Kaempferol tetrasaccharides restore skin atrophy via PDK1 inhibition in human skin cells and tissues: Bench and clinical studies.

Skin aging is a major risk factor for the dermal diseases, and interventions to attenuate cellular senescence are expected to reduce the risk for age-related diseases involving skin atrophy. However, blocking cell death or extending proliferation causally results in side effects and an increased cancer risk. For identification of a safer approach, we focused on PDK1 inhibition, which could revert cellular senescence and reduce senescence factors in skin in vitro, in a human skin equivalent model and in an exploratory, placebo-controlled, interventional trial.

Hepatitis C Virus Nonstructural 5A Protein Interacts with Telomere Length Regulation Protein: Implications for Telomere Shortening in Patients Infected with HCV.

Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance.

A Basic Domain-Derived Tripeptide Inhibits MITF Activity by Reducing its Binding to the Promoter of Target Genes.

The keratinocytes in UV-irradiated skin produce and secrete α-melanocyte-stimulating hormone. α-Melanocyte-stimulating hormone upregulates the expression of MITF in melanocytes through the cAMP‒protein kinase A‒CREB signaling pathway. Thereafter, MITF induces the expression of melanogenic genes, including the tyrosinase gene TYR and TYRP-1 and TYRP-2 genes, which leads to the synthesis and accumulation of melanin.

Application of green tea catechins, polysaccharides, and flavonol prevent fine dust induced bronchial damage by modulating inflammation and airway cilia.

Airborne fine dust particles (FDPs) have been identified as major toxins in air pollution that threaten human respiratory health. While searching for an anti-FDP reagent, we found that green tea extract (GTE) and fractions rich in flavonol glycosides (FLGs) and crude tea polysaccharides (CTPs) had protective effects against FDP-stimulated cellular damage in the BEAS-2B airway epithelial cell line. The GTE, FLGs, and CTPs significantly increased viability and lowered oxidative stress levels in FDP-treated cells.

Cortactin Interacts with Hepatitis C Virus Core and NS5A Proteins: Implications for Virion Assembly.

Hepatitis C virus (HCV) exploits cellular proteins to facilitate viral propagation. To identify the cellular factors involved in the HCV life cycle, we previously performed protein microarray assays using either HCV nonstructural 5A (NS5A) protein or core protein as a probe. Interestingly, cellular cortactin strongly interacted with both NS5A and core.

Small Molecule from Natural Phytochemical Mimics Dietary Restriction by Modulating FoxO3a and Metabolic Reprogramming.

Many studies utilizing animal models have revealed the genetic and pharmacogenetic modulators of the rate of organismal aging. However, finding routes for healthy aging during extended life remains one of the largest questions. With regards to an antiaging reagent, it has been shown that natural phytochemical syringaresinol (SYR) delays cellular senescence by activating sirtuin1 (SIRT1).

Nonstructural NS5A Protein Regulates LIM and SH3 Domain Protein 1 to Promote Hepatitis C Virus Propagation.

Hepatitis C virus (HCV) propagation is highly dependent on cellular proteins. To identify the host factors involved in HCV propagation, we previously performed protein microarray assays and identified the LIM and SH3 domain protein 1 (LASP-1) as an HCV NS5A-interacting partner. LASP-1 plays an important role in the regulation of cell proliferation, migration, and protein-protein interactions.

The natural phytochemical trans-communic acid inhibits cellular senescence and pigmentation through FoxO3a activation.

Ageing is characterized by the accumulation of chronic and irreversible oxidative damage, chronic inflammation and organ dysfunction. To attenuate these ageing-related changes, various natural phytochemicals are often applied. Trans-communic acid (TCA), an active component of brown pine leaf extract, has antimicrobial and cancer chemopreventive activity and inhibits ultraviolet B (UVB)-induced MMP-1 expression.

Anti-melanogenic activity of schaftoside in Rhizoma Arisaematis by increasing autophagy in B16F1 cells.

Skin pigmentation involves multiple processes, including melanin synthesis, transport, and melanosome release. Melanin content determines skin color and protects against UV radiation-induced damage. Autophagy is a cooperative process between autophagosomes and lysosomes that degrades cellular components and organelles.

Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10-p63 axis in epithelial homeostasis.

Skin tissues, in particular the epidermis, are severely affected by zinc deficiency. However, the zinc-mediated mechanisms that maintain the cells that form the epidermis have not been established. Here, we report that the zinc transporter ZIP10 is highly expressed in the outer root sheath of hair follicles and plays critical roles in epidermal development.

Requirement of Zinc Transporter SLC39A7/ZIP7 for Dermal Development to Fine-Tune Endoplasmic Reticulum Function by Regulating Protein Disulfide Isomerase.

Skin is the first area that manifests zinc deficiency. However, the molecular mechanisms by which zinc homeostasis affects skin development remain largely unknown. Here, we show that zinc-regulation transporter-/iron-regulation transporter-like protein 7 (ZIP7) localized to the endoplasmic reticulum plays critical roles in connective tissue development.

Neuronal maturation in the hippocampal dentate gyrus via chronic oral administration of extract is independent of cyclooxygenase 2 signaling pathway in diet-induced obesity mouse model.

Recently, we reported that (AA) has anti-adipogenic properties and in . Reduction of adipogenesis by AA treatment may dampen systemic inflammation and protect neurons from cytokine-induced damage. Therefore, the present study was undertaken to assess whether AA increases neuronal maturation by reducing inflammatory responses, such as those mediated by cyclooxygenase 2 (COX-2).

Amber Light (590 nm) Induces the Breakdown of Lipid Droplets through Autophagy-Related Lysosomal Degradation in Differentiated Adipocytes.

Lipolysis in the adipocytes provides free fatty acids for other tissues in response to the energy demand. With the rapid increase in obesity-related diseases, finding novel stimuli or mechanisms that regulate lipid metabolism becomes important. We examined the effects of visible light (410, 457, 505, 530, 590, and 660 nm) irradiation on lipolysis regulation in adipocytes differentiated from human adipose-derived stem cells (ADSCs).

Synthesis and in-vitro evaluation of 2-amino-4-arylthiazole as inhibitor of 3D polymerase against foot-and-mouth disease (FMD).

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease of livestock caused by a highly variable RNA virus, foot-and-mouth disease virus (FMDV). One of the targets to suppress expansion of and to control FMD is 3D polymerase (FMDV 3Dpol). In this study, 2-amino-4-arylthiazole derivatives were synthesized and evaluated for their inhibitory activity against FMDV 3Dpol.

Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity.

The SLC45A2 gene encodes a Membrane-Associated Transporter Protein (MATP). Mutations of this gene cause oculocutaneous albinism type 4 (OCA4). However, the molecular mechanism of its action in melanogenesis has not been elucidated.

Increased Cell Proliferations and Neurogenesis in the Hippocampal Dentate Gyrus of Ahnak Deficient Mice.

Expression of the giant protein Ahnak has been reported in endothelial cells of the blood brain barrier and in non-neuronal cells including myelinating Schwann cells. However, the function of Ahnak in neurogenesis has not been determined. In the present study, we report for the first time the effects of Ahnak on adult hippocampal neurogenesis using Ahnak(-/-) mice.

The natural phytochemical dehydroabietic acid is an anti-aging reagent that mediates the direct activation of SIRT1.

Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid of confers, such as pinus species (P. densiflora, P. sylvestris) and grand fir (Abies grandis), and it induces various biological actions including antimicrobial, antiulcer, and cardiovascular activities.

Hyperosmotic stress reduces melanin production by altering melanosome formation.

Many tissues of the human body encounter hyperosmotic stress. The effect of extracellular osmotic changes on melanin production has not yet been elucidated. In this study, we determined that hyperosmotic stress induced by organic osmolytes results in reduced melanin production in human melanoma MNT-1 cells.

Molecular pathogenesis of spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins.

The zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mutant ZIP13 proteins found in human patients: ZIP13(G64D), in which Gly at amino acid position 64 is replaced by Asp, and ZIP13(ΔFLA), which contains a deletion of Phe-Leu-Ala. We demonstrated that both the ZIP13(G64D) and ZIP13(ΔFLA) protein levels are decreased by degradation via the valosin-containing protein (VCP)-linked ubiquitin proteasome pathway.

DW1029M, a novel botanical drug candidate, inhibits advanced glycation end-product formation, rat lens aldose reductase activity, and TGF-β1 signaling.

DW1029M is a botanical extract consisting of Morus bark and Puerariae radix, produced by Dong-Wha Pharmaceutical, for nephroprotective drug development; it has been in phase II clinical trials in Korea. In our mechanistic investigations, we found that DW1029M inhibits advanced glycation end products (AGEs), rat lens aldose reductase (RLAR), and transforming growth factor (TGF)-β1 signaling, all of which are implicated in diabetic complications such as diabetic nephropathy and diabetic retinopathy. DW1029M inhibits AGE formation via Fe(2+) chelation.

Anti-obesity phenotypic screening looking to increase OBR cell surface expression.

The leptin receptor, OBR, is involved in the regulation of whole-body energy homeostasis. Most obese people are resistant to leptin and do not respond to the hormone. The prevention and reversal of leptin resistance is one of the major current goals of obesity research.

Inhibition of HCV replicon cell growth by 2-arylbenzofuran derivatives isolated from Mori Cortex Radicis.

Medicinal herbs are increasingly used in the search for safe and efficient drug candidates for hepatitis C virus infection. In this study, we have investigated the anti-HCV effect of compounds from Mori Cortex Radicis. During a screening for extracts with anti-HCV affinity from medicinal plants (173 species), the methanol extract of Mori Cortex Radicis was selected.