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Isiaka A Lawal, Monsurat M Lawal, Samson O Akpotu, Mayowa A Azeez, Patrick Ndungu, Brenda Moodley
The adsorption of sulfamethoxazole (SMZ) and ketoprofen (KET) using carbon nanotubes (CNTs) and CNTs modified with ionic liquids (ILs) was investigated. Two ionic liquids (1-benzyl, 3-hexyl imidazolium, IL1 and 1-benzyl, 3-decahexyl imidazolium, IL2) were synthesized, and characterized by nuclear magnetic resonance (1 H and 13 C NMR) and high resolution-mass spectrometry (HR-MS). CNTs and modified CNTs were characterized using FT-IR, X-ray diffraction (XRD), surface area and porosity analysis, thermal gravimetric analysis (TGA), Zeta potential, Raman and scanning electron microscopy (SEM)...
June 18, 2018: Ecotoxicology and Environmental Safety
D Roumanes, A R Falsey, S Quataert, S Secor-Socha, F E-H Lee, H Yang, S Bandyopadhyay, J Holden-Wiltse, D J Topham, E E Walsh
Background: The pathogenesis of respiratory syncytial virus (RSV) in older adults may be due to age-related T-cell immunosenescence. Thus, we evaluated CD4 and CD8 T-cell responses during RSV infection in adults across the age spectrum. Methods: Peripheral blood mononuclear cells collected during RSV infection in adults, age 26-96 years, were stimulated with live RSV and peptide pools representing F, M, NP, and G proteins and analyzed by flow cytometry. Results: There were no significant age-related differences in frequency of CD4+ T cells synthesizing interferon (IFN)γ, interleukin (IL)2, IL4, IL10, or tumor necrosis factor (TNF)α or in CD8+IFNγ+ T cells...
June 16, 2018: Journal of Infectious Diseases
Mohammad Firoz Alam, Mohammed M Safhi, Tarique Anwer, Rahimullah Siddiqui, Gyas Khan, Sivakumar Sivagurunathan Moni
The aim of this research was to investigate the therapeutic potential of Vanillylacetone against carbon tetrachloride (CCl4 ) induced hepatotoxicity in mice through understanding the serum marker, oxidative stress mechanism and cytokine networks. Carbon tetrachloride is highly hepatotoxic used as research based on animal model. The mice were classified into five groups and each had eight mice. Group-I was controlled and the vehicle was given orally. Group-II was toxic and carbon tetrachloride (1.5 ml/kg) twice a week for 15 days was administered by intra-peritoneal injections...
June 14, 2018: Experimental and Molecular Pathology
Daniel Primo, Lydia Scarfò, Aliki Xochelli, Mattias Mattsson, Pamela Ranghetti, Ana Belén Espinosa, Alicia Robles, Julian Gorrochategui, Joaquín Martínez-López, Javier de la Serna, Marcos González, Alberto Chaparro Gil, Eduardo Anguita, Sandra Iraheta, Veerendra Munugalavadla, Christophe Quéva, Stacey Tannheimer, Richard Rosenquist, Kostas Stamatopoulos, Joan Ballesteros, Paolo Ghia
PI3Kδ (idelalisib) and BTK (ibrutinib) inhibitors have demonstrated significant clinical activity in chronic lymphocytic leukemia (CLL) interfering with the cross-talk between CLL cells and the lymph node microenviroment, yet their mechanism of action remains to be fully elucidated. Here, we developed an ex vivo model with the aim of reproducing the effects of the microenvironment that would help shed light on the in vivo mechanism of action of idelalisib and ibrutinib and predict their clinical efficacy in individual patients...
May 25, 2018: Oncotarget
Catherine J Reynolds, Kathryn Quigley, Xiaoming Cheng, Apurva Suresh, Sundas Tahir, Fiyyaz Ahmed-Jushuf, Khizr Nawab, Katherine Choy, Simone Alexandra Walker, Sara A Mathie, Malcolm Sim, Janet Stowell, Jiten Manji, Tracey Pollard, Daniel M Altmann, Rosemary J Boyton
RATIONALE: IL-8 dependent inflammation is a hallmark of host lung innate immunity to bacterial pathogens, yet in many human lung diseases including COPD, bronchiectasis, and pulmonary fibrosis, there are progressive, irreversible pathologic, changes associated with elevated levels of IL-8 in the lung. OBJECTIVES: To better understand the duality of IL-8 dependent host immunity to bacterial infection and lung pathology, we targeted human IL-8 to express transgenically in murine bronchial epithelium, investigating the impact of over-expression on lung bacterial clearance, host immunity, lung pathology and function...
June 12, 2018: American Journal of Respiratory Cell and Molecular Biology
Dharmendra Singh, Manisha Ghate, Sheela Godbole, Smita Kulkarni, Madhuri Thakar
Background: CD1d restricted invariant natural killer T (iNKT) cells are important in the activation and regulation of immune responses. Limited information is available regarding the functional role of iNKT cells in the human immunodeficiency virus (HIV) disease progression. Methodology: α-GalCer stimulated iNKT cells were characterized for their functionality in terms of cytokine production (IFN-γ, TNF-α, IL-2, IL-4, and IL-21) and CD107a expression in HIV-1 infected [23 long-term non progressors (LTNPs), 28 progressors, 18 patients before and after suppressive anti-retroviral treatment (ART)] along with 25 HIV-1 negative subjects using multicolor flow cytometry...
2018: Frontiers in Immunology
Xhevat Lumi, Mateja M Jelen, Daša Jevšinek Skok, Emanuela Boštjančič, Metka Ravnik-Glavač, Marko Hawlina, Damjan Glavač
The present study investigated the distribution of genotypes within single nucleotide polymorphisms (SNPs) in genes, related to PVR pathogenesis across European subpopulations. Genotype distributions of 42 SNPs among 96 Slovenian healthy controls were investigated and compared to genotype frequencies in 503 European individuals (Ensembl database) and their subpopulations. Furthermore, a case-control status was simulated to evaluate effects of allele frequency changes on statistically significant results in gene-association studies investigating functional polymorphisms...
2018: Journal of Ophthalmology
Mohammad Firoz Alam, Gyas Khan, Mohammed M Safhi, Saeed Alshahrani, Rahimullah Siddiqui, Sivakumar Sivagurunathan Moni, Tarique Anwer
Thymoquinone is the active constituent of Nigella sativa , having antioxidant and anti-inflammatory actions. In present study, we have analyzed the effects of thymoquinone on doxorubicin (DOX) induced cardiotoxicity in mice. In this experiment, thirty mice (25-35 gm) were divided into five groups (Groups A, B, C, D, and E) each containing six animals. Normal saline was given to a control group (Group A) for 14 days. Cardiotoxicity was induced by DOX (15 mg/kg, i.p.) in Group B, once on the 13th day of the study, and Groups C and D also received DOX (15 mg/kg, i...
2018: Cardiology Research and Practice
Zachary S Morris, Emily I Guy, Lauryn R Werner, Peter M Carlson, Clinton M Heinze, Jasdeep S Kler, Sara M Busche, Abigail A Jaquish, Raghava N Sriramaneni, Lakeesha Carmichael, Hans Loibner, Stephen D Gillies, Alan J Korman, Amy K Erbe, Jacquelyn A Hank, Alexander L Rakhmilevich, Paul M Harari, Paul M Sondel
In situ vaccination is an emerging cancer treatment strategy that uses local therapies to stimulate a systemic antitumor immune response. We previously reported an in situ vaccination effect when combining radiation (RT) with intra-tumor (IT) injection of tumor-specific immunocytokine (IC), a fusion of tumor-specific antibody and IL2 cytokine. In mice bearing two tumors, we initially hypothesized that delivering RT plus IT-IC to the "primary" tumor would induce a systemic antitumor response causing regression of the "secondary" tumor...
May 10, 2018: Cancer Immunology Research
Ling Zhao, Hongbin Zhao, Wen Qin, Gen Li, Junjie Tang, Jiuna Wang
To investigate the mechanism of cAMP/Ca 2+ signaling pathway inducing bone marrow mesenchymal stem cells to differentiate into neuronal cells, we cultured the bone marrow mesenchymal stem cells D1 cells in the present study. D1 cells were divided into two groups: control group and salidroside inducing groups. Control group was cultured with complete culture solution D/F12, while salidroside inducing groups were induced with 100 mg·L -1 salidroside for different time periods (24, 48 and 72 hours). PCR-array assay was used to detect expression of 84 calcium related mRNA, and significantly different genes were chosen to analyse...
June 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
Mie Okutani, Takamitsu Tsukahara, Yoshihiro Kato, Kikuto Fukuta, Ryo Inoue
A characteristic subset of T cells, known as double positive T cells (DPTC) and expressing both cluster of differentiation 4 (CD4) and CD8, is observed in porcine peripheral blood. Previous studies suggested that DPTC might be memory cells. However, detailed phenotypes and functions of DPTC are yet to be fully elucidated and thus, the relatedness of DPTC with memory phenotypes remains unclear. In this study, DPTC gene expression profiles in peripheral blood were analyzed by DNA microarray in Experiment 1 and compared with those of CD4 single positive T cells (4SPTC) and CD8 single positive T cells (8SPTC)...
May 8, 2018: Animal Science Journal, Nihon Chikusan Gakkaihō
David L Owen, Shawn A Mahmud, Kieng B Vang, Ryan M Kelly, Bruce R Blazar, Kendall A Smith, Michael A Farrar
The cytokine IL-2 is critical for promoting the development, homeostasis, and function of regulatory T (Treg) cells. The cellular sources of IL-2 that promote these processes remain unclear. T cells, B cells, and dendritic cells (DCs) are known to make IL-2 in peripheral tissues. We found that T cells and DCs in the thymus also make IL-2. To identify cellular sources of IL-2 in Treg cell development and homeostasis, we used Il2FL/FL mice to selectively delete Il2 in T cells, B cells, and DCs. Because IL-15 can partially substitute for IL-2 in Treg cell development, we carried out the majority of these studies on an Il15-/- background...
June 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Stephanie A K Angarita, Brian Truong, Suhail Khoja, Matthew Nitzahn, Abha K Rajbhandari, Irina Zhuravka, Sergio Duarte, Michael G Lin, Alex K Lam, Stephen D Cederbaum, Gerald S Lipshutz
The transplantation, engraftment, and expansion of primary hepatocytes have the potential to be an effective therapy for metabolic disorders of the liver including those of nitrogen metabolism. To date, such methods for the treatment of urea cycle disorders in murine models has only been minimally explored. Arginase deficiency, an inherited disorder of nitrogen metabolism that presents in the first two years of life, has the potential to be treated by such methods. To explore the potential of this approach, we mated the conditional arginase deficient mouse with a mouse model deficient in fumarylacetoacetate hydrolase (FAH) and with Rag2 and IL2-Rγ mutations to give a selective advantage to transplanted (normal) human hepatocytes...
June 2018: Molecular Genetics and Metabolism
V Cervera-Carrascon, M Siurala, J M Santos, R Havunen, S Tähtinen, P Karell, S Sorsa, A Kanerva, A Hemminki
Releasing the patient's immune system against their own malignancy by the use of checkpoint inhibitors is delivering promising results. However, only a subset of patients currently benefit from them. One major limitation of these therapies relates to the inability of T cells to detect or penetrate into the tumor resulting in unresponsiveness to checkpoint inhibition. Virotherapy is an attractive tool for enabling checkpoint inhibitors as viruses are naturally recognized by innate defense elements which draws the attention of the immune system...
2018: Oncoimmunology
Samuele Cazzamalli, Barbara Ziffels, Fontaine Widmayer, Patrizia Murer, Giovanni Pellegrini, Francesca Pretto, Sarah Wulhfard, Dario Neri
Purpose: Antibody-drug conjugates and small-molecule-drug conjugates have been proposed as alternatives to conventional anticancer cytotoxic agents, with the potential to deliver bioactive payloads to the site of disease, helping spare normal tissues. Experimental Design: Here, we describe a novel small-molecule-drug conjugate, based on a high-affinity ligand specific to carbonic anhydrase IX. The product featured a peptidic linker, suitable for cleavage in the tumor extracellular environment, and monomethyl auristatin E as cytotoxic payload...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hristo Georgiev, Inga Ravens, Georgia Papadogianni, Stephan Halle, Bernard Malissen, Gabriela G Loots, Reinhold Förster, Günter Bernhardt
Follicular helper (TFH) and regulatory (TFR) cells are critical players in managing germinal center (GC) reactions that accomplish effective humoral immune responses. Transcriptome analyses were done comparing gene regulation of TFH and TFR cells isolated from Peyer's Patches (PP) and immunized peripheral lymph nodes (pLNs) revealing many regulatory patterns common to all follicular cells. However, in contrast to TFH cells, the upregulation or downregulation of many genes was attenuated substantially in pLN TFR cells when compared to those of PP...
2018: Frontiers in Immunology
A Fleury, C Alaez, A Dessein, M Rosetti, B Saenz, M Hernández, R J Bobes, R Ramírez-Aquino, E Sciutto, C Gorodezky, G Fragoso
Neurocysticercosis (NC) is caused by the establishment of the metacestode stage of Taenia solium in the human central nervous system. A great heterogeneity in the susceptibility to the infection and to the disease has been reported. While the factors involved in this heterogeneity are not completely understood, clearly different immune-inflammatory profiles have been associated to each condition. This study evaluated the association of cytokine single nucleotide polymorphisms (SNPs) with susceptibility to infection and disease severity in NC patients...
April 21, 2018: Human Immunology
Keisuke Watanabe, Yanping Luo, Tong Da, Sonia Guedan, Marco Ruella, John Scholler, Brian Keith, Regina M Young, Boris Engels, Suvi Sorsa, Mikko Siurala, Riikka Havunen, Siri Tähtinen, Akseli Hemminki, Carl H June
Pancreatic ductal adenocarcinoma (PDA) is characterized by its highly immunosuppressive tumor microenvironment (TME) that limits T cell infiltration and induces T cell hypofunction. Mesothelin-redirected chimeric antigen receptor T cell (meso-CAR T cell) therapy has shown some efficacy in clinical trials but antitumor efficacy remains modest. We hypothesized that combined meso-CAR T cells with an oncolytic adenovirus expressing TNF-α and IL-2 (Ad5/3-E2F-D24-TNFa-IRES-IL2, or OAd-TNFa-IL2) would improve efficacy...
April 5, 2018: JCI Insight
Jonathan Alexander Pasternak, Glenn Hamonic, Jill Van Kessel, Colette L Wheler, Michael K Dyck, Heather L Wilson
PROBLEM: Induction of the local mucosal immune system within the reproductive tract is widely considered to be a key component in the development of effective prophylactic vaccines to control the spread of sexually transmitted infections. Here, we examine the capacity of the upper reproductive tract to act as a site of immune induction following. METHOD OF STUDY: Two vaccines formulated with a triple adjuvant combination and either recombinant bovine herpesvirus (tgD) protein or ovalbumin (OVA) were delivered at varying doses to the uterine lumen of rabbits and the resulting immune response evaluated after 32 days...
April 1, 2018: American Journal of Reproductive Immunology: AJRI
Jiehua Zhou, Daniel Lazar, Haitang Li, Xin Xia, Sangeetha Satheesan, Paige Charlins, Denis O'Mealy, Ramesh Akkina, Sheena Saayman, Marc S Weinberg, John J Rossi, Kevin V Morris
Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV-1, as they have the potential to maintain sustained viral inhibition with reduced treatment interventions. Such an option may represent a long-term treatment alternative to highly active antiretroviral therapy. Methods: We previously described a therapeutic approach, referred to as transcriptional gene silencing (TGS), whereby small noncoding RNAs directly inhibit the transcriptional activity of HIV-1 by targeting sites within the viral promoter, specifically the 5' long terminal repeat (LTR)...
2018: Theranostics
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