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L-Y Hu, J-B Cui, X-M Xu, Z-H Huang, H-T Jiao
OBJECTIVE: Traumatic lung injury (TLI) can cause inflammation and oxidative stress, or even leads to acute respiratory distress syndrome (ARDS) and death. Nuclear factor erythroid-2 related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signal pathway participates in disease occurrence and progression via regulating inflammatory and oxidative stress response, but with its expression and functional roles in TLI largely unknown. MATERIALS AND METHODS: Wistar rats were randomly divided into control group, TLI group by crushing method, and Nrf2 activation group which received Nrf2 specific agonist sulforaphane 30 min before TLI treatment...
March 2018: European Review for Medical and Pharmacological Sciences
Silvana Neves Ferraz de Assunção, Ney Christian Amaral Boa Sorte, Crésio De Aragão Dantas Alves, Patrícia S Almeida Mendes, Carlos Roberto Brites Alves, Luciana Rodrigues Silva
INTRODUCTION: Non-alcoholic fatty liver disease is characterized by the intrahepatic deposition of fat. It is the most prevalent liver disease in the world, affecting obese children and adolescents. Its pathophysiology is not fully understood, although it is often related to insulin resistance. This in turn would be due to an inflammatory condition common to obesity. Thus, the objective of this study was to describe the behavior of proinflammatory cytokines in obese children and adolescents, with and without non-alcoholic fatty liver disease...
January 16, 2018: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
Erhao Zhang, Jieyi Gu, Jianpeng Xue, Chenyu Lin, Chen Liu, Mengwei Li, Jingchao Hao, Sarra Setrerrahmane, Xiaowei Chi, Weiyan Qi, Jialiang Hu, Hanmei Xu
BACKGROUND: Chimeric antigen receptors (CARs) presented on T cell surfaces enable redirection of T cell specificity, which has enormous promise in antitumor therapy. However, excessive activity and poor control over such engineered T cells cause significant safety challenges, such as cytokine release syndrome and organ toxicities. To enhance the specificity and controllable activity of CAR-T cells, we report a novel switchable dual-receptor CAR-engineered T (sdCAR-T) cell and a new switch molecule of FITC-HM-3 bifunctional molecule (FHBM) in this study...
March 20, 2018: Journal of Hematology & Oncology
Longcan Mei, Yanping Zhou, Lizhe Zhu, Changlin Liu, Zhuo Wu, Fangkui Wang, Gefei Hao, Di Yu, Hong Yuan, Yanfang Cui
A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm...
March 20, 2018: International Journal of Molecular Sciences
Hui Gao, Zhuo Dong, Xinkou Gong, Juancong Dong, Yuyu Zhang, Wei Wei, Rui Wang, Shunzi Jin
Exposure to ionizing radiation often induces T helper (Th) cell differentiation, resulting in an imbalance of Th1 and Th2 cellular subtypes, which can affect the efficacy of cancer radiotherapy. The aim of this study was to analyze differential expression of Th1, Th2 and Th3/Type 1 regulatory T cell (Tr1) subtype-related genes and cytokines in mouse thymocytes after high- and low-dose systemic radiation, using functional classification gene arrays and Elisa assays, and to explore the molecular mechanisms underlying radiation's immune effects and their relationship with Th1/Th2 immunity...
March 15, 2018: Journal of Radiation Research
John E Mullinax, MacLean Hall, Sangeetha Prabhakaran, Jeffrey Weber, Nikhil Khushalani, Zeynep Eroglu, Andrew S Brohl, Joseph Markowitz, Erica Royster, Allison Richards, Valerie Stark, Jonathan S Zager, Linda Kelley, Cheryl Cox, Vernon K Sondak, James J Mulé, Shari Pilon-Thomas, Amod A Sarnaik
Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Experimental design: Thirteen patients with metastatic melanoma were enrolled...
2018: Frontiers in Oncology
Xueting Liu, Liping Zeng, Zhongqiu Zhao, Yang Xie, Shan Wang, Junyan Zhang, Ying He, Zehong Zou, Jianguo Zhang, Ailin Tao
Staphylococcal enterotoxin A is well known as a superantigen and able to be used for cancer immunotherapy. In this study, recombinant Staphylococcal enterotoxin A was genetically conjugated to epidermal growth factor to produce a chimeric protein recombinant Staphylococcal enterotoxin A-epidermal growth factor expressed in Escherichia coli. The recombinant Staphylococcal enterotoxin A-epidermal growth factor protein was purified using Strep-Tactin affinity chromatography and Endotoxin Removal Resin and identified by sodium dodecyl sulfate-polyacrylamide gel electropheresis and liquid chromatography-tandem mass spectrometry analysis...
January 1, 2018: Technology in Cancer Research & Treatment
Lyle W Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B Willberg, James E Ussher, Dominique Goedhals, Jacob Hurst, Rodney E Phillips, Helen McShane, Cloete van Vuuren, John Frater
Background: Human immunodeficiency virus (HIV)-infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)-specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods: Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated...
March 13, 2018: Journal of Infectious Diseases
Adriano Luís Soares De Souza, Stefan Rudin, Rui Chang, Keith Mitchell, Timothy Crandall, Shuning Huang, Ji-Kyung Choi, Shinji L Okitsu, Danielle L Graham, Blake Tomkinson, Tammy Dellovade
INTRODUCTION: Antigen-specific immunotherapy could provide a targeted approach for the treatment of multiple sclerosis that removes the need for broad-acting immunomodulatory drugs. ATX-MS-1467 is a mixture of four peptides identified as the main immune-dominant disease-associated T-cell epitopes in myelin basic protein (MBP), an autoimmune target for activated autoreactive T cells in multiple sclerosis. Previous animal studies have shown that ATX-MS-1467 treatment prevented the worsening of signs of disease in experimental autoimmune encephalitis (EAE) in the humanized (DR2 × Ob1)F1 mouse in a dose-dependent fashion...
March 14, 2018: Neurology and Therapy
Denise C Hsu, Kimberly F Breglio, Luxin Pei, Chun-Shu Wong, Bruno B Andrade, Virginia Sheikh, Margery Smelkinson, Constantinos Petrovas, Adam Rupert, Leonardo Gil-Santana, Adrian Zelazny, Steven M Holland, Kenneth Olivier, Daniel Barber, Irini Sereti
Background: Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)-associated IRIS has not been fully elucidated. Methods: We investigated monocyte and CD4+ T-cell responses in vitro, tumor necrosis factor (TNF) expression in tissues, and plasma cytokines and inflammatory markers, in 13 HIV-infected patients with MAC-IRIS and 14 HIV-uninfected patients with pulmonary MAC infection...
March 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Hisanori Fukunaga, Yasuko Tatewaki, Tatsushi Mutoh, Hideo Shimomura, Shuzo Yamamoto, Chiaki Terao, Tomoko Totsune, Manabu Nakagawa, Yasuyuki Taki
BACKGROUND Primary cardiac lymphoma is rare and can be an aggressive disease, depending on the grade. A case is reported of low-grade primary cardiac lymphoma associated with a pericardial effusion. 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) imaging was useful in the diagnosis and in evaluating the disease activity in this case. CASE REPORT A 72-year-old Japanese woman visited a general practitioner, complaining of dyspnea associated with cardiac tamponade. Pericardiocentesis was performed, and Group V malignant cells were identified by cytology, suspicious for malignant lymphoma...
March 14, 2018: American Journal of Case Reports
Alexandros Briasoulis, Chakradhari Inampudi, Mohan Pala, Rabea Asleh, Paulino Alvarez, Jay Bhama
Approximately 50% of heart transplant programs currently employ a strategy of induction therapy (IT) with either interleukin-2 receptor antagonists (IL2RA) or polyclonal anti-thymocyte antibodies (ATG) during the early postoperative period. However, the overall utility of such therapy is uncertain and data comparing induction protocols are limited. The authors searched PubMed, the Cochrane Central Register of Controlled Trials, and through January 2018 for randomized controlled trials (RCTs) or observational controlled studies of IT vs no IT and IL2RA vs ATG...
March 13, 2018: Heart Failure Reviews
Lin Yuan, Wanli Li, Qianqian Huo, Chenhong Du, Zhixiang Wang, Baodi Yi, Mingfa Wang
This study investigated the effects of xylo-oligosaccharide (XOS) and flavomycin (FLA) on the performance and immune function of broiler chickens. A total of 150 ArborAcres broilers were randomly divided into three groups and fed for six weeks from one day of age in cascade cages. The diets of each test group were (1) a basal diet, (2) the basal diet supplemented with 2 mg/kg FLA, and (3) the basal diet supplemented with 2 mg/kg XOS. At 21 and 42 days, the growth performance index values and short-chain fatty acid (SCFA) concentrations in the cecum were quantified...
2018: PeerJ
Ariel E Marciscano, Ravi A Madan
Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis...
March 8, 2018: Current Treatment Options in Oncology
Zineb Lakhrif, Alexis Moreau, Bruno Hérault, Anne Di-Tommaso, Matthieu Juste, Nathalie Moiré, Isabelle Dimier-Poisson, Marie-Noëlle Mévélec, Nicolas Aubrey
Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination against Toxoplasma gondii requires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity to T. gondii . In this study, we explore an original vaccination strategy that combines administration via mucosal and systemic routes of fusion proteins able to target the major T...
2018: Frontiers in Immunology
Xiaoling Xie, Weijun Zhou, Yuxing Hu, Yiran Chen, Honghao Zhang, Yuhua Li
The identification and characterization of tumor-associated antigens (TAAs) that generate specific cytotoxic T lymphocytes (CTLs) are vital to the development of cancer immunotherapy. The epidermal growth factor receptor (EGFR) pathway substrate 8 gene (Eps8) is involved in regulating cancer progression and might be an ideal antigen. In this study, we searched for novel human leukocyte antigen (HLA)-A*2402-restricted epitopes derived from the Eps8 protein via the HLA-binding prediction algorithm. Among four candidates, peptides 327 (EFLDCFQKF), 534 (KYAKSKYDF) and 755 (LFSLNKDEL) induced peptide-specific CTLs to secrete higher levels of interferon-gamma (IFN-γ) and showed enhanced cytotoxic activity against malignant cancer cells...
March 7, 2018: Cell Death & Disease
Svetlana G Semushina, Dmitry A Aronov, Ekaterina V Moiseeva
Earlier, naturally arising mammary cancer in BLRB female mice was shown to reproduce some key pathological characteristics of the familial set of human breast cancer. Then we advanced a novel 3S-paradigm of anticancer research that helped to develop selection criteria and to estimate benefit/risk of local interleukin-2 (IL-2) effects in this spontaneous mouse model. In this paper, the efficacy of single and triple local IL-2 doses is compared using properly selected murine BLRB females based on our previously published data...
March 6, 2018: Pathology Oncology Research: POR
Rebecca K Sheean, Fiona C McKay, Erika Cretney, Christopher R Bye, Nirma D Perera, Doris Tomas, Richard A Weston, Karlene J Scheller, Elvan Djouma, Parvathi Menon, Stephen D Schibeci, Najwa Marmash, Justin J Yerbury, Stephen L Nutt, David R Booth, Graeme J Stewart, Mathew C Kiernan, Steve Vucic, Bradley J Turner
Importance: Neuroinflammation appears to be a key modulator of disease progression in amyotrophic lateral sclerosis (ALS) and thereby a promising therapeutic target. The CD4+Foxp3+ regulatory T-cells (Tregs) infiltrating into the central nervous system suppress neuroinflammation and promote the activation of neuroprotective microglia in mouse models of ALS. To our knowledge, the therapeutic association of host Treg expansion with ALS progression has not been studied in vivo. Objective: To assess the role of Tregs in regulating the pathophysiology of ALS in humans and the therapeutic outcome of increasing Treg activity in a mouse model of the disease...
March 5, 2018: JAMA Neurology
Jonathan T Sockolosky, Eleonora Trotta, Giulia Parisi, Lora Picton, Leon L Su, Alan C Le, Akanksha Chhabra, Stephanie L Silveria, Benson M George, Indigo C King, Matthew R Tiffany, Kevin Jude, Leah V Sibener, David Baker, Judith A Shizuru, Antoni Ribas, Jeffrey A Bluestone, K Christopher Garcia
Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal ( ortho ) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts...
March 2, 2018: Science
Milou C Schimmelpennink, Adriane D M Vorselaars, Frouke T van Beek, Heleen A Crommelin, Vera H M Deneer, Ruth G M Keijsers, Marcel Veltkamp
BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α) is effective third-line therapy in severe sarcoidosis. The originator product of Infliximab, Remicade® , is expensive, limiting universal access. Recently, a less expensive biosimilar of infliximab, Inflectra® , has become available, but the efficacy and tolerability has not been studied in sarcoidosis. METHODS: In this retrospective cohort study, 29 patients treated with the infliximab biosimilar Inflectra® , were analysed...
February 19, 2018: Respiratory Medicine
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