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1.
Parasite Immunol ; 40(7): e12535, 2018 07.
Article in English | MEDLINE | ID: mdl-29745990

ABSTRACT

Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL), deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. The significantly raised plasma levels of IL-4/IL-13 and IL-10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages. Accordingly, the classical markers for IL-4-driven monocytes/macrophages [M(IL-4)] were studied namely intramonocytic CD206+ , circulating CCL22 and CCL17, and were unchanged. Furthermore, the mRNA expression of Kruppel-like factor 4 (KLF4), peroxisome proliferator-activated receptors (PPAR)-γ and arginase-I (ARG-I) in peripheral blood mononuclear cells was unaltered. However, markers for IL-10-driven monocytes/macrophages [M(IL-10)], namely soluble CD163, intramonocytic IL-10, and circulating CXCL13 were significantly increased. Monocytes/macrophages of patients with VL demonstrated an increased expression of markers for M(IL-10), along with the absence of markers for M(IL-4). Taken together, in human VL, manipulation of these IL-10 polarized monocytes-macrophages may pave the way for improved therapeutic outcomes.


Subject(s)
Interleukin-10/analysis , Leishmania donovani/immunology , Leishmaniasis, Visceral/immunology , Adult , Aged , Female , Humans , Kruppel-Like Factor 4 , Leishmaniasis, Visceral/parasitology , Leukocytes, Mononuclear/immunology , Macrophages/immunology , Male , Middle Aged , Monocytes/immunology , Respiratory Burst
2.
Clin Pharmacol Ther ; 101(5): 575-577, 2017 May.
Article in English | MEDLINE | ID: mdl-28032900

ABSTRACT

Cancer is a highly heterogeneous disease, both between and within different target organs. Precision cancer prevention requires understanding the molecular pathways leading to cancer on a "per-person" level, identification of individuals most at risk for developing cancer, and tailoring interventions to accommodate pathogenesis, risk, and individual responses to interventions. This commentary will discuss how an investment in precision prevention research can accelerate cancer prevention agent development-the key to reducing cancer incidence and mortality.


Subject(s)
Medical Oncology/trends , Neoplasms/prevention & control , Precision Medicine/trends , Humans , Medical Oncology/standards , Precision Medicine/standards
3.
Radiat Prot Dosimetry ; 173(4): 293-301, 2017 Apr 15.
Article in English | MEDLINE | ID: mdl-26945800

ABSTRACT

Thermoluminescence (TL) characteristics of Y2O3:Er3+ nanophosphor exposed to UV radiations were investigated. Combustion synthesis method was employed to synthesise the nanophosphors. The confirmation for the pure cubic phase was done by powder X-ray diffraction. The particles formed were found to have 23.19 nm size and it was calculated by the Debye-Scherrer formula for [222] plane and is in close agreement with those obtained using transmission electron microscopy analysis. scanning electron microscopy micrograph reveals porous, irregular shaped particles with large agglomeration of particles whereas Fourier transform infrared spectroscopy studies confirm the presence of organic residua OH and CO in the samples. TL characteristics of UV irradiated Y2O3:Er3+ for (1-5) mol % were investigated. All the TL glow curves show almost similar glow curves having a single broad peak at 113.26, 113.82 113.72, 113.74 and 113.72°C for 1, 2, 3, 4 and 5 mol %, respectively, of Er3+ ions. The effects of heating rate were also studied and the trapping parameters, namely activation energy (E), order of kinetics (b) and frequency factor (s) were determined using Chen's peak shape method and computerised glow curve deconvolution technique suggested by Kitis for second-order kinetics. They were also discussed in detail for their possible usage in dosimetry.


Subject(s)
Nanostructures/chemistry , Spectroscopy, Fourier Transform Infrared , Ultraviolet Rays , Kinetics , Microscopy, Electron, Transmission , X-Ray Diffraction
4.
Luminescence ; 31(3): 728-37, 2016 May.
Article in English | MEDLINE | ID: mdl-26394709

ABSTRACT

In this work, we report the synthesis of Y2O3:Er(3+), Y2O3:Yb(3+) and Y2O3:Er(3+),Yb(3+) nanophosphors by the combustion synthesis method using urea as fuel. The doping agents were incorporated in the form of erbium nitrate and ytterbium nitrate. X-Ray diffraction (XRD) patterns revealed that the synthesized particles have a body-centered cubic structure with space group Ia-3. The photoluminescence (PL) properties were investigated after UV and infrared irradiation at room temperature. A strong characteristic emission of Er(3+) and Yb(3+) ions was identified, and the influence of doping concentration on the PL properties was systematically studied. Energy transfer from Yb(3+) to Er(3+) ions was observed in Y2O3 nanophosphors. The obtained result may be useful in potential applications such as bioimaging.


Subject(s)
Luminescence , Metals, Rare Earth/chemistry , Nanoparticles/chemistry , Oxygen/chemistry , Particle Size , Photochemical Processes , Surface Properties
5.
Radiat Prot Dosimetry ; 119(1-4): 62-5, 2006.
Article in English | MEDLINE | ID: mdl-16698970

ABSTRACT

Calcium fluoride CaF2 is an interesting host lattice for rare earth (RE) activators. CaF2 crystals doped with different concentrations of Dy, Ce, Er and Gd have been grown by the Bridgman technique and their deformation luminescence (DL) induced by room temperature gamma irradiation has been recorded. When a uniaxial pressure is applied on to gamma-irradiated CaF2:RE crystals, initially the DL intensity increases with time, attains a maximum value and then it decreases with time. Although the DL intensity produced during the release of pressure is less, its rise and decay behaviours are similar to that obtained during the application of pressure. The DL intensity depends on dopant, concentration of dopant, irradiation doses and mass of the load or applied pressure. It is suggested that the moving dislocation produced during deformation of crystals capture holes from hole trapped centres (like perturbed Vk centre) and the subsequent radiative recombination of the dislocation holes with electrons give rise to DL.


Subject(s)
Calcium Fluoride/chemistry , Calcium Fluoride/radiation effects , Luminescent Measurements/instrumentation , Thermoluminescent Dosimetry/instrumentation , Crystallization/methods , Dose-Response Relationship, Radiation , Elasticity , Equipment Design , Equipment Failure Analysis , Gamma Rays , Luminescent Measurements/methods , Pressure , Radiation Dosage , Reproducibility of Results , Sensitivity and Specificity , Thermoluminescent Dosimetry/methods
6.
Biochemistry ; 29(11): 2852-60, 1990 Mar 20.
Article in English | MEDLINE | ID: mdl-2346749

ABSTRACT

The binding of the antitumor drug CC-1065 has been studied with nuclear magnetic resonance (NMR) spectroscopy. This study involves two parts, the elucidation of the covalent binding site of the drug to DNA and a detailed investigation of the noncovalent interactions of CC-1065 with a DNA fragment through analysis of 2D NOE (NOESY) experiments. A CC-1065-DNA adduct was prepared, and an adenine adduct was released upon heating. NMR (1H and 13C) analysis of the adduct shows that the drug binds to N3 of adenine by reaction of its cyclopropyl group. The reaction pathway and product formed were determined by analysis of the 13C DEPT spectra. An octamer duplex, d(CGATTAGC.GCTAATCG), was synthesized and used in the interaction study of CC-1065 and the oligomer. The duplex and the drug-octamer complex were both analyzed by 2D spectroscopy (COSY, NOESY). The relative intensity of the NOEs observed between the drug (CC-1065) and the octamer duplex shows conclusively that the drug is located in the minor groove, covalently attached to N3 of adenine 6 and positioned from the 3'----5' end in relation to strand A [d(CGATTA6GC)]. A mechanism for drug binding and stabilization can be inferred from the NOE data and model-building studies.


Subject(s)
Adenine/analogs & derivatives , Antibiotics, Antineoplastic/metabolism , DNA Adducts , DNA/metabolism , Indoles , Leucomycins/metabolism , Base Sequence , Chemical Phenomena , Chemistry , Duocarmycins , Magnetic Resonance Spectroscopy/methods , Molecular Sequence Data , Nucleic Acid Conformation
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