GABA neurons, and α6*-nAChR transcripts were expressed in most DA neurons, but only a minority of VTA GABA neurons from GAD67 GFP mice...
September 13, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28900386/altered-developmental-expression-of-the-astrocyte-secreted-factors-hevin-and-sparc-in-the-fragile-x-mouse-model
#10
Jessica Wallingford, Angela L Scott, Kelly Rodrigues, Laurie C Doering
Astrocyte dysfunction has been indicated in many neurodevelopmental disorders, including Fragile X Syndrome (FXS). FXS is caused by a deficiency in fragile X mental retardation protein (FMRP). FMRP regulates the translation of numerous mRNAs and its loss disturbs the composition of proteins important for dendritic spine and synapse development. Here, we investigated whether the astrocyte-derived factors hevin and SPARC, known to regulate excitatory synapse development, have altered expression in FXS. Specifically, we analyzed the expression of these factors in wild-type (WT) mice and in fragile X mental retardation 1 (Fmr1) knock-out (KO) mice that lack FMRP expression...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28894266/generation-of-a-new-mouse-model-of-glaucoma-characterized-by-reduced-expression-of-the-ap-2%C3%AE-and-ap-2%C3%AE-proteins
#11
Maria Monica Barzago, Mami Kurosaki, Maddalena Fratelli, Marco Bolis, Chiara Giudice, Laura Nordio, Elisa Cerri, Luciano Domenici, Mineko Terao, Enrico Garattini
We generated 6 transgenic lines with insertion of an expression plasmid for the R883/M xanthine dehydrogenase (XDH) mutant protein. Approximately 20% of the animals deriving from one of the transgenic lines show ocular abnormalities and an increase in intra-ocular pressure which are consistent with glaucoma. The observed pathologic phenotype is not due to expression of the transgene, but rather the consequence of the transgene insertion site, which has been defined by genome sequencing. The insertion site maps to chromosome 1qA3 in close proximity to the loci encoding AP-2β and AP-2δ, two proteins expressed in the eye...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893927/mutant-huntingtin-inhibits-%C3%AE-b-crystallin-expression-and-impairs-exosome-secretion-from-astrocytes
#12
Yan Hong, Ting Zhao, Xiao-Jiang Li, Shihua Li
In the brain, astrocytes secrete diverse substances that regulate neuronal function and viability. Exosomes, which are vesicles produced through the formation of multivesicular bodies and their subsequent fusion with the plasma membrane, are also released from astrocytes via exocytotic secretion. Astrocytic exosomes carry heat shock proteins that can reduce the cellular toxicity of misfolded proteins and prevent neurodegeneration. Although mutant huntingtin (mHtt) affects multiple functions of astrocytes, it remains unknown whether mHtt impairs the production of exosomes from astrocytes...
September 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28893538/indispensable-role-of-lipoprotein-bound-apoe-in-adipogenesis-and-endocytosis-induced-by-postprandial-trl
#13
Mingyu Zhang, Yanhong Li, Xuehong Wei, Feng Tian, Fan Ouyang, Shuiping Zhao, Ling Liu
Diet-associated obesity is coexisted with postprandial hypertriglyceridemia that indicates increased number of triglyceride-rich lipoproteins (TRL). This study aimed to investigate the effect of postprandial TRL-bound apolipoprotein E (ApoE) on adipogenesis and potential mechanisms. 3T3-L1 cells were cultured with (i) human TRL (h-TRL) with or without insulin, or (ii) TRL from wild type mice (WT-TRL) or ApoE knock-out mice (EKO-TRL) and insulin. The differentiating adipocytes were incubated with different kinds of TRL labeled by red fluorescence and confocal microscopy was performed...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28888922/microrna-20a-participates-in-the-aerobic-exercise-based-prevention-of-coronary-artery-disease-by-targeting-pten
#14
Dongwei Wang, Yi Wang, Juan Ma, Wenping Wang, Bingbing Sun, Tengfei Zheng, Ming Wei, Yangli Sun
BACKGROUND: Exercise can reduce the coronary artery disease (CAD) incidence. MiRNA-20a has been reported to distinctly expressed after sustain physical activity. However, its expression and regulation pattern in CAD model with or without exercise has not been reported. OBJECTIVE: In present study, we aim to investigate regulatory mechanism of miR-20a in exercise-associated reduced-CAD incidence and miR-20a-dependent signaling pathways. METHODS: Eight weeks old male ApoE/LDLR double knock out mice were recruited for this study...
September 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28888577/crispr-knock-out-ctla-4-enhances-the-anti-tumor-activity-of-cytotoxic-t-lymphocytes
#15
Long Shi, Tongyu Meng, Zhilong Zhao, Jinsheng Han, Wei Zhang, Fei Gao, Jianhui Cai
T cell-mediated anti-tumor immunity plays a pivotal role in cancer immune surveillance. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a protein receptor mainly expressed in activated T cells and regulatory T cells. CTLA-4 competes with CD28 for ligand binding and generates inhibitory signals to attenuate T cell activation. The blockade of CTLA-4 mediated immune inhibitory checkpoint has been associated with enhanced anti-tumor immunity. In this study, we use CRISPR-Cas9 system to knock out (KO) CTLA-4 from cytotoxic T lymphocytes (CTLs) and evaluate its effect on the anti-tumor activity of the CTLs...
September 6, 2017: Gene
https://www.readbyqxmd.com/read/28887652/disruption-of-adenylyl-cyclase-type-5-mimics-exercise-training
#16
John J Guers, Jie Zhang, Sara C Campbell, Marko Oydanich, Dorothy E Vatner, Stephen F Vatner
Exercise training is key to healthful longevity. Since exercise training compliance is difficult, it would be useful to have a therapeutic substitute that mimicked exercise training. We compared the effects of exercise training in wild-type (WT) littermates with adenylyl cyclase type 5 knock out (AC5 KO) mice, a model of enhanced exercise performance. Exercise performance, measured by maximal distance and work to exhaustion, was increased in exercise-trained WT to levels already attained in untrained AC5 KO...
September 8, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28887630/ncb5or-deficiency-in-the-cerebellum-and-midbrain-leads-to-dehydration-and-alterations-in-thirst-response-fasted-feeding-behavior-and-voluntary-exercise-in-mice
#17
Matthew A Stroh, Michelle K Winter, Kenneth E McCarson, John P Thyfault, Hao Zhu
Cytosolic NADH-cytochrome-b5-oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues. We have previously reported that global ablation of NCB5OR in mice results in early-onset lean diabetes with decreased serum leptin levels and increased metabolic and feeding activities. The conditional deletion of NCB5OR in the mouse cerebellum and midbrain (conditional knock out, CKO mice) results in local iron dyshomeostasis and altered locomotor activity. It has been established that lesion to or removal of the cerebellum leads to changes in nutrient organization, visceral response, feeding behavior, and body weight...
September 8, 2017: Cerebellum
https://www.readbyqxmd.com/read/28887197/reduction-in-open-field-activity-in-the-absence-of-memory-deficits-in-the-app-nl-g-f-knock-in-mouse-model-of-alzheimer-s-disease
#18
Lauren S Whyte, Kim M Hemsley, Adeline A Lau, Sofia Hassiotis, Takashi Saito, Takaomi C Saido, John J Hopwood, Timothy J Sargeant
The recent development of knock-in mouse models of Alzheimer's disease provides distinct advantages over traditional transgenic mouse models that rely on over-expression of amyloid precursor protein. Two such knock-in models that have recently been widely adopted by Alzheimer's researchers are the App(NL-F) and App(NL-G-F) mice. This study aimed to further characterise the behavioural phenotype and amyloid plaque distribution of App(NL-G-F/NL-G-F) (C57BL/6J background) mice at six-months of age. An attempt to replicate a previous study that observed deficits in working memory in the Y-maze, showed no difference between App(NL-G-F/NL-G-F) and wild-type mice...
September 5, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28887018/dpp9-enzyme-activity-controls-survival-of-mouse-migratory-tongue-muscle-progenitors-and-its-absence-leads-to-neonatal-lethality-due-to-suckling-defect
#19
Munkyung Kim, Maryline Minoux, Alessandro Piaia, Benjamin Kueng, Berangere Gapp, Delphine Weber, Corinne Haller, Samuel Barbieri, Kenji Namoto, Thorsten Lorenz, Johann Wirsching, Frederic Bassilana, William Dietrich, Filippo M Rijli, Iwona Ksiazek
Dipeptidyl peptidase 9 (DPP9) is an intracellular N-terminal post-proline-cleaving enzyme whose physiological function remains largely unknown. We investigated the role of DPP9 enzyme in vivo by characterizing knock-in mice expressing a catalytically inactive mutant form of DPP9 (S729A; DPP9(ki/ki) mice). We show that DPP9(ki/ki) mice die within 12-18hours after birth. The neonatal lethality can be rescued by manual feeding, indicating that a suckling defect is the primary cause of neonatal lethality. The suckling defect results from microglossia, and is characterized by abnormal formation of intrinsic muscles at the distal tongue...
September 5, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28886971/traf6-a-player-in-cvb3-induced-myocarditis
#20
Oana N Ursu, Tina Beyer, Martina Sauter, Annunziata Fragasso, Sandra Bundschuh, Karin Klingel, Barbara Munz
Coxsackievirus B3 (CVB3) is an important inducer of myocarditis, which, in susceptible individuals, can chronify and eventually lead to the development of dilated cardiomyopathy and heart failure. The respective mechanisms are not completely understood. Here, we analyzed expression of the TRAF6 gene, encoding TNF receptor-associated factor 6 (TRAF6), a signal transduction scaffold protein that acts downstream of cytokine receptors, in heart tissue of susceptible and non-susceptible mouse strains. We found that after infection, TRAF6 expression was upregulated in both non-susceptible C57BL/6 wildtype and susceptible A...
September 5, 2017: Cytokine
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