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https://www.readbyqxmd.com/read/27927007/ginsenoside-re-inhibits-osteoclast-differentiation-in-mouse-bone-marrow-derived-macrophages-and-zebrafish-scale-model
#1
Chan-Mi Park, Hye-Min Kim, Dong Hyun Kim, Ho-Jin Han, Haneul Noh, Jae-Hyuk Jang, Soo-Hyun Park, Han-Jung Chae, Soo-Wan Chae, Eun Kyoung Ryu, Sangku Lee, Kangdong Liu, Haidan Liu, Jong-Seog Ahn, Young Ock Kim, Bo-Yeon Kim, Nak-Kyun Soung
Ginsenosides, which are the active materials of ginseng, have biological functions that include anti-osteoporotic effects. Aqueous ginseng extract inhibits osteoclast differentiation induced by receptor activator of NF-kappaB ligand (RANKL). Aqueous ginseng extract produces chromatography peaks characteristic of ginsenosides. Among these peaks, ginsenoside Re is a major component. However, the preventive effects of ginsenoside Re against osteoclast differentiation are not known. We studied the effect of ginsenoside Re on osteoclast differentiation, RANKL induced tartrate-resistant acid phosphatase (TRAP) activity, and formation of multinucleated osteoclasts in vitro...
December 6, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27926996/small-molecule-modulator-of-sigma-2-receptor-is-neuroprotective-and-reduces-cognitive-deficits-and-neuro-inflammation-in-experimental-models-of-alzheimer-s-disease
#2
Bitna Yi, James J Sahn, Pooneh Memar Ardestani, Andrew K Evans, Luisa Scott, Jessica Z Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan Pierce-Shimomura, Stephen F Martin, Mehrdad Shamloo
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R binding ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease (AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca(2+) levels in human SK-N-SH neuroblastoma cells. The Sig2R antagonists SAS-0132 and JVW-1009 are neuroprotective in a C...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926992/inherited-diseases-caused-by-mutations-in-cathepsin-protease-genes
#3
REVIEW
Stephanie Ketterer, Alejandro Gomez-Auli, Larissa E Hillebrand, Agnese Petrera, Anett Ketscher, Thomas Reinheckel
Lysosomal cathepsins are proteolytic enzymes increasingly recognized as prognostic markers and potential therapeutic targets in a variety of diseases. In those conditions the cathepsins are mostly overexpressed, thereby driving the respective pathogenic processes. Although less known, there are also diseases with a genetic deficiency of cathepsins. In fact, nowadays six out of the fifteen human proteases called "cathepsins" have been linked to inherited syndromes. However, only three of these syndromes are typical lysosomal storage diseases, while the others are apparently caused by defective cleavage of specific protein substrates...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926989/targeting-gm-csf-in-epithelial-and-vascular-remodeling-in-experimental-eosinophilic-esophagitis
#4
Eóin N McNamee, Kathryn A Biette, Juliet Hammer, Rachel Harris, Heather Miyazawa, James J Lee, Glenn T Furuta, Joanne C Masterson
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated clinicopathologic disease of the esophagus characterized by an eosinophil-predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting GM-CSF (an agonist cytokine linked with eosinophil survival and activation) would be protective in a pre-clinical model of EoE...
December 7, 2016: Allergy
https://www.readbyqxmd.com/read/27926984/involvement-of-chemokine-cxcl11-in-the-development-of-morphine-tolerance-in-rats-with-cancer-induced-bone-pain
#5
Genhua Guo, Yawen Peng, Bingrui Xiong, Daiqiang Liu, Huilian Bu, Xuebi Tian, Hui Yang, Zhen Wu, Fei Cao, Feng Gao
Morphine is viewed as one of the classical treatments for intractable pain, but its role is limited by side effects, including analgesic tolerance. A few chemokines have been reported to be engaged in the mechanisms of morphine tolerance. However, the exact roles of CXCL11 in chronic morphine tolerance remain unknown. In this study, Walker 256 mammary gland carcinoma cells were inoculated into the tibia of rats to provoke cancer-induced bone pain (CIBP). Then morphine was intrathecally administered twice daily for 7 consecutive days to induce drug tolerance...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926982/trpv4-channels-mediate-na-k-cl-co-transporter-induced-brain-edema-after-traumatic-brain-injury
#6
Kwok-Tung Lu, Tai-Chun Huang, Ya-Hsin Tsai, Yi-Ling Yang
Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) plays an important role in traumatic brain injury (TBI)-induced brain edema via the mitogen-activated protein kinases (MAPK) cascade. The transient receptor potential vanilloid type 4 (TRPV4) channel participates in neurogenic inflammation, pain transmission and edema. In this study, we investigated the relationship between NKCC1 and TRPV4 and the related signaling pathways in TBI-induced brain edema and neuronal damage. TBI was induced by the calibrated weight-drop device...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926980/role-and-regulation-of-p27-in-neuronal-apoptosis
#7
Surbhi Jaiswal, Pushkar Sharma
It is necessary for the cell cycle machinery of neurons to be suppressed to promote differentiation and maintenance of their terminally differentiated state. Reactivation of the cell cycle in response to neurotoxic insults leads to neuronal cell death and some cell cycle related proteins contribute to the process. p27 kip1 (p27), an inhibitor of Cyclin Dependent Kinases (CDKs), prevents unwarranted CDK activation. In the present study, we have elucidated a novel mechanism via which p27 promotes apoptosis of neurons stimulated by neurotoxic amyloid peptide Aβ42 (Amyloid β1-42 peptide)...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926978/potential-blood-biomarkers-in-chronic-spontaneous-urticaria
#8
Pavel Kolkhir, Fiona Andre, Martin K Church, Marcus Maurer, Martin Metz
BACKGROUND: Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is defined as the recurrence of wheals, angioedema, or both for >6 weeks due to known or unknown causes. As of yet, disease diagnosis is purely clinical. Objective tools are needed to monitor the activity of CSU and the efficacy of treatment. Recently, several reports have suggested that blood parameters may be considered as potential disease-related biomarkers. OBJECTIVE: To review available literature on blood biomarkers for CSU diagnosis, activity monitoring, duration, patient subgroups allocation or response to treatment...
December 7, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27926950/c6-and-c7-substituted-3-4-dihydro-2-1h-quinolinones-as-inhibitors-of-monoamine-oxidase
#9
L Meiring, J Petzer, A Petzer
Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform...
December 7, 2016: Drug Research
https://www.readbyqxmd.com/read/27926948/intrinsic-subtype-switching-and-acquired-erbb2-her2-amplifications-and-mutations-in-breast-cancer-brain-metastases
#10
Nolan Priedigkeit, Ryan J Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J Watters, Roby Thomas, Jose P Leone, Peter C Lucas, Rohit Bhargava, Ronald L Hamilton, Juliann Chmielecki, Shannon L Puhalla, Nancy E Davidson, Steffi Oesterreich, Adam M Brufsky, Leonie Young, Adrian V Lee
Importance: Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies. Objective: To determine whether there are intrinsic subtype differences between primary tumors and matched BrM and to uncover BrM-acquired alterations that are clinically actionable. Design, Setting, and Participants: In total, 20 cases of primary breast cancer tissue and resected BrM (10 estrogen receptor [ER]-negative and 10 ER-positive) from 2 academic institutions were included...
December 7, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27926947/correction-cd40-activation-rescues-antiviral-cd8-t-cells-from-pd-1-mediated-exhaustion
#11
Masanori Isogawa, Josan Chung, Yasuhiro Murata, Kazuhiro Kakimi, Francis V Chisari
[This corrects the article DOI: 10.1371/journal.ppat.1003490.].
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926943/the-mouse-cytomegalovirus-gene-m42-targets-surface-expression-of-the-protein-tyrosine-phosphatase-cd45-in-infected-macrophages
#12
Nadine Thiel, Kirsten A Keyser, Niels A W Lemmermann, Jennifer D Oduro, Karen Wagner, Carina Elsner, Anne Halenius, Tihana Lenac Roviš, Melanie M Brinkmann, Stipan Jonjić, Luka Cicin-Sain, Martin Messerle
The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926939/a-bystander-mechanism-explains-the-specific-phenotype-of-a-broadly-expressed-misfolded-protein
#13
Lauren Klabonski, Ji Zha, Lakshana Senthilkumar, Tali Gidalevitz
Misfolded proteins in transgenic models of conformational diseases interfere with proteostasis machinery and compromise the function of many structurally and functionally unrelated metastable proteins. This collateral damage to cellular proteins has been termed 'bystander' mechanism. How a single misfolded protein overwhelms the proteostasis, and how broadly-expressed mutant proteins cause cell type-selective phenotypes in disease are open questions. We tested the gain-of-function mechanism of a R37C folding mutation in an endogenous IGF-like C...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27926936/scaling-properties-of-dimensionality-reduction-for-neural-populations-and-network-models
#14
Ryan C Williamson, Benjamin R Cowley, Ashok Litwin-Kumar, Brent Doiron, Adam Kohn, Matthew A Smith, Byron M Yu
Recent studies have applied dimensionality reduction methods to understand how the multi-dimensional structure of neural population activity gives rise to brain function. It is unclear, however, how the results obtained from dimensionality reduction generalize to recordings with larger numbers of neurons and trials or how these results relate to the underlying network structure. We address these questions by applying factor analysis to recordings in the visual cortex of non-human primates and to spiking network models that self-generate irregular activity through a balance of excitation and inhibition...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#15
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926929/functional-and-evolutionary-analyses-identify-proteolysis-as-a-general-mechanism-for-nlrp1-inflammasome-activation
#16
Joseph Chavarría-Smith, Patrick S Mitchell, Alvin M Ho, Matthew D Daugherty, Russell E Vance
Inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the Caspase-1 protease. Human NLRP1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. Recently, specific variants of mouse and rat NLRP1 were found to be activated upon N-terminal cleavage by the anthrax lethal factor protease. However, agonists for other NLRP1 variants, including human NLRP1, are not known, and it remains unclear if they are also activated by proteolysis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926914/comorbidities-in-turkish-patients-with-rheumatoid-arthritis-association-with-the-health-related-quality-of-life-in-terms-of-disease-activity-functional-and-radiological-status-severity-of-pain-and-social-and-emotional-functioning
#17
Yesim Garip, Filiz Eser, Hatice Bodur
AIMS: The aim of our study was to investigate the comorbidities in Turkish RA patients and evaluate the impact of comorbidities on health-related quality of life (HRQoL) in terms of disease activity, functional and radiological status, severity of pain, and social and emotional functioning. METHODS: In a cross-sectional setting, a total of 160 RA patients who were admitted to our outpatient clinic between December 2013 and February 2014 were consecutively enrolled in the study...
November 23, 2016: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/27926890/physical-activity-exercise-and-diabetes-a-position-statement-of-the-american-diabetes-association
#18
REVIEW
Sheri R Colberg, Ronald J Sigal, Jane E Yardley, Michael C Riddell, David W Dunstan, Paddy C Dempsey, Edward S Horton, Kristin Castorino, Deborah F Tate
No abstract text is available yet for this article.
November 2016: Diabetes Care
https://www.readbyqxmd.com/read/27926879/in%C3%A2-vitro-derivation-and-propagation-of-spermatogonial-stem-cell-activity-from-mouse-pluripotent-stem-cells
#19
Yukiko Ishikura, Yukihiro Yabuta, Hiroshi Ohta, Katsuhiko Hayashi, Tomonori Nakamura, Ikuhiro Okamoto, Takuya Yamamoto, Kazuki Kurimoto, Kenjiro Shirane, Hiroyuki Sasaki, Mitinori Saitou
The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells (PSCs) is a key goal in reproductive science. We show here that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells (PGCLCs) induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and are expandable as cells that resemble germline stem cells (GSCs), a primary cell line with SSC activity. Remarkably, GSC-like cells (GSCLCs), but not PGCLCs, colonize adult testes and, albeit less effectively than GSCs, contribute to spermatogenesis and fertile offspring...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926878/the-csk-associated-adaptor-pag-inhibits-effector-t-cell-activation-in-cooperation-with-phosphatase-ptpn22-and-dok-adaptors
#20
Dominique Davidson, Ming-Chao Zhong, Pier Paolo Pandolfi, Silvia Bolland, Ramnik J Xavier, Brian Seed, Xin Li, Hua Gu, André Veillette
The transmembrane adaptor PAG (Cbp) has been proposed to mediate membrane recruitment of Csk, a cytoplasmic protein tyrosine kinase playing a critical inhibitory role during T cell activation, by inactivating membrane-associated Src kinases. However, this model has not been validated by genetic evidence. Here, we demonstrate that PAG-deficient mice display enhanced T cell activation responses in effector, but not in naive, T cells. PAG-deficient mice also have augmented T cell-dependent autoimmunity and greater resistance to T cell anergy...
December 6, 2016: Cell Reports
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