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Many macro and micro species, from terrestrial and aquatic environments, produce structurally unique compounds and, in many countries, still are the primary sources of medicines. In fact, secondary metabolites are an important source of chemotherapeutic agents but are also lead compounds for synthetic modification and the optimization of biological activity. Therefore, the exploitation of secondary metabolites, or their inspired synthetic compounds, offers excellent opportunities for the pharmaceutical industry. This Medicines Special Issue focuses on the great potential of secondary metabolites for therapeutic application. The Special Issue contains 16 articles reporting relevant experimental results, and an overview of bioactive secondary metabolites, their biological effects, and new methodologies that improve and accelerate the process of obtained lead compounds with regard to new drug development. We would like to thank all 83 authors, from all over the world, for their valuable contributions to this Special Issue.

Juniperus --- secondary metabolites --- diterpenes --- flavonoids --- lignans --- cytotoxic --- antitumor --- antibacterial --- amentoflavone --- deoxypodophyllotoxin --- frankincense --- Boswellia --- cembranoids --- cneorubenoids --- boswellic acids --- molecular docking --- Scabiosa --- flavonoids --- iridoids --- pentacyclic triterpenoids --- antioxidant --- anti-inflammatory --- antibacterial --- anticancer --- Cordyceps militaris --- xanthine oxidase --- antioxidant --- antibacterial --- cordycepin --- GC-MS --- Artemisia species --- Artemisia vachanica --- artemisinin --- HPLC-PAD --- Tajikistan --- Malus x domestica --- Tuscany --- ancient varieties --- nutraceutics --- antioxidants --- polyphenols --- sugars --- pectin --- defensins --- secondary metabolites --- plant defense --- antimicrobial and anticancer activity --- medicine --- innate immunity --- cannabis --- cannabinoids --- therapeutics --- toxicology --- analytical determination --- legalization --- natural products --- biosynthetic gene clusters --- secondary metabolites --- antiSMASH --- Mitragyna speciosa --- kratom --- secondary metabolites --- therapeutic uses --- toxicology --- analysis --- Maytenus chiapensis --- Celastraceae --- quinonemethide triterpenoids --- pristimerin --- tingenone --- HPLC-PDA --- Ocimum sanctum --- Lamiaceae --- (-)-rabdosiin --- cytotoxic activity --- triterpenoids --- phenolic derivatives --- nanoemulsion --- essential oils --- vector control --- infectious diseases --- TCM --- phytochemistry --- LC-MS/MS --- antioxidant activity --- ABTS --- DPPH --- FRAP --- ascorbic acid --- EGCG --- total phenolics --- antimicrobial activity --- sargaquinoic acid --- sarganaphthoquinoic acid --- antiplasmodial --- malaria --- PPAR-? --- sargahydroquinoic acid --- sarganaphthoquinoic acid --- sargachromenoic acid --- inflammation --- bowel diseases --- secondary metabolites --- biological activities --- medicinal applications --- plants --- seaweeds

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Cancer survival rates and successful organ transplantation in patients continues to increase due to improvements in early diagnosis and treatments. Since immuno-suppressive therapies are frequently used, the mortality rate due to secondary infections has become an ever-increasing problem. Opportunistic fungal infections are probably the deadliest threat to these patients due to their difficult early diagnosis, the limited effect of antifungal drugs and the appearance of resistances. In recent years, a considerable effort has been devoted to investigating the role of many virulence traits in the pathogenic outcome of fungal infections. New virulence factors (hypoxia adaptation, CO2 sensing, pH regulation, micronutrient acquisition, secondary metabolites, immunity regulators, etc.) have been reported and their molecular mechanisms of action are being thoroughly investigated. The recent application of gene-editing technologies such as CRISPr-Cas9, has opened a whole new window to the discovery of new fungal virulence factors. Accurate fungal genotyping, Next Generation Sequencing and RNAseq approaches will undoubtedly provide new clues to interpret the plethora of molecular interactions controlling these complex systems. Unraveling their intimate regulatory details will provide insights for a more target-focused search or a rational design of more specific antifungal agents. This Special Issue is show significant discoveries, proofs of concept of new theories or relevant observations in fungal pathogenesis and its regulation.

Fungal virulence --- Fungal genotyping --- Biofilm formation --- Immune evasion --- CO2 sensing --- pH regulation --- Micronutrient acquisition --- Trehalose biosynthesis --- Secondary metabolites and toxins --- Regulation of antifungals resistance --- Criptococcus, Candida, Aspergillus, Scedosporium, Fusarium, Pneumocysits

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Throughout most of history, medicinal plants and their active metabolites have represented a valuable source of compounds used to prevent and to cure several diseases. Interest in natural compounds is still high as they represent a source of novel biologically/pharmacologically active compounds. Due to their high structural diversity and complexity, they are interesting structural scaffolds that can offer promising candidates for the study of new drugs, functional foods, and food additives.Plant extracts are a highly complex mixture of compounds and qualitative and quantitative analyses are necessary to ensure their quality. Furthermore, greener methods of extraction and analysis are needed today.This book is based on articles submitted for publication in the Special Issue entitled “Qualitative and Quantitative Analysis of Bioactive Natural Products” that collected original research and reviews on these topics.

Talaromyces pinophilus --- talarodiolide --- macrodiolides --- GC/MS --- secondary metabolites --- anthocyanins --- red cabbage --- recycling preparative high performance liquid chromatography --- stability --- UHPLC-MS/MS --- decursin --- decursinol angelate --- nodakenin --- decursinol --- Ginkgo biloba Extract (GBE) --- chromatogram-bioactivity correlation --- bioactive compounds --- endothelial function --- wine --- volatile compounds --- terrain conditions --- odor-activity values --- SPME-GC/MS --- Bolbostemma paniculatum --- identification --- LTQ-Orbitrap --- UPLC --- multivariate statistical analysis --- cannabidiol --- CBD oil --- terpenes --- hemp seed oil --- GC-MS --- HPLC-Q-Exactive-Orbitrap-MS --- Rossa da inverno sel. Rojo Duro onion cultivar --- geographical origin --- amino acids content --- HPLC analysis --- statistical evaluations --- food traceability --- aleuritolic acid --- autophagy --- apoptosis --- HPLC --- Curcuma longa --- turmeric --- curcuminoids --- turmerone --- quantification --- Quercus acuta leaf --- antioxidant --- antibacterial activity --- Staphylococcus aureus --- Erigeron breviscapus extract --- UPLC-ESI-MS/MS --- cerebral ischemia reperfusion injury --- scutellarin --- scutellarein --- HPLC --- Podospermum --- Scorzonera --- triterpenes --- ginseng berry extract --- ginsenosides --- stereoselective and simultaneous analysis --- pharmacokinetics --- oral administration --- saffron --- crocins --- UHPLC analysis --- separation optimisation --- artificial neural network --- response surface methodology --- bioactive natural compounds --- secondary metabolites --- Alzheimer’s disease --- Olea europaea L. --- liquid chromatography --- gas chromatography --- mass spectrometry --- secondary metabolites --- olive leaves --- Moroccan region --- phenolic compounds --- liquid chromatography-mass spectrometry --- chemometrics --- metabolic profiling --- Sorbus --- fruit powders --- phenolic compounds --- carotenoids --- sugars --- organic acids --- chili --- capsaicinoids --- phenolics --- free radical-scavenging --- geographical variation --- 1-triacontanol --- HPLC-ELSD --- biostimulant --- method validation --- Myristica fragrans --- nutmeg --- essential oil --- ionic liquids --- hydrodistillation --- MODDE experimental design --- rice --- phenolic compounds --- phenolic acids --- flavonoids --- anthocyanins --- proanthocyanidins --- antioxidant activity --- extraction --- HPLC methods --- phenolic compounds --- Spondias spp. --- UPLC-MS --- antioxidant capacity --- Iris lactea Pall. var. chinensis (Fisch.) Koidz. --- HPLC-Q-TOF-MS/MS --- qualitative analysis --- quantitative analysis --- C-glycosylflavone --- traditional Chinese medicine decoction --- quality evaluation --- UPLC-QTOF-MS --- UFLC-QQQ-MS --- ShenFu prescription decoction

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Seaweeds are recognized as highly nutritious, and their use in gastronomy is increasing. Their health benefits and their potential to prevent several diseases have also been established. In this Special Issue several health effects are discussed, with more emphasis on their antitumor activity and potential use to treat Alzheimer’s disease. The key bioactive metabolites, from which phlorotannins can be highlighted, are presented, as well as some important in vivo studies. Altogether, the chapters provide in-depth information about the biological activities of seaweed metabolites, contributing to elucidate the health effects of seaweed.

Padina pavonica --- osteosarcoma --- apoptosis --- algae --- chemo-preventive agent --- phytol --- fucosterol --- fatty acid --- laurinterol --- Laurencia --- antitumoral --- breast cancer explants --- organotypic culture --- ex vivo --- phlorotannin --- eckmaxol --- high-speed counter-current chromatography --- NMR spectroscopy --- mass spectrometry --- isolation and purification --- Ecklonia maxima --- fucoidan --- age-related macular degeneration --- VEGF --- oxidative stress --- Saccharina latissima --- Fucus vesiculosus --- Fucus distichus subsp. evanescens --- Fucus serratus --- Laminaria digitata --- Symphyocladia latiuscula --- bromophenols --- mushroom tyrosinase --- B16F10 --- melanin --- red seaweed --- bioactives --- extraction --- biorefinery --- seaweed --- gut microbiota --- prebiotics --- dietary fibre --- complex polysaccharides --- polyphenols --- polyunsaturated fatty acids --- carotenoids --- phytochemicals --- Padina pavonica --- marine algae --- osteoporosis --- bone metabolism --- bone health --- nutraceutical --- Bifurcaria bifurcata --- linear diterpenes --- extraction --- identification --- biological activities --- macroalgae --- high value applications --- phlorotannin --- amyloid-? aggregation --- insulin glycation --- dynamic simulation --- kidney --- ischemia-reperfusion injury --- Ecklonia cava --- phlorotannins --- Alzheimer’s disease --- seaweeds --- cholinesterases --- beta-secretase --- beta-amyloid aggregation --- neuroprotection --- K14HPV16 --- genotoxicity assay --- papillomavirus --- cancer --- seaweeds --- hyperpigmentation --- skin aging --- skincare --- photo-protection --- seaweeds --- secondary metabolites --- in vivo studies --- clinical trials --- health effects --- dieckol --- eckol --- fucoxanthin --- kahalalide F

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Cyanobacteria are a group of ubiquitous photosynthetic prokaryotes. Their occurrence has been increasing worldwide, due to anthropogenic activities and climate change. Several cyanobacterial species are able to synthesize a high number of bioactive molecules, among them, cyanotoxins (microcystins, cylindrospermopsin, nodularin, etc.), which are considered a health concern. For risk assessment of cyanotoxins, more scientific knowledge is required to perform adequate hazard characterization, exposure evaluation and, finally, risk characterization of these toxins. This Special Issue “Cyanobacteria and Cyanotoxins: New Advances and Future Challenges” presents new research or review articles related to different aspects of cyanobacteria and cyanotoxins, and contributes to providing new toxicological data and methods for a more realistic risk assessment.

cylindrospermopsin --- in vitro --- cytotoxicity --- oxidative stress --- genotoxicity --- microcystins --- taste-and-odor compounds --- water source --- drinking water treatment plant --- cyanobacterial thresholds --- arctic --- benthic mats --- cyanotoxins --- ELISA --- 16S rRNA gene --- apoptosis --- microcystin-LR (MC-LR) --- reproductive toxicity --- resveratrol --- sirtuin 1 (SIRT1) --- Aphanizomenon flos-aquae --- blue-green algae supplements --- cyanotoxins --- microcystin --- cylindrospermopsin --- saxitoxin --- cylindrospermopsin --- monoclonal antibody --- time-resolved fluoroimmunoassay --- method validation --- detection --- cyanobacteria --- cyanotoxins --- nutrient enrichment --- akinetes --- harmful algal blooms --- PCR --- phylogenetic analyses --- microcystin-LR --- Procambarus clarkii --- energy budget --- astaxanthin --- cylindrospermopsin --- anatoxin-a --- PSP toxins --- microcystins --- cyanobacteria --- Nostocales --- drinking water --- marine cyanobacteria --- cyanotoxins --- marine sponges --- secondary metabolites --- marine natural compounds --- bioassays --- Artemia salina --- Paracentrotus lividus --- hemolytic essay --- reservoir --- Yangtze estuary --- 16S rRNA gene sequencing --- shotgun metagenomic sequencing --- bacterial community --- microbial metabolisms --- [d-Leu1]Microcystin-LR --- Lithobates catesbeianus --- tadpoles --- exposure --- Histopathological evaluation --- microcystins --- cylindrospermopsin --- method validation --- UPLC-MS/MS --- lettuce --- genotoxicity --- mutagenicity --- Cylindrospermopsin --- Microcystin-LR --- mixture