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Yuko Fujiwara, Marilina Piemontese, Yu Liu, Jeff D Thostenson, Jinhu Xiong, Charles A O'Brien
The cytokine receptor activator of NFkB ligand (RANKL) produced by osteocytes is essential for osteoclast formation in cancellous bone under physiological conditions and RANKL production by B lymphocytes is required for the bone loss caused by estrogen deficiency. Here, we examined whether RANKL produced by osteocytes is also required for the bone loss caused by estrogen deficiency. Mice lacking RANKL in osteocytes were protected from the increase in osteoclast number and the bone loss caused by ovariectomy...
October 12, 2016: Journal of Biological Chemistry
S N Cox, F Pesce, J S El-Sayed Moustafa, F Sallustio, G Serino, C Kkoufou, A Giampetruzzi, N Ancona, M Falchi, F P Schena
BACKGROUND: IgA nephropathy (IgAN) is a common complex disease with a strong genetic involvement. We aimed to identify novel, rare, highly penetrant risk variants combining family-based linkage analysis with whole-exome sequencing (WES). METHODS: Linkage analysis of 16 kindreds of South Italian ancestry was performed using an 'affected-only' strategy. Eight most informative trios composed of two familial cases and an intrafamilial control were selected for WES. High-priority variants in linked regions were identified and validated using Sanger sequencing...
October 11, 2016: Journal of Internal Medicine
Silvia Torices, Antonio Julia, Pedro Muñoz, Ignacio Varela, Alejandro Balsa, Sara Marsal, Antonio Fernández-Nebro, Francisco Blanco, Marcos López-Hoyos, Víctor Martinez-Taboada, Jose L Fernández-Luna
BACKGROUND: Toll-like receptor (TLR) family members are key players in inflammation. TLR10 has been poorly studied in chronic inflammatory disorders, and its clinical relevance in rheumatoid arthritis (RA) is as yet unknown. We aimed at identifying TLR10 variants within all coding regions of the gene in patients with RA as well as studying their functional and clinical significance. METHODS: TLR10 gene variants were studied by performing sequencing of 66 patients with RA and 30 control subjects...
October 4, 2016: Arthritis Research & Therapy
Mohamed Salah I Abaza, Mohammad Afzal, Raja'a J Al-Attiyah, Radhika Guleri
BACKGROUND: Natural products are valuable sources for anticancer agents. In the present study, methylferulate (MF) was identified for the first time from Tamarix aucheriana. Spectral data were used for identification of MF. The potential of MF to control cell growth, cell cycle, apoptosis, generation of reactive oxygen species (ROS), cancer cell invasion, nuclear factor kappa B (NFkB) DNA-binding activity and proteasomal activities, as well as the enhancement of chemosensitivity in human colorectal cancer cells, were evaluated...
October 1, 2016: BMC Complementary and Alternative Medicine
Ahmet Topal, Muhammed Atamanalp, Ertan Oruç, Hüseyin Serkan Erol
We investigated changes in nuclear factor kappa B (NFkB) activity, antioxidant responses and histopathological effects in the liver, gill and kidney tissues of rainbow trout exposed to nickel chloride (Ni). Two different concentrations (1 mg/L and 2 mg/L) were administrated to fish for 21 days. Tissues were taken from all fish for NFkB activity, histopathological examination and determination of superoxide dismutase (SOD), catalase (CAT) enzyme activity and of lipid peroxidation (LPO), and glutathione (GSH) levels...
January 2017: Chemosphere
Lincy Edatt, K Haritha, T V Sruthi, P Aswini, V B Sameer Kumar
MMP9 is a member of the family of zinc-containing endopeptidases which degrade various components of the extracellular matrix, thereby regulating matrix remodeling. Since matrix remodeling plays an important role during growth and progression of cancer and considering the fact that, tumor cells switch to aerobic glycolysis as its major energy source, this study was designed to analyze if partial inhibition of glycolysis (the major energy pathway during hypoxia) can be used as a means to control matrix remodeling in terms of MMP9 activity and expression...
October 4, 2016: Molecular and Cellular Biochemistry
Jordan Kardos, Shengjie Chai, Lisle E Mose, Sara R Selitsky, Bhavani Krishnan, Ryoichi Saito, Michael D Iglesia, Matthew I Milowsky, Joel S Parker, William Y Kim, Benjamin G Vincent
We report the discovery of a claudin-low molecular subtype of high-grade bladder cancer that shares characteristics with the homonymous subtype of breast cancer. Claudin-low bladder tumors were enriched for multiple genetic features including increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased frequency of PPARG amplification. While claudin-low tumors showed the highest expression of immune gene signatures, they also demonstrated gene expression patterns consistent with those observed in active immunosuppression...
March 17, 2016: JCI Insight
David Chiron, Céline Bellanger, Antonin Papin, Benoit Tessoulin, Christelle Dousset, Sophie Maiga, Anne Moreau, Julie Esbelin, Valérie Trichet, Selina Chen-Kiang, Philippe Moreau, Cyrille Touzeau, Steven Le Gouill, Martine Amiot, Catherine Pellat-Deceunynck
Mantle cell lymphoma (MCL) accumulates in lymphoid organs but disseminates early on in extranodal tissues. Although proliferation remains located in lymphoid organs only, suggesting a major role of the tumor ecosystem, few studies have assessed MCL microenvironment. We therefore cocultured primary circulating MCL cells from 21 patients several weeks ex vivo with stromal or lymphoid-like (CD40L) cells to determine which interactions could support their proliferation. We showed that coculture with lymphoid-like cells, but not stromal cells, induced cell-cycle progression, which was amplified by MCL-specific cytokines (IGF-1, BAFF, IL-6, IL-10)...
October 3, 2016: Blood
Bakri M Assas, Scott Levison, Matthew Little, Hazel England, Laura Battrick, James Bagnall, John McLaughlin, Pawel Paszek, Kathryn J Else, Joanne L Pennock
Infliximab (IFX) has been used repeatedly in mouse pre-clinical models with associated claims that anti-inflammatory effects are due to inhibition of mouse TNFα. However the mechanism of action in mice remains unclear. In this study, the binding specificity of IFX for mouse TNFα was investigated ex vivo using ELISA, flow cytometry and western blot. IFX did not bind directly to soluble or membrane-bound mouse TNFα nor did it have any effect on TNFα-induced NfKb stimulation in mouse fibroblasts. The efficacy of IFX treatment was then investigated in vivo using a TNFα independent T...
September 26, 2016: Clinical and Experimental Immunology
Archita Das, Varadarajan Sudhahar, Gin-Fu Chen, Ha Won Kim, Seock-Won Youn, Lydia Finney, Stefan Vogt, Jay Yang, Junghun Kweon, Bayasgalan Surenkhuu, Masuko Ushio-Fukai, Tohru Fukai
Copper (Cu), an essential nutrient, promotes wound healing, however, target of Cu action and underlying mechanisms remain elusive. Cu chaperone Antioxidant-1 (Atox1) in the cytosol supplies Cu to the secretory enzymes such as lysyl oxidase (LOX), while Atox1 in the nucleus functions as a Cu-dependent transcription factor. Using mouse cutaneous wound healing model, here we show that Cu content (by X-ray Fluorescence Microscopy) and nuclear Atox1 are increased after wounding, and that wound healing with and without Cu treatment is impaired in Atox1(-/-) mice...
September 26, 2016: Scientific Reports
Claire Hoenen, Audrey Gustin, Cindy Birck, Mélanie Kirchmeyer, Nicolas Beaume, Paul Felten, Luc Grandbarbe, Paul Heuschling, Tony Heurtaux
Parkinson's disease (PD) is histologically described by the deposition of α-synuclein, whose accumulation in Lewy bodies causes dopaminergic neuronal death. Although most of PD cases are sporadic, point mutations of the gene encoding the α-synuclein protein cause inherited forms of PD. There are currently six known point mutations that result in familial PD. Oxidative stress and neuroinflammation have also been described as early events associated with dopaminergic neuronal degeneration in PD. Though it is known that microglia are activated by wild-type α-synuclein, little is known about its mutated forms and the signaling cascades responsible for this microglial activation...
2016: PloS One
Helena Ågerstam, Nils Hansen, Sofia von Palffy, Carl Sandén, Kristian Reckzeh, Christine Karlsson, Henrik Lilljebjörn, Niklas Landberg, Maria Askmyr, Carl Högberg, Marianne Rissler, Kimmo Porkka, Hans Wadenvik, Satu Mustjoki, Johan Richter, Marcus Järås, Thoas Fioretos
Chronic myeloid leukemia (CML) is currently treated with tyrosine kinase inhibitors but these do not effectively eliminate the CML stem cells. As a consequence, CML stem cells persist and cause relapse in most patients upon drug discontinuation. Furthermore, no effective therapy exists for the advanced stages of the disease. IL1RAP (IL1R3) is a co-receptor of IL1R1 and has been found upregulated on CML stem cells. Here we show that primitive (CD34(+)CD38(-)) CML cells, in contrast to corresponding normal cells, express a functional IL1 receptor complex and respond with NFKB activation and marked proliferation in response to IL1...
September 12, 2016: Blood
Erdal Karaoz, Pınar Cetinalp Demircan, Gülay Erman, Eda Güngörürler, Ayla Eker Sarıboyacı
: Objective; Mesenchymal Stem Cells (MSCs), which they posses the immune suppressive characteristics on induced T-cells, were shown to be applicable in prevention and treatment of Graft versus Host Disease. However, the knowledge on effective cell source is still limited. In this study, MSCs from different human tissues, i.e. bone marrow (BM), wharton's jelly (WJ) and adipose tissue (AT), were isolated, and the immune-suppression of induced T-cells was aimed to analyze comparatively. MATERIALS AND METHODS: MSCs were co-cultured with phytohemaglutinin (PHA)-induced T-cells with co-culture techniques with and without cell-to-cell contact...
September 9, 2016: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
L Kamrani Moghaddam, S Ramezani Paschepari, M A Zaimy, A Abdalaian, A Jebali
The aim of this study was to investigate the effect of hexagonal selenium nanoparticles modified by SiRNA (HSNM-SiRNA) to inhibit epidermal growth factor receptor (EGFR) signaling in Human non-small-cell lung cancer (NSCLC). After synthesis, HSNM-SiRNA and HSNs were separately exposed to NSCLC cell lines (A549, H1299, H520, and H1975), and incubated for 6 h at 37 °C. Next, the expression of NFKB, MYC, STAT, ELK1, and GAPDH was evaluated by western blot and real-time PCR. The percentage of apoptotic cells and cell cycle progression were measured when exposed to HSNM-SiRNA and HSNs...
September 2016: Cancer Gene Therapy
Débora Guerini Souza, Bruna Bellaver, Larissa Daniele Bobermin, Diogo Onofre Souza, André Quincozes-Santos
Guanosine, a guanine-based purine, has been shown to exert beneficial roles in in vitro and in vivo injury models of neural cells. Guanosine is released from astrocytes and modulates important astroglial functions, including glutamatergic metabolism, antioxidant, and anti-inflammatory activities. Astrocytes are crucial for regulating the neurotransmitter system and synaptic information processes, ionic homeostasis, energy metabolism, antioxidant defenses, and the inflammatory response. Aging is a natural process that induces numerous changes in the astrocyte functionality...
September 1, 2016: Purinergic Signalling
Cui Yang, Zhengtao Li, Saimei Yan, Yonghui He, Rong Dai, George Pek-Heng Leung, Shitian Pan, Jinyan Yang, Rong Yan, Guanhua Du
BACKGROUND AND PURPOSE: Vascular inflammation is a major factor contributing to the development of vascular diseases. The aim of this study was to investigate the role of α3-containing nicotinic acetylcholine receptors subtype (α3-nAChRs) in vascular inflammation. EXPERIMENTAL APPROACH: Vascular inflammation was studied in the apolipoprotein E knock-out (ApoE(-/-) ) mice fed with a high-fat diet. Inflammatory markers were detected in mouse aortic endothelial cells (MAECs) and macrophages after α3-nAChRs were antagonized pharmacologically or after the gene of α3-nAChRs was silenced...
August 29, 2016: British Journal of Pharmacology
Julian Biau, Emmanuel Chautard, Frank Court, Bruno Pereira, Pierre Verrelle, Flavien Devun, Leanne De Koning, Marie Dutreix
Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a xenograft model beforehand. We studied a selection of 89 protein markers of interest in 14 human cell cultures and respective subcutaneous xenografts using the reverse-phase protein array technology...
August 2016: Translational Oncology
Andressa Cristina Antunes Santos, Carolina Argondizo Correia, Dalila Cunha de Oliveira, Amanda Nogueira-Pedro, Primavera Borelli, Ricardo Ambrosio Fock
Protein malnutrition (PM) is a major public health problem in developing countries, affecting the inflammatory response and increasing susceptibility to opportunistic infections. For this reason, an adequate nutritional intervention can improve the quality of life of patients. Glutamine (GLN) is a nonessential amino acid, but can be considered "conditionally essential" for macrophage function in stress situations, in which it plays a role in the improvement of the inflammatory response. Concerning this issue, in the current study, it was of interest to evaluate some biological aspects of peritoneal cells from a protein malnutrition (PM) mouse model challenged with lipopolysaccharide (LPS) and treated intravenously with GLN...
August 26, 2016: Inflammation
Muskan Gupta, Gurcharan Kaur
BACKGROUND: Microglial-mediated neuroinflammation is a key factor underlying the pathogenesis of various neurodegenerative diseases and also an important target for the development of the neuroinflammation-targeted therapeutics. Conventionally, the nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed, but they are associated with long-term potential risks. Natural products are the cornerstone of modern therapeutics, and Ashwagandha is one such plant which is well known for its immunomodulatory properties in Ayurveda...
2016: Journal of Neuroinflammation
Genna R Prather, James A MacLean, Mingxin Shi, Daniel K Boadu, Marilène Paquet, Kanako Hayashi
Endometriosis causes severe chronic pelvic pain and infertility. Because the standard medication and surgical treatments of endometriosis show high recurrence of symptoms, it is necessary to improve current treatment options. In the initial study, we examined whether niclosamide can be a useful drug for endometriosis in a preclinical setting. Endometriotic implants were induced using an established mouse model involving transimplantation of mouse endometrial fragments to the peritoneal wall of recipient mice...
August 17, 2016: Biology of Reproduction
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