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Environment, T-cells

Adam C Labonte, Sun-Sang J Sung, Lucas T Jennelle, Aditya P Dandekar, Young S Hahn
: The liver maintains an immunologically tolerant environment as a result of continuous exposure to food and bacterial constituents from the digestive tract. Hepatotropic pathogens can take advantage of this niche and establish lifelong chronic infections causing hepatic fibrosis and hepatocellular carcinoma. Macrophages (Mϕ) play a critical role in regulation of immune responses to hepatic infection and regeneration of tissue. However, the factors crucial for Mϕ in limiting hepatic inflammation or resolving liver damage have not been fully understood...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Michael R Gillings, Ian T Paulsen, Sasha G Tetu
Antibiotic resistance arises as a consequence of complex interactions among genes, mobile elements, and their bacterial hosts, coupled with the intense selection pressures imposed by humans in an attempt to control bacterial growth. Understanding the evolution of resistance requires an understanding of interacting cellular and genetic components. Here, we review how DNA analysis has helped reconstruct the origins of the mosaic, multiresistant mobile elements that have spread through pathogens in the last 60 years...
October 21, 2016: Annals of the New York Academy of Sciences
Joern Pezoldt, Jochen Huehn
Upon differentiation, T cells acquire tissue-specific homing properties allowing efficient targeting of effector T cells into distinct inflamed organs. Priming of T cells within skin-draining, peripheral lymph nodes (pLNs) leads to the expression of E- and P-selectin ligands, which facilitate migration into inflamed skin, whereas activation within gut-draining, mesenteric LNs (mLNs) results in induction of chemokine receptor CCR9 and integrin α4β7, both required for migration of effector T cells into mucosal tissues...
September 29, 2016: European Journal of Microbiology & Immunology
Naoshi Nishida, Masatoshi Kudo
Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of patients with advanced stage of disease remains unfavorable. Several immune therapies have been applied to HCC, and their responses have not been satisfactory. The immune response to cancer is determined by the balance between the antigenicity of the tumor and the microenvironment of cancer tissues. Generally, accumulated genetic mutations are observed in HCC, which may lead to increased neoantigens on cancer cells with high antigenicity...
October 21, 2016: Oncology
Michael S Zhang, Jon C D Houtman
Glycerol monolaurate (GML) is a monoglyceride with well characterized anti-microbial properties. Because of these properties, GML is widely used in food, cosmetics, and personal care products and currently being tested as a therapeutic for menstrual associated toxic shock syndrome, superficial wound infections, and HIV transmission. Recently, we have described that GML potently suppresses select T cell receptor (TCR)-induced signaling events, leading to reduced human T cell effector functions. However, how soluble host factors present in the blood and at sites of infection affect GML-mediated human T cell suppression is unknown...
2016: PloS One
O Lidický, M Šírová, T Etrych
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7...
October 20, 2016: Physiological Research
T Titma, R Shimmo, J Siigur, A Kahru
Heavy metals are found naturally on Earth and exposure to them in the living environment is increasing as a consequence of human activity. The toxicity of six different metal oxide nanoparticles (NP) at different points in time was compared using resazurin assay. After incubating Caco2 and A549 cells with 100 μg/mL of Sb2O3, Mn3O4 and TiO2 nanoparticles (NPs) for 24 h no toxic effects were observed while Co3O4 and ZnO NPs had moderate effects and CuO NPs were toxic below 100 μg/mL (24 h EC25 = 11 for A549 and 71 μg/mL for Caco2)...
October 19, 2016: Cytotechnology
Colleen E Dugan, James P Grinias, Sebastian D Parlee, Mahmoud El-Azzouny, Charles R Evans, Robert T Kennedy
Microfluidics is an enabling technology for both cell biology and chemical analysis. We combine these attributes with a microfluidic device for on-line solid-phase extraction (SPE) and mass spectrometry (MS) analysis of secreted metabolites from living cells in culture on the chip. The device was constructed with polydimethylsiloxane (PDMS) and contains a reversibly sealed chamber for perfusing cells. A multilayer design allowed a series of valves to control an on-chip 7.5 μL injection loop downstream of the cell chamber with operation similar to a six-port valve...
October 19, 2016: Analytical and Bioanalytical Chemistry
Aneela Yasmeen, Sarfraz Kiani, Afshan Butt, Abdul Qayyum Rao, Faheem Akram, Aftab Ahmad, Idrees Ahmad Nasir, Tayyab Husnain, Shahid Mansoor, Imran Amin, Shaheen Aftab, Muhammad Zubair, Muhammad Nouman Tahir, Sohail Akhtar, Jodi Scheffler, Brian Scheffler
The conserved coat or V2 gene of begomoviruses is responsible for viral movement in the plant cells. RNAi technology was used to silence V2 gene for resistance against these viruses in transgenic plants. The transformation of the RNAi-based gene construct targeting V2 gene of CLCuKoV-Bur, cloned under 35S promoter, was done in two elite cotton varieties MNH-786 and VH-289 using shoot apex cut method of gene transformation. The transformation efficiency was found to be 3.75 and 2.88 % in MNH-786 and VH-289, respectively...
October 18, 2016: Molecular Biotechnology
A Andrade, J Hope, A Allen, V Yorgan, D Lipscombe, J Q Pan
CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human CaV3.3 α1 subunit, a subtype of voltage-gated calcium channel that contributes to T-type currents. Recently, two de novo missense variations, T797M and R1346H, of hCaV3.3 were identified in individuals with schizophrenia. Here we show that R1346H, but not T797M, is associated with lower hCaV3.3 protein levels, reduced glycosylation, and lower membrane surface levels of hCaV3.3 when expressed in human cell lines compared to wild-type...
October 19, 2016: Scientific Reports
Adam R Wolfe, Nicholaus J Trenton, Bisrat G Debeb, Richard Larson, Brian Ruffell, Khoi Chu, Walter Hittelman, Michael Diehl, Jim M Reuben, Naoto T Ueno, Wendy A Woodward
Inflammatory breast cancer (IBC) is a unique and deadly disease with unknown drivers. We hypothesized the inflammatory environment contributes to the IBC phenotype. We used an in vitro co-culture system to investigate interactions between normal and polarized macrophages (RAW 264.7 cell line), bone-marrow derived mesenchymal stem cells (MSCs), and IBC cells (SUM 149 and MDA-IBC3). We used an in vivo model that reproduces the IBC phenotype by co-injecting IBC cells with MSCs into the mammary fat pad. Mice were then treated with a macrophage recruitment inhibitor, anti-CSF1...
October 15, 2016: Oncotarget
Debasish Sen, Stephen M Jones, Erin M Oswald, Henry Pinkard, Kaitlin Corbin, Matthew F Krummel
Myeloid-derived cells such as monocytes, dendritic cells (DCs), and macrophages are at the heart of the immune effector function in an inflammatory response. But because of the lack of an efficient imaging system to trace these cells live during their migration and maturation in their native environment at sub-cellular resolution, our knowledge is limited to data available from specific time-points analyzed by flow cytometry, histology, genomics and other immunological methods. Here, we have developed a ratiometric imaging method for measuring monocyte maturation in inflamed mouse lungs in situ using real-time using 2-photon imaging and complementary methods...
2016: PloS One
Ryan Dean Fortune, Raymond J Grill, Christine Beeton, Mark Tanner, Redwan Huq, David S Loose
Spinal cord injury (SCI) results in devastating changes to almost all aspects of a patient's life. In addition to a permanent loss of sensory and motor function, males will also frequently exhibit a profound loss of fertility through poorly understood mechanisms. We demonstrate that SCI causes measureable pathology in the testis both acutely (24 hours) and chronically, up to 1.5 years post injury, leading to loss in sperm motility and viability. SCI has been shown in humans and rats to induce leukocytospermia, with the presence of inflammatory cytokines, anti-sperm antibodies, and reactive oxygen species found within the ejaculate...
October 18, 2016: Journal of Neurotrauma
Lan He, Priscilla T Y Law, Siaw Shi Boon, Chuqing Zhang, Wendy C S Ho, Lawrence Banks, C K Wong, Juliana C N Chan, Paul K S Chan
Epidemiological evidence supports that infection with high-risk types of human papillomavirus (HPV) can interact with host and environmental risk factors to contribute to the development of cervical, oropharyngeal, and other anogenital cancers. In this study, we established a mouse epithelial cancer cell line, designated as Chinese University Papillomavirus-1 (CUP-1), from C57BL/KsJ mice through persistent expression of HPV-16 E7 oncogene. After continuous culturing of up to 200 days with over 60 passages, we showed that CUP-1 became an immortalized and transformed epithelial cell line with continuous E7 expression and persistent reduction of retinoblastoma protein (a known target of E7)...
2016: PloS One
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
Mahzad Akbarpour, Abdelnaby Khalyfa, Zhuanghong Qiao, Alex Gileles-Hillel, Isaac Almendros, Ramon Farré, David Gozal
STUDY OBJECTIVE: The presence of obstructive sleep apnea (OSA) in patients with cancer appears to be accompanied by poorer outcomes. However, the mechanisms underlying such association are unknown. Tumor infiltrating lymphocytes (TILs), including CD8+ T cells, function as cytotoxic T lymphocytes (CTLs), and mount immune responses to cancer by the release of cytolytic enzymes, including granzyme B (GzmB), perforin (Prf) and cytokines such as interferon (IFN)-γ. METHODS: Using established in vivo mouse models, we investigated CD8+ T cells and cancer stem cells (CSC) in intermittent hypoxia (IH) and sleep fragmentation (SF) in the context of tumor environment...
October 10, 2016: Sleep
Lorenza Rattazzi, Giuseppa Piras, Samuel Brod, Koval Smith, Masahiro Ono, Fulvio D'Acquisto
T cells are known to be plastic and to change their phenotype according to the cellular and biochemical milieu they are embedded in. In this study, we transposed this concept at a macroscopic level assessing whether changes in the environmental housing conditions of C57/BL6 mice would influence the phenotype and function of T cells. Our study shows that exposure to 2 weeks in an enriched environment (EE) does not impact the T cell repertoire in vivo and causes no changes in the early TCR-driven activation events of these cells...
2016: Frontiers in Immunology
Amanda Tivnan, Tatjana Heilinger, Ed C Lavelle, Jochen H M Prehn
Glioblastoma (GBM) is an aggressive brain tumour, associated with extremely poor prognosis and although there have been therapeutic advances, treatment options remain limited. This review focuses on the use of immunotherapy, harnessing the power of the host's immune system to reject cancer cells. Key challenges in glioma specific immunotherapy as with many other cancers are the limited immunogenicity of the cancer cells and the immunosuppressive environment of the tumour. Although specific antigens have been identified in several cancers; brain tumours, such as GBM, are considered poorly immunogenic...
October 14, 2016: Journal of Neuro-oncology
Natalie C Sadler, Hans C Bernstein, Matthew R Melnicki, Moiz A Charania, Eric A Hill, Lindsey N Anderson, Matthew E Monroe, Richard D Smith, Alexander S Beliaev, Aaron T Wright
: Photobiologically synthesized hydrogen (H2) gas is carbon-neutral to produce and clean to combust, making it an ideal biofuel. Cyanothece sp. ATCC 51142 is a cyanobacterium capable of performing simultaneous oxygenic photosynthesis and H2 production, a highly perplexing phenomenon because H2 evolving enzymes are O2-sensitive. We employed a systems-level in vivo chemoproteomic profiling approach to explore the cellular dynamics of protein thiol redox, and how thiol redox mediates the function of the dinitrogenase NifHDK, an enzyme complex capable of aerobic hydrogenase activity...
October 14, 2016: Applied and Environmental Microbiology
Emili Montserrat, Tycho Bauman, Julio Delgado
Medicine has been 'personalized' (i.e. centred in persons) since its foundation. Recently, however, the term 'personalized medicine' (or, better, 'precision medicine') has been introduced to define 'a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease'. This concept has gained momentum thanks to next-generation-sequencing (NGS) techniques that allow identification of molecular characteristics unique to the patient and to the tumour...
March 2016: Best Practice & Research. Clinical Haematology
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