Unveiling the link between NADPH oxidase 2 activation and mitochondrial superoxide formation in leukemic cell killing induced by arsenic trioxide.

This study focused on the interplay between NADPH oxidase 2 (NOX 2) activation and mitochondrial superoxide (mitoO) formation induced by clinically relevant concentrations of arsenic trioxide (ATO; AsO) in acute promyelocytic leukemia (APL) cells. Carefully controlled inhibitor studies and small interfering RNA mediated downregulation of p47 (a component of the NOX 2 complex) expression demonstrated that, in an APL cell line, ATO promotes upstream NOX 2 activation critically connected with the formation of mitoO and with the ensuing mitochondrial permeability transition (MPT)-dependent apoptosis. Instead, acute myeloid leukemia (AML) cell lines respond to ATO with low NOX 2 activation, resulting in a state that is non-permissive for mitoO formation.

Training radiology residents to evaluate deep myometrial invasion in endometrial cancer patients on MRI: A learning curve study.

Purpose: To evaluate the impact of a four-month training program on radiology residents' diagnostic accuracy in assessing deep myometrial invasion (DMI) in endometrial cancer (EC) using MRI.

Method: Three radiology residents with limited EC MRI experience participated in the training program, which included conventional didactic sessions, case-centric workshops, and interactive classes. Utilizing a training dataset of 120 EC MRI scans, trainees independently assessed subsets of cases over five reading sessions.

ERO1α primes the ryanodine receptor to respond to arsenite with concentration dependent Ca release sequentially triggering two different mechanisms of ROS formation.

A 6 h exposure of U937 cells to 2.5 μM arsenite stimulates low Ca release from the inositol 1, 4, 5-triphosphate receptor (IPR), causing a cascade of causally connected events, i.e.

Arsenite enhances ERO1α expression via ryanodine receptor dependent and independent mechanisms.

Arsenite is a potent carcinogen and toxic compound inducing an array of deleterious effects via different mechanisms, which include the Ca-dependent formation of reactive oxygen species. The mechanism whereby the metalloid affects Ca homeostasis involves an initial stimulation of the inositol 1, 4, 5-triphosphate receptor, an event associated with an endoplasmic reticulum (ER) stress leading to increased ERO1α expression, and ERO1α dependent activation of the ryanodine receptor (RyR). Ca release from the RyR is then critically connected with the mitochondrial accumulation of Ca.

Inhibition of activity/expression, or genetic deletion, of ERO1α blunts arsenite geno- and cyto-toxicity.

Our recent studies suggest that arsenite stimulates the crosstalk between the inositol 1, 4, 5-triphosphate receptor (IPR) and the ryanodine receptor (RyR) via a mechanism dependent on endoplasmic reticulum (ER) oxidoreductin1α (ERO1α) up-regulation. Under these conditions, the fraction of Ca released by the RyR via an ERO1α-dependent mechanism was promptly cleared by the mitochondria and critically mediated O formation, responsible for the triggering of time-dependent events associated with strand scission of genomic DNA and delayed mitochondrial apoptosis. We herein report that, in differentiated C2C12 cells, this sequence of events can be intercepted by genetic deletion of ERO1α as well as by EN460, an inhibitor of ERO1α activity.

Crosstalk between ERO1α and ryanodine receptor in arsenite-dependent mitochondrial ROS formation.

Arsenite, a well-established human carcinogen and toxic compound, promotes the formation of mitochondrial superoxide (mitoO) via a Ca-dependent mechanism, in which an initial stimulation of the inositol 1, 4, 5-trisphosphate receptor (IPR) is followed by the activation of the ryanodine receptor (RyR), critical for providing Ca to the mitochondria. We now report that, under the same conditions, arsenite triggers endoplasmic reticulum (ER) stress and a threefold increase in ER oxidoreductin 1α (ERO1 α) levels in proliferating U937 cells. EN460, an inhibitor of ERO1 α, recapitulated all the effects associated with RyR inhibition or downregulation, including prevention of RyR-induced Ca accumulation in mitochondria and the resulting O formation.

Functional organization of the endoplasmic reticulum dictates the susceptibility of target cells to arsenite-induced mitochondrial superoxide formation, mitochondrial dysfunction and apoptosis.

Arsenite induces many critical effects associated with the formation of reactive oxygen species (ROS) through different mechanisms. We focused on Ca-dependent mitochondrial superoxide (mitoO) formation and addressed questions on the effects of low concentrations of arsenite on the mobilization of the cation from the endoplasmic reticulum and the resulting mitochondrial accumulation. Using various differentiated and undifferentiated cell types uniquely expressing the inositol-1, 4, 5-triphosphate receptor (IPR), or both the IPR and the ryanodine receptor (RyR), we determined that expression of this second Ca channel is an absolute requirement for mitoO formation and for the ensuing mitochondrial dysfunction and downstream apoptosis.

Electronic detection of Drechslera sp. fungi in charentais melon ( Cucumis melo Naudin) using carbon-nanostructure-based sensors.

The development of chemical sensor technology in recent years has stimulated an interest regarding the use of characteristic volatiles and odors as a rapid and early indication of deterioration in fruit quality. The fungal infestation by Drechslera sp. in melons is a severe problem, and we demonstrate that electronic sensors based on carbon nanostructures are able to detect the presence of these fungi in melon.