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Neuronal function relies on the establishment of proper connections between neurons and their target cells during development. This basic statement involves several cellular processes, such as neuronal differentiation, the polarized outgrowth of axons and dendrites from differentiated neurons, and the pathfinding of axons towards target cells. The subsequent recognition of complementary synaptic partners finally triggers the formation, maturation, and maintenance of functional synapses. Morphogens are secreted signaling molecules commanding tissue patterning and cell identity during early embryonic development. Remarkably, growing evidence over the last years arising from different invertebrate and vertebrate model organisms has shown that, after cell fate has been established, morphogens also control the precise wiring and function in the developing and mature nervous system. Accordingly, dysfunctions of the signaling pathways activated by these molecules contribute to synaptic disassembly and altered function in diseases affecting the nervous system. We consider it timely to bring together cumulative evidence pointing to crucial roles for signaling activated by different morphogens in the establishment of precise contacts between neurons and their synaptic partners. Therefore, this research topic issue combines review and research articles aimed to cover the functional relevance of such morphogens on the different steps involved in synaptic assembly and function. Diverse model systems of physiological or pathological conditions have been included, as well as different cellular, biochemical and molecular approaches. Altogether, they contribute in different and complementary ways to build a holistic view of the roles that early development morphogens play during the assembly, maintenance and/or regeneration of functional synapses.

Shh --- Nervous System --- BMP --- neurodegeneration --- synapse --- Wnt --- Morphogens --- Neurogenesis

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The Hedgehog signaling pathway is an evolutionarily conserved pathway that governs complex developmental processes, including stem cell maintenance, proliferation, differentiation, and patterning. Several recent studies have shown that the aberrant activation of Hedgehog signaling is associated with neoplastic transformation, cancer cell proliferation, metastasis, multiple cancers’ drug resistance, and survival rates. This book focuses on several aspects of Hedgehog signaling in organogenesis and the tumor microenvironment, and presents reviews and original papers on recent efforts in the field of Hedgehog signaling.

Cyp26 enzymes --- congenital anomalies --- CRE/LoxP --- hedgehog signaling --- mouse models --- retinoic acid --- smoothened --- sonic hedgehog --- sonic hedgehog (SHH) --- oral squamous cell carcinoma (OSCC) --- tumor microenvironment (TME) --- tumor-associated macrophages (TAMs) --- cancer-associated fibroblasts (CAFs) --- tumor-associated angiogenesis --- hedgehog --- growth plate --- endochondral ossification --- chondrocyte --- osteoblast --- bone disease --- TMJ --- synovial joint --- articular disc --- Ihh --- PTHrP --- osteoarthritis --- epithelial–mesenchymal interaction (EMI) --- prostate cancer --- external genitalia --- androgen --- basement membrane --- bone morphogenetic protein --- stem cell --- animal experiment --- fracture healing --- cancer stem cells --- hypospadias --- urethra --- penis --- bone --- hedgehog signalling --- tooth development --- epithelial and mesenchymal interaction --- Gli1 --- mesenchymal stem cell --- lineage tracing analysis --- stem cell marker --- n/a --- epithelial-mesenchymal interaction (EMI)

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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