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The amino-acid L-glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Its extracellular concentration must be tightly regulated to avoid exitotoxicity-phenomena involved in the development and progression of neurodegenerative such as Alzheimer’ s disease, Parkinson’ s disease and amyotrophic lateral sclerosis. These are the astrocytes that are primarily involved in the regulation of extracellular glutamate. This regulation is carried out by transporters. This transport mechanism is energy consuming since it is coupled with the operation of a pump Na+/K+ATPase. Once inside the cell, glutamate can be converted to glutamine by the enzyme glutamine synthetase. This reaction is also energy consuming. The AMP-kinase, energy censor of the cell, is activated by modifications in the ratio of AMP I ATP when the cell is subjected to a decrease in ATP during energy stress, AMP-kinase is trying to restore the energy homeostasis by activating ATP-producing catabolic pathways and by inhibiting anabolic pathways that consume ATP. In the literature, AMPK has been described as regulating the transport systems of glucose and of glutamate transporters EAAT3 and EAAT4. In addition, mTOR whose signaling pathway is regulated closely by AMPK is involved in the regulation of glutamate transporter GLT 1. In this study, we wanted to characterize the influence of AMPK on the transport of glutamate in astrocytes. We have shown that AMPK induces astrocytes stellation. We also showed that AMPK does not involve modifying the transport of glutamate and glutamine synthetase activity in the short term. These results show the decoupling between the glutamate transport’s function in the astrocytes and the metabolic sensor’s role of AMPK. The primary results in treatments with different AICAR doses seem to indicate a decrease of the GS activity and of the transporting capacity of glutamate. The mitochondrial metabolism’s decrease observed after long term treatments shows that those two mechanisms aren’t completely independent of the general cellular metabolism L’acide aminé L-glutamate est le neurotransmetteur excitateur principal du système nerveux central SNC des mammifères. Sa concentration extracellulaire doit être finement régulée afin d’éviter les phénomènes d’exitotoxicité impliqués dans le développement et la progression de maladies neurodégénératives telles que la maladie d’Alzheimer, de Parkinson et la sclérose latérale amyotrophique. Ce sont les astrocytes qui sont essentiellement impliqués dans la régulation extracellulaire du glutamate. Cette régulation est réalisée par des transporteurs. Ce mécanisme de transport est consommateur d’énergie car il est couplé avec le fonctionnement d’une pompe Na+/K+ATPase. Une fois à l’intérieur de la cellule, le glutamate peut être transformé en glutamine par l’enzyme glutamine synthétase (GS). Cette réaction est également consommatrice d’énergie. L’AMP-kinase (AMPK), «senseur énergétique» de la cellule, est activée par des modifications du ratio AMP/ATP lorsque la cellule est soumise à une diminution de l’ATP. Lors de stress énergétique, l’AMPK tente de rétablir l’homéostasie énergétique en activant les voies cataboliques productrices d’ATP et en inhibant les voies anaboliques consommatrices d’ATP. Dans la littérature, 1’AMPK a été décrite comme régulant les systèmes de transport du glucose et des transporteurs de glutamate EAAT3 et EAAT4. De plus, la protéine mTOR dont l voie de signalisation est régulée de près par l’AMPK est impliquée dans la régulation du transporteur GLT1 du glutamate. Dans cette étude, nous avons donc voulu caractériser l’influence de l’AMPK sur le transport du glutamate dans les astrocytes. Nous avons pu montrer que l’AMPK induit la stellation des astrocytes après des traitements à l’AICAR. Nous avons également montré que l’activation AMPK n’entrainait pas de modification du transport du glutamate et de l’activité de la glutamine synthétase après des traitements de différentes doses d’AICARt1’AICAR à court terme. Ces résultats permettent de mettre en évidence un découplage entre la fonction de la prise en charge dans les astrocytes et le rôle de «senseur métabolique» de l’AMPK. Les résultats préliminaires lors des traitements à différentes doses d’AICAR à long terme, semble indiquer une diminution de l’activité GS et de la capacité de transport du glutamate. La diminution du métabolisme mitochondriale observée après les traitements à long terme montre que ces deux mécanismes ne sont pas totalement indépendants du métabolisme général de la cellule

Adelynate Kinase --- Amino-Acid N-Acetyltransferase --- SLC1A2 protein, human --- Central Nervous System

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Mycotoxins are a Public Health concern that in last year have reached the top 10 food and product hazard categories in the Rapid Alert System for Food and Feed (RASFF), with almost six hundred notifications. The toxicological effects of mycotoxins are evaluated through the extrapolation of results from in vivo and in vitro assays. Studies of mycotoxins’ effects at the cellular level precede those in organs and systems. All these studies are key steps for risk assessment and following legislation for mycotoxins. This Special Issue of Toxins comprises 10 original contributions and two reviews. The Issue reports new findings regarding toxic mechanisms, the use of innovative techniques to study the potential toxicity of mycotoxins not only individually but in combination, reflecting a real scenario according to current studies of mycotoxins.

Medicine --- Destruxin A --- Bombyx mori --- binding protein --- BmTudor-sn --- Bm12 cell --- Ochratoxin A (OTA) --- human Stem Cells --- mycotoxins --- cells --- cytotoxicity --- cell culture --- T-2 toxin --- HT-2 toxin --- apoptosis --- autophagy --- endophyte --- fungi --- neurotoxin --- lolitrems --- ochratoxin A --- beauvericin --- mixtures --- HepG2 cells --- genotoxicity --- cell cycle --- Fusarium --- Aspergillus --- Penicillium --- Alternaria --- emerging mycotoxin --- in vitro --- IPEC-J2 --- occurrence data --- trichothecene --- biosynthetic pathway --- acetyltransferase --- deacetylase --- deoxynivalenol --- 3-acetyldeoxynivalenol --- isotrichodermol --- isotrichodermin --- differentiated Caco-2 cells --- cell apoptosis --- transcriptome analysis --- hepatocyte --- chicken --- acute toxicity --- combined toxicity --- cell protection --- silibinin --- in silico prediction --- co-culture models --- mycotoxin interaction --- Loewe additivity --- combination index --- isobologram --- Chou-Talalay method --- MixLow --- IPEC-J2 cells --- RNA-seq --- inflammation --- MAPKs --- n/a --- Medicine.

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Mycotoxins are a Public Health concern that in last year have reached the top 10 food and product hazard categories in the Rapid Alert System for Food and Feed (RASFF), with almost six hundred notifications. The toxicological effects of mycotoxins are evaluated through the extrapolation of results from in vivo and in vitro assays. Studies of mycotoxins’ effects at the cellular level precede those in organs and systems. All these studies are key steps for risk assessment and following legislation for mycotoxins. This Special Issue of Toxins comprises 10 original contributions and two reviews. The Issue reports new findings regarding toxic mechanisms, the use of innovative techniques to study the potential toxicity of mycotoxins not only individually but in combination, reflecting a real scenario according to current studies of mycotoxins.

Medicine. --- Destruxin A --- Bombyx mori --- binding protein --- BmTudor-sn --- Bm12 cell --- Ochratoxin A (OTA) --- human Stem Cells --- mycotoxins --- cells --- cytotoxicity --- cell culture --- T-2 toxin --- HT-2 toxin --- apoptosis --- autophagy --- endophyte --- fungi --- neurotoxin --- lolitrems --- ochratoxin A --- beauvericin --- mixtures --- HepG2 cells --- genotoxicity --- cell cycle --- Fusarium --- Aspergillus --- Penicillium --- Alternaria --- emerging mycotoxin --- in vitro --- IPEC-J2 --- occurrence data --- trichothecene --- biosynthetic pathway --- acetyltransferase --- deacetylase --- deoxynivalenol --- 3-acetyldeoxynivalenol --- isotrichodermol --- isotrichodermin --- differentiated Caco-2 cells --- cell apoptosis --- transcriptome analysis --- hepatocyte --- chicken --- acute toxicity --- combined toxicity --- cell protection --- silibinin --- in silico prediction --- co-culture models --- mycotoxin interaction --- Loewe additivity --- combination index --- isobologram --- Chou-Talalay method --- MixLow --- IPEC-J2 cells --- RNA-seq --- inflammation --- MAPKs

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Biomarkers are of critical medical importance for oncologists, allowing them to predict and detect disease and to determine the best course of action for cancer patient care. Prognostic markers are used to evaluate a patient’s outcome and cancer recurrence probability after initial interventions such as surgery or drug treatments and, hence, to select follow-up and further treatment strategies. On the other hand, predictive markers are increasingly being used to evaluate the probability of benefit from clinical intervention(s), driving personalized medicine. Evolving technologies and the increasing availability of “multiomics” data are leading to the selection of numerous potential biomarkers, based on DNA, RNA, miRNA, protein, and metabolic alterations within cancer cells or tumor microenvironment, that may be combined with clinical and pathological data to greatly improve the prediction of both cancer progression and therapeutic treatment responses. However, in recent years, few biomarkers have progressed from discovery to become validated tools to be used in clinical practice. This Special Issue comprises eight review articles and five original studies on novel potential prognostic and predictive markers for different cancer types.

MSI2 --- OSCC --- oral cancer --- musashi 2 --- prognosis --- N-cadherin --- EMT --- breast cancer --- new metastasis --- eribulin --- blood --- biomarker --- bladder cancer --- immune checkpoint inhibitor --- CD8+ T effector cells --- microRNA --- biomarkers --- head and neck cancer --- laryngeal cancer --- prediction --- metastasis --- lifestyle habit --- chemo-/radio resistance --- therapeutic target --- AKT --- AR --- castration-resistant prostate cancer (CRPC) --- MAPK --- mTOR --- PI3K --- prostate cancer --- therapeutic resistance --- WNT --- miRNA --- melanoma --- melanoma resistance to MAPK/MEK inhibitors --- resistance to immune checkpoint inhibitors --- TNBC --- BRCA1/2 --- HRR --- PDL1 --- TILs --- PI3KCA --- PTEN --- CTCs --- CSC --- pancreatic cancer --- K-RAS oncogene --- oncogene dependency --- targeted therapies --- genomic mutations --- transcriptomics --- metabolomics --- selenoproteins --- cancer --- HUB nodes --- major histocompatibility complex (MHC) --- human leukocyte antigen (HLA) --- antigen processing machinery (APM) molecules --- carcinogenesis --- tumor predisposition --- cancer immunotherapy --- pheochromocytoma --- paraganglioma --- head and neck neoplasms --- head and neck tumors --- genetic syndromes --- mutations --- hyperglycemia --- cardioncology --- nivolumab --- cytokines --- cardiotoxicity --- acetyltransferase --- cancer prognosis --- NAA10 --- n/a

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Dear Colleagues, The brain is vulnerable to injury. Following injury in the brain, apoptosis or necrosis may occur easily, leading to various functional disabilities. Neuronal death is associated with a number of neurological disorders including hypoxic ischemia, epileptic seizures, and neurodegenerative diseases. The brain subjected to injury is regarded to be responsible for the alterations in neurotransmission processes, resulting in functional changes. Oxidative stress produced by reactive oxygen species has been shown to be related to the death of neurons in traumatic injury, stroke, and neurodegenerative diseases. Therefore, scavenging or decreasing free radicals may be crucial for preventing neural tissues from harmful adversities in the brain. Neurotrophic factors, bioactive compounds, dietary nutrients, or cell engineering may ameliorate the pathological processes related to neuronal death or neurodegeneration and appear beneficial for improving neuroprotection. As a result of neuronal death or neuroprotection, the brain undergoes activity-dependent long-lasting changes in synaptic transmission, which is also known as functional plasticity. Neuroprotection implying the rescue from neuronal death is now becoming one of global health concerns. This Special Issue attempts to explore the recent advances in neuroprotection related to the brain. This Special Issue welcomes original research or review papers demonstrating the mechanisms of neuroprotection against brain injury using in vivo or in vitro models of animals as well as in clinical settings. The issues in a paper should be supported by sufficient data or evidence. Prof. Bae Hwan Lee Guest Editor

Research & information: general --- global cerebral ischemia --- amiloride --- sodium–hydrogen exchanger-1 --- zinc --- neuronal death --- neuroprotection --- neurodegenerative disorder --- choline acetyltransferase (ChAT) --- trimethyltin (TMT) --- bean phosphatidylserine (Bean-PS) --- brain-derived neurotrophic factor --- moderate hypoxia --- physical exercise --- psychomotor function --- reaction time --- cortisol --- catecholamines --- nitrite --- endotheline-1 --- lactate --- pyridoxine deficiency --- ischemia --- gerbil --- homocysteine --- cell death --- glia --- neurogenesis --- N-acetyl-l-cysteine --- transient receptor potential melastatin 2 --- neurodegeneration --- Alzheimer’s disease --- metabolic disease --- adiponectin --- insulin --- antioxidants --- stroke --- preventive gene therapy --- adenoviral vector --- VEGF --- GDNF --- NCAM --- human umbilical cord blood mononuclear cells --- antioxidant --- brain --- neurodegenerative disease --- oxidative stress --- PGC-1α --- vascular endothelial growth factor --- vascular endothelial growth factor receptor 2 --- PI3K/AKT --- MEK/ERK --- status epilepticus --- hippocampus --- middle cerebral artery occlusion --- reperfusion injury --- lipid emulsion --- excitotoxicity --- apoptosis --- GPR4 receptor --- MPP+ --- Parkinson’s disease --- CRISPR/cas9 --- ischemic stroke --- blood brain barrier --- nanoparticle-based drug delivery --- brain targeting --- BDNF --- miRNAs --- synaptic plasticity --- depression --- glioblastoma --- astrocytes --- astrocytic networks --- connexin 43 --- calcium activity --- neural injury --- nimodipine --- subarachnoid haemorrhage --- acid-sensing ion channels --- oxygen-glucose deprivation --- liver growth factor --- inflammation --- microglia --- Tg2576 transgenic mice --- amyloid-beta --- oculomotor system --- trophic factors --- motoneurons --- axotomy --- amyotrophic lateral sclerosis --- electroneutral transport --- cation-chloride cotransporters --- KCCs --- NKCCs --- WNK-SPAK/OSR1 --- ascorbic acid --- aging --- organotypic hippocampal slice culture --- n/a --- sodium-hydrogen exchanger-1 --- Alzheimer's disease --- Parkinson's disease