Polyphenols act synergistically with doxorubicin and etoposide in leukaemia cell lines

The study aimed to assess the effects of polyphenols when used in combination with doxorubicin and etoposide, and to determine whether polyphenols sensitised leukaemia cells, causing inhibition of cell proliferation, cell cycle arrest and induction of apoptosis. This study is based on findings in solid cancer tumours, which have shown that polyphenols can sensitize cells to chemotherapy, and induce apoptosis and/or cell-cycle arrest. This could enable a reduction of chemotherapy dose and off-target effects, whilst maintaining treatment efficacy. Quercetin, apigenin, emodin, rhein and cis-stilbene were investigated alone and in combination with etoposide and doxorubicin in two lymphoid and two myeloid leukaemia cells lines. Measurements were made of ATP levels (using CellTiter-Glo assay) as an indication of total cell number, cell cycle progression (using propidium iodide staining and flow cytometry) and apoptosis (NucView caspase 3 assay and Hoechst 33342/propidium iodide staining). Effects of combination treatments on caspases 3, 8 and 9 activity were determined using Glo luminescent assays, glutathione levels were measured using the GSH-Glo Glutathione Assay and DNA damage determined by anti-γH2AX staining. Doxorubicin and etoposide in combination with polyphenols synergistically reduced ATP levels, induced apoptosis and increased S and/or G2/M phase cell cycle arrest in lymphoid leukaemia cell lines. However, in the myeloid cell lines the effects of the combination treatments varied; doxorubicin had a synergistic or additive effect when combined with quercetin, apigenin, emodin, and cis-stilbene, but had an antagonistic effect when combined with rhein. Combination treatment caused a synergistic downregulation of glutathione levels and increased DNA damage, driving apoptosis via caspase 8 and 9 activation. However, in myeloid cells where antagonistic effects were observed, this was associated with increased glutathione levels and a reduction in DNA damage and apoptosis. This study has demonstrated that doxorubicin and etoposide activity were enhanced by polyphenols in lymphoid leukaemia cells, however, differential responses were seen in myeloid cells with antagonistic responses seen in some combination therapies

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Sistema de entierros entre los Huaxtecos prehispanicos.

Du Solier W. Sistema de entierros entre los Huaxtecos prehispanicos.. In: Journal de la Société des Américanistes. Tome 36, 1947. pp. 195-214

Cerámica arqueológica de San Cristóbal Ecatepec.. Anales del Instituto Nacional de Antropología e Historia. Num. 31 Tomo III (1947-1948) Sexta Época (1939-1966)

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Hydrodynamic modelling of short-term dispersion in a macro-tidal sea, validation by high-resolution radionuclide tracer measurements

International audienceThis work aims to validate the dispersion parameters of hydrodynamic models for the short term (hour to week), and short distances (100 m-30 km), by using high precision and high frequency measurements of tritium obtained in the release plume. An instantaneous 2D hydrodynamic model has been developed with a mesh size of 110m and an area of 50x50 km. More than 7,000 samples have been collected and measured for tritium concentrations in 2002 and 2003. Currents and bathymetric measurements, as well as drifters observations complete these measurements. Results confirm the efficiency of the hydrodynamic model, main differences being attributable to bathymetry incertitudes. After calibration, the model gives accurate results during six hours following a release. The obtained field database represents an exceptional tool for hydrodynamic models validation in realistic conditions of releases, tide and wind, in an area where the current dynamic is particularly strong (more than 5 m/s during high tides). The dispersion parameters obtained will be applied for other hydrodynamic models covering continental macro-tidal seas. Such models will be used to simulate soluble pollutants dispersion, with known uncertainties, in realistic chronic or accidental release conditions