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The current enthusiasm for nanomaterials raises many questions in terms of public health. The use of nanoparticles is indeed becoming of their toxicity. A panel of amorphous manodispersed silica nanoparticles (SNP) is used here as a model to investigate some mechanisms and determinants of toxicity that could possibly be extrapolated to other nanoparticles.
A well-known mechanism in nanotoxicity involves reactive oxygen species (ROS) this mechanisms is investigated here with several tests exploring the different levels at which ROS may be involved. The release of ROS in the presence of SNP has been studied in acellular and cellular medium. Similarly, the effects of SNP on the gene expression of heme oxygenase-1 as well as on the oxidation state if glutathione was also investigated. We found no experimental argument in favour of the intervention of ROS in the presence of the SNP.
Another common mechanism of cytotoxicity is studied here: the membranolytic effects of nanoparticles. To this end, erythrocytes have been exposed to different SNPs. An haemolytic activity of the SNP was noticed and a linear regression taking into account the different physico-chemical characteristics of the SNPs showed that only the diameter is determinant for their haemolytic activity: the larger is the diameter the more haemolytic they are.
The addition of chloroquine (positively charged) to the haemolysis test reduced the haemolytic effect of silica particles (>100nm) because of its electrostatic interaction with their surface. In the case if silica nanoparticles (<100nm, negatively charged) chloroquine caused an increase of the haemolytic activity. The apparent hydrodynamic diameter of SNP in the presence of chloroquine was measured to try explaining these results. We noted a significant increase in the presence of chloroquine, confirming the effect of size on the membranolytic effect.
It appears from these different experiments that there is no argument in favour of a toxicity mechanism implicating ROS. The membranolytic effect has been demonstrated and the fact that the chloroquine modified the haemolytic activity of SNP suggests the presence of an interactional mechanism between SNPs surface and the cells membrane L’engouement actuel pour les nanomatériaux suscite de nombreuses questions sur le plan de la santé publique. L’utilisation des nanoparticules est en effet de plus en plus répandue et leur grande diversité pose problème lorsqu’il s’agit d’évaluer leur toxicité. Un panel de nanoparticules de silice (SNP) amorphes monodispersées est utilisé ici comme modèle pour investiguer certains mécanismes et déterminants de la toxicité qui pourront éventuellement être extrapolés à d’autres nanoparticules.
Un mécanisme bien connu en nanotoxicologie implique les espèces réactives de l’oxygène (ROS). Ce mécanisme est investigué ici grâce à plusieurs tests explorant les différents niveaux auxquels les ROS peuvent intervenir. La libération de ROS en présence de SNP a donc été étudiée en milieux acellulaire et cellulaire. De même, l’effet des SNP sur l’expression génique de la hème oxygénase-1 ainsi que sur l’état d’oxydation du glutathion a également été investigué. Nous n’avons pas trouvé d’argument expérimental en faveur de l’intervention des ROS en présence de SNP.
Un autre mécanisme fréquent de cytotoxicité est étudié ici : l’action membranolytique des nanoparticules. Pour ce faire, des érythrocytes sont exposés aux différentes SNP. Une hémolyse a été observée et une régression linéaire prenant en compte les différentes caractéristiques physico-chimiques des SNP a mis en évidence que seul le diamètre est déterminant pour l’activité hémolytique : plus leur diamètre est grand plus elles sont hémolytiques.
L’ajout de chloroquine (chargée positivement) au test d’hémolyse diminue l’effet hémolytique de particules de silice (>100nm) par absorption électrostatique à leur surface. Dans le cas des SNP (<100nm ; chargée négativement), la chloroquine a provoqué une augmentation de l’activité hémolytique. Le diamètre hydrodynamique apparent des SNP en présence de chloroquine a été mesuré pour essayer d’expliquer ces résultats. Celui-ci subit une augmentation importante en présence de chloroquine, confirmant l’influence de la taille sur l’effet membranolytique.
Il apparaît donc à travers ces différentes expériences qu’il n’y a pas d’argument en faveur d’un mécanisme de toxicité impliquant les ROS. L’effet membranolytique a été démontré et le fait que la chloroquine ait modifié l’activité hémolytique des SNP suggère la présence d’un mécanisme interactionnel entre la surface des SNP et les cellules

Nanoparticles --- Silicon Dioxide --- Reactive Oxygen Species --- Chloroquine

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Antibodies, Monoclonal --- Liposomes --- Chloroquine --- Malaria --- therapeutic use --- immunology --- administration & dosage --- drug therapy

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Malaria is one of the leading killers in the world today. Though drugs against malaria have a long history, attempts to develop novel therapeutics spanned the twentieth century and continue today. In this historical study, Leo B. Slater shows the roots and branches of an enormous drug development project during World War II. Fighting around the globe, American soldiers were at high risk for contracting malaria, yet quinine-a natural cure-became harder to acquire. A U.S. government-funded antimalarial program, initiated by the National Research Council, brought together diverse laboratories and specialists to provide the best drugs to the nation's military. This wartime research would deliver chloroquinine-long the drug of choice for prevention and treatment of malaria-and a host of other chemotherapeutic insights. A massive undertaking, the antimalarial program was to biomedical research what the Manhattan Project was to the physical sciences. A volume in the Critical Issues in Health and Medicine series, edited by Rima D. Apple and Janet Golden.

History, 20th Century. --- Biomedical Research --- Malaria --- Chloroquine --- Antimalarials --- Quinoline --- Antimalarial agents --- Antiprotozoal agents --- Ague --- Chills and fever --- Intermittent fever --- Malarial fever --- Fever --- Protozoan diseases --- 20th Cent. History (Medicine) --- 20th Cent. History of Medicine --- 20th Cent. Medicine --- Historical Events, 20th Century --- History of Medicine, 20th Cent. --- History, Twentieth Century --- Medical History, 20th Cent. --- Medicine, 20th Cent. --- 20th Century History --- 20th Cent. Histories (Medicine) --- 20th Century Histories --- Cent. Histories, 20th (Medicine) --- Cent. History, 20th (Medicine) --- Century Histories, 20th --- Century Histories, Twentieth --- Century History, 20th --- Century History, Twentieth --- Histories, 20th Cent. (Medicine) --- Histories, 20th Century --- Histories, Twentieth Century --- History, 20th Cent. (Medicine) --- Twentieth Century Histories --- Twentieth Century History --- history. --- Therapeutic use --- History --- Research --- Treatment --- Chemotherapy

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Nutritional deficiencies, and different nutritional and dietary lifestyles, whether poor or absent of essential nutrients, aside from excess intake, can lead to inflammatory complications and loss of function. Bioactive compounds are non-nutritional components derived from plants, foods, and beverages with a multitude of biological effects. The improvement of analytical techniques has allowed scientific community to state that the regular consumption of bioactive phytochemicals is related to the prevention of numerous pathologies, through mechanisms that involve oxidative stress reduction, gene expression modulation, and even enzymatic activation inhibition.

Medicine --- quercetin --- nervous system --- molecular signals --- pharmacological potential --- cognitive impairment. --- micronuclei --- radioprotectors --- radiation effects --- melanoma --- PNT2 --- B16F10 cells --- Ulmus parvifolia --- wound healing --- matrix metalloproteinase --- transforming growth factor --- skin rejuvenation --- kaempferol --- naringin --- orientin --- rutin --- vitexin --- chlorogenic acid --- citric acid --- malic acid --- quinic acid --- rosmarinic acid --- curcumin --- nanocurcumin --- neurological disorders --- nanocarriers --- liposomes --- cancer --- diet --- flavonoids --- food supplements --- hormesis --- phytoestrogens --- sulforaphane --- resveratrol --- cardiovascular disease --- nanomedicine --- liposome --- nanoformulation --- RNA-dependent RNA polymerase --- remdesivir --- chloroquine --- SARS-CoV-2 --- COVID-19 --- spike glycoproteins --- Acorus calamus --- ethnomedicinal --- phytochemistry --- toxicity --- pharmacological action --- clinical trial --- neuroprotective --- neurological --- metabolic application --- kurarinone --- coronavirus --- HCoV-OC43 --- autophagy --- infection --- MRC-5 cell --- LC3 --- p62/SQSTM1 protein --- n/a

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This Special Issue of Cancers focuses on new advances in the treatment of renal cell carcinoma, both surgical and pharmacological (and combinations of these), and novel approaches to tackle treatment resistance and improve our understanding of this phenomenon.

Medicine --- renal cell carcinoma --- autophagy --- hydroxychloroquine --- chloroquine --- ROC-325 --- cysteine cathepsins --- cysteine cathepsin inhibitors --- lysosome --- renal cancer --- metastatic renal cell carcinoma --- immune-based combination therapies --- network meta-analysis --- PD-L1 --- predictive --- biomarker --- treatment --- TKIs --- mRCC --- biomarkers --- soluble factors --- immunotherapy --- renal cell carcinoma (RCC) --- sunitib resistance --- artesunate (ART) --- Traditional Chinese Medicine (TCM) --- growth inhibition --- ferroptosis --- reactive oxygen species (ROS) --- clear cell renal cell carcinoma --- ccRCC --- RCC --- kidney cancer --- evolution --- evolutionary trajectory --- metastatic --- second line therapy --- renal cell cancer --- immune checkpoint inhibitors --- tyrosine kinase inhibitors --- individualization --- genomic signature --- transcriptomic analysis