Papers by Tomohiro Hakozaki
Skin health and disease, Feb 4, 2022
Niacinamide is vitamin B3, an essential nutrient. In the body, it is converted to the co-factors ... more Niacinamide is vitamin B3, an essential nutrient. In the body, it is converted to the co-factors NADH and NADPH that are involved in many biochemical reactions. Dietary deficiency of this water-soluble member of the vitamin B family causes pellagra, a disease which includes dermatitis and red lesions. Pellagra caused thousands of deaths in the United States in the first half of the twentieth century, until simple dietary supplementation with this absorbable vitamin was found to cure the disorder. NAD+ and NADPH levels in skin cells decline with age. Thus, supplementing skin with the precursor to these vital co-factors has the potential to provide appearance benefits to aging skin. Since niacinamide penetrates the skin’s surface readily, it is bioavailable from topical application for targeted delivery to specific skin sites. Clinical evaluations of topical formulations containing this vitamin have identified a wide range of skin care benefits. Among the many cosmetic effects for ski...
Un procede d'amelioration de l'apparence d'une tache hyperpigmentee peut inclure l... more Un procede d'amelioration de l'apparence d'une tache hyperpigmentee peut inclure l'etape d'application d'une composition sur la tache hyperpigmentee a la surface de la peau, la composition comprenant une quantite sure et efficace d'un agent a action rapide destine aux taches hyperpigmentees, l'agent a action rapide etant un extrait de Laminaria Saccharina , et une quantite sure et efficace d'un agent a action lente destine aux taches hyperpigmentees, l'agent a action lente etant choisi parmi la vitamine B3, le 1,3-dihydroxy-4-alkylbenzene et leurs combinaisons, la composition etant appliquee au moins quotidiennement pendant une duree suffisante pour permettre a l'agent a action rapide et a l'agent a action lente d'ameliorer l'apparence de la tache hyperpigmentee. Le procede peut inclure l'etape d'identification d'une tache hyperpigmentee sur une surface cutanee faciale.
L'invention concerne un procede permettant d'inhiber l'activite de la tyrosinase qui ... more L'invention concerne un procede permettant d'inhiber l'activite de la tyrosinase qui peut impliquer l'application d'une composition comprenant un extrait de laminaria saccharina a un substrat qui requiert l'inhibition de la tyrosinase. Le procede peut en outre comprendre l'etape d'identification d'un substrat necessitant l'inhibition de la tyrosinase. Ladite composition peut etre laissee sur le substrat et/ou appliquee de maniere repetee au substrat afin d'obtenir l'inhibition souhaitee de l'activite de la tyrosinase.
La presente invention concerne un procede de generation d'une signature d'expression geni... more La presente invention concerne un procede de generation d'une signature d'expression genique associee a l'hyperpigmentation permettant d'identifier des liens entre des perturbagenes et des genes associes a l'etat de pigmentation de la peau. Ledit procede comprend les etapes consistant a utiliser un profil d'expression genique associe a un echantillon de cellules cutanees humaines traite au moyen d'au moins un agent de modification de la pigmentation de la peau de reference en suspension dans une composition servant d'excipient, et un profil d'expression genique associe a un echantillon de cellules cutanees humaines traite au moyen de la seule composition servant d'excipient ; a comparer lesdits profils d'expression pour determiner une signature d'expression genique comprenant un ensemble de genes s'exprimant de facon differente ; a assigner un identificateur a chaque gene constituant la signature d'expression genique et a ordon...
L'invention concerne des procedes d'echantillonnage de tissu de peau humaine et des model... more L'invention concerne des procedes d'echantillonnage de tissu de peau humaine et des modeles permettant de valider des hypotheses pour des mecanismes commandant la pigmentation de la peau ainsi que des procedes permettant de commander les niveaux de pigment de la peau dans le tissu de peau ex-vivo. Le procede consiste a produire un premier echantillon de tissu de peau humaine en culture et a tester l'efficacite de l'agent d'essai pour commander la pigmentation de la peau, et a comparer le profil transcriptionnel genere a partir de l'echantillon de tissu de peau humaine traite au profil transcriptionnel d'un controle pour valider l'hypothese selon laquelle l'agent d'essai commande la pigmentation de la peau.
Journal of Clinical and Cosmetic Dermatology, 2019
Volume 3-Issue 1 | DOI: binding to the Antioxidant Response Element (ARE) present in the promoter... more Volume 3-Issue 1 | DOI: binding to the Antioxidant Response Element (ARE) present in the promoter of major antioxidant enzymes. The Nrf2-ARE pathway is stimulated by changes in the redox state of the cell and functions to restore homeostasis by upregulating antioxidant, xenobiotic metabolizing, and other cytoprotective proteins and enzymes constituting over 600 gene targets [8-9]. Scientific literature is also progressively uncovering a substantial role for Nrf2 in the metabolism and protection of skin cells [10-13]. Most research links redox imbalance to the pathogenesis of vitiligo [14-16]. Redox implications including systemic increases in oxidant status with simultaneous decreases in antioxidant status; downregulation of enzymatic antioxidants like Catalase (CAT), Glutathione Peroxidase (GPX), and Glucose-6-phosphate Dehydrogenase (G6PD); and upregulation of ROS Hydrogen Peroxide (H 2 O 2) and Peroxynitrite (ONOO-) have been documented [17-25]. Various scientific studies associate vitiligo with multiple classical manifestations of oxidative stress such as lipid peroxidation, impaired signaling, structural irregularities, and dysfunction of cellular
Journal of Clinical Medicine
Sleep shortage is a major concern in modern life and induces various psycho-physical disorders, i... more Sleep shortage is a major concern in modern life and induces various psycho-physical disorders, including skin problems. In cosmeceutics, females are aware that sleep deprivation worsens their facial skin tone. Here, we measured the effects of sleep deprivation on facial skin yellowness and examined yellow chromophores, such as bilirubin and carotenoids, in blood serum as potential causes of yellowness. Total sleep deprivation (0 h sleep overnight, N = 28) and repeated partial sleep deprivation (4 h sleep for 5 consecutive days, N = 10) induced significant increases in facial skin yellowness. The higher yellowness was sustained even after both sleep deprivation types stopped. However, circulating levels of yellow chromophores were unchanged in the total sleep deprivation study. Neither circulating interleukin-6 nor urinary biopyrrin levels were affected by total sleep deprivation, suggesting that apparent oxidative stress in the body was not detected in the present total deprivation...
L'invention concerne des procedes cosmetiques d'augmentation de la transcription genique ... more L'invention concerne des procedes cosmetiques d'augmentation de la transcription genique activee par ARE dans une cellule de peau, par la mise en contact de cellules de peau dans une partie cible de la peau avec une quantite efficace de niacinamide et de nicotinamide riboside en combinaison pour augmenter la transcription genique activee par ARE ou augmenter de facon synergique la transcription genique activee par ARE d'au moins certaines des cellules de peau mises en contact avec la niacinamide et le nicotinamide riboside. Les procedes cosmetiques permettent egalement une reduction synergique de l'epuisement d'adenosine triphosphate (ATP) induit par ROS dans une cellule de peau et la restauration du taux de production d'ATP glycolytique dans une cellule de peau qui a ete reduite suite a un stress oxydatif induit par ROS.
Cosmeceuticals and Cosmetic Practice, 2013
Journal of Clinical Medicine
Galactomyces ferment filtrate (GFF, Pitera™) is a cosmetic ingredient known to have multiple skin... more Galactomyces ferment filtrate (GFF, Pitera™) is a cosmetic ingredient known to have multiple skin care benefits, such as reducing redness and pore size via the topical application of its moisturizer form. Although GFF is known to act partly as an antioxidative agonist for the aryl hydrocarbon receptor (AHR), its significance in keratinocyte biology is not fully understood. In this study, we conducted a transcriptomic analysis of GFF-treated human keratinocytes. Three different lots of GFF consistently modulated 99 (22 upregulated and 77 downregulated) genes, including upregulating cytochrome P450 1A1 (CYP1A1), a specific downstream gene for AHR activation. GFF also enhanced the expression of epidermal differentiation/barrier-related genes, such as small proline-rich proteins 1A and 1B (SPRR1A and SPRR1B), as well as wound healing-related genes such as serpin B2 (SERPINB2). Genes encoding components of tight junctions claudin-1 (CLDN1) and claudin-4 (CLDN4) were also target genes upr...
International Journal of Molecular Sciences
Sallow and/or dull skin appearance is greatly attributable to the yellow components of skin tone.... more Sallow and/or dull skin appearance is greatly attributable to the yellow components of skin tone. Bilirubin is a yellow chromophore known to be made in the liver and/or spleen and is transported throughout the body via the blood stream. Recent publications suggest bilirubin may be synthesized in other cells/organs, including the skin. We found human keratinocytes express the transcripts involved in bilirubin biosynthesis. In parallel, we also found human keratinocytes could indeed synthesize bilirubin in monolayer keratinocytes and in a 3D human skin-equivalent model. The synthesized amount was substantial enough to contribute to skin yellowness. In addition, oxidative stress enhanced bilirubin production. Using UnaG, a protein that forms a fluorescent species upon binding to bilirubin, we also visualized the intracellular expression of bilirubin in keratinocytes. Finally, we screened a compound library and discovered that the sucrose laurate/dilaurate (SDL) combination significantl...
Regulatory Toxicology and Pharmacology, 2022
Journal of Cosmetics, Dermatological Sciences and Applications, 2011
Saccharomycopsis ferment filtrate (SFF), mainly used in skin care products, has been reported to ... more Saccharomycopsis ferment filtrate (SFF), mainly used in skin care products, has been reported to inhibit inflammatory nitric oxide production and prevent epidermal damage. However, the effects of SFF on epidermal keratinocytes have not yet been explored. We investigated the effects of SFF on skin barrier function using human primary epidermal keratinocytes. Cell viability was determined by MTT assay. The mRNA and protein expression levels of tight junction proteins (claudin-1, -3, -4, occludin, ZO-1) were analyzed by RT-PCR and Western blotting, respectively. The effect of SFF on the barrier formation of epidermal keratinocytes was measured by transepithelial electrical resistance (TER). Rescue of cell death from H 2 O 2 treatment was evaluated by annexin V staining. SFF, at concentrations that did not cause significant change of cell viability, induced dose-dependent cell-cell adhesion and formation of an organized monolayer structure. Pretreatment of keratinocytes with EGTA, a Ca 2+ chelator, did not inhibit the cell-cell adhesion of keratinocytes by SFF, indicating a Ca 2+ -independent mechanism. The mRNA and protein levels of claudin-1 in keratinocytes were up-regulated by SFF treatment in a dose-dependent manner. The expressions of other tight junctions (TJs) including claudin-3 & 4, occludin and ZO-1 were also similarly increased in SFF-treated epidermal keratinocytes. The promoting effect of SFF on the barrier function of epidermal keratinocytes was further confirmed by the increased TER value in SFF-treated epidermal keratinocytes. Annexin V staining confirmed that SFF markedly decreased the number of dead cells resulted from H 2 O 2 injury . Taken together, our results provided the first evidence that SFF enhanced keratinocytes barrier function by increasing the expression of TJs and TER.
Degradation of melanosomes in light skin (LS, i.e. phototype I/II) appears to occur more rapidly ... more Degradation of melanosomes in light skin (LS, i.e. phototype I/II) appears to occur more rapidly than dark skin (DS, i.e. phototype IV/V). Hydrolytic enzymes known to reside and be expressed in a differential pattern within the interfollicular epidermis are implicated in playing a role in epidermal differentiation and potentially melanosome degradation. The aim of this present study was to evaluate the differential expression of hydrolytic enzymes that may correlate with physiological and phenotypic differences seen between DS and LS. Expression of six hydrolytic enzymes was confirmed by microarray analysis of the suprabasal epidermis from LS and DS. Specific lysosomal hydrolases identified by microarray analysis were analyzed by indirect immunofluorescence (IIF) and immunoblot analysis. Immunogold electron microscopy (IEM) was completed to visualize cellular expression of the hydrolytic enzyme cathepsin L2 (Cath L2) and biochemical assay was performed to ascertain Cath L2 activity. Immunoblotting of light and dark epidermal lysates demonstrated that of the six enzymes initially analyzed, both prostatic acid phosphatase (ACPP) and Cath L2 were reproducibly upregulated in DS and LS, respectively. IIF and IEM analyses of Cath L2 in tissue confirmed this differential expression. Biochemical analysis of Cath L2 in light and dark epidermal lysates displays increased activity of Cath L2 in LS. The results of this study confirm differential expression of ACPP and Cath L2 in DS and LS at gene and protein level. Additionally, Cath L2 displays increased activity in LS-derived epidermal lysates. This study indentified two acid hydrolases that may play a role in melanosome degradation and pigment processing.
Textbook of Aging Skin, 2010
ABSTRACT
Journal of Investigative Dermatology, 2011
Modification of skin complexion coloration has traditionally been accomplished by interruption or... more Modification of skin complexion coloration has traditionally been accomplished by interruption or attenuation of melanogenesis and/or melanosome transfer. Post-transfer modification of pigmented melanosomes provides an attractive and distinct avenue of modulating skin pigmentation. The processing of melanosomes during keratinocyte (KC) terminal differentiation and the degradative variability observed between light and dark skin (LS and DS) remains enigmatic. To evaluate this, we developed a model system to investigate the loss of fluorescently labeled and isolated melanosomes by cultured human KCs. The extent of melanosome loss has been qualitatively assessed using transmission electron microscopy and indirect immunofluorescence with confocal microscopy, and quantitatively assessed using flow cytometry analysis. Results show that melanosomes are incorporated into the cytoplasm of both light and dark keratinocytes (LKCs and DKCs) and trafficked to a perinuclear region. Within 48 hours, confocal microscopy images suggest that LKCs display accelerated melanosome loss. This time-dependent decrease in carboxyfluorescein diacetate (CFDA) fluorescence was then quantitatively analyzed using flow cytometry. Consistent with the results of the confocal analysis, over a 48-hour time frame, LKCs appear to lose melanosomes more efficiently than DKCs. These experiments show that melanosomes are more rapidly lost in KCs derived from LS as opposed to DS.
Japanese Journal of Applied Physics, 1997
Rf plasma chemical vapor deposition from silane was numerically analyzed. When a substrate was mo... more Rf plasma chemical vapor deposition from silane was numerically analyzed. When a substrate was moved away from the plasma, gas-phase polymerization increased the contribution of oligomer radicals to film deposition. In addition, the contribution of silylene radicals became lower compared with that of silyl radicals. As a result of the trade-off between these two effects, an optimal plasma-substrate distance, where a high-quality a-Si:H film was obtained, appeared. Dilution of feed silane with hydrogen effectively reduced gas-phase polymerization and enhanced the generation of hydrogen radicals that create silyl radicals selectively through a reaction with silane. Improvement of the film quality as a result of plasma-substrate separation and hydrogen dilution was thus explained by the change in the composition of film precursors.
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Papers by Tomohiro Hakozaki