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Paclitaxel (PTX) is the standard first-line treatment of ovarian cancer, but its efficacy is limited by multidrug resistance. Therefore, it is crucial to identify effective drug targets to facilitate PTX sensitivity for ovarian cancer treatment. Seventy PTX-administrated ovarian cancer patients were recruited in this study for gene expression and survival rate analyses. Muscleblind-like-3 (MBNL3) gain-of-function and loss-of-function experiments were carried out in ovarian cancer cells (parental and PTX-resistant) and xenograft model. Cancer cell viability, apoptosis, spheroids formation, Nanog gene silencing were examined and conducted to dissect the underlying mechanism of MBNL3-mediated PTX resistance. High expression of MBNL3 was positively correlated with PTX resistance and poor prognosis of ovarian cancer. MBNL3 increased cell viability and decreased apoptosis in ovarian stem-like cells, through upregulating Nanog. This study suggests the MBNL3-Nanog axis is a therapeutic target for the treatment of PTX resistance in ovarian cancer management.
Information about pain and injury from equipment on a particular deployment is not disaggregated in the literature; thus, the nature of the issue is unclear.
To determine the prevalence of pain or injury during a particular deployment that military personnel attributed to equipment they used on this deployment; and to document the types of equipment they identified, the type of pain or injury and how they thought the pain or injury occurred.
This paper analyses data from a deployment and health survey of Australian Defence Force personnel. The participants are 8932 personnel who deployed to Iraq and 6534 who deployed to Afghanistan. Participants indicated whether they experienced pain or injury from equipment they used on deployment and detailed their experiences in response to an open-ended question (n = 563).
Sixteen per cent of Iraq-deployed and 21% of Afghanistan-deployed participants reported pain or injury from equipment they used on deployment. Body armour was the most common equipment identified; however, a wide range of equipment was related to pain or injury. A new finding is that pain or injury related to armour was attributed to its wear in vehicles and during vehicle ingress or egress.
Knowledge of the nature of pain or injury related to equipment used on deployment may help inform improved designs and practices to reduce or prevent avoidable harm to serving personnel.
Knowledge of the nature of pain or injury related to equipment used on deployment may help inform improved designs and practices to reduce or prevent avoidable harm to serving personnel.
Electroplating processes are widely used in metal industries to improve the resistance properties of manufactured metal parts. Workers in this industry are potentially exposed both to hexavalent chromium (Cr(VI)) and to other chromium compounds [mostly trivalent chromium (Cr(III))], due to the use of chromic acid baths. The goal of this study was to validate urinary chromium as a Cr(VI) exposure biomarker in the presence of exposure to other chromium compounds.
A biomonitoring study consisted in monitoring airborne chromium exposure and urinary chromium for one working week in 93 workers from nine electroplating companies. Chromium concentrations were measured in all urinations of each volunteer for the working week. Individual airborne soluble and insoluble Cr(VI) as well as Cr(III) concentrations were measured for all of the shifts of the week. The main statistical analysis consisted in modelling, in a Bayesian framework, the pre- and post-shift urinary chromium as a function of airborne Cr(III) and airich justifies using a BLV for assessing workers’ exposure. The estimated BLV was close to the recommended French BLV, which is 1.8 µg g-1 creatinine, in the electroplating industry.
In the present context of mixed exposure to Cr(III) and Cr(VI) in electroplating, this study showed that urinary chromium depended only on airborne Cr(VI) concentrations, which justifies using a BLV for assessing workers’ exposure. The estimated BLV was close to the recommended French BLV, which is 1.8 µg g-1 creatinine, in the electroplating industry.Legionella spp. are ubiquitous bacteria principally found in water networks and ∼20 species are implicated in Legionnaire’s disease. Among them, Legionella pneumophila is an intracellular pathogen of environmental protozoa, responsible for ∼90% of cases in the world. Legionella pneumophila regulates in part its virulence by a quorum sensing system named “Legionella quorum sensing,” composed of a signal synthase LqsA, two histidine kinase membrane receptors LqsS and LqsT and a cytoplasmic receptor LqsR. To date, this communication system was only found in L. pneumophila. Here, we investigated 58 Legionella genomes to determine the presence of a lqs cluster or homologous receptors using TBlastN. This analysis revealed three categories of species 19 harbored a complete lqs cluster, 20 did not possess lqsA but maintained the receptor lqsR and/or lqsS, and 19 did not have any of the lqs genes. selleck kinase inhibitor No correlation was observed between pathogenicity and the presence of a quorum sensing system. We determined by RT-qPCR that the lqsA gene was expressed at least in four strains among different species available in our laboratory. Furthermore, we showed that the lqs genomic region was conserved even in species possessing only the receptors of the quorum sensing system, indicating an ancestral acquisition and various loss dynamics during evolution. This system could therefore function in interspecific communication as well.Cellular liquid-liquid phase separation is a physiologically inevitable phenomenon in molecularly crowded environments inside cells and serves to compartmentalize biomolecules to facilitate several functions, forming cytoplasmic and nuclear RNA granules. Abnormalities in the phase separation process in RNA granules are implicated in the onset of several neurodegenerative diseases; the initial liquid-like phase-separated droplets containing pathogenic proteins are prone to aberrantly mature into solid-like droplets. RNAs are involved in the maturation of physiological and pathological RNA granules and are essential for governing the fate of phase-transition processes. Notably, RNA G-quadruplex (G4RNA), which is the secondary structure of nucleic acids that are formed in guanine-rich sequences, appears to be an advantageous scaffold for RNA-derived phase separation because of its multivalent interactions with RNAs and RNA-binding proteins. Here, we summarize the properties of RNA granules in physiological and pathological phase separation and discuss the potential roles of G4RNA in granules.