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Mário R Martins, Rogério L D Santos, Kleber D N Jatahy, Marina C D Matta, Thales P Batista, José Iran C Júnior, Maria D F S Begnami, Leuridan C Torres
BACKGROUND AND OBJECTIVES: OX40, a membrane-bound molecule of the tumor-necrosis-factor-receptor superfamily, is a critical costimulatory receptor during the immune response, especially to T cells, but studies described their presence of OX-40 on neutrophils and monocytes, suggesting a potential role in the activation of immune response. Our aim was to characterize costimulatory receptors OX40 expression on circulating leukocytes in gastric cancer to identify novel targets for immunotherapy...
March 12, 2018: Journal of Surgical Oncology
Sathana Dushyanthen, Zhi Ling Teo, Franco Caramia, Peter Savas, Christopher P Mintoff, Balaji Virassamy, Melissa A Henderson, Stephen J Luen, Mariam Mansour, Michael H Kershaw, Joseph A Trapani, Paul J Neeson, Roberto Salgado, Grant A McArthur, Justin M Balko, Paul A Beavis, Phillip K Darcy, Sherene Loi
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo...
September 19, 2017: Nature Communications
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
March 2017: Cell Biology International
Bettina Langhans, Hans Dieter Nischalke, Benjamin Krämer, Annekristin Hausen, Leona Dold, Peer van Heteren, Robert Hüneburg, Jacob Nattermann, Christian P Strassburg, Ulrich Spengler
BACKGROUND & AIMS: CD4(+) regulatory T cells (Tregs) expand during chronic hepatitis C virus (HCV) infection, inhibit antiviral immunity and promote fibrosis. Direct-acting antiviral agents (DAA) have revolutionized HCV therapy. However, it is unclear if Tregs are normalized after DAA-induced HCV elimination. METHODS: We analyzed Tregs before (baseline), at end of therapy (EOT), 12 and 24weeks (SVR12, SVR24) and long-term (51±14weeks) after EOT in 26 genotype-1-infected patients who were successfully treated with sofosbuvir (SOF) plus interferon (IFN)/ribavirin (n=12) and IFN-free DAA regimens (SOF plus daclatasvir or simeprevir; n=14)...
May 2017: Journal of Hepatology
Tzu-Yu Shao, Ling-Hui Hsu, Chien-Hui Chien, Bor-Luen Chiang
Recent studies have revealed various Foxp3(-) regulatory T (Treg) cell subsets effectively protect mice from colitis. In the present study, we demonstrated that B cells induced a particular subset of regulatory T (Treg-of-B) cells, expressing programmed cell death 1 (PD-1), inducible costimulator (ICOS), lymphocyte-activation gene 3 (LAG3), glucocorticoid-induced tumor necrosis factor receptor (GITR), and OX-40, did not express Foxp3. Treg-of-B cells produced abundant levels of IL-10 and low levels of IL-4 and TGF-β...
2016: Scientific Reports
Se Jin Im, Masao Hashimoto, Michael Y Gerner, Junghwa Lee, Haydn T Kissick, Matheus C Burger, Qiang Shan, J Scott Hale, Judong Lee, Tahseen H Nasti, Arlene H Sharpe, Gordon J Freeman, Ronald N Germain, Helder I Nakaya, Hai-Hui Xue, Rafi Ahmed
Chronic viral infections are characterized by a state of CD8+ T-cell dysfunction that is associated with expression of the programmed cell death 1 (PD-1) inhibitory receptor. A better understanding of the mechanisms that regulate CD8+ T-cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8+ T cells. Here we identify a population of virus-specific CD8+ T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV)...
September 15, 2016: Nature
Guillaume Froehlicher, Etienne Lorchat, François Fernique, Chaitanya Joshi, Alejandro Molina-Sánchez, Ludger Wirtz, Stéphane Berciaud
N-layer transition metal dichalcogenides provide a unique platform to investigate the evolution of the physical properties between the bulk (three-dimensional) and monolayer (quasi-two-dimensional) limits. Here, using high-resolution micro-Raman spectroscopy, we report a unified experimental description of the Γ-point optical phonons in N-layer 2H-molybdenum ditelluride (MoTe2). We observe series of N-dependent low-frequency interlayer shear and breathing modes (below 40 cm(-1), denoted LSM and LBM) and well-defined Davydov splittings of the mid-frequency modes (in the range 100-200 cm(-1), denoted iX and oX), which solely involve displacements of the chalcogen atoms...
October 14, 2015: Nano Letters
E-Y Kwon, G S Cha, E Jeong, J-Y Lee, S-J Kim, C D Surh, J Choi
BACKGROUND AND OBJECTIVE: Epitope spreading is one of valid mechanisms operating in immunopathological processes of infection-induced autoimmune diseases. We hypothesized that the peptide 19 from Porphyromonas gingivalis heat shock protein (HSP) 60 (Pep19) may be the dominant epitope from which epitope-specific immune response to subdominant epitopes may diversify sequentially into autoimmune responses directed at human neoepitopes in P. gingivalis-induced periodontitis and autoimmune diseases...
June 2016: Journal of Periodontal Research
Hisashi Ōkawa, Masaaki Sadakiyo, Kazuya Otsubo, Ko Yoneda, Teppei Yamada, Masaaki Ohba, Hiroshi Kitagawa
Proton conduction of the La(III)M(III) compounds, LaM(ox)3·10H2O (abbreviated to LaM; M = Cr, Co, Ru, La; ox(2-) = oxalate) is studied in view of their networks. LaCr and LaCo have a ladder structure, and the ladders are woven to form a channel network. LaRu and LaLa have a honeycomb sheet structure, and the sheets are combined to form a layer network. The occurrence of these structures is explained by the rigidness versus flexibility of [M(ox)3](3-) in the framework with large La(III). The channel networks of LaCr and LaCo show a remarkably high proton conductivity, in the range from 1 × 10(-6) to 1 × 10(-5) S cm(-1) over 40-95% relative humidity (RH) at 298 K, whereas the layer networks of LaCr and LaCo show a lower proton conductivity, ∼3 × 10(-8) S cm(-1) (40-95% RH, 298 K)...
September 8, 2015: Inorganic Chemistry
Yun Yan, Lugao Tian, Xuelian Xiang, Wei Ding, Gengqing Song, Junying Xu
OBJECTIVES: Gastric electrical stimulation (GES) has great potential for the treatment of obesity. We investigated the impact of chronic GES on the alteration of adipose tissue and the regulation of neuropeptide Y (NPY), orexin (OX), α-melanocyte-stimulating hormone (α-MSH) and oxytocin (OXT), and their receptors in several tissues. MATERIAL AND METHODS: Most of the experiments included three groups of diet-induced obesity rats: (1) sham-GES (SGES); (2) GL-6mA (GES with 6 mA, 4 ms, 40 Hz, 2 s on, 3 s off at lesser curvature); and (3) SGES-PF (SGES rats receiving pair feeding to match the consumption of GL-6mA rats)...
2016: Scandinavian Journal of Gastroenterology
C Lawrence Kien, Dwight E Matthews, Matthew E Poynter, Janice Y Bunn, Naomi K Fukagawa, Karen I Crain, David B Ebenstein, Emily K Tarleton, Robert D Stevens, Timothy R Koves, Deborah M Muoio
Palmitic acid (PA) is associated with higher blood concentrations of medium-chain acylcarnitines (MCACs), and we hypothesized that PA may inhibit progression of FA β-oxidation. Using a cross-over design, 17 adults were fed high PA (HPA) and low PA/high oleic acid (HOA) diets, each for 3 weeks. The [1-(13)C]PA and [13-(13)C]PA tracers were administered with food in random order with each diet, and we assessed PA oxidation (PA OX) and serum AC concentration to determine whether a higher PA intake promoted incomplete PA OX...
September 2015: Journal of Lipid Research
Toby O Smith, Yasir A Hameed, Jane L Cross, Catherine Henderson, Opinder Sahota, Chris Fox
BACKGROUND: Hip fracture is a major fall-related injury which causes significant problems for individuals, their family and carers. Over 40% of people with hip fracture have dementia or cognitive impairment, and their outcomes after surgery are poorer than those without dementia. It is not clear which care and rehabilitation interventions achieve the best outcomes for these people. OBJECTIVES: (a) To assess the effectiveness of models of care including enhanced rehabilitation strategies designed specifically for people with dementia following hip fracture surgery compared to usual care...
June 15, 2015: Cochrane Database of Systematic Reviews
Yanwu Hu, Kai Liu, Mengtong Yan, Yang Zhang, Yadi Wang, Liqun Ren
PURPOSE: Icariin, a flavonoid isolated from the traditional Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to process anti-inflammatory, antioxidative actions and anti-atherosclerosis activity in vivo and in vitro. The purpose of this study was to investigate the effects and mechanisms of icariin on atherosclerosis by human umbilical vein endothelial cells (HUVECs). METHODS: The effects of icariin on the activity of HUVECs induced by oxidized low-density lipoprotein (ox-LDL) were detected by MTT assay...
2015: International Journal of Clinical and Experimental Medicine
Nikki B Marshall, Ewa Lukomska, Carrie M Long, Michael L Kashon, Douglas D Sharpnack, Ajay P Nayak, Katie L Anderson, B Jean Meade, Stacey E Anderson
Triclosan is an antimicrobial chemical incorporated into many personal, medical and household products. Approximately, 75% of the U.S. population has detectable levels of triclosan in their urine, and although it is not typically considered a contact sensitizer, recent studies have begun to link triclosan exposure with augmented allergic disease. We examined the effects of dermal triclosan exposure on the skin and lymph nodes of mice and in a human skin model to identify mechanisms for augmenting allergic responses...
September 2015: Toxicological Sciences: An Official Journal of the Society of Toxicology
Shaowei Wu, Di Yang, Hongying Wei, Bin Wang, Jing Huang, Hongyu Li, Masayuki Shima, Furong Deng, Xinbiao Guo
Ambient particulate air pollution has been associated with increased oxidative stress and atherosclerosis, but the chemical constituents and pollution sources behind the association are unclear. We investigated the associations of various chemical constituents and pollution sources of ambient fine particles (PM2.5) with biomarkers of oxidative stress in a panel of 40 healthy university students. Study participants underwent repeated blood collections for 12 times before and after relocating from a suburban campus to an urban campus with high air pollution levels in Beijing, China...
September 2015: Chemosphere
Sara Labiano, Asis Palazon, Ignacio Melero
Lymphocytes and myeloid cells sense hypoxia by the hypoxia-inducible factor (HIF) transcriptional system and via other molecular mechanisms. Low O2 availability is a hallmark of most solid tumors in which infiltrating leukocytes experience severe hypoxia once away from nurturing blood vessels. HIF controls migration, differentiation, and effector functions on immune cells. Importantly, in the tumor microenvironment the hypoxia response modulates the expression levels for important molecular targets in immunotherapy such as CD137, OX-40, FOXP3, and PD-L1...
June 2015: Seminars in Oncology
Dorothy Forbes, Scott C Forbes, Catherine M Blake, Emily J Thiessen, Sean Forbes
BACKGROUND: This is an update of our previous 2013 review. Several recent trials and systematic reviews of the impact of exercise on people with dementia are reporting promising findings. OBJECTIVES: Primary objectiveDo exercise programs for older people with dementia improve their cognition, activities of daily living (ADLs), neuropsychiatric symptoms, depression, and mortality? Secondary objectivesDo exercise programs for older people with dementia have an indirect impact on family caregivers' burden, quality of life, and mortality?Do exercise programs for older people with dementia reduce the use of healthcare services (e...
2015: Cochrane Database of Systematic Reviews
Rama Krishna Y V Reddy, Jaideep Mahendra, Prema Gurumurthy, Jayamathi, Sai Babu
INTRODUCTION: Although the cardiovascular disease (CVD) burden is rising in different countries, the morbidity and mortality rate is not reduced to much extent because of lack of application of the biomarkers for diagnosing CVD. Hence, we aimed to establish the predictable biomarkers in conjunction to framingham risk score in order to predict the risk for CVD in non cardiac patients. MATERIALS AND METHODS: Three hundred subjects were screened for the study who came for the master health checkup...
February 2015: Journal of Clinical and Diagnostic Research: JCDR
Seema Garg, S V Madhu, Shilpa Suneja
BACKGROUND & OBJECTIVES: Lipoprotein associated phospholipase A 2 (Lp-PLA 2 ) is an important risk predictor of coronary artery disease (CAD). This study was aimed to evaluate Lp-PLA 2 activity and oxidized low density lipoprotein (oxLDL) in newly diagnosed patients of type 2 diabetes mellitus and to determine the correlation of Lp-PLA 2 activity with oxLDL and plasma glucose levels. METHODS: Blood samples were collected in patients with newly diagnosed type 2 diabetes (n=40) before any treatment was started and healthy controls (n=40)...
January 2015: Indian Journal of Medical Research
Yi Liang, Jun-Ying Du, Yu-Jie Qiu, Jun-Fan Fang, Jin Liu, Jian-Qiao Fang
OBJECTIVE: To investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia. METHODS: There were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day...
September 2016: Chinese Journal of Integrative Medicine
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