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In the past, ‘traditional’ moderate-intensity continuous training (60-75% peak heart rate) was the type of physical activity most frequently recommended for both athletes and clinical populations (cf. American College of Sports Medicine guidelines). However, growing evidence indicates that high-intensity interval training (80-100% peak heart rate) could actually be associated with larger cardiorespiratory fitness and metabolic function benefits and, thereby, physical performance gains for athletes. Similarly, recent data in obese and hypertensive individuals indicate that various mechanisms – further improvement in endothelial function, reductions in sympathetic neural activity, or in arterial stiffness – might be involved in the larger cardiovascular protective effects associated with training at high exercise intensities. Concerning hypoxic training, similar trends have been observed from ‘traditional’ prolonged altitude sojourns (‘Live High Train High’ or ‘Live High Train Low’), which result in increased hemoglobin mass and blood carrying capacity. Recent innovative ‘Live Low Train High’ methods (‘Resistance Training in Hypoxia’ or ‘Repeated Sprint Training in Hypoxia’) have resulted in peripheral adaptations, such as hypertrophy or delay in muscle fatigue. Other interventions inducing peripheral hypoxia, such as vascular occlusion during endurance/resistance training or remote ischemic preconditioning (i.e. succession of ischemia/reperfusion episodes), have been proposed as methods for improving subsequent exercise performance or altitude tolerance (e.g. reduced severity of acute-mountain sickness symptoms). Postulated mechanisms behind these metabolic, neuro-humoral, hemodynamics, and systemic adaptations include stimulation of nitric oxide synthase, increase in anti-oxidant enzymes, and down-regulation of pro-inflammatory cytokines, although the amount of evidence is not yet significant enough. Improved O2 delivery/utilization conferred by hypoxic training interventions might also be effective in preventing and treating cardiovascular diseases, as well as contributing to improve exercise tolerance and health status of patients. For example, in obese subjects, combining exercise with hypoxic exposure enhances the negative energy balance, which further reduces weight and improves cardio-metabolic health. In hypertensive patients, the larger lowering of blood pressure through the endothelial nitric oxide synthase pathway and the associated compensatory vasodilation is taken to reflect the superiority of exercising in hypoxia compared to normoxia. A hypoxic stimulus, in addition to exercise at high vs. moderate intensity, has the potential to further ameliorate various aspects of the vascular function, as observed in healthy populations. This may have clinical implications for the reduction of cardiovascular risks. Key open questions are therefore of interest for patients suffering from chronic vascular or cellular hypoxia (e.g. work-rest or ischemia/reperfusion intermittent pattern; exercise intensity; hypoxic severity and exposure duration; type of hypoxia (normobaric vs. hypobaric); health risks; magnitude and maintenance of the benefits). Outside any potential beneficial effects of exercising in O2-deprived environments, there may also be long-term adverse consequences of chronic intermittent severe hypoxia. Sleep apnea syndrome, for instance, leads to oxidative stress and the production of reactive oxygen species, and ultimately systemic inflammation. Postulated pathophysiological changes associated with intermittent hypoxic exposure include alteration in baroreflex activity, increase in pulmonary arterial pressure and hematocrit, changes in heart structure and function, and an alteration in endothelial-dependent vasodilation in cerebral and muscular arteries. There is a need to explore the combination of exercising in hypoxia and association of hypertension, developmental defects, neuro-pathological and neuro-cognitive deficits, enhanced susceptibility to oxidative injury, and possibly increased myocardial and cerebral infarction in individuals sensitive to hypoxic stress. The aim of this Research Topic is to shed more light on the transcriptional, vascular, hemodynamics, neuro-humoral, and systemic consequences of training at high intensities under various hypoxic conditions.

repeated sprint training in hypoxia --- hypoxia --- ischemic preconditioning --- resistance training in hypoxia --- cerebral deoxygenation --- muscle activation --- HIF-1? --- anaerobic metabolism --- critical power --- muscle deoxygenation --- altitude training --- metaboreflex

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The Special Issue "In Vitro and In Vivo Models of Colorectal Cancer for Clinical Application", edited by Marta Baiocchi and Ann Zeuner for Cancers, collects original research papers and reviews, depicting the current state and the perspectives of CRC models for preclinical and translational research. Original research papers published in this issue focus on some of the hottest topics in CRC research, such as circulating tumor cells, epigenetic regulation of stemness states, new therapeutic targets, molecular CRC classification and experimental CRC models such as organoids and PDXs. Additionally, four reviews on CRC stem cells, immunotherapy and drug discovery provide an updated viewpoint on key topics linking benchtop to bedside research in CRC.

colorectal cancer --- organoids --- 3D bioprinting --- patient-derived xenograft --- cancer-on-chip --- drug combination --- cancer stem cells --- drug resistance --- clinical trials --- tumor-initiating cells --- tumor heterogeneity --- patient-derived cancer models --- single-cell RNA-sequencing --- tumor metabolism --- transcriptional programs --- tumor cell differentiation --- immunotherapy --- methods --- chromosomal instability --- DNA damage --- targeted therapy --- decitabine --- colon cancer --- DNA methylation --- clinical translation study --- machine learning --- patient-derived tumor organoid --- precision medicine --- radiation response --- rectal cancer --- PDX model --- CRC --- mutation analysis --- histological examination --- animal models --- in vitro culture --- cancer stem cell methods --- SATB2 --- colorectal carcinoma --- prognosis --- CDX2 --- circulating tumor cells --- CTC cluster --- size-based method --- ScreenCell® --- epithelial mesenchymal transition --- hypoxia --- HIF-1α --- immunofluorescence analysis --- sequential filtration

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This book will cover topics related to the preparation and use of heterogeneous catalytic systems for the transformation of renewable sources, as well as of materials deriving from agro-industrial wastes and by-products. At the same time, the ever-increasing importance of bioproducts, due to the acceptance and request of consumers, makes the upgrade of biomass into chemicals and materials not only an environmental issue, but also an economical advantage.

isoselenourea --- malignant --- chemotherapeutics --- epigenetics --- antitumor activity --- methylseleninic acid --- mTOR inhibitors --- tumor heterogeneity --- hypoxia --- ER stress --- melanoma --- EMT --- lipid peroxidation --- immune evasion --- hypoxia-inducible factors (HIFs) --- selenium-binding protein 1 --- glutathione --- DNA damage --- hSP56 --- apoptosis --- tocopherol --- anticancer --- viability --- SELENBP1 --- selenium --- clear-cell renal cell carcinoma microRNAs --- SBP1 --- entosis --- PD-L1 --- miRNA --- cancer stem cells --- cell plasticity --- disease --- clear cell renal cell carcinoma --- HIF --- head and neck cancer --- selenium species --- VEGF --- STAT3 --- hypoxia-inducible factor --- methylselenocysteine --- anticancer agent --- Se-containing nanoparticles --- DNA damage and repair --- radiation --- seleno-l-methionine --- cancer --- tumor microenvironment --- methylselenoesters

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MicroRNAs (miRs) are small noncoding RNAs that function as post-transcriptional regulators of gene expression and have important roles in almost all biological pathways. Deregulated miR expression has been detected in numerous cancers, where miRs act as both oncogene and tumor suppressors. Due to their important roles in tumorigenesis, miRs have been investigated as prognostic and diagnostic biomarkers and as useful targets for therapeutic intervention. From a therapeutic point of view, two modalities can serve to rectify gene networks in cancer cells. For oncomiRs, a rational means is downregulation through antagomirs. Moreover, observations of the pathological reductions in tumor-suppressive miRs have inspired the concept of “miR replacement therapy” to enhance the amount of these miRs, thereby restoring them to normal levels. However, the clinical applicability of miR-based therapies is severely limited by the lack of effective delivery systems. Therefore, to understand the role of this new class of regulators, we need to identify the mRNA targets regulated by individual miRs as well as to develop specific, efficient, and safe delivery systems for therapeutic miRs.

Breast cancer --- Hypoxia inducible factor 1-alpha (HIF-1α) --- MicroRNA (miRNA) --- miR526b --- miR655 --- Oxidative stress --- Migration --- Cyclooxygenase-2 (COX-2) --- Prostaglandin E2 receptor 4 (EP4) --- PI3K/Akt --- adipokines --- endometrial cancer --- estrogens --- hyperinsulinemia --- insulin --- insulin resistance --- insulin signaling --- insulin-like growth factors --- microRNA --- miRNA --- ovarian cancer --- survival --- prognostic factor --- serum LDH --- blood biomarker --- circulating microRNA --- plasma --- immunotherapy --- immune checkpoint inhibitors --- metastatic melanoma --- hepatocellular carcinoma --- metastasis --- exosome --- bioinformatics analysis --- renal cancer --- RCC --- ccRCC --- meta-analysis --- miRNAs --- normal B-cell development --- B-CLL --- miRNA-transcription factor network --- regulation --- biomarker --- therapy --- prognosis --- diagnosis --- progression --- prediction --- smoking --- non-small cell lung cancer --- methylation --- miR-584-5p --- YKT6 --- snoRNA --- 2′-O-methylation --- pseudouridylation --- malignant melanoma --- cancer stem cell --- stemness --- head and neck squamous cell carcinoma --- colon cancer --- cancer stem cells --- microRNAs --- deformability --- PARP --- replication stress --- targeted therapy --- breast cancer --- circulating biomarkers --- medulloblastoma --- brain tumour --- subgroups --- stem cells --- n/a --- 2'-O-methylation

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This Special Issue Book, “Marine Bioactive Peptides: Structure, Function, andTherapeutic Potential"" includes up-to-date information regarding bioactivepeptides isolated from marine organisms. Marine peptides have been found invarious phyla, and their numbers have grown in recent years. These peptidesare diverse in structure and possess broad-spectrum activities that have greatpotential for medical applications. Various marine peptides are evolutionaryancient molecular factors of innate immunity that play a key role in host defense.A plethora of biological activities, including antibacterial, antifungal, antiviral,anticancer, anticoagulant, endotoxin-binding, immune-modulating, etc., makemarine peptides an attractive molecular basis for drug design. This Special IssueBook presents new results in the isolation, structural elucidation, functionalcharacterization, and therapeutic potential evaluation of peptides found inmarine organisms. Chemical synthesis and biotechnological production of marinepeptides and their mimetics is also a focus of this Special Issue Book.

cone snail --- tilapia --- n/a --- animal models --- BRICHOS domain --- recombinant peptide --- calcium absorption --- plastein reaction --- antioxidant activity --- endothelial dysfunction --- C3a --- lung cancer --- invertebrate immunity --- identification --- zinc bioavailability --- NA-inhibitory peptide --- nuclear magnetic resonance (NMR) --- review --- ACE-inhibitory activity --- intestinal absorption --- hairtail (Trichiurus japonicas) --- DU-145 cells --- peptide --- crustacean --- venom duct --- Kalloconus --- drug design --- molecular symmetry --- arenicin --- ?-helix --- APETx2 --- conotoxins --- functional diversity --- docking --- conotoxin --- neuraminidase --- angiotensin II --- polychaeta --- influenza virus --- phylogeny --- gene expression --- host defense peptide --- Perinereis aibuhitensis --- anti-diabetic activity --- conopeptides --- SHRs --- Chlorella pyrenoidosa protein hydrolysate (CPPH) --- metastasis --- Caco-2 cell monolayer --- Nrf2 --- caco-2 cells --- HUVEC --- PYP15 --- sea cucumber --- decapeptide --- cytotoxic --- arenicin-1 --- marine peptides --- cell proliferation --- Conus --- Conus ateralbus --- self-production of hydrogen peroxide --- antimicrobial activity --- molecular dynamics --- machine learning --- tachyplesins --- ion channels --- gut microbiota --- Anthopleura anjunae oligopeptide --- signaling pathways --- half-fin anchovy hydrolysates --- NF-?B --- Chlorella pyrenoidosa protein hydrolysate-calcium chelate (CPPH-Ca) --- antihypertensive effect --- QAGLSPVR --- antimicrobial peptides --- vasculogenic mimicry --- antibacterial --- ?-hairpin --- innate immunity --- transcriptome sequencing --- HIF-1? --- Gracilariopsis lemaneiformis --- function --- ACE-inhibitory peptide --- complement --- peptide-zinc complex --- structure-activity relationship --- multi-functional peptides --- cod skin --- adsorption --- Maillard reaction products --- molecular docking --- antibacterial peptide --- PI3K/AKT/mTOR signaling pathway --- Arenicola marina --- structure–activity relationship --- antimicrobial peptide --- Rana-box --- acid-sensing ion channel --- Neptunea arthritica cumingii --- apoptosis --- membrane damage --- proteolytic system --- toxin --- polyphemusins --- computational studies --- muscle --- oyster zinc-binding peptide --- abalone --- pain relief --- transport routes --- cytotoxicity --- dexamethasone --- cell death --- host?microbe relationship --- anti-LPS factor --- MMPs --- protein synthesis --- structure --- Pyropia yezoensis peptide --- cone snails --- chemical synthesis --- prostate cancer --- Ugr 9-1 --- myotube atrophy