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Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of protein tyrosine phosphatases with the ability to dephosphorylate Ser/Thr and Tyr residues from proteins, as well as from other non-proteinaceous substrates including signaling lipids. DUSPs include, among others, MAP kinase (MAPK) phosphatases (MKPs) and small-size atypical DUSPs. MKPs are enzymes specialized in regulating the activity and subcellular location of MAPKs, whereas the function of small-size atypical DUSPs seems to be more diverse. DUSPs have emerged as key players in the regulation of cell growth, differentiation, stress response, and apoptosis. DUSPs regulate essential physiological processes, including immunity, neurobiology and metabolic homeostasis, and have been implicated in tumorigenesis, pathological inflammation and metabolic disorders. Accordingly, alterations in the expression or function of MKPs and small-size atypical DUSPs have consequences essential to human disease, making these enzymes potential biological markers and therapeutic targets. This Special Issue covers recent advances in the molecular mechanisms and biological functions of MKPs and small-size atypical DUSPs, and their relevance in human disease.

hematopoietic cells --- DEPArray --- n/a --- neuroblastoma --- liver steatosis --- MAPK phosphatase --- DUSP-4 --- granule neurons --- neuronal differentiation --- DUSP10 --- cytokines --- MAPKs --- single cell analysis --- macrophage --- asthma --- E. coli infection --- MAPK --- Cpp1 --- nucleotide receptors --- atypical DUSP --- RSV --- Pmp1 --- cannabinoids --- astrocytes --- sepsis --- influenza --- signaling --- triple-negative breast cancer (TNBC) --- differentiation --- HDAC6 (histone deacetylase isoform 6) --- atypical dual-specificity phosphatases --- microtubules --- respiratory viruses --- MK-STYX (MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein) --- dual-specificity phosphatase --- Msg5 --- TLR signaling --- mitogen-activated protein kinase --- fungal MKPs --- macrophages --- MAP Kinase Phosphatase-2 --- inflammation --- Sdp1 --- circulating tumor cells (CTCs) --- MAP kinases --- MAP kinase phosphatases --- P2X7 --- proliferation --- BDNF --- P2Y13 --- T cell --- hypertriglyceridemia --- integrated omics analysis --- post-translational modification --- rhinovirus --- protein stability --- ubiquitination --- dual-specificity phosphatases --- Mkp-1 --- cancer --- brain metastasis --- HER2 --- COPD --- pseudophosphatase

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Vascular smooth muscle (VSM) constitutes most of the tunica media in blood vessels and plays an important role in the control of vascular tone. Ca2+ is a major regulator of VSM contraction and is strictly regulated by an intricate system of Ca2+ mobilization and Ca2+ homeostatic mechanisms. The interaction of a physiological agonist with its plasma membrane receptor stimulates the hydrolysis of membrane phospholipids and increases the generation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 stimulates Ca2+ release from the intracellular stores in the sarcoplasmic reticulum. Agonists also stimulate Ca2+ influx from the extracellular space via voltage-gated, receptor-operated, and store-operated channels. Ca2+ homeostatic mechanisms tend to decrease the intracellular free Ca2+ concentration ([Ca2+]i) by activating Ca2+ extrusion via the plasmalemmal Ca2+ pump and the Na+/Ca2+ exchanger and the uptake of excess Ca2+ by the sarcoplasmic reticulum and possibly the mitochondria. A threshold increase in [Ca2+]i activates Ca2+-dependent myosin light chain (MLC) phosphorylation, stimulates actin-myosin interaction, and initiates VSM contraction. The agonist-induced maintained increase in DAG also activates specific protein kinase C (PKC) isoforms, which in turn cause phosphorylation of cytoplasmic substrates that increase the contractile myofilaments force sensitivity to Ca2+ and thereby enhance VSM contraction. Agonists could also activate Rho kinase (ROCK), leading to inhibition of MLC phosphatase and further enhancement of the myofilaments force sensitivity to Ca2+. The combined increases in [Ca2+]i, PKC and ROCK activity cause significant vasoconstriction and could also stimulate VSM hypertrophy and hyperplasia. The protracted and progressive activation of these processes could lead to pathological vascular remodeling and vascular disease.

Muscle contraction. --- Vascular diseases. --- Vascular smooth muscle. --- Ion Channels --- Muscle Proteins --- Microfilament Proteins --- Hemodynamics --- Muscle, Smooth --- Molecular Motor Proteins --- Cardiovascular Diseases --- Blood Vessels --- Diseases --- Muscles --- Contractile Proteins --- Cardiovascular Physiological Processes --- Cardiovascular System --- Adenosine Triphosphatases --- Membrane Glycoproteins --- Biopolymers --- Membrane Transport Proteins --- Cytoskeletal Proteins --- Polymers --- Tissues --- Carrier Proteins --- Acid Anhydride Hydrolases --- Proteins --- Cardiovascular Physiological Phenomena --- Membrane Proteins --- Anatomy --- Musculoskeletal System --- Amino Acids, Peptides, and Proteins --- Circulatory and Respiratory Physiological Phenomena --- Macromolecular Substances --- Hydrolases --- Chemicals and Drugs --- Phenomena and Processes --- Enzymes --- Enzymes and Coenzymes --- Myosins --- Muscle, Smooth, Vascular --- Vasoconstriction --- Calcium Channels --- Vascular Diseases --- Human Anatomy & Physiology --- Health & Biological Sciences --- Physiology --- Vascular resistance. --- Blood pressure. --- Vascular smooth muscle --- Physiology. --- physiology. --- Signal transduction --- Calcium --- Blood pressure --- AngII, angiotensin II --- ATP, adenosine triphosphate --- CPI-17, PKC-potentiated phosphatase inhibitor protein-17 kDa --- CAM, calmodulin --- DAG, diacylglycerol --- ET-1, endothelin --- IP3, inositol 1,4,5-trisphosphate --- MAPK, mitogen-activated protein kinase --- MARCKs, myristoylated alanine-rich C-kinase substrate --- MEK, MAPK kinase --- MLC, myosin light chain --- NCX, Na+-Ca2+ exchanger --- PDBu, phorbol 12,13-dibutyrate; PIP2, phosphatidylinositol 4,5-bisphosphate --- PKC, protein kinase C --- PMA, phorbol myristate acetate --- RACKs, receptors for activated C-kinase --- ROCK, Rho-kinase --- VSMC, vascular smooth muscle cell

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Supporting initiation, development and resolution of appropriate immune responses is key to survival. Many nutrients and dietary components have been purported to have a role in supporting optimal immune function. This is vital throughout the life course, from the development and programming of the immune system in early life, to supporting immunity and reducing chronic inflammation in older people. In this special issue of Nutrients, we examine the evidence for the role of diet and dietary components in promoting protective immunity.

immunonutrition --- supplementation --- superoxide dismutase (SOD) --- fermented milk --- selenocysteine --- dendritic cells --- lipoxygenase (LOX) --- chronic inflammatory conditions --- formulation --- immune system --- cytokines --- skeletal muscle --- zinc --- non-digestible carbohydrates --- Toll-like receptor --- carbohydrates --- fiber --- lymphocytes --- antibody --- infants --- liver --- macrophage --- inflammatory process --- probiotic --- plant --- older people --- gut barrier --- infection --- amino acids --- gut --- T helper 1 (Th1) --- immunity --- T cells --- bioactive peptide --- inhibitor of kappa kinase (IKK) --- inflammation --- adhesion molecules --- leukocytes --- human milk oligosaccharides --- vitamin D --- food structure --- vitamin E --- mitogen-activated protein Kinase (MAPK) --- gut microbiota --- weaning --- homeostasis --- intestinal immune system --- extra-cellular signal regulated kinases (ERK) --- cyclooxygenase (COX) --- oxidative stress --- life course --- polyphenols --- oligosaccharides --- micronutrients --- Th17 --- obesity --- tolerance --- arachidonic acid --- growth factors --- anti-inflammation --- age-related immunity --- prebiotic --- biomarker --- microbiome --- functional foods --- immunosenescence --- nutrition --- molecular mechanisms --- metabolism --- macronutrients --- toll-like receptor 4 --- sepsis --- nutrition guidelines --- microbiota --- immunomodulation --- inflammatory markers --- elderly --- Th1/Th17 response --- adults --- reactive oxygen species (ROS) --- anorexia nervosa --- macrophages --- autoimmune diseases --- fatty acids --- T cell --- Treg --- breast milk --- nitric oxide synthase (NOS) --- chemokines --- anti-tumorigenic --- metabolites --- deficiency --- protein hydrolysate --- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) --- cancer

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Plants have served mankind as an important source of foods and medicines. While we all consume plants and their products for nutritional support, a majority of the world population also rely on botanical remedies to meet their health needs, either as their own “traditional medicine” or as “complementary and alternative medicine”. From a pharmaceutical point of view, many compounds obtained from plant sources have long been known to possess bio/pharmacological activities, and historically, plants have yielded many important drugs for human use, from morphine discovered in the early nineteenth century to the more recent paclitaxel and artemisinin. Today, we are witnessing a global resurgence in interest and use of plant-based therapies and botanical products, and natural products remain an important and viable source of lead compounds in many drug discovery programs.This Special Issue on “Plant Natural Products for Human Health” compiles a series of scientific reports to demonstrate the medicinal potentials of plant natural products. It covers a range of disease targets, such as diabetes, inflammation, cancer, neurological disease, cardiovascular disease, liver damage, bacterial, and fungus infection and malarial. These papers provide important insights into the current state of research on drug discovery and new techniques. It is hoped that this Special Issue will serve as a timely reference for researchers and scholars who are interested in the discovery of potentially useful molecules from plant sources for health-related applications.

PhGs --- bitter orange --- immunomodulator --- A549 cells --- bergapten --- triptolide --- BMP/Smad --- phytochemicals --- antioxidant enzymes --- kumquat --- MTT assay --- HepaRG cells --- human health --- nanoparticles --- dendritic cells --- drug discovery --- biofilm --- catechin --- antitubercular activity --- Panax notoginseng saponins --- animals --- mouse-hair growth --- A? --- curcumin --- WNT/?-catenin --- copaiba --- AD --- Plasmodium parasites --- traditional medicine --- procyanidin A2 --- PET inhibition --- rheumatoid arthritis --- cannabinoid type 1 receptor --- iridoids --- inflammatory bowel disease --- acute liver injury --- human-hair-follicle dermal papilla cells --- Neuroprotective --- dihydromyricetin --- AMPK --- thromboembolism --- ginseng --- drug design and development --- endoplasmic reticulum stress --- mitogen-activated protein kinase --- Nrf2 --- prenylated flavonoids --- inflammation --- preclinical studies --- plants --- dietary supplements --- Glycyrrhiza uralensis --- aspirin --- Tripterygium wilfordii --- P. eryngii --- reperfusion --- ethnopharmacology --- glucans --- innovation --- hpatoprotection --- hinokitiol --- phytocannabinoid --- antistaphylococcal activity --- Shh/Gli --- green tea --- sesquiterpenoids --- adjuvant-induced arthritis --- yuzu --- hepatotoxicity --- p53/Bax --- Keap1 --- nuclear factor-kappaB --- oxidative stress --- pharmacokinetic study --- cinnamamides --- toxicity --- APAP --- Astragali Radix --- computational softwares --- plant natural product --- onion --- anti-malaria activity --- lipogenesis --- bleeding time --- diterpenoids --- Penthorum chinense Pursh --- myocardial hypertrophy --- automation --- adjuvant --- grapefruit --- melanoma cell --- essential oil --- sweet orange --- Amadori rearrangement compounds --- heme oxygenase --- global health --- calorie restriction --- bergamot --- liposomes --- EGCG --- celastrol --- herb–drug interactions --- cannabigerol --- anti-inflammation --- OH· free radical --- molecular targets --- gluconeogenesis --- microbiome --- SIRT1 --- fucoidan --- heart --- PC12 cells --- acetaminophen --- omics --- time-kill assay --- arthritis --- lychee seed --- bioinformatics --- structure–activity relationship --- precision medicine --- orange petitgrain --- immune modulation --- antiproliferation --- flavonoids --- scoulerine --- oleoresin --- triterpenic acids --- Cannabis sativa --- NAFLD --- biological activity --- differentiation --- oxygen consumption rate --- mitochondrial bioenergetics --- neroli --- apoptosis --- targeted delivery --- platelet activation --- protein kinase --- heat-process --- hepatic steatosis --- hyperglycemia --- natural products --- lemon --- genistein --- neuroinflammation --- astragaloside IV --- cytoxicity --- flavonoid --- paracetamol --- medicinal plants --- insulin resistance --- resveratrol --- mandarin --- garlic --- TGF-? --- morin hydrate --- sirtuin 3 --- MMPs --- gomisin N --- lime --- Ziziphus jujuba --- antifungal activity --- ischemia --- migration --- caspases --- small molecules