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In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function. Although it has been reported in AML initiation and development, the contribution of NOX to the ROS production in AML remains to be clarified. The aim of this study was to investigate the NOX expression and function in AML, and to examine the role of NOX in blast proliferation and differentiation. First, we interrogated the NOX expression in primary cells from public datasets, and investigated their association with prognostic markers. Next, we explored the NOX expression and activity in AML cell lines, and studied the impact of NOX knockdown on cell proliferation and differentiation. We found that NOX2 is ubiquitously expressed in AML blasts, and particularly in cells from the myelomonocytic (M4) and monocytic (M5) stages, however, it is less expressed in LSCs and in relapsed AML. This is consistent with an increased expression throughout normal hematopoietic differentiation, and is reflected in AML cell lines. Nevertheless, no endogenous NOX activity could be detected in the absence of PMA stimulation. Furthermore, CYBB knockdown, although hampering induced NOX2 activity, did not affect the proliferation and differentiation of THP-1 and HL-60 cells. In summary, our data suggest that NOX2 is a marker of AML blast differentiation, while AML cell lines lack any NOX2 endogenous activity.

International audience; Acriflavine (ACF) is an antiseptic with anticancer properties, blocking the growth of solid and haematopoietic tumour cells. Moreover, this compound has been also shown to overcome the resistance of cancer cells to chemotherapeutic agents. ACF has been shown to target hypoxia-inducible factors (HIFs) activity, which are key effectors of hypoxia-mediated chemoresistance. In this study, we showed that ACF inhibits the growth and survival of chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cell lines in normoxic conditions. We further demonstrated that ACF down-regulates STAT5 expression in CML and AML cells but activates STAT3 in CML cells in a HIF-independent manner. In addition, we demonstrated that ACF suppresses the resistance of CML cells to tyrosine kinase inhibitors, such as imatinib. Our data suggest that the dual effect of ACF might be exploited to eradicate de novo or acquired resistance of myeloid leukaemia cells to chemotherapy.

Introduction This systematic review aims to study the feasibility, procedural, approaches, outcomes and complications of robot-assisted plastic and reconstructive surgery in patients and models. Method A systematic review was performed. Medline, Web of Science, Scopus, and Cochrane Library databases were searched. Articles investigating usage of surgeon-controlled robotic technology during plastic and reconstructive surgeries without manual intervention were eligible. Results Forty-one articles were included: 15 case series and 13 case reports, 8 cohort studies, 3 reviews and two surveys. Cohort size was 482, including: 426 patients (mean age: 54.9 years), 27 cadavers, 6 animal models, and 23 survey participants. All studies used the Da Vinci surgical system. The commonest procedure was transoral tumour resection. The commonest indication for reconstruction was head and neck squamous cell carcinoma (56%). The most frequently used flap was local musculo-mucosal (45%). Seventy-nine complications were reported. Conclusions Robot-assisted plastic and reconstructive surgery provides clinical outcomes comparable to conventional techniques. Advantages include reported improved cosmesis, functional outcomes and greater surgeon comfort. Disadvantages included longer operating and set-up times, a learning curve, breaking of microneedles, high monetary costs and authors consistently recommended improved end-effectors. All authors were optimistic about the use of robotics in plastic and reconstructive surgery.

Atherosclerosis remains and continues to be the leading cause of death and disability in the world. The implication of Renin-angiotensin-aldosterone system (RAAS) in the development of the disease is well experimentally and clinically documented. However, due to the complexity of the system, these studies remain dispersed and give no clear global view of the association between the system and the disease. In this regard, we studied the functional organization of a set of 37 genes encoding classical and newly discovered RAAS participants, including substrate, enzymes and receptors. This set was called extended RAAS (extRAAS). Using statistical analysis of human carotid atheroma transcriptome involving gene clustering, we revealed special features of extRAAS expression associated with atheromatous remodeling. An important feature of this pattern was the coordination of 2 clusters of genes that are known to favor atheroma formation. The first cluster constitutes genes that encode for angiotensin peptidases, including ACE, CTSG, CTSD and RNPEP. Whereas the second encode for receptors (AGTR1, MR, GR and LNPEP). We hypothesized that the local pattern of extRAAS gene expression plays a key role in the development of atherosclerosis by orienting the metabolism of active peptides, L'Athérosclérose est la principale cause de décès et d'invalidité dans le monde. L'implication du système rénine-angiotensine-aldostérone (RAAS) dans le développement de la maladie est expérimentalement et cliniquement bien documentée. Toutefois, en raison de la complexité du système, ces études ne donnent pas de vision claire sur l'association entre le système et la maladie. À cet égard, nous avons étudié l'organisation fonctionnelle d'un ensemble de 37 gènes codant pour les composants classiques et nouvellement découverts du RAAS, y compris les substrats, les enzymes et les récepteurs. Cet ensemble a été appelé RAAS étendu (extRAAS). En utilisant une analyse statistique des données du transcriptome de l'athérome carotidien humain, nous avons révélé des caractéristiques spéciales de l'expression de l'extRAAS associées au remodelage athéromateux. Une caractéristique importante de ce modèle est la coordination de 2 groupes de gènes qui sont connus pour favoriser la formation de l'athérome. Le premier groupe est constitué de gènes codant pour les peptidases de l'angiotensine, y compris ACE, CTSG, CTSD et RNPEP. Le deuxième groupe est constitué des gènes codant pour les récepteurs AGTR1, MR, GR et LNPEP

Atherosclerosis remains and continues to be the leading cause of death and disability in the world. The implication of Renin-angiotensin-aldosterone system (RAAS) in the development of the disease is well experimentally and clinically documented. However, due to the complexity of the system, these studies remain dispersed and give no clear global view of the association between the system and the disease. In this regard, we studied the functional organization of a set of 37 genes encoding classical and newly discovered RAAS participants, including substrate, enzymes and receptors. This set was called extended RAAS (extRAAS). Using statistical analysis of human carotid atheroma transcriptome involving gene clustering, we revealed special features of extRAAS expression associated with atheromatous remodeling. An important feature of this pattern was the coordination of 2 clusters of genes that are known to favor atheroma formation. The first cluster constitutes genes that encode for angiotensin peptidases, including ACE, CTSG, CTSD and RNPEP. Whereas the second encode for receptors (AGTR1, MR, GR and LNPEP). We hypothesized that the local pattern of extRAAS gene expression plays a key role in the development of atherosclerosis by orienting the metabolism of active peptides, L'Athérosclérose est la principale cause de décès et d'invalidité dans le monde. L'implication du système rénine-angiotensine-aldostérone (RAAS) dans le développement de la maladie est expérimentalement et cliniquement bien documentée. Toutefois, en raison de la complexité du système, ces études ne donnent pas de vision claire sur l'association entre le système et la maladie. À cet égard, nous avons étudié l'organisation fonctionnelle d'un ensemble de 37 gènes codant pour les composants classiques et nouvellement découverts du RAAS, y compris les substrats, les enzymes et les récepteurs. Cet ensemble a été appelé RAAS étendu (extRAAS). En utilisant une analyse statistique des données du transcriptome de l'athérome carotidien humain, nous avons révélé des caractéristiques spéciales de l'expression de l'extRAAS associées au remodelage athéromateux. Une caractéristique importante de ce modèle est la coordination de 2 groupes de gènes qui sont connus pour favoriser la formation de l'athérome. Le premier groupe est constitué de gènes codant pour les peptidases de l'angiotensine, y compris ACE, CTSG, CTSD et RNPEP. Le deuxième groupe est constitué des gènes codant pour les récepteurs AGTR1, MR, GR et LNPEP