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MicroRNAs (miRNAs) are small noncoding RNAs that are 19–24 nucleotides in length, following maturation. Recent evidence has demonstrated their key role as post-transcriptional regulators of gene expression through the binding of specific sequences within target messenger RNA (mRNA). miRNAs are involved in the synthesis of a very large number of proteins, and it is speculated that they could regulate up to 30% of the human genome. They control virtually every cellular process and are essential for animal development, cell differentiation, and homeostasis. Altered miRNA expression has been linked to such pathological events as inflammatory, degenerative, or autoimmune processes and have been associated with several diseases, including cancer, cardiovascular diseases, diabetes mellitus, and rheumatic and neurological disorders. Recently, miRNAs have been found in many different biological fluids, and this observation suggests the potential of miRNAs as new candidate biomarkers for diagnosis, classification, prognosis, and responsiveness in the treatment of different pathological conditions. Furthermore, the development of therapeutic strategies that involve either restoring or repressing miRNAs expression and activity has attracted much attention. Significant progress has been made in the systems for delivery of miRNAs, even if substantial improvements in this area are still necessary. Although they have been extensively studied, a number of interesting questions regarding the physiological and pathological role of miRNAs have been postulated, and their potential diagnostic and therapeutic role remain yet unanswered. Reactive oxygen species (ROS) are free radical-containing oxygen molecules derived from cellular oxidative metabolism, including enzyme activities and mitochondrial respiration, and play a pivotal role in many cellular functions. Whereas ROS are essential for normal cellular processes, their aberrant production, or failure of the capacity to scavenge excessive ROS, induces an altered redox status with excessive synthesis of free radicals, leading to an imbalance in the redox environment of the cell. The loss of normal ROS levels causes lipid, protein, and DNA damage, which contribute to the development of various pathologies including neurological disorders, rheumatic and cardiovascular diseases, diabetes, and cancer. Increasing evidence highlights that there is crosstalk between miRNAs and components of redox signaling, even if this complex and the characteristics of mutual interaction need to be amply elucidated. Hence, both miRNAs and oxidative stress are involved in the multifactorial development and progression of acute and chronic diseases by influencing numerous signaling and metabolic pathways. The Special Issue entitled "Crosstalk between MicroRNA and Oxidative Stress in Physiology and Pathology" of the International Journal of Molecular Sciences includes original articles and reviews that provide new insights into the interaction between miRNAs and oxidative stress under normal and pathological conditions which can assist in the development of new therapeutic strategies. Finally, I would like to thank all the authors for their excellent contribution. I hope this Special Issue will provide readers with updated knowledge about the role of miRNAs and oxidative stress in physiology and pathology.

miR-27a-5p --- acute myocardial infarction --- autophagy --- apoptosis --- hypoxia --- MicroRNA (miRNA) --- miR526b --- miR655 --- oxidative stress --- reactive oxygen species (ROS) --- superoxide (SO) --- Thioredoxin Reductase 1 (TXNRD1) --- breast cancer --- nucleic acid medicine --- pancreatic cancer --- clinical trial --- siRNA --- antisense oligonucleotide --- MicroRNA --- signal transduction --- therapeutic target --- miRNAs --- ROS --- noncoding RNA --- microRNA --- long noncoding RNA --- mitochondrial dysfunction --- nitrosative stress. exosome --- cross-talk --- systemic lupus erythematosus --- visfatin --- resistin --- osteoarthritis --- synovial fibroblasts --- synovitis --- NF-κB --- thyroid hormone --- liver cancer --- metabolism --- physiology --- ASH --- NAFLD --- NASH --- HCC --- HCV --- HBV --- endometriosis --- high-grade serous ovarian cancer --- endometriosis-associated ovarian cancer --- epithelial-to-mesenchymal transition --- chemoresistance --- antioxidants --- miRNA --- cancer --- diabetes --- beta cells --- microRNAs --- translation regulation --- neurodegeneration --- Alzheimer’s disease --- Parkinson’s disease --- Huntington’s disease --- ALS --- reactive oxygen species --- redox signaling --- therapeutic tolerance --- therapeutic resistance --- n/a --- Alzheimer's disease --- Parkinson's disease --- Huntington's disease

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MicroRNAs (miRNAs) are small noncoding RNAs that are 19–24 nucleotides in length, following maturation. Recent evidence has demonstrated their key role as post-transcriptional regulators of gene expression through the binding of specific sequences within target messenger RNA (mRNA). miRNAs are involved in the synthesis of a very large number of proteins, and it is speculated that they could regulate up to 30% of the human genome. They control virtually every cellular process and are essential for animal development, cell differentiation, and homeostasis. Altered miRNA expression has been linked to such pathological events as inflammatory, degenerative, or autoimmune processes and have been associated with several diseases, including cancer, cardiovascular diseases, diabetes mellitus, and rheumatic and neurological disorders. Recently, miRNAs have been found in many different biological fluids, and this observation suggests the potential of miRNAs as new candidate biomarkers for diagnosis, classification, prognosis, and responsiveness in the treatment of different pathological conditions. Furthermore, the development of therapeutic strategies that involve either restoring or repressing miRNAs expression and activity has attracted much attention. Significant progress has been made in the systems for delivery of miRNAs, even if substantial improvements in this area are still necessary. Although they have been extensively studied, a number of interesting questions regarding the physiological and pathological role of miRNAs have been postulated, and their potential diagnostic and therapeutic role remain yet unanswered. Reactive oxygen species (ROS) are free radical-containing oxygen molecules derived from cellular oxidative metabolism, including enzyme activities and mitochondrial respiration, and play a pivotal role in many cellular functions. Whereas ROS are essential for normal cellular processes, their aberrant production, or failure of the capacity to scavenge excessive ROS, induces an altered redox status with excessive synthesis of free radicals, leading to an imbalance in the redox environment of the cell. The loss of normal ROS levels causes lipid, protein, and DNA damage, which contribute to the development of various pathologies including neurological disorders, rheumatic and cardiovascular diseases, diabetes, and cancer. Increasing evidence highlights that there is crosstalk between miRNAs and components of redox signaling, even if this complex and the characteristics of mutual interaction need to be amply elucidated. Hence, both miRNAs and oxidative stress are involved in the multifactorial development and progression of acute and chronic diseases by influencing numerous signaling and metabolic pathways. The Special Issue entitled "Crosstalk between MicroRNA and Oxidative Stress in Physiology and Pathology" of the International Journal of Molecular Sciences includes original articles and reviews that provide new insights into the interaction between miRNAs and oxidative stress under normal and pathological conditions which can assist in the development of new therapeutic strategies. Finally, I would like to thank all the authors for their excellent contribution. I hope this Special Issue will provide readers with updated knowledge about the role of miRNAs and oxidative stress in physiology and pathology.

Medicine --- miR-27a-5p --- acute myocardial infarction --- autophagy --- apoptosis --- hypoxia --- MicroRNA (miRNA) --- miR526b --- miR655 --- oxidative stress --- reactive oxygen species (ROS) --- superoxide (SO) --- Thioredoxin Reductase 1 (TXNRD1) --- breast cancer --- nucleic acid medicine --- pancreatic cancer --- clinical trial --- siRNA --- antisense oligonucleotide --- MicroRNA --- signal transduction --- therapeutic target --- miRNAs --- ROS --- noncoding RNA --- microRNA --- long noncoding RNA --- mitochondrial dysfunction --- nitrosative stress. exosome --- cross-talk --- systemic lupus erythematosus --- visfatin --- resistin --- osteoarthritis --- synovial fibroblasts --- synovitis --- NF-κB --- thyroid hormone --- liver cancer --- metabolism --- physiology --- ASH --- NAFLD --- NASH --- HCC --- HCV --- HBV --- endometriosis --- high-grade serous ovarian cancer --- endometriosis-associated ovarian cancer --- epithelial-to-mesenchymal transition --- chemoresistance --- antioxidants --- miRNA --- cancer --- diabetes --- beta cells --- microRNAs --- translation regulation --- neurodegeneration --- Alzheimer's disease --- Parkinson's disease --- Huntington's disease --- ALS --- reactive oxygen species --- redox signaling --- therapeutic tolerance --- therapeutic resistance

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Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

Medicine --- clear cell renal cell carcinoma --- tumor evolution --- tumor ecology --- intratumor heterogeneity --- multisite tumor sampling --- targeted therapy --- uterine carcinosarcoma --- endometrial carcinoma --- metaplastic carcinoma --- epithelial-to-mesenchymal transition --- clonality --- mutation --- TP53 --- PI3K/AKT pathway --- gene expression --- miRNA expression --- tumor microenvironment --- interstitial pH --- acidosis --- tumor heterogeneity --- magnetic resonance imaging --- hyperpolarized 13C MRI --- carbonic anhydrase --- lactic acid --- positron emission tomography --- esophageal squamous cell carcinoma --- precision medicine --- natural killer cells --- tumor mutation burden --- immunotherapy --- PET --- heterogeneity --- radiomics --- radiopharmaceuticals --- SUV --- nuclear medicine --- colon cancer --- Wnt signaling --- phenotypic plasticity --- EMT --- hybrid E/M --- collective and single-cell migration --- beta-catenin paradox --- breast cancer --- immune microenvironment --- DCIS --- ADH --- mammary gland --- cell fate --- 3D cultures --- organoids --- signaling --- single-cell RNAseq --- tumor endothelial cell --- metastasis --- angiocrine factor --- microsatellite instability --- colorectal cancer --- immune checkpoints --- deficient mismatch repair --- plasticity --- biomechanics --- circulating tumor cells (CTCs) --- extracellular vesicles --- metastatic niche --- epigenetics --- CTC-clusters --- single-cell analysis --- cellular heterogeneity --- circulating tumor cells --- pancreatic cancer --- epithelial mesenchymal plasticity --- target discovery --- review --- genomics --- intra-tumour heterogeneity --- subclonal diversity --- treatment resistance

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Recent years have seen the idea of a close association between nutrition and the modulation of cancer development/progression reinforced. An increasing amount of experimental and epidemiological evidence has been produced supporting the concept that many different bioactive components of food (e.g. polyphenols, mono- and polyunsaturated fatty acids, methyl-group donors, etc.) may be implicated in either the promotion of or the protection against carcinogenesis. At the cellular level, such compounds can have an impact on different but sometimes intertwined processes, such as growth and differentiation, DNA repair, programmed cell death, and oxidative stress. In addition, compelling evidence is starting to build up of the existence of primary epigenetic targets of dietary compounds, such as oncogenic/oncosuppressor miRNAs or DNA-modifying enzymes, which in turn impair gene expression and function. Since there is a growing interest in the study of the biochemical and molecular role played by food components and its impact on cellular processes and/or gene expressions directed towards the fine-tuning of cancer phenotypes, in this Special Issue researchers contributed with either research or review articles presenting the latest findings on the intracellular pathways and mechanisms affected by natural bioactive dietary molecules.

berberine --- signaling pathways --- oncogenic cascades --- TRAIL --- microRNAs --- cancer therapy --- colon cancer cells --- ethanol --- Nrf2 --- HO-1 --- ER stress --- autophagy --- MMPs --- formononetin --- cancer --- preclinical models --- cell signaling --- angiogenesis --- nobiletin --- colorectal cancer --- chemoprevention --- bioactivities --- experimental therapeutics --- HDAC --- multiple myeloma --- oleacein --- breast cancer --- persistent organic pollutants --- breast cancer risk --- breast cancer prognostic --- systematic review --- carrageenan --- invasion --- metastasis --- RacGAP1 --- radiotherapy --- marine sponge --- natural product --- anticancer drug --- oral cancer inhibition --- phytochemicals --- small organic agents --- Piper eriopodon, alkenylphenols --- human cancer cells --- cell death --- apoptosis --- caspase-independent cell death --- XIAP antagonists --- XIAP-BIR3 domain --- Calocedrus formosana --- lung cancer --- yatein --- cell-cycle arrest --- xenograft --- isorhamnetin --- G2/M arrest --- ROS --- AMPK --- pancreatic cancer --- epigallocatechin-3-gallate (EGCG) --- gemcitabine --- glycolysis --- phosphofructokinase --- natural polyphenols --- anticancer activities --- molecular mechanisms --- Streptomyces --- mangrove --- anti-proliferative --- colon cancer --- epithelial mesenchymal transition --- inflammation --- malignant cancer --- natural anti-inflammatory compounds --- pro-resolving lipids --- anticancer drugs --- flavonoids --- natural compounds --- Xenopus laevis --- AOM/DSS model --- melanoma cells --- nicotine --- α9-nAChR --- PD-L1 --- STAT3 --- gigantol --- AKT --- JAK/STAT --- cancer stem cell --- tumor maintenance --- tumor density --- proteomics --- honokiol --- anticancer --- mechanism --- signalling pathway --- uterine sarcoma --- fucoidan --- isobolography --- colchicine alkaloid --- mesoporous silica nanoparticles --- targeted delivery system --- PD-1 immune checkpoint inhibitor and cancer immunotherapy --- glucose transport --- drugs --- innate immunity --- β-glucans --- nutrition --- immunotherapy --- estrogen --- estrogen receptor alpha --- polyphenols --- daidzein --- daidzein metabolites --- paclitaxel --- breast cancer cells --- obesity --- renin–angiotensin system --- eicosapentaenoic acid --- adipocyte inflammation --- olive leaf extract --- oleuropein --- Seahorse analysis --- cancer metabolism --- glycolytic markers --- Malva pseudolavatera Webb &amp --- Berthel. --- acute myeloid leukemia --- reactive oxygen species --- brain cancer --- gliomas --- schwannomas --- malignant tumors of the peripheral nerve sheath (MPNST) --- neurofibromas --- bioavailability --- nanoparticle-based delivery systems --- natural bioactive compound --- gallic acid --- EGFR signaling --- p53 --- EGCG --- non-coding RNAs --- anti-cancer drug --- NSCLC --- EGFR TKI --- FASN inhibitors --- resistance --- n/a --- renin-angiotensin system

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This special issue brings together cutting edge research and insightful commentary on the currentl state of the Cancer Nanomedicine field.

Technology: general issues --- antibody drug conjugate (ADC) --- PD-L1 --- tumor spheroid disruption --- immune modulation --- doxorubicin --- graphene oxide --- adsorption --- cathepsin D --- cathepsin L --- anti-metastatic enzyme cancer therapy --- nanoparticles --- targeted delivery system --- siRNA --- osteopontin --- mammary carcinoma --- mesenchymal stem cells (MSCs) --- TAT peptide --- PLGA --- paclitaxel --- nano-engineered MSCs --- orthotopic lung tumor model --- intracranial glioma --- immunotherapy --- CPMV --- viral nanoparticles --- in situ vaccine --- albumin nanoparticles --- microbubble --- ultrasound --- theranostics --- hepatocellular carcinoma --- VX2 tumor --- intra-arterial chemotherapy --- lung cancer --- nanomedicine --- clinical status --- cancer therapy --- breast cancer --- cell signaling --- active targeting --- passive targeting --- EPR effect --- oncogenes --- nanoparticle --- drug delivery --- ligand --- tumor targeting --- biodistribution --- Mesoporous silica nanoparticle --- drug delivery system --- target treatment --- lanthanide metal --- hyaluronic acid --- hyaluronidase --- drug combination --- everolimus --- dual-targeting --- magnetic nanoparticles --- monoclonal antibodies --- nanostructured lipid carrier --- platelet membrane --- biomimicry --- plasmonic photothermal therapy --- gold nanorods --- surgery --- bleeding --- dogs --- cats --- stimuli-responsive --- DOX --- SN38 --- CSCs --- single-walled carbon nanotubes --- chirality separation --- NASH --- drug-gene delivery --- near IR hyperspectral imaging --- plasmonics --- copper --- VEGF --- glioblastoma --- differentiated neuroblastoma --- peptidomimetics --- real-time quantitative polymerase chain reaction (qPCR) --- actin --- combinatorial therapy --- anticancer and antibacterial activity --- temoporfin --- drug-in-cyclodextrin-in-liposome --- hybrid nanoparticles --- multicellular tumor spheroids --- cyclodextrins --- photodynamic therapy article --- yet reasonably common within the subject discipline --- antitumor strategy --- biomimetic core–shell nanoparticles --- NK cell-derived exosomes --- folate receptor --- albumin nanoparticle --- microfluidic --- cabazitaxel --- polydopamine nanoparticles --- size --- cytotoxicity --- iron affinity --- FA-DABA-SMA --- self-assembly --- oncogenic proteins --- intracellular disruption --- folic receptor alpha --- pancreatic cancer --- parvifloron D --- albumin --- erlotinib --- photodynamic therapy --- lipid nanoparticles --- tumor vectorization --- verteporfin --- ovarian carcinomatosis --- spheroids --- integrin --- RGD peptide --- cancer diagnosis --- radiotherapy --- hyperthermia therapy --- biomimetic --- nanocarrier --- membrane-wrapped --- cancer --- targeted delivery --- photothermal therapy --- imaging --- cancer nanomedicine --- tumor microenvironment --- nano–bio interactions --- clinical translation --- magnetic nanowires --- magnetic hyperthermia --- magnetic actuation --- magnetic drug targeting --- titanate nanotubes --- gold nanoparticles --- vectorization --- colloidal stability --- docetaxel --- prostate cancer --- mangiferin --- anti-topoisomerase activity --- extracellular vesicles --- exosomes --- chemico-physical functionalization --- loading --- translational medicine --- nanotechnology: bioengineering --- anacardic acid --- mitoxantrone --- targeted drug delivery --- liposomes --- melanoma --- apoptosis --- ascorbic acid --- angiogenesis --- epithelial-to-mesenchymal transition --- hypoxia --- immunosuppression --- metabolism --- nanotherapeutics --- tumour microenvironment --- DNA origami --- liposome --- remote loading --- acute toxicity --- organoids --- magnetic silica-coated iron oxide nanochains --- photothermal treatment --- hyperthermia --- collagen --- cellular microenvironment --- lymphadenectomy --- magnetometer --- sentinel lymph node dissection --- SPION --- superparamagnetic iron oxide nanoparticles --- Vδ2 T cells --- zoledronic acid --- polymeric nanoconstruct --- anti-tumor immunity --- colorectal carcinoma --- β-cyclodextrin nanosponges --- BALB-neuT mice --- brain tumours --- glioma --- blood brain barrier --- polymeric nanoparticles --- PEGylation --- dioleoylphosphatidylethanolamine --- poly(hydroxyethyl acrylate-co-allyl methyl sulfide) copolymer --- folate --- oxidation-sensitive release --- cellular interaction --- in vitro anti-cancer activity --- triple negative breast cancer --- organotin --- mesoporous silica nanoparticles --- MDA-MB-231 --- theranostic nanomaterials --- nanobiotechnology --- molecular imaging --- nanosystems --- nanomicelles --- ovarian cancer --- tumour targeting --- chemotherapeutics --- riboflavin --- vitamin B2 --- nanomedicines --- secondary structure --- mixed micelle --- pH responsive --- targeted therapy --- anti-cancer --- shear stress --- flow --- in vitro --- therapeutics --- diagnostics --- Immunotherapy