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https://www.readbyqxmd.com/read/28732081/il-6-variant-is-associated-with-metastasis-in-breast-cancer-patients
#1
Chike O Abana, Brian S Bingham, Ju Hwan Cho, Amy J Graves, Tatsuki Koyama, Robert T Pilarski, A Bapsi Chakravarthy, Fen Xia
INTRODUCTION: Although tumor metastases remain significant drivers of mortality, the genetic factors that increase the risks of metastases are not fully identified. Interleukin 6 (IL-6) has emerged as an important factor in breast cancer progression with IL-6 single nucleotide polymorphism (SNP) variants shown to affect survival. We hypothesized that SNPs of the IL-6 promoter at rs1800795 in breast cancer patients are associated with distant metastases. METHODS: We performed an initial case-control study using Vanderbilt University Medical Center's BioVU, a genomic biobank linked to de-identified electronic medical records in the Synthetic Derivative database, to identify germline SNPs that may predict the development of metastatic disease to any site from any solid tumor including breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#2
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28730733/the-potential-impact-of-radix-paeoniae-alba-in-embryonic-development-of-mice
#3
Wei Xu, Ling Xu, Bin Deng, Jing Leng, Nong Tang, Li Chun Zhao, Hong Hai Zhou, Zhong Zhen Zhao, Zhi Jun Yang, Ting Ting Xiao, Xiao Ying Tian, Alan H M Ho, Nickie W K Chan, Yeuk Lung Chow, Chi Yi Chow, Min Xu
Although Radix Paeoniae Alba (RPA) has been ranked as one of the top 6 herbs used frequently to prevent and treat miscarriages clinically, there is no clear evidence regarding its safety in embryonic development. This study aims to evaluate the potential impacts of RPA on embryonic stem cells (ESCs) and pregnant mice. Cytotoxicity assays of the extract were performed in ESCs and 3T3 cells. Pregnant ICR mice were orally treated with RPA extracts at dosages of 0 (G1 group as negative controls), 2, 8 and 32 g/kg/day (G2, G3 and G4 groups) respectively from the gestation day (Gd) 6-15...
July 21, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28730511/intermediate-molecular-mass-hyaluronan-and-cd44-receptor-interactions-enhance-neutrophil-phagocytosis-and-il-8-production-via-p38-and-erk1-2-mapk-signalling-pathways
#4
Cheng-Hsun Lu, Chia-Huei Lin, Ko-Jen Li, Chieh-Yu Shen, Cheng-Han Wu, Yu-Min Kuo, Ting-Syuan Lin, Chia-Li Yu, Song-Chou Hsieh
CD44 is a common leukocyte adhesion molecule expressed on the surface of various cells. Hyaluronan (HA), the natural ligand of CD44, is a simple repeated disaccharide with variable molecular mass that is widely distributed on cell surfaces and the connective tissue matrix. The binding of small molecular mass HA (SMM-HA, MW < 80 kDa) to CD44 on immune-related cells elicits cell proliferation, differentiation, and cytokine production. However, the effects and molecular basis of intermediate molecular mass HA (IMM-HA, MW ≈ 500 kDa)-CD44 interactions on polymorphonuclear neutrophil (PMN) functions have not been elucidated...
July 20, 2017: Inflammation
https://www.readbyqxmd.com/read/28730071/effect-of-sorafenib-in-a-murine-high-risk-penetrating-keratoplasty-model
#5
Yang Kyung Cho, Eun Young Shin, Hironori Uehara, Balamurali K Ambati
AIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subconjunctival injection in mice that underwent high risk penetrating keratoplasty (HRPK). Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28729914/effects-of-mtor-on-neurological-deficits-after-transient-global-ischemia
#6
Jihong Xing, Jian Lu
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR and its downstream products to brain injuries and neurological deficiencies after cardiac arrest (CA) induced-transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Our results showed that expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in CA rats compared to their controls...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28728858/-dress-complicated-by-hemophagocytic-lymphohistiocytosis-in-an-infant-treated-for-congenital-toxoplasmosis
#7
S Rioualen, J Dufau, C Flatres, P Lavenant, L Misery, J-M Roué
BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe disease that may be complicated by hemophagocytic lymphohistiocytosis but this is rarely described in children. PATIENTS AND METHODS: We report the case of a 5-week old infant hospitalized in a pediatric intensive care unit for hemophagocytic lymphohistiocytosis with prolonged fever, splenomegaly, cytopenia, fibrinogen≤1.5g/L, ferritin≥500μg/L, and soluble IL-2 receptor≥2400U/mL...
July 17, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/28728856/achaete-scute-complex-homologue-2-accelerates-the-development-of-sj%C3%A3-gren-s-syndrome-like-disease-in-the-nod-shiltj-mouse
#8
Sung-Min Kim, Jeong-Eun Kwon, Jin-Sil Park, Hyeon-Beom Seo, Kyung-Ah Jung, Young-Mee Moon, Jennifer Lee, Seung-Ki Kwok, Mi-La Cho, Sung-Hwan Park
Achaete-scute complex homologue 2 (Ascl2) has been reported to induce the differentiation and activation of follicular helper T (TFH) cells, which are essential for development of Sjögren's syndrome (SS). This study examined whether Ascl2 plays a role in the development of SS. NOD/ShiLtJ mice were injected with an Ascl2-overexpression vector, and the infiltration of lymphocytes into salivary and lacrimal glands was assessed. The expression of inflammatory cytokines and chemoattractants for T or B cells was measured...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28727604/preclinical-development-of-ebi-005-an-il-1-receptor-1-inhibitor-for-the-topical-ocular-treatment-of-ocular-surface-inflammatory-diseases
#9
Joseph Kovalchin, Bracken King, Allyson Masci, Elizabeth Hopkins, Jeremy Fry, Jay Hou, Christian Li, Kelly Tenneson, Steve Weber, Gary Wolfe, Kathy Collins, Eric S Furfine
OBJECTIVE: Topical interleukin (IL)-1 receptor (R)1 blockade is therapeutically active in reducing signs and symptoms of dry eye disease. Herein, we describe in vitro and in vivo nonclinical Investigational New Drug (IND)-enabling studies of EBI-005, a novel protein chimera of IL-1β and IL-1 receptor antagonist (IL-1Ra or anakinra) that potently binds IL-1R1 and blocks signaling. These studies provide an assessment of receptor affinity, drug bioavailability, immunogenic response, safety, and tolerability in mice and rabbits...
July 18, 2017: Eye & Contact Lens
https://www.readbyqxmd.com/read/28727113/feed-withdrawal-and-transportation-effects-on-salmonella-enterica-levels-in-market-weight-pigs
#10
S D Eicher, M H Rostagno, D C Lay
Feed withdrawal and transport commonly occur together in pigs. Objectives of this study were to determine if these preslaughter stressors, feed withdrawal and transportation, affect the levels of , stress hormone concentrations, and immune functions in infected market pigs. A 2 × 2 factorial analysis of a randomized complete block design with feed withdrawal and transport as fixed effects was used. Sixty market-weight pigs were individually inoculated with serovar Typhimurium. The experiment was replicated 3 times (blocking factor) with 20 pigs per replicate...
July 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726542/generation-and-functional-characterization-of-anti-human-and-anti-mouse-il-36r-antagonist-monoclonal-antibodies
#11
Rajkumar Ganesan, Ernest L Raymond, Detlev Mennerich, Joseph R Woska, Gary Caviness, Christine Grimaldi, Jennifer Ahlberg, Rocio Perez, Simon Roberts, Danlin Yang, Kavita Jerath, Kristopher Truncali, Lee Frego, Eliud Sepulveda, Priyanka Gupta, Su-Ellen Brown, Michael D Howell, Keith A Canada, Rachel Kroe-Barrett, Jay S Fine, Sanjaya Singh, M Lamine Mbow
Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP)...
July 20, 2017: MAbs
https://www.readbyqxmd.com/read/28726269/previous-physical-exercise-alters-hepatic-profile-of-oxidative-inflammatory-status-and-limits-the-secondary-brain-damage-induced-by-severe-tbi-in-rats
#12
Mauro Robson Torres de Castro, Ana Paula de Oliveira Ferreira, Guilherme Lago Busanello, Luís Roberto Hart da Silva, Mauro Eduardo Porto da Silveira Junior, Fernando Fiorin, Gabriela Arrifano, Maria Elena Crespo López, Rômulo Pillon Barcelos, María J Cuevas, Guilherme Bresciani, Javier González-Gallego, Michele Rechia Fighera, Luiz Fernando Freire Royes
Although systemic responses have been described after traumatic brain injury (TBI), little is known regarding potential interactions between brain and peripheral organs after neuronal injury. In this sense, we decided to investigate whether peripheral oxidative/inflammatory response contributes to the neuronal dysfunction after TBI as well as prophylactic role of exercise training. Animals were submitted to fluid percussion injury (FPI) after 6 weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha (LXR-α), ATP-binding cassette transporter (ABCA1), and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 expression per se in liver...
July 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28725012/phycocyanin-attenuates-pulmonary-fibrosis-via-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#13
Chengcheng Li, Yan Yu, Wenjun Li, Bo Liu, Xudong Jiao, Xinyu Song, Changjun Lv, Song Qin
Our aim was to investigate the effects of phycocyanin (PC) on bleomycin (BLM)-induced pulmonary fibrosis (PF). In this study, C57 BL/6 wild-type (WT) mice and toll-like receptor (TLR) 2 deficient mice were treated with PC for 28 days following BLM exposure. Serum and lung tissues were collected on days 3, 7 and 28. Data shows PC significantly decreased the levels of hydroxyproline (HYP), vimentin, surfactant-associated protein C (SP-C), fibroblast specific protein-1 (S100A4) and α-smooth muscle actin (α-SMA) but dramatically increased E-cadherin and podoplanin (PDPN) expression on day 28...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724920/interleukin-36%C3%AE-provides-protection-against-hsv-1-infection-but-does-not-modulate-initiation-of-adaptive-immune-responses
#14
Katelynn A Milora, Siva R Uppalapati, Julio C Sanmiguel, Wei Zou, Liselotte E Jensen
Interleukin-36 (IL-36) represents three cytokines, IL-36α, IL-36β and IL-36γ, which bind to the same receptor, IL-1RL2; however, their physiological function(s) remain poorly understood. Here, the role of IL-36 in immunity against HSV-1 was examined using the flank skin infection mouse model. Expression analyses revealed increased levels of IL-36α and IL-36β mRNA in infected skin, while constitutive IL-36γ levels remained largely unchanged. In human keratinocytes, IL-36α mRNA was induced by HSV-1, while IL-1β and TNFα increased all three IL-36 mRNAs...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724747/interleukin-1-receptor-in-seizure-susceptibility-after-traumatic-injury-to-the-pediatric-brain
#15
Bridgette D Semple, Terence J O'Brien, Kayleen Gimlin, David K Wright, Shi Eun Kim, Pablo M Casillas-Espinosa, Kyria M Webster, Steven Petrou, Linda J Noble-Haeusslein
Epilepsy after pediatric traumatic brain injury (TBI) is associated with poor quality of life. This study aimed to characterize post-traumatic epilepsy in a mouse model of pediatric brain injury, and to evaluate the role of interleukin-1 (IL-1) signaling as a target for pharmacological intervention. Male mice received a controlled cortical impact or sham surgery at postnatal day 21, approximating a toddler-aged child. Mice were treated acutely with an IL-1 receptor antagonist (IL-1Ra; 100 mg/kg s.c.) or vehicle...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28724382/activation-of-cannabinoid-receptor-type-2-attenuates-surgery-induced-cognitive-impairment-in-mice-through-anti-inflammatory-activity
#16
Lingling Sun, Rui Dong, Xin Xu, Xi Yang, Mian Peng
BACKGROUND: Neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD). Accumulated evidence indicates that cannabinoid receptor type 2 (CB2R) can mediate anti-inflammatory and immunomodulatory effects in part by controlling microglial activity. However, the impact of CB2R on postoperative cognition has not been investigated. We hypothesized that CB2R is involved in surgery-induced cognitive impairment in adult mice. METHODS: Adult C57BL/6 mice were subjected to intramedullary fixation surgery for tibial fracture under isoflurane anesthesia and CB2R agonist (JWH133) or CB2R antagonist (AM630) treatment...
July 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28723569/xiap-loss-triggers-ripk3-and-caspase-8-driven-il-1%C3%AE-activation-and-cell-death-as-a-consequence-of-tlr-myd88-induced-ciap1-traf2-degradation
#17
Kate E Lawlor, Rebecca Feltham, Monica Yabal, Stephanie A Conos, Kaiwen W Chen, Stephanie Ziehe, Carina Graß, Yifan Zhan, Tan A Nguyen, Cathrine Hall, Angelina J Vince, Simon M Chatfield, Damian B D'Silva, Kenneth C Pang, Kate Schroder, John Silke, David L Vaux, Philipp J Jost, James E Vince
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723271/development-of-three-orthogonal-assays-suitable-for-the-identification-and-qualification-of-pikfyve-inhibitors
#18
Kylie Fogarty, Mohammed Kashem, Andras Bauer, Alexandra Bernardino, Debra Brennan, Brian Cook, Neil Farrow, Teresa Molinaro, Richard Nelson
FYVE-type zinc finger-containing phosphoinositide kinase (PIKfyve) catalyzes the formation of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) from phosphatidylinositol 3-phosphate (PI(3)P). PIKfyve has been implicated in multiple cellular processes, and its role in the regulation of toll-like receptor (TLR) pathways and the production of proinflammatory cytokines has sparked interest in developing small-molecule PIKfyve inhibitors as potential therapeutics to treat autoimmune and inflammatory diseases. We developed three orthogonal assays to identify and qualify small-molecule inhibitors of PIKfyve: (1) a purified component microfluidic enzyme assay that measures the conversion of fluorescently labeled PI(3)P to PI(3,5)P2 by purified recombinant full-length human 6His-PIKfyve (rPIKfyve); (2) an intracellular protein stabilization assay using the kinase domain of PIKfyve expressed in HEK293 cells; and (3) a cell-based functional assay that measures the production of interleukin (IL)-12p70 in human peripheral blood mononuclear cells stimulated with TLR agonists lipopolysaccharide and R848...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28722170/activation-of-the-b-cell-receptor-successively-activates-nf-%C3%AE%C2%BAb-and-stat3-in-chronic-lymphocytic-leukemia-cells
#19
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Ivo Veletic, Alessandra Ferrajoli, Jan Burger, Philip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 minutes, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hours. Here we show that this process takes longer because it requires transcriptional activity of NF-κB...
July 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28721208/new-perspectives-on-the-regulation-of-type-ii-inflammation-in-asthma
#20
REVIEW
Mireya Becerra-Díaz, Marsha Wills-Karp, Nicola M Heller
Asthma is a chronic inflammatory disease of the lungs which has been thought to arise as a result of inappropriately directed T helper type-2 (Th2) immune responses of the lungs to otherwise innocuous inhaled antigens. Current asthma therapeutics are directed towards the amelioration of downstream consequences of type-2 immune responses (i.e. β-agonists) or broad-spectrum immunosuppression (i.e. corticosteroids). However, few approaches to date have been focused on the primary prevention of immune deviation...
2017: F1000Research
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