Inhibition of α-melanocyte-stimulating hormone-induced melanogenesis and molecular mechanisms by polyphenol-enriched fraction of Tagetes erecta L. flower.

Background: The pursuit for safe and efficacious skin-whitening agents has prompted a dedicated exploration of plant-derived compounds. Notably, Tagetes erecta L. flowers have been used as a medicinal extract and possessed in vitro mushroom tyrosinase activity.

Investigating rutin as a potential transforming growth factor-β type I receptor antagonist for the inhibition of bleomycin-induced lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition characterized by the abnormal regulation of extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). In this study, we investigated the potential of rutin, a natural flavonoid, in attenuating transforming growth factor-β (TGF-β)-induced ECM regulation and EMT through the inhibition of the TGF-β type I receptor (TβRI)-mediated suppressor of mothers against decapentaplegic (SMAD) signaling pathway. We found that non-toxic concentrations of rutin attenuated TGF-β-induced ECM-related genes, including fibronectin, elastin, collagen 1 type 1, and TGF-β, as well as myoblast differentiation from MRC-5 lung fibroblast cells accompanied by the downregulation of α-smooth muscle actin.

Pinostrobin Suppresses the α-Melanocyte-Stimulating Hormone-Induced Melanogenic Signaling Pathway.

Pinostrobin is a dietary flavonoid found in several plants that possesses pharmacological properties, such as anti-cancer, anti-virus, antioxidant, anti-ulcer, and anti-aromatase effects. However, it is unclear if pinostrobin exerts anti-melanogenic properties and, if so, what the underlying molecular mechanisms comprise. Therefore, we, in this study, investigated whether pinostrobin inhibits melanin biosynthesis in vitro and in vivo, as well as the potential associated mechanism.

A non-polar fraction of Saponaria officinalis L. acted as a TLR4/MD2 complex antagonist and inhibited TLR4/MyD88 signaling in vitro and in vivo.

Targeting Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2) signaling is regarded as a potential strategy for treating inflammatory diseases. Saponaria officinalis L. is rich in saponin, which include quillaic acid, gypsogenin, saponarin, and hederagenin.

Anthocyanin-enriched polyphenols from Hibiscus syriacus L. (Malvaceae) exert anti-osteoporosis effects by inhibiting GSK-3β and subsequently activating β-catenin.

Background: The bark and petal of Hibiscus syriacus L. (Malvaceae) have been used to relieve pain in traditional Korean medicine. Recently, we identified anthocyanin-enriched polyphenols from the petal of H.

Protective Effect of Anthocyanin-Enriched Polyphenols from L. (Malvaceae) against Ultraviolet B-Induced Damage.

Anthocyanin-enriched polyphenols from the flower petals of L. (Malvaceae, AHs) possess anti-septic shock, anti-oxidant, and anti-melanogenic properties. However, whether AHs positively or negatively regulate ultraviolet B (UVB)-mediated photoaging and photodamage remains unclear.

Bisphenol A: A potential Toll-like receptor 4/myeloid differentiation factor 2 complex agonist.

In addition to endocrine disruption, bisphenol A (BPA) is known to induce inflammation through the activation of nuclear factor-κB (NF-κB). However, detailed studies on the mechanism of NF-κB activation by BPA have not been sufficiently conducted. In the present study, we observed that low concentrations of BPA (≤1 μM) upregulated the release of proinflammatory mediators, including nitric oxide (NO) and prostaglandin E (PGE), as well as proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-12, and IL-6.

Anthocyanins isolated from Hibiscus syriacus L. attenuate lipopolysaccharide-induced inflammation and endotoxic shock by inhibiting the TLR4/MD2-mediated NF-κB signaling pathway.

Background: Hibiscus syriacus L. has been used as a medicinal plant in many Asian countries. However, anti-inflammatory activity of H.

GSK-3β-Targeting Fisetin Promotes Melanogenesis in B16F10 Melanoma Cells and Zebrafish Larvae through β-Catenin Activation.

Fisetin is found in many fruits and plants such as grapes and onions, and exerts anti-inflammatory, anti-proliferative, and anticancer activity. However, whether fisetin regulates melanogenesis has been rarely studied. Therefore, we evaluated the effects of fisetin on melanogenesis in B16F10 melanoma cell and zebrafish larvae.

Fermented Oyster Extract Promotes Osteoblast Differentiation by Activating the Wnt/β-Catenin Signaling Pathway, Leading to Bone Formation.

The Pacific oyster, , is well-known as a nutritious food. Recently, we revealed that fermented extract of (FO) inhibited ovariectomy-induced osteoporosis, resulting from suppression of osteoclastogenesis. However, since the beneficial effect of FO on osteogenesis is poorly understood, it was examined in mouse preosteoblast MC3T3-E1 cells, human osteosarcoma MG-63 osteoblast-like cells, and zebrafish larvae in this study.

Anthocyanins from L. Inhibit Melanogenesis by Activating the ERK Signaling Pathway.

L. exhibited promising potential as a new source of food and colorants containing various anthocyanins. However, the function of anthocyanins from L.

Flumequine-Mediated Upregulation of p38 MAPK and JNK Results in Melanogenesis in B16F10 Cells and Zebrafish Larvae.

Flumequine is a well-known second generation quinolone antibiotic that induces phototoxicity. However, the effect of flumequine on skin melanogenesis is unclear. Therefore, we, for the first time, investigated whether flumequine regulates melanogenesis.

Camptothecin induces mitotic arrest through Mad2-Cdc20 complex by activating the JNK-mediated Sp1 pathway.

Camptothecin (CPT) is a popular therapeutic agent that targets topoisomerase I. Our findings demonstrated that CPT-induced microtubule polymerization results in markedly increased histone H3 phosphorylation. CPT also enhanced interactions between the mitotic checkpoint proteins, Mad2 and Cdc20, and thereby increased mitotic arrest.

Camptothecin enhances c-Myc-mediated endoplasmic reticulum stress and leads to autophagy by activating Ca-mediated AMPK.

Camptothecin (CPT) from Camptotheca acuminate was discovered for anticancer drugs, which targets topoisomease I. However, whether CPT regulates c-Myc expression has not been understood in endoplasmic reticulum (ER) stress and autophagy. In this study, we found that CPT enhanced c-Myc expression and that the transient knockdown of c-Myc abrogated reactive oxygen species (ROS) generation, which resulted in the accumulation of ER stress-regulating proteins, such as PERK, eIF2α, ATF4, and CHOP.

Evaluation of the effect of pre-operative over-fasting on post-operative vomiting in children undergoing bone marrow aspiration at a tertiary care setting in Sri Lanka: A prospective cohort study.

Background And Aims: Non-adherence to standard fasting guidelines may result in perioperative complications. We aimed to determine the association between pre-operative over-fasting and post-operative vomiting amongst children undergoing bone marrow aspiration under general anaesthesia.

Methods: A prospective cohort study was conducted from May 2015 to April 2016 in children undergoing bone marrow aspiration under general anaesthesia and their caregivers.

TRAIL attenuates sulforaphane-mediated Nrf2 and sustains ROS generation, leading to apoptosis of TRAIL-resistant human bladder cancer cells.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can preferentially initiate apoptosis in malignant cells with minimal toxicity to normal cells. Unfortunately, many human cancer cells are refractory to TRAIL-induced apoptosis through many unknown mechanisms. Here, we report that TRAIL resistance can be reversed in human bladder cancer cell lines by treatment with sulforaphane (SFN), a well-known chemopreventive isothiocyanate in various cruciferous vegetables.

Barriers to healthy dietary choice amongst students in Sri Lanka as perceived by school principals and staff.

Sri Lanka has experienced a massive demographic, environmental, economic and social transition in recent decades. Over this period of time the country has undergone rapid urbanization leading to accompanying shifts in lifestyle and it suffers a double burden of under- and over-nutrition. Current programmes in the country focus on improving the dietary behaviour of secondary school students.

Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations.

The transient receptor potential channels (TRPs) respond to chemical irritants and temperature. TRPV1 responds to the itch-inducing endogenous signal histamine, and TRPA1 responds to the itch-inducing chemical chloroquine. We showed that, in sensory neurons, TRPV4 is important for both chloroquine- and histamine-induced itch and that TRPV1 has a role in chloroquine-induced itch.

Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRP-GRPR signaling.

Central serotonin (5-hydroxytryptophan, 5-HT) modulates somatosensory transduction, but how it achieves sensory modality-specific modulation remains unclear. Here we report that enhancing serotonergic tone via administration of 5-HT potentiates itch sensation, whereas mice lacking 5-HT or serotonergic neurons in the brainstem exhibit markedly reduced scratching behavior. Through pharmacological and behavioral screening, we identified 5-HT1A as a key receptor in facilitating gastrin-releasing peptide (GRP)-dependent scratching behavior.

Subcellular optogenetics - controlling signaling and single-cell behavior.

Variation in signaling activity across a cell plays a crucial role in processes such as cell migration. Signaling activity specific to organelles within a cell also likely plays a key role in regulating cellular functions. To understand how such spatially confined signaling within a cell regulates cell behavior, tools that exert experimental control over subcellular signaling activity are required.

A G-protein subunit translocation embedded network motif underlies GPCR regulation of calcium oscillations.

G-protein βγ subunits translocate reversibly from the plasma membrane to internal membranes on receptor activation. Translocation rates differ depending on the γ subunit type. There is limited understanding of the role of the differential rates of Gβγ translocation in modulating signaling dynamics in a cell.

The structure of dynamic GPCR signaling networks.

G-protein-coupled receptors (GPCRs) stimulate signaling networks that control a variety of critical physiological processes. Static information on the map of interacting signaling molecules at the basis of many cellular processes exists, but little is known about the dynamic operation of these networks. Here we focus on two questions.

Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration.

There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision.

Optically triggering spatiotemporally confined GPCR activity in a cell and programming neurite initiation and extension.

G-protein-coupled receptor (GPCR) activity gradients evoke important cell behavior but there is a dearth of methods to induce such asymmetric signaling in a cell. Here we achieved reversible, rapidly switchable patterns of spatiotemporally restricted GPCR activity in a single cell. We recruited properties of nonrhodopsin opsins--rapid deactivation, distinct spectral tuning, and resistance to bleaching--to activate native Gi, Gq, or Gs signaling in selected regions of a cell.

G-protein signaling leverages subunit-dependent membrane affinity to differentially control βγ translocation to intracellular membranes.

Activation of G-protein heterotrimers by receptors at the plasma membrane stimulates βγ-complex dissociation from the α-subunit and translocation to internal membranes. This intermembrane movement of lipid-modified proteins is a fundamental but poorly understood feature of cell signaling. The differential translocation of G-protein βγ-subunit types provides a valuable experimental model to examine the movement of signaling proteins between membranes in a living cell.