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https://www.readbyqxmd.com/read/28726298/faah-but-not-magl-inhibition-modulates-acute-tlr3-induced-neuroimmune-signaling-in-the-rat-independent-of-sex
#1
Lisa E Flannery, Rebecca J Henry, Daniel M Kerr, David P Finn, Michelle Roche
Toll-like receptor (TLR)3 is a key component of the innate immune response to viral infection. The present study firstly examined whether sex differences exist in TLR3-induced inflammatory, endocrine, and sickness responses. The data revealed that TLR3-induced expression of interferon- or NFkB-inducible genes (IFN-α/β, IP-10, or TNF-α), either peripherally (spleen) or centrally (hypothalamus), did not differ between male and female rats, with the exception of TLR3-induced IFN-α expression in the spleen of female, but not male, rats 8 hr post TLR3 activation...
July 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28724427/curcumin-the-spicy-modulator-of-breast-carcinogenesis
#2
REVIEW
Urmila Banik, Subramani Parasuraman, Arun Kumar Adhikary, Nor Hayati Othman
Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose...
July 19, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28710771/detailed-longitudinal-sampling-of-glioma-stem-cells-in-situ-reveals-chr7-gain-and-chr10-loss-as-repeated-events-in-primary-tumor-formation-and-recurrence
#3
Mehmet Baysan, Kevin Woolard, Margaret C Cam, Wei Zhang, Hua Song, Svetlana Kotliarova, Demosthenes Balamatsias, Amanda Linkous, Susie Ahn, Jennifer Walling, Galina I Belova, Howard A Fine
Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation as well as in response to therapeutic intervention, can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, as well as from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence...
July 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28710019/effects-of-human-blood-levels-of-two-pah-mixtures-on-the-ahr-signalling-activation-pathway-and-cyp1a1-and-comt-target-genes-in-granulosa-non-tumor-and-granulosa-tumor-cell-lines
#4
Karolina Zajda, Anna Ptak, Agnieszka Rak, Elżbieta Fiedor, Adam Grochowalski, Tomasz Milewicz, Ewa L Gregoraszczuk
Epidemiological studies have shown a link between problems with offspring of couples living in a contaminated environment in comparison to those who live in an uncontaminated environment. We measured the concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs) in maternal and cord blood. To explore the mechanism of the effects of PAH mixtures on nonluteinized granulosa cells (HGrC1) and granulosa tumor cells (COV434), as well as cell proliferation and apoptosis, we investigated the effect of PAH mixtures on the expression of the aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and aryl hydrocarbon receptor repressor (AHRR) genes, as well as the expression and activity of target genes cytochrome P450 1A1 (CYP1A1) and catechol-O-methyltransferase (COMT)...
July 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28706608/the-effects-of-melilotus-officinalis-extract-on-expression-of-daxx-nfkb-and-vegf-genes-in-the-streptozotocin-induced-rat-model-of-sporadic-alzheimer-s-disease
#5
Niloofar Bazazzadegan, Marzieh Dehghan Shasaltaneh, Kioomars Saliminejad, Koorosh Kamali, Mehdi Banan, Hamid Reza Khorram Khorshid
BACKGROUND: Possible mechanisms of Alzheimer Disease (AD) such as inflammation and oxidative stresses in the brain led us to investigate potential AD therapeutics of Melilotus officinalis, an herbal extract, with possible role as an anti-inflammatory and anti-oxidant agent. Among different genes which had important role in Sporadic AD (SAD), three genes including DAXX, NFkB and VEGF have shown significant statistical diversity in the brains of Alzheimer patients. METHODS: These genes were chosen to be investigated for neuroprotective effects of the extract by comparing the expression level in the hippocampus of Sporadic AD (SAD) rat model using quantitative polymerase chain reaction (qPCR) in the treated and untreated groups...
July 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28706254/mir-30a-targets-il-1%C3%AE-and-regulates-islet-functions-as-an-inflammation-buffer-and-response-factor
#6
Xin Jiang, Chenke Xu, Fan Lei, Meijian Liao, Wei Wang, Naihan Xu, Yaou Zhang, Weidong Xie
Diabetes is an inflammatory disease. Inflammation plays an important role in islet functions. However, the exact mechanisms by which inflammation affects islet functions remain unclear. In this study, we investigated the regulatory effects of miR-30a on inflammation and islet functions. The results indicate that miR-30a serves as an inflammation-resolving buffer factor by targeting interleukin 1a (IL-1α) in immune cells and in islet cells, which might play an important role in inflammation homeostasis. miR-30a ameliorates islet functions in an inflammatory micro-environment by targeting the IL-1α/nuclear factor kappa B (NFKB) p65 subunit (p65)/p62 (SQSTM1)/insulin axis, which can be developed into a novel antidiabetic approach...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28699667/mantle-cell-lymphoma-2017-update-on-diagnosis-risk-stratification-and-clinical-management
#7
Julie M Vose
DISEASE OVERVIEW: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4-5 years. DIAGNOSIS: Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1...
August 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28698398/tnfr-tnf-%C3%AE-signaling-pathway-regulates-apoptosis-of-alveolar-macrophages-in-coal-workers-pneumoconiosis
#8
Qing-Zeng Qian, Xiang-Ke Cao, Hai-Yan Liu, Guo-Ying Zheng, Qing-Qiang Qian, Fu-Hai Shen
We explored the role of TNFR/TNF-α signalingin apoptosis among alveolar macrophages (AM) and its relevance to the development of coal workers' pneumoconiosis (CWP). Purified alveolar macrophages (AMs) were prepared from bronchoalveolar lavage fluid harvested from 366 CWP patients and 120 healthy subjects enrolled inthe study. The purified AMs were then divided into control, SOD, anti-TNFR, TNFR and NFkB inhibitor groups and analyzed for apoptosis usingflow cytometry (sub-diploid peak) and western blotting (Bcl-2, Caspase-3 and Caspase-8 expression)...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28687617/proinflammatory-cxcl12-cxcr4-cxcr7-signaling-axis-drives-myc-induced-prostate-cancer-in-obese-mice
#9
Achinto Saha, Songyeon Ahn, Jorge Blando, Fei Su, Mikhail G Kolonin, John DiGiovanni
Obesity is a prognostic risk factor in the progression of prostate cancer (PCa), however, the molecular mechanisms involved are unclear. In this study, we provide preclinical proof of concept for the role of a pro-inflammatory CXCL12-CXCR4/CXCR7 signaling axis in an obesity-driven mouse model of HiMyc prostate cancer. Analysis of the stromal vascular fraction (SVF) from periprostatic white adipose tissue (ppWAT) from obese HiMyc mice at 6 months of age revealed a dramatic increase in mRNAs encoding various chemokines, cytokines, growth factors and angiogenesis mediators, with CXCL12 among the most significantly upregulated genes...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28685617/aerobic-exercise-prevents-rarefaction-of-pial-collaterals-and-increased-stroke-severity-that-occur-with-aging
#10
Wojciech Rzechorzek, Hua Zhang, Brian K Buckley, Kunjie Hua, Daniel Pomp, James E Faber
Variation in extent of the brain's collateral circulation is an important determinant of variation in the severity of stroke and efficacy of revascularization therapies. However, the number and diameter of pial collateral "arterioles" decrease with aging in associated with reduced eNOS and increased oxidative stress. We tested whether exercise reduces this aging-induced rarefaction. Twelve-month-old mice were randomized to sedentary or voluntary wheel-running. At 26 months' age, permanent MCA occlusion was followed 72 h later by determination of infarct volume and vascular casting after maximal dilation...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28663582/bet-protein-proteolysis-targeting-chimera-protac-exerts-potent-lethal-activity-against-mantle-cell-lymphoma-cells
#11
B Sun, W Fiskus, Y Qian, K Rajapakshe, K Raina, K G Coleman, A P Crew, A Shen, D T Saenz, C P Mill, A J Nowak, N Jain, L Zhang, M Wang, J D Khoury, C Coarfa, C M Crews, K N Bhalla
Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and NFkB target genes, which undermines the growth and survival of MCL cells. However, BETi treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4, which potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells...
June 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28662157/sex-dependent-aortic-valve-pathology-in-patients-with-rheumatic-heart-disease
#12
Feng Xiao, Rui Zheng, Di Yang, Kejiang Cao, Shijiang Zhang, Bingruo Wu, Yongfeng Shao, Bin Zhou
BACKGROUND: Rheumatic heart disease is an autoimmune disease caused by group A streptococci infection and frequently affects the aortic valve. Sex differences are common in the disease progression, treatment, and outcome. However, little is known about the sex differences in the pathology of aortic valves in rheumatic heart disease. DESIGN: We studied the end-stage calcific aortic valves from male versus female patients to reveal the sex-dependent pathology differences and molecular changes associated with requiring valve replacement...
2017: PloS One
https://www.readbyqxmd.com/read/28654673/double-hit-of-nemo-gene-in-preeclampsia
#13
Agata Sakowicz, Tadeusz Pietrucha, Magda Rybak-Krzyszkowska, Hubert Huras, Agnieszka Gach, Bartosz Sakowicz, Mateusz Banaszczyk, Mariusz Grzesiak, Lidia Biesiada
The precise etiology of preeclampsia is unknown. Family studies indicate that both genetic and environmental factors influence its development. One of these factors is NFkB, whose activation depends on NEMO (NFkB essential modulator. This is the first study to investigate the association between the existence of single nucleotide variant of the NEMO gene and the appearance of preeclampsia. A total of 151 women (72 preeclamptic women and 79 controls) and their children were examined. Sanger sequencing was performed to identify variants in the NEMO gene in the preeclamptic mothers...
2017: PloS One
https://www.readbyqxmd.com/read/28653353/preclinical-evaluation-of-the-bet-bromodomain-inhibitor-bay-1238097-for-the-treatment-of-lymphoma
#14
Elena Bernasconi, Eugenio Gaudio, Pascale Lejeune, Chiara Tarantelli, Luciano Cascione, Ivo Kwee, Filippo Spriano, Andrea Rinaldi, Afua A Mensah, Elaine Chung, Anastasios Stathis, Stephan Siegel, Norbert Schmees, Matthias Ocker, Emanuele Zucca, Bernard Haendler, Francesco Bertoni
The epigenome is often deregulated in cancer and treatment with inhibitors of bromodomain and extra-terminal proteins, the readers of epigenetic acetylation marks, represents a novel therapeutic approach. Here, we have characterized the anti-tumour activity of the novel bromodomain and extra-terminal (BET) inhibitor BAY 1238097 in preclinical lymphoma models. BAY 1238097 showed anti-proliferative activity in a large panel of lymphoma-derived cell lines, with a median 50% inhibitory concentration between 70 and 208 nmol/l...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28650102/endocrine-influence-on-neuroinflammation-the-use-of-reporter-systems
#15
REVIEW
Nicoletta Rizzi, Alessandro Villa, Valeria Benedusi, Electra Brunialti, Nicoletta Cesari, Paolo Ciana, Adriana Maggi
Most of the ageing-associated pathologies are coupled with a strong inflammatory component that accelerates the progress of the physio-pathological functional decline related to ageing. The currently available pharmacological tools for the control of neuroinflammation present several side effects which restrict their application, particularly in chronic disorders. The discovery of the potential anti-inflammatory action exerted by endogenous estrogens and that activation of ERα results in a significant decrease of inflammation at the cellular level and in models of inflammatory diseases, prompted us to embark in a series of studies aimed at the generation of reporter systems allowing to i...
June 26, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28634361/uridine-ameliorates-dextran-sulfate-sodium-dss-induced-colitis-in-mice
#16
Manish Kumar Jeengar, Dinesh Thummuri, Mattias Magnusson, V G M Naidu, Srinivas Uppugunduri
Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621668/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#17
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28617818/proteome-profiling-in-il-1%C3%AE-and-vegf-activated-human-umbilical-vein-endothelial-cells-delineates-the-interlink-between-inflammation-and-angiogenesis
#18
Thomas Mohr, Verena Haudek-Prinz, Astrid Slany, Johannes Grillari, Michael Micksche, Christopher Gerner
Endothelial cells represent major effectors in inflammation and angiogenesis, processes that drive a multitude of pathological states such as atherosclerosis and cancer. Both inflammation and angiogenesis are interconnected with each other in the sense that many pro-inflammatory proteins possess proangiogenic properties and vice versa. To elucidate this interplay further, we present a comparative proteome study of inflammatory and angiogenic activated endothelial cells. HUVEC were stimulated with interleukin 1-β and VEGF, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28585218/lipotoxicity-in-obesity-benefit-of-olive-oil
#19
Saad Elias, Sbeit Wisam, Arraf Luai, Barhoum Massad, Assy Nimer
The clinical implication of Lipotoxicity in obesity derives primarily from its potential to progress to insulin resistance, endothelial dysfunction and atherosclerosis. Olive oil rich diet decrease accumulation of triglyceride in the liver, improved postprandial triglyceride levels, improve glucose and GLP-1 response in insulin resistant subjects, and up regulate GLUT-2 expression in the liver. The exact molecular mechanism is unknown but, decreasing NFkB activation, decreasing LDL oxidation and improving insulin resistance by less production of inflammatory cytokines (TNF-a, IL-6) and improvement of kinases JNK-mediated phosphorylation of IRS-1 are the principle mechanisms...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28578651/immunomodulatory-effect-of-g2013-a-l-guluronic-acid-on-thetlr2-and-tlr4-in-human-mononuclear-cells
#20
Laleh Sharifi, Monireh Mohsenzadegan, Asghar Aghamohammadi, Nima Rezaei, Farzaneh Tofighi Zavareh, Saied Bokaie, Mona Moshiri, Gholamreza Azizi, Abbas Mirshafiey, Zahra Aghazadeh
BACKGROUND: Inhibition of Toll-like receptors (TLRs) signaling have been established as a new method for development of anti-inflammatory drugs instead of NSAIDs (non-steroid anti-inflammatory drugs). Since the immunomodulatory role of G2013 was reported in some recent experiments, we decided to assess the effects of G2013 (a-L-Guluronic acid) on the protein expression of TLR2 and TLR4, their downstream signaling cascade, and the secretion of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs)...
June 4, 2017: Current Drug Discovery Technologies
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