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https://www.readbyqxmd.com/read/29791797/modulating-macrophage-polarization-through-ccr2-inhibition-and-multivalent-engagement
#1
Michael B Deci, Scott W Ferguson, Sydney L Scatigno, Juliane Nguyen
Excessive or prolonged recruitment of inflammatory monocytes to damaged tissue can significantly worsen patient outcomes. Monocytes migrate to sites of tissue inflammation in response to high local concentrations of CCL2, a chemokine that binds to and signals through the CCR2 receptor. While the role of CCR2 in cellular migration is well studied, it is unclear how CCR2 inhibition affects macrophage polarization and if multivalency can increase downstream signaling effects. Using affinity selection with a phage library, we identified a novel scFv (58C) that binds specifically and with high affinity to the N-terminal domain of CCR2 (KD = 59...
May 23, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29791764/synergy-between-peroxisome-proliferator-activated-receptor-%C3%AE-agonist-and-radiotherapy-in-cancer
#2
Guodong Huang, Limei Yin, Jie Lan, Ruizhan Tong, Mengqian Li, Feifei Na, Xianming Mo, Chong Chen, Jianxin Xue, You Lu
ANGIOGENESIS AND INFLAMMATION ARE CRUCIAL PROCESSES, THROUGH WHICH THE: tumor microenvironment (TME) influences tumor progression. In this STUDY, WE REVEALED THAT PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR Γ (PPARΓ) IS: NOT ONLY EXPRESSED IN CT26 AND 4T1 TUMOR CELL LINES BUT ALSO IN CELLS OF TME,: including endothelial cells and tumor-associated macrophages (TAMs). In addition, WE DEMONSTRATED THAT ROSIGLITAZONE MAY INDUCE TUMOR VESSEL NORMALIZATION AND REDUCE: TAM infiltration. Additionally, 4T1 and CT26 tumor-bearing mice treated with ROSIGLITAZONE IN COMBINATION WITH RADIOTHERAPY DISPLAYED A SIGNIFICANT REDUCTION IN: lesion size and lung metastasis...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29791013/frontline-science-buprenorphine-decreases-ccl2-mediated-migration-of-cd14-cd16-monocytes
#3
Matias Jaureguiberry-Bravo, Lillie Lopez, Joan W Berman
HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB)...
May 23, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29790398/acute-inflammatory-biomarker-responses-to-diffuse-traumatic-brain-injury-in-the-rat-monitored-by-a-novel-microdialysis-technique
#4
Fredrik Clausen, Niklas Marklund, Lars Hillered
Neuroinflammation is a major contributor to the progressive brain injury process induced by traumatic brain injury (TBI), and may play an important role in the pathophysiology of axonal injury. The immediate neuroinflammatory cascade cannot be characterized in the human setting. Therefore, we used the midline fluid percussion injury model of diffuse TBI in rats and a novel microdialysis (MD) method providing stable diffusion-driven biomarker sampling. Immediately post-injury, bilateral amphiphilic tri-block polymer coated MD probes (100 kDa cut off membrane) were inserted and perfused with Dextran 500 kDa-supplemented artificial CSF to optimize protein capture...
May 23, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29786075/tp53-gain-of-function-mutation-promotes-inflammation-in-glioblastoma
#5
Seok Won Ham, Hee-Young Jeon, Xiong Jin, Eun-Jung Kim, Jun-Kyum Kim, Yong Jae Shin, Yeri Lee, Se Hoon Kim, Seon Yong Lee, Sunyoung Seo, Min Gi Park, Hye-Mi Kim, Do-Hyun Nam, Hyunggee Kim
Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29777767/biglycan-is-a-new-high-affinity-ligand-for-cd14-in-macrophages
#6
Heiko Roedig, Madalina V Nastase, Helena Frey, Kristin Moreth, Jinyang Zeng-Brouwers, Chiara Poluzzi, Louise Tzung-Harn Hsieh, Christian Brandts, Simone Fulda, Malgorzata Wygrecka, Liliana Schaefer
Sterile inflammation is a therapeutic target in many diseases where it represents an important initiator of disease progression. However, the detailed mechanisms underlying its evolution and biological relevance are not yet completely elucidated. Biglycan, a prototype extracellular matrix-derived damage-associated molecular pattern, mediates sterile inflammation in macrophages through Toll-like receptor (TLR) 2 and/or TLR4-dependent signaling pathways. Here we discovered that soluble biglycan is a novel high-affinity ligand for CD14, a well-known GPI-anchored co-receptor for TLRs...
May 16, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29777718/malnutrition-is-associated-with-diminished-baseline-and-mycobacterial-antigen-stimulated-chemokine-responses-in-latent-tuberculosis-infection
#7
Rajamanickam Anuradha, Saravanan Munisankar, Yukthi Bhootra, Nathella Pavan Kumar, Chandrakumar Dolla, Subash Babu
OBJECTIVES: Previous studies have demonstrated a diminution in the baseline and mycobacterial antigen - specific cytokines in low body mass index (LBMI) individuals with latent tuberculosis infection (LTBI). We hypothesized that LBMI might be also associated with alteration in the baseline and antigen - stimulated levels of chemokines in LTBI. METHODS: To test this hypothesis, we examined baseline, TB- antigen and mitogen stimulated levels of chemokines in these individuals and compared them with those with LTBI and normal BMI (NBMI)...
May 16, 2018: Journal of Infection
https://www.readbyqxmd.com/read/29777108/factor-xiiia-expressing-inflammatory-monocytes-promote-lung-squamous-cancer-through-fibrin-cross-linking
#8
Alessandro Porrello, Patrick L Leslie, Emily B Harrison, Balachandra K Gorentla, Sravya Kattula, Subrata K Ghosh, Salma H Azam, Alisha Holtzhausen, Yvonne L Chao, Michele C Hayward, Trent A Waugh, Sanggyu Bae, Virginia Godfrey, Scott H Randell, Cecilia Oderup, Liza Makowski, Jared Weiss, Matthew D Wilkerson, D Neil Hayes, H Shelton Earp, Albert S Baldwin, Alisa S Wolberg, Chad V Pecot
Lung cancer is the leading cause of cancer-related deaths worldwide, and lung squamous carcinomas (LUSC) represent about 30% of cases. Molecular aberrations in lung adenocarcinomas have allowed for effective targeted treatments, but corresponding therapeutic advances in LUSC have not materialized. However, immune checkpoint inhibitors in sub-populations of LUSC patients have led to exciting responses. Using computational analyses of The Cancer Genome Atlas, we identified a subset of LUSC tumors characterized by dense infiltration of inflammatory monocytes (IMs) and poor survival...
May 18, 2018: Nature Communications
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
#9
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/29774637/potassium-octatitanate-fibers-induce-persistent-lung-and-pleural-injury-and-are-possibly-carcinogenic-in-male-fischer-344-rats
#10
Mohamed Abdelgied, Ahmed M El-Gazzar, David B Alexander, William T Alexander, Takamasa Numano, Masaaki Iigou, Aya Naiki-Ito, Hirotsugu Takase, Khaled Abbas Abdou, Akihiko Hirose, Yuhji Taquahashi, Jun Kanno, Hiroyuki Tsuda, Satoru Takahashi
Potassium octatitanate fibers (K2 O•8TiO2 , POT fibers) are widely used as an alternative to asbestos. We investigated the pulmonary and pleural toxicity of POT fibers with reference to 2 non-fibrous titanium dioxide nanoparticles (nTiO2 ), photo-reactive anatase (a-nTiO2 ) and inert rutile (r-nTiO2 ). Ten-week old male F344 rats were administered 0.5 ml of 250-μg/ml suspensions of POT fibers, a-nTiO2 , or r-nTiO2 , eight times (1 mg/rat) over a 15 day period by trans-tracheal intrapulmonary spraying (TIPS)...
May 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29772277/severity-therapeutic-and-activity-tear-biomarkers-in-dry-eye-disease-a-clinical-trial-sub-analysis
#11
José Pinto-Fraga, Amalia Enríquez-de-Salamanca, Margarita Calonge, María J González-García, Alberto López-Miguel, Alberto López-de la Rosa, Carmen García-Vázquez, Virginia Calder, Michael E Stern, Itziar Fernández
PURPOSE: To evaluate the effect of 0.1%-fluorometholone (FML) on tear inflammatory molecule levels after 22-days treatment in dry eye disease (DED) patients exposed to an adverse controlled environment (ACE), identifying different biomarkers. METHODS: Sub-analysis of a double-masked randomized clinical trial. Forty-one DED patients received 4-drops daily of topical FML (FML-group) or polyvinyl-alcohol (PA-group) for 22 days. At day 21, patients were exposed to an ACE...
May 14, 2018: Ocular Surface
https://www.readbyqxmd.com/read/29771686/spleen-mediates-a-distinct-hematopoietic-progenitor-response-supporting-tumor-promoting-myelopoiesis
#12
Chong Wu, Huiheng Ning, Mingyu Liu, Jie Lin, Shufeng Luo, Wenjie Zhu, Jing Xu, Wen-Chao Wu, Jing Liang, Chun-Kui Shao, Jiaqi Ren, Bin Wei, Jun Cui, Min-Shan Chen, Limin Zheng
Cancer progression is associated with alterations of intra- and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs)...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29769838/selected-biomarkers-correlate-with-the-origin-and-severity-of-sepsis
#13
Michal Holub, Olga Džupová, Michaela Růžková, Alžběta Stráníková, Eva Bartáková, Jan Máca, Jiří Beneš, Heiko Herwald, Ondřej Beran
The microbial etiology and source of sepsis influence the inflammatory response. Therefore, the plasma levels of cytokines (IL-6, IL-8, and IL-10), chemokines (CCL2/MCP-1, MIP-1 β ), heparin-binding protein (HBP), soluble CD14 (sCD14), and cortisol were analyzed in blood from septic patients obtained during the first 96 hours of intensive care unit hospitalization. The etiology was established in 56 out of a total of 62 patients enrolled in the study. Plasma concentrations of MCP-1, sCD14, IL-6, and IL-10 were significantly higher in patients with community-acquired pneumonia (CAP; n = 10) and infective endocarditis (IE; n = 11) compared to those with bacterial meningitis (BM; n = 18)...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29769661/circulating-mir-374a-5p-is-a-potential-modulator-of-the-inflammatory-process-in-obesity
#14
Ayo P Doumatey, William J He, Amadou Gaye, Lin Lei, Jie Zhou, Gary H Gibbons, Adebowale Adeyemo, Charles N Rotimi
Obese individuals without expected metabolic co-morbidities are referred to as metabolically healthy obese (MHO). The molecular mechanisms underlying this phenotype remain elusive. MicroRNAs may be involved in the MHO phenotype. To test this hypothesis, we screened 179 serum miRNAs in 20 African-American women (10 MHOs and 10 metabolically abnormal obese individuals -MAO). We identified 8 differentially expressed miRNAs (DEMs) with validation in an independent sample of 64 MHO and 34 MAO. Of the eight DEMs in the screening phase (p ≤ 0...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768624/analysis-of-the-immunological-biomarker-profile-during-acute-zika-virus-infection-reveals-the-overexpression-of-cxcl10-a-chemokine-linked-to-neuronal-damage
#15
Felipe Gomes Naveca, Gemilson Soares Pontes, Aileen Yu-Hen Chang, George Allan Villarouco da Silva, Valdinete Alves do Nascimento, Dana Cristina da Silva Monteiro, Marineide Souza da Silva, Lígia Fernandes Abdalla, João Hugo Abdalla Santos, Tatiana Amaral Pires de Almeida, Matilde Del Carmen Contreras Mejía, Tirza Gabrielle Ramos de Mesquita, Helia Valeria de Souza Encarnação, Matheus de Souza Gomes, Laurence Rodrigues Amaral, Ana Carolina Campi-Azevedo, Jordana Graziela Coelho-Dos-Reis, Lis Ribeiro do Vale Antonelli, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Rajendranath Ramasawmy
BACKGROUND: Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES: To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS: We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining...
May 14, 2018: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/29763882/thymoquinone-influences-the-expression-of-genes-involved-in-self-renewal-and-immunomodulatory-potential-of-mouse-bone-marrow-derived-mesenchymal-stem-cells-in-vitro
#16
Elham Alimoradi, Sajjad Sisakhtnezhad, Hassan Akrami
Thymoquinone (TQ) is an active ingredient of some medicinal herbs. Despite extensive studies on the biological and pharmacological properties of TQ, its effect on the characteristics of stem cells remains to be clarified. Therefore, this study was aimed to investigate the effect of TQ on viability, proliferation and immunomodulatory potential of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) in vitro. The BM-MSCs were isolated from young NMRI mice. The cytotoxic effect of TQ on the BM-MSCs was evaluated using MTT assay...
May 7, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29763838/the-overweight-increases-circulating-inflammatory-mediators-commonly-associated-with-obesity-in-young-individuals
#17
Laís Roquete Lopes, Silvana Mara Luz Turbino Ribeiro, Vivian Paulino Figueiredo, Ana Luísa Junqueira Leite, Roney Luiz de Carvalho Nicolato, Juliana Assis Estanislau Gomes, Fernando Luiz Pereira de Oliveira, Andre Talvani
Obesity is a serious and growing world healthy problem affecting developed and developing countries. The new conception of obesity as a basal inflammatory condition has opened a new window of possibilities to identify inflammatory biomarkers to be used in the diagnosis or prognosis of obesity-associated comorbidities. This present work aims the identification of the adipokines (leptin and resistin), chemokines (CCL2, CCL5, CXCL16) and the BMP-2 and their association with the clinical, biochemical (fasting glucose, hemogram, cholesterol, T3, T4 and TSH) and anthropometric (weight, height, body circumferences, skinfold thickness and percentage of body fat) parameters in young adults (18-30 years old) presenting obesity and overweight...
May 11, 2018: Cytokine
https://www.readbyqxmd.com/read/29762676/interleukin-38-is-a-protective-cytokine-for-lethal-sepsis
#18
Fang Xu, Shihui Lin, Xingxing Yan, Chuanjiang Wang, Hongmei Tu, Yibing Yin, Ju Cao
Background: IL-38 is the most recently characterized cytokine of the IL-1 family. However, its role in sepsis remains unknown. Methods: Circulating IL-38 was measured in two cohorts of adult and pediatric patients with sepsis. Using two murine models of lipopolysaccharide (LPS)-induced endotoxinemia and cecal ligation and puncture (CLP)-induced sepsis, the effects of IL-38 on survival, inflammation, tissue injury, or bacterial clearance were assessed. Results: Serum IL-38 concentrations were significantly elevated in adult and pediatric patients with sepsis relative to corresponding healthy adult and pediatric controls, respectively...
May 12, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29760708/dual-tlr2-9-recognition-of-herpes-simplex-virus-infection-is-required-for-recruitment-and-activation-of-monocytes-and-nk-cells-and-restriction-of-viral-dissemination-to-the-central-nervous-system
#19
Erdenebileg Uyangaa, Jin Young Choi, Ajit Mahadev Patil, Ferdaus Mohd Altaf Hossain, Sung Ok Park, Bumseok Kim, Koanhoi Kim, Seong Kug Eo
The importance of TLR2 and TLR9 in the recognition of infection with herpes simplex virus (HSV) and HSV-caused diseases has been described, but some discrepancies remain concerning the benefits of these responses. Moreover, the impact of TLR2/9 on innate and adaptive immune responses within relevant mucosal tissues has not been elucidated using natural mucosal infection model of HSV. Here, we demonstrate that dual TLR2/9 recognition is essential to provide resistance against mucosal infection with HSV via an intravaginal route...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760352/time-dependent-changes-in-local-and-serum-levels-of-inflammatory-cytokines-as-markers-for-incised-wound-aging-of-skeletal-muscles
#20
Mohammed Hassan Gaballah, Tetsuya Horita, Masataka Takamiya, Keisuke Yokoji, Mamiko Fukuta, Hideaki Kato, Yasuhiro Aoki
Wound age estimation is an important research field in forensic pathology. The expression levels of cytokines in the incised skeletal muscle were analyzed using a mouse model to explore the applicability for wound aging. A 5-mm long incisional wound was made at the biceps femoris muscle, and the muscle and serum were sampled at 6, 12, 24 and 48 hours after injury. Using a multiplex bead-based immunoassay, we measured the tissue levels of nine cytokines (IL-1β, IL-6, IL-7, CCL2, CCL3, CCL4, CXCL1, CXCL2, and CXCL10), which are all involved in the pathways of inflammatory response and tissue injury...
2018: Tohoku Journal of Experimental Medicine
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