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https://www.readbyqxmd.com/read/29777869/subconjunctival-dendrimer-drug-therapy-for-the-treatment-of-dry-eye-in-rabbits-with-induced-autoimmune-dacryoadenitis
#1
Hui Lin, Ying Liu, Siva P Kambhampati, Chih-Chien Hsu, Rangaramanujam M Kannan, Samuel C Yiu
PURPOSE: To investigate the efficacy of a single subconjunctival injection of dendrimer-dexamethasone to treat dry eye in a rabbit model of induced autoimmune dacryoadenitis (AID). METHOD: Dendrimer biodistribution after subconjuntival injection in AID animals was evaluated using Cy5-labelled dendrimer (D-Cy5) and confocal microscopy. Diseased animals were treated with free dexamethasone (Free-Dex), dendrimer-dexamethasone (D-Dex), or saline via a single subconjunctival injection...
May 16, 2018: Ocular Surface
https://www.readbyqxmd.com/read/29776955/high-fat-diet-induced-inflammation-accelerates-prostate-cancer-growth-via-il6-signaling
#2
Takuji Hayashi, Kazutoshi Fujita, Satoshi Nojima, Yujiro Hayashi, Kosuke Nakano, Yu Ishizuya, Cong Wang, Yoshiyuki Yamamoto, Toshiro Kinouchi, Kyosuke Matsuzaki, Kentaro Jingushi, Taigo Kato, Atsunari Kawashima, Akira Nagahara, Takeshi Ujike, Motohide Uemura, Maria Del Carmen Rodriguez Pena, Jennifer B Gordetsky, Eiichi Morii, Kazutake Tsujikawa, George J Netto, Norio Nonomura
OBJECTIVE: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation. MATERIALS AND METHODS: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+; Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29776017/pharmacokinetics-and-c-reactive-protein-modelling-of-anti-il-6-antibody-pf-04236921-in-healthy-volunteers-and-patients-with-autoimmune-disease
#3
Cheryl Li, Satoshi Shoji, Jean Beebe
AIMS: The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-IL-6 monoclonal antibody, and its pharmacokinetics/pharmacodynamics (PK/PD) relationship on serum C-Reactive Protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Crohn's disease (CD) METHODS: Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from 2 phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study, and a Phase 2 SLE study were included...
May 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29775920/il-33-stimulates-expression-of-the-gpr84-ex33-fatty-acid-receptor-gene-and-of-cytokine-and-chemokine-genes-in-human-adipocytes
#4
Mohamed S Zaibi, Małgorzata A Kępczyńska, Parvathy Harikumar, Suliman Y Alomar, Paul Trayhurn
Expression of GPCR fatty acid sensor/receptor genes in adipocytes is modulated by inflammatory mediators, particularly IL-1β. In this study we examined whether the IL-1 gene superfamily member, IL-33, also regulates expression of the fatty acid receptor genes in adipocytes. Human fat cells, differentiated from preadipocytes, were incubated with IL-33 at three different dose levels for 3 or 24 h and mRNA measured by qPCR. Treatment with IL-33 induced a dose-dependent increase in GPR84 mRNA at 3 h, the level with the highest dose being 13...
May 15, 2018: Cytokine
https://www.readbyqxmd.com/read/29775732/il4-10-fusion-protein-has-chondroprotective-anti-inflammatory-and-potentially-analgesic-effects-in-the-treatment-of-osteoarthritis
#5
C Steen-Louws, J Popov-Celeketic, S C Mastbergen, K Coeleveld, C E Hack, N Eijkelkamp, M Tryfonidou, S Spruijt, J A G van Roon, F P J G Lafeber
OBJECTIVE: Effective disease-modifying drugs for osteoarthritis (DMOAD) should preferably have chondroprotective, anti-inflammatory, and analgesic activity combined in a single molecule. We developed a fusion protein of IL4 and IL10 (IL4-10 FP), in which the biological activity of both cytokines is preserved. The present study evaluates the chondroprotective, anti-inflammatory, and analgesic activity of IL4-10 FP in in vitro and in vivo models of osteoarthritis. METHODS: Human osteoarthritic cartilage tissue and synovial tissue were cultured with IL4-10 FP...
May 15, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29775600/variation-in-interleukin-6-receptor-gene-associates-with-risk-of-crohn-s-disease-and-ulcerative-colitis
#6
C A Parisinos, S Serghiou, M Katsoulis, M J George, R S Patel, H Hemingway, A D Hingorani
Interleukin 6 (IL6) is an inflammatory cytokine; signaling via its receptor (IL6R) is believed to contribute to development of inflammatory bowel diseases (IBD). The single nucleotide polymorphism rs2228145 in IL6R associates with increased levels of soluble IL6R (s-IL6R), as well as reduced IL6R signaling and risk of inflammatory disorders; its effects are similar to those of a therapeutic monoclonal antibody that blocks IL6R signaling. We used the effect of rs2228145 on s-IL6R level as an indirect marker to investigate whether reduced IL6R signaling associates with risk of ulcerative colitis (UC) or Crohn's disease (CD)...
May 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29770602/full-title-cultures-of-a-human-synovial-cell-line-to-evaluate-platelet-rich-plasma-and-hyaluronic-acid-effects
#7
E Olivotto, G Merli, E Assirelli, C Cavallo, E Belluzzi, R Ramonda, M Favero, G Filardo, A Roffi, E Kon, B Grigolo
Synovial inflammation plays an important role in osteoarthritis (OA) pathogenesis. Different biological compounds have been tested mainly on chondrocytes, to treat early stages of OA. However, since OA has been recently defined as "an organ" pathology, investigation on synoviocytes is also needed. Therefore the aim of the present study was to validate a human fibroblast-like synoviocytes cell line (K4IM) to test the effects of platelet-rich plasma (PRP) and hyaluronan (HA) on anabolic and catabolic gene expression and on HA secretion from cell cultures...
May 16, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29766758/anti-inflammatory-peptide-attenuates-edema-and-promotes-bmp-2-induced-bone-formation-in-spine-fusion
#8
Juliane D Glaeser, Khosrowdad Salehi, Linda Kanim, Dmitriy Sheyn, Zachary NaPier, Phillip Behrens, Leslie Garcia, Jason M Cuéllar, Hyun W Bae
Recombinant human bone morphogenic protein-2 (BMP-2) loaded absorbable collagen sponges (ACS) have been successfully used to enhance bone formation and to induce spinal fusion in humans. However, side effects, such as soft-tissue edema and inflammation, have been reported. NEMO binding domain peptide (NBD) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of immune response. In this study, we investigated NBD's potential to reduce BMP-2-induced soft-tissue inflammation without affecting BMP-2-mediated spinal fusion in rat...
May 16, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29764837/il22-promotes-kras-mutant-lung-cancer-by-induction-of-a-pro-tumor-immune-response-and-protection-of-stemness-properties
#9
Nasim Khosravi, Mauricio S Caetano, Amber M Cumpian, Nese Unver, Cynthia De la Garza Ramos, Oscar Noble, Soudabeh Daliri, Belinda J Hernandez, Berenice A Gutierrez, Scott E Evans, Samir Hanash, Andrei M Alekseev, Yi Yang, Seon Hee Chang, Roza Nurieva, Humam Kadara, Jichao Chen, Edwin J Ostrin, Seyed Javad Moghaddam
Somatic KRAS mutations are the most common oncogenic variants in lung cancer and are associated with poor prognosis. Using a Kras-induced lung cancer mouse model, CC-LR, we previously showed a role for inflammation in lung tumorigenesis through activation of the NF-kB pathway, along with induction of interleukin 6 (IL6) and an IL17-producing CD4+ T-helper cell response. IL22 is an effector molecule secreted by CD4+ and γδ T cells that we previously found to be expressed in CC-LR mice. IL22 mostly signals through the STAT3 pathway and is thought to act exclusively on non-hematopoietic cells with basal IL22 receptor (IL22R) expression on epithelial cells...
May 15, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29763853/text-mining-and-network-analysis-to-find-functional-associations-of-genes-in-high-altitude-diseases
#10
Balu Bhasuran, Devika Subramanian, Jeyakumar Natarajan
BACKGROUND AND OBJECTIVES: Travel to elevations above 2500 m is associated with the risk of developing one or more forms of acute altitude illness such as acute mountain sickness (AMS), high altitude cerebral edema (HACE) or high altitude pulmonary edema (HAPE). Our work aims to identify the functional association of genes involved in high altitude diseases. METHOD: In this work we identified the gene networks responsible for high altitude diseases by using the principle of gene co-occurrence statistics from literature and network analysis...
May 2, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29763582/the-pathogenic-role-of-dendritic-cells-in-non-infectious-anterior-uveitis
#11
M O'Rourke, U Fearon, C M Sweeney, S A Basdeo, J M Fletcher, C C Murphy, M Canavan
BACKGROUND: Anterior uveitis (AU) is characterised by infiltration of immune cells into the anterior chamber of the eye. Dendritic cells (DC) are professional antigen presenting cells that initiate and promote inflammation. This study aims to characterise DC in AU and to examine the effects of aqueous humor (AqH) on DC maturation and function. METHODS: The frequency and phenotype of AU and healthy control (HC) circulating DC was examined. AU and HC AqH was immunostained and assessed by flow cytometry...
May 12, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29760677/one-week-exposure-to-a-free-choice-high-fat-high-sugar-diet-does-not-interfere-with-the-lipopolysaccharide-induced-acute-phase-response-in-the-hypothalamus-of-male-rats
#12
Evita Belegri, Leslie Eggels, Susanne E la Fleur, Anita Boelen
Obesity has been associated with increased susceptibility to infection in humans and rodents. Obesity is also associated with low-grade hypothalamic inflammation that depends not only on body weight but also on diet. In the present study, we investigated if the bacterial endotoxin [lipopolysaccharide (LPS)]-induced acute phase response is aggravated in rats on a 1-week free-choice high-fat high-sugar (fcHFHS) diet and explained by diet-induced hypothalamic inflammation. Male Wistar rats were on an fcHFHS diet or chow for 1 week and afterwards intraperitoneally injected with LPS or saline...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29760177/epigenetic-promoter-dna-methylation-of-mir-124-promotes-hiv-1-tat-mediated-microglial-activation-via-mecp2-stat3-axis
#13
Palsamy Periyasamy, Annadurai Thangaraj, Ming-Lei Guo, Guoku Hu, Shannon Callen, Shilpa Buch
The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B that were also accompanied by increased global DNA methylation...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29759145/thymoquinone-increases-the-expression-of-neuroprotective-proteins-while-decreasing-the-expression-of-pro-inflammatory-cytokines-and-the-gene-expression-nf%C3%AE%C2%BAb-pathway-signaling-targets-in-lps-ifn%C3%AE-activated-bv-2-microglia-cells
#14
Makini K Cobourne-Duval, Equar Taka, Patricia Mendonca, Karam F A Soliman
Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines. Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil...
July 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29753051/variation-in-doses-and-duration-of-particulate-matter-exposure-in-bronchial-epithelial-cells-results-in-upregulation-of-different-genes-associated-with-airway-disorders
#15
Priya Tripathi, Furong Deng, Anne M Scruggs, Yahong Chen, Steven K Huang
Exposure to particulate matter < 2.5 μm (PM2.5 ) is associated with a variety of airway diseases. Although studies have demonstrated that high doses of PM2.5 cause cytotoxicity and changes to gene expression in bronchial epithelial cells, the effect of lower doses and repeated exposure to PM2.5 are less well studied. Here, we treated BEAS-2B cells with varying doses of PM2.5 for 1-7 days and examined the expression of a variety of genes implicated in airway disorders. At high doses, PM2.5 increased the expression of IL6, TNF, TSLP, CSF2, PTGS2, IL4R, and SPINK5...
May 9, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29752408/interleukin-6-mediated-trans-signaling-inhibits-transforming-growth-factor-%C3%AE-signaling-in-trabecular-meshwork-cells
#16
Miyuki Inoue-Mochita, Toshihiro Inoue, Sachi Kojima, Akiko Futakuchi, Tomokazu Fujimoto, Saori Sato-Ohira, Utako Tsutsumi, Hidenobu Tanihara
Glaucoma is one of the major causes of blindness, and TGF-β2 has been found to be elevated in the aqueous humor of eyes with primary open-angle glaucoma (POAG). TGF-β2 in aqueous humor causes the glaucoma-related fibrosis of human trabecular meshwork (HTM), suggesting an important role of TGF-β in POAG pathogenesis. Here, we sought to elucidate the effects of IL-6 trans-signaling on TGF-β signaling in HTM cells. Using a multiplex immunoassay, POAG patients decreased IL-6 levels and increased soluble IL-6 receptor (sIL-6R) levels compared with the controls...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29751216/pellino-1-is-a-novel-regulator-of-tnf-and-tlr-signalling-in-human-myometrial-and-amnion-cells
#17
Ratana Lim, Gillian Barker, Martha Lappas
Preterm birth is the primary cause of neonatal deaths and morbidities. Pathological processes causally linked to preterm birth are inflammation and infection. Pellino-1 (Peli1) has previously been found to regulate the inflammatory response in non-gestational tissues in response to toll-like receptor (TLR) ligands and pro-inflammatory cytokines. The aims of this study were to determine the effect of labor on Peli1 expression in myometrium and fetal membranes, and the effect of Peli1 silencing by siRNA (siPELI1) on the production of pro-inflammatory and pro-labor mediators...
April 14, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29750565/pregnancy-late-in-rodent-life-has-detrimental-effects-on-the-heart
#18
Eunhee Chung, Kaylan M Haizlip, Leslie A Leinwand
During pregnancy, the heart undergoes significant and numerous changes, including hypertrophy that are usually described as physiological and reversible. Two aspects of the cardiac response to pregnancy are relatively understudied: advanced maternal age and multiple pregnancies (multiparity). Repeated breeder mice (RB) that have undergone 5 to 7 consecutive pregnancies were sacrificed 21 days after the weaning of their last pups and were compared to age-matched primiparous, one-time pregnant mice (O1P). The ages of the old mouse groups were similar (12 {plus minus} 1 month)...
May 11, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29749709/bacteria-induced-susceptibility-to-candida-albicans-superinfection-in-mice-via-monocyte-methyltransferase-setdb2
#19
Chen Xiao-Ping, Zheng Hao, Li Wen-Ge, Chen Guo-Dong, Lu Jin-Xing
Systemic bacterial infections are prone to secondary Candida albicans superinfection. However, the molecular mechanisms involved remain poorly understood. In this study, a model comprising sub-lethal cecal ligation and puncture (CLP) plus C. albicans intravenous injection (i.v.) was applied to mimic the situation in superinfection. Compared with mice without systemic bacterial infection, mice with systemic bacterial infection had lower anti-fungal gene expression (including Il1b, Tnf, Il6, Ifnb, Ifng, Cxcl1, and Ccr2) in monocytes, and less inflammatory monocytes and neutrophils infiltrating into the kidney when challenged with C...
May 11, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29748248/bromodomain-protein-brd4-is-increased-in-human-placentas-from-women-with-early-onset-preeclampsia
#20
Stella Liong, Gillian Barker, Martha Lappas
Preeclampsia affects 5% of all pregnancies and is a serious disorder of pregnancy, characterised by high maternal blood pressure, placental hypoxia, fluid retention (oedema) and proteinuria. Women with preeclampsia are associated with exaggerated levels of pro-inflammatory cytokines, chemokines and anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFLT1). Studies in non-gestational tissues have described the bromodomain (BRD) and extraterminal family of proteins, in particular BRD4 to play a critical role in propagating inflammation and is currently a therapeutic target for treating cancer, lung inflammation and asthma...
June 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
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