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We have developed one thermal and one light-mediated method for direct Minisci-type C-H amidation of 1,3-azoles, which are applicable to thiazoles, benzothiazoles, benzimidazoles, and for the first time, imidazoles. The new visible light-mediated approach can be rendered photosensitiser/photocatalyst-free and likely proceeds via an electron donor-acceptor (EDA) complex, the first direct Minisci-type amidation to do so.
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BACKGROUND: Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias. METHODS: We evaluated pairwise associations among handgrip strength, adult height and genetically determined height [using a polygenic score (PGS) for height in a mediation framework and a two-sample Mendelian randomisation approach] by means of multivariable regression model using a prospective cohort of Chinese living in Singapore. We additionally evaluated pathway enrichments of height-related genes in relation to increased handgrip strength to discover common biological mechanisms underlying associations of genetically determined height with handgrip strength. RESULTS: Height PGS exhibited a positive association with handgrip strength at late life after adjusting for midlife body weight and other baseline exposures (cigarette smoking, education and physical activity status, P=1.2×10-9). Approximately 66.4% of the total effect of height PGS on handgrip strength was mediated through adult height (ßindirect-effect=0.034, Pindirect-effect=1.4×10-40). Two-sample Mendelian randomisation evaluations showed a consistent causal relationship between increased height and increased handgrip strength in late life (P between 6.6×10-4 and 3.9×10-18), with insignificant horizontal pleiotropic effects (PMR-Egger intercept=0.853). Pathway analyses of genes related to both increased adult height and handgrip strength revealed enrichment in ossification and adipogenesis pathways (Padj between 0.034 to 6.8×10-4). CONCLUSIONS: The study highlights on a potentially causal effect between increased adult height and increased handgrip strength at late life, which may be explained by related biological processes underlying preservation of muscle mass and strength in ageing.
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Water pollution remains a major environmental concern, with increased toxic by-products being released into water bodies. Many of these chemical contaminants persist in the environment and bio-accumulate in aquatic organisms. At present, toxicological tests are mostly based on laboratory tests, and effective methods for monitoring wild aquatic environments remain lacking. In the present study, we used a well-characterized toxic chemical, 3,3',4,4',5-polychlorinated biphenyl (PCB126), as an example to try to identify common biomarker genes to be used for predictive toxicity of this toxic substance. First, we used two laboratory fish models, the zebrafish (Danio rerio) and medaka (Oryzias latipes), to expose PCB126 to obtain liver transcriptomic data by RNA-seq. Comparative transcriptomic analyses indicated generally conserved and concerted changes from the two species, thus validating the transcriptomic data for biomarker gene selection. Based on the common up- and downregulated genes in the two species, we selected nine biomarker genes to further test in other fish species. The first validation experiment was carried out using the third fish species, Mozambique tilapia (Oreochromis mossambicus), and essentially, all these biomarker genes were validated for consistent responses with the two laboratory fish models. Finally, to develop universal PCR primers suitable for potentially all teleost fish species, we designed degenerate primers and tested them in the three fish species as well as in another fish species without a genomic sequence available: guppy (Poecilia reticulata). We found all the biomarker genes showed consistent response to PCB126 exposure in at least 50% of the species. Thus, our study provides a promising strategy to identify common biomarker genes to be used for teleost fish analyses. By using degenerate PCR primers and analyzing multiple biomarker genes, it is possible to develop diagnostic PCR arrays to predict water contamination from any wild fish species sampled in different water bodies.
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OBJECTIVES: To investigate whether chronotype is a moderator variable that also interacts with shift type and whether they jointly influence the attention performance of nurses working in acute and critical care units. METHODS: We adopted a longitudinal research design focusing on nurses working rotating shifts in the emergency room and intensive care units at a medical center. A total of 40 complete samples were obtained. Data analysis was conducted using the generalized estimating equations in SAS 9.4. RESULTS: The mean (SD) age of the participants was 26.35 (2.12) years. After controlling for age, gender, and sleep duration, an interaction effect was discovered between a specific chronotype and shift type; that is, the interaction effect between chronotype and shift type was only significant when comparing late-types working the night shift with early- and intermediate-types working the night shift (B = -18.81, P = .011). The least squares means of the mean reaction time of the interaction effects between the 2 chronotype groups and the 3 shift types found that the mean reaction time of late-types working the night shift was 11.31 ms (P = .044) slower compared with working the day shift. CONCLUSIONS: The chronotype is a moderator variable between shift type and mean reaction time, such that matching the chronotype of nurses in acute and critical care units with the appropriate shift type improved their mean reaction time. It is hoped that the results of this study could serve as a reference for acute and critical care nurses when scheduling their shifts.
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Atención , Personal de Enfermería en Hospital , Horario de Trabajo por Turnos , Tolerancia al Trabajo Programado , Humanos , Adulto , Femenino , Masculino , Estudios Longitudinales , Personal de Enfermería en Hospital/psicología , Tolerancia al Trabajo Programado/fisiología , Ritmo Circadiano , Unidades de Cuidados Intensivos , Tiempo de Reacción , Sueño , Enfermería de Cuidados Críticos , Adulto Joven , Servicio de Urgencia en Hospital , CronotipoRESUMEN
The Microsoft Kinect depth sensor, with its built-in software that automatically captures joint coordinates without markers, could be a potential tool for ergonomic studies. This study investigates the performance of Kinect in limb segment lengths using dual-energy X-ray absorptiometry (DXA) as a reference. Healthy children and adults (n = 76) were recruited for limb length measurements by Kinect and DXA. The results showed consistent ratios of arm, forearm, thigh, and leg lengths to height, which were 0.16, 0.14, 0.23, and 0.22 respectively, for both age groups and methods. Kinect exhibited perfect correlation among all limb lengths, indicating fixed proportions assumed by its algorithm. Comparing the two methods, there was a strong correlation (R = 0.850-0.985) and good to excellent agreement (ICC = 0.829-0.977), except for the right leg in adults, where agreement was slightly lower but still moderate (ICC = 0.712). The measurement bias between the methods ranged from - 1.455 to 0.536 cm. In conclusion, Kinect yields outcomes similar to DXA, indicating its potential utility as a tool for ergonomic studies. However, the built-in algorithm of Kinect assumes fixed limb proportions for individuals, which may not be ideal for studies focusing on investigating limb discrepancies or anatomical differences.
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Absorciometría de Fotón , Humanos , Adulto , Masculino , Niño , Femenino , Absorciometría de Fotón/métodos , Adulto Joven , Algoritmos , Programas Informáticos , Adolescente , Persona de Mediana Edad , Antropometría/métodosRESUMEN
OBJECTIVE: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. METHODS: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. RESULTS: Our results demonstrated that viscolin at a concentration of 10 µM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. CONCLUSION: Viscolin has potential utility as a therapeutic agent in the treatment of stroke.
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In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.
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Antiinflamatorios , Antioxidantes , Ginkgo biloba , Miembro Posterior , Músculo Esquelético , Extractos Vegetales , Daño por Reperfusión , Animales , Ginkgo biloba/química , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Extractos Vegetales/farmacología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/irrigación sanguínea , Ratones , Miembro Posterior/irrigación sanguínea , Masculino , Ratas , Antioxidantes/farmacología , Antiinflamatorios/farmacología , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Interleucina-6/metabolismo , Ratas Sprague-Dawley , Extracto de GinkgoRESUMEN
Background: The incidence of thyroid cancer has increased over the decades, and patients prefer short thin scars after thyroidectomy due to their cosmetic visibility. Several scar assessment methods have been used to determine the most cosmetically optimal surgical method, but a widely accepted measurement tool is still lacking. This study investigates the usage status in the thyroid scar scale according to time, region, and study method. Methods: The authors searched for articles on thyroid scars published between January 2000 and September 2022 in the PubMed database. The study included clinical studies that mentioned thyroid scar and scar scale, excluding articles that did not evaluate neck scars. Statistical analysis was performed using IBM SPSS Statistics 29. Results: A total of 35 studies were included. Among them, 17 used the Vancouver Scar Scale (VSS), 17 used the Patient and Observer Scar Assessment Scale (POSAS), four used the Manchester Scar Scale (MSS), and four used the Stony Brook Scar Evaluation Scale (SBSES). VSS and POSAS were the most commonly used scar evaluation methods. VSS tended to be used frequently in Asia, while POSAS was used frequently in Europe and in randomized controlled trials. Conclusion: VSS and POSAS are popular thyroid scar assessment methods, with regional variations. Standardization is needed for meaningful comparisons. Patient's subjective evaluations should be considered, given the cosmetic importance of thyroid scars.
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A novel coagulase-negative Staphylococcus strain (H164T) was isolated from soymilk in Taiwan. Comparative sequence analysis of the 16S rRNA gene revealed that the H164T strain is a member of the genus Staphylococcus. We used multilocus sequence analysis (MLSA) and phylogenomic analyses to demonstrate that the novel strain was closely related to Staphylococcus gallinarum, Staphylococcus nepalensis, Staphylococcus cohnii, and Staphylococcus urealyuticus. The average nucleotide identity and digital DNA-DNA hybridization values between H164T and its closest relatives were <95% and <70%, respectively. The H164T strain could also be distinguished from its closest relatives by the fermentation of d-fructose, d-maltose, d-trehalose, and d-mannitol, as well as by the activities of α-glucosidase and alkaline phosphatase. The major cellular fatty acids were C15:0 iso and C15:0 anteiso, and the predominant menaquinones were MK-7 and MK-8, respectively. The major cellular fatty acids and predominant menaquinones were C15:0 iso and C15:0 anteiso and MK-7 and MK-8, respectively. In conclusion, this strain represents a novel species, named Staphylococcus hsinchuensis sp. nov., with the type strain H164T (=BCRC 81404T = NBRC 116174T).
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Platelets assume a pivotal role in the cardiovascular diseases (CVDs). Thus, targeting platelet activation is imperative for mitigating CVDs. Ginkgetin (GK), from Ginkgo biloba L, renowned for its anticancer and neuroprotective properties, remains unexplored concerning its impact on platelet activation, particularly in humans. In this investigation, we delved into the intricate mechanisms through which GK influences human platelets. At low concentrations (0.5-1 µM), GK exhibited robust inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Intriguingly, thrombin and U46619 remained impervious to GK's influence. GK's modulatory effect extended to ATP release, P-selectin expression, intracellular calcium ([Ca2+ ]i) levels and thromboxane A2 formation. It significantly curtailed the activation of various signaling cascades, encompassing phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß and mitogen-activated protein kinases. GK's antiplatelet effect was not reversed by SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor), and GK had no effect on the phosphorylation of vasodilator-stimulated phosphoproteinSer157 or Ser239 . Moreover, neither cyclic AMP nor cyclic GMP levels were significantly increased after GK treatment. In mouse studies, GK notably extended occlusion time in mesenteric vessels, while sparing bleeding time. In conclusion, GK's profound impact on platelet activation, achieved through inhibiting PLCγ2-PKC cascade, culminates in the suppression of downstream signaling and, ultimately, the inhibition of platelet aggregation. These findings underscore the promising therapeutic potential of GK in the CVDs.
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Biflavonoides , Nucleótidos Cíclicos , Fosfolipasas , Humanos , Animales , Ratones , Nucleótidos Cíclicos/metabolismo , Nucleótidos Cíclicos/farmacología , Fosfolipasa C gamma/metabolismo , Ácido Araquidónico/farmacología , Ácido Araquidónico/metabolismo , Fosfolipasas/metabolismo , Fosfolipasas/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Agregación Plaquetaria/farmacología , Activación Plaquetaria , Plaquetas/metabolismo , Agregación Plaquetaria , Proteína Quinasa C/metabolismo , Fosforilación , Colágeno/metabolismoRESUMEN
Prothymosin α (ProT), a highly acidic nuclear protein with multiple cellular functions, has shown potential neuroprotective properties attributed to its antinecrotic and antiapoptotic activities. The present study aimed to investigate the beneficial effect of ProT on neuroplasticity after ischemiareperfusion injury and elucidate its underlying mechanism of action. Primary cortical neurons were either treated with ProT or overexpressing ProT by gene transfection and exposed to oxygenglucose deprivation for 2 h in vitro. Immunofluorescence staining for ProT and MAP2 was performed to quantify ProT protein expression and assess neuronal arborization. Mice treated with vehicle or ProT (100 µg/kg) and ProT overexpression in transgenic mice received middle cerebral artery occlusion for 50 min to evaluate the effect of ProT on neuroplasticityassociated protein following ischemiareperfusion injury. The results demonstrated that in cultured neurons ProT significantly increased neurite lengths and the number of branches, accompanied by an upregulation mRNA level of brainderived neurotrophic factor. Furthermore, ProT administration improved the protein expressions of synaptosomalassociated protein, 25 kDa and postsynaptic density protein 95 after ischemicreperfusion injury in vivo. These findings suggested that ProT can potentially induce neuroplasticity effects following ischemiareperfusion injury.
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Daño por Reperfusión , Timosina , Timosina/análogos & derivados , Ratones , Animales , Ratones Transgénicos , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Regulación hacia Arriba , Timosina/genética , Timosina/farmacología , Timosina/metabolismo , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
Adverse drug reactions (ADRs) are an inherent aspect of drug use. While approximately 80% of ADRs are predictable, immune system-mediated ADRs, often unpredictable, are a noteworthy subset. Skin-related ADRs, in particular, are frequently unpredictable. However, the wide spectrum of skin manifestations poses a formidable diagnostic challenge. Comprehending the pathomechanisms underlying ADRs is essential for accurate diagnosis and effective management. The skin, being an active immune organ, plays a pivotal role in ADRs, although the precise cutaneous immunological mechanisms remain elusive. Fortunately, clinical manifestations of skin-related ADRs, irrespective of their severity, are frequently rooted in immunological processes. A comprehensive grasp of ADR morphology can aid in diagnosis. With the continuous development of new pharmaceuticals, it is noteworthy that certain drugs including immune checkpoint inhibitors have gained notoriety for their association with ADRs. This paper offers an overview of immunological mechanisms involved in cutaneous ADRs with a focus on clinical features and frequently implicated drugs.
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During the COVID-19 pandemic, the world population faced various mental health challenges, highlighting a need for new community-based psychosocial interventions. This study aimed to investigate the effectiveness and feasibility of Nature-Based Therapy (NBT) for the community experiencing psychological distress during the pandemic. A multi-site trial comparing NBT and control groups was conducted in Korea with 291 participants exhibiting mild to severe depression or anxiety. A total of 192 participated in 30 sessions of therapeutic gardening, while 99 remained in the control group. Psychological distress and well-being were assessed using seven measures of depression, anxiety, daily activity, life satisfaction, mindfulness, stress, and loneliness. The effect sizes (Cohen's d) of NBT compared to the control group were medium to large: depression (0.583), anxiety (0.728), daily activity (1.002), life satisfaction (0.786), mindfulness (0.645), stress (0.903), and loneliness (0.695). Multilevel analysis revealed significant Time × Group interaction effects for all measures. Pearson correlation (r = - 0.28 to 0.71) showed that changes in all variables correlated significantly with each other, with small to large effect sizes. Therapeutic alliance at post-test positively moderated the intervention effects on the outcomes. We concluded that NBT is a promising psychosocial intervention for treating psychological distress for community dwellers.
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COVID-19 , Distrés Psicológico , Humanos , Ansiedad/terapia , COVID-19/psicología , Atención Plena , Pandemias , Estrés Psicológico/terapia , Estrés Psicológico/psicologíaRESUMEN
Primary cilia play a significant role in influencing cell fate, including apoptosis in multiple cell types. In the lesional epidermis of vitiligo patients, a reduced number of ciliated cells was observed. Our study also revealed a downregulation of oral-facial digital syndrome type 1 (OFD1) in the affected skin of vitiligo patients. However, it remains unknown whether primary cilia are involved in the control of melanocyte apoptosis. While both intraflagellar transport 88 (IFT88) and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) are associated with ciliogenesis in melanocytes, only the knockdown of OFD1, but not IFT88 and RPGRIP1L, resulted in increased melanocyte apoptosis. OFD1 knockdown led to a decrease in the expression of proteins involved in cell-extracellular matrix (ECM) interactions, including paxillin. The OFD1 amino acid residues 601-1012 interacted with paxillin, while the amino acid residues 1-601 were associated with ciliogenesis, suggesting that the OFD1 domains responsible for paxillin binding are distinct from those involved in ciliogenesis. OFD1 knockdown, but not IFT88 knockdown, inhibited melanocyte adhesion to the ECM, a defect that was restored by paxillin overexpression. In summary, our findings indicate that the downregulation of OFD1 induces melanocyte apoptosis, independent of any impairment in ciliogenesis, by reducing melanocyte adhesion to the ECM via paxillin.
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Adhesión Celular , Melanocitos , Paxillin , Vitíligo , Humanos , Matriz Extracelular/metabolismo , Melanocitos/metabolismo , Paxillin/genética , Paxillin/metabolismo , Proteínas/metabolismo , Vitíligo/metabolismoRESUMEN
There is growing evidence that oxidative stress plays a role in melasma and disrupts primary cilia formation. Additionally, primary cilia have been suggested to have an inhibitory role in melanogenesis. This study examined the potential link between oxidative stress, skin hyperpigmentation, and primary cilia. We compared the expression levels of the nuclear factor E2-related factor 2 (NRF2), intraflagellar transport 88 (IFT88), and glioma-associated oncogene homologs (GLIs) in skin samples from patients with melasma, both in affected and unaffected areas. We also explored the roles of NRF2, IFT88, and GLIs in ciliogenesis and pigmentation using cultured adult human keratinocytes, with or without melanocytes. Our findings revealed decreased levels of NRF2, heme oxygenase-1, IFT88, and GLIs in lesional skin from melasma patients. The knockdown of NRF2 resulted in reduced expressions of IFT88 and GLI1, along with fewer ciliated cells. Furthermore, NRF2, IFT88, or GLI1 knockdown led to increased expressions in protease-activated receptor-2 (PAR2), K10, involucrin, tyrosinase, and/or melanin. These effects were reversed by the smoothened agonist 1.1. Calcium also upregulated these proteins, but not NRF2. The upregulation of involucrin and PAR2 after NRF2 knockdown was mitigated with a calcium chelator. In summary, our study suggests that oxidative stress in NRF2-downregulated melasma keratinocytes impedes ciliogenesis and related molecular processes. This inhibition stimulates keratinocyte differentiation, resulting in melanin synthesis and melanosome transfer, ultimately leading to skin hyperpigmentation.
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Colorectal cancer (CRC) ranks among the most prevalent forms of cancer globally, and its late-stage survival outcomes are less than optimal. A more nuanced understanding of the underlying mechanisms behind CRC's development is crucial for enhancing patient survival rates. Existing research suggests that the expression of Cell Wall Biogenesis 43 C-Terminal Homolog (CWH43) is reduced in CRC. However, the specific role that CWH43 plays in cancer progression remains ambiguous. Our research seeks to elucidate the influence of CWH43 on CRC's biological behavior and to shed light on its potential as a therapeutic target in CRC management. Utilizing publicly available databases, we examined the expression levels of CWH43 in CRC tissue samples and their adjacent non-cancerous tissues. Our findings indicated lower levels of both mRNA and protein expressions of CWH43 in cancerous tissues. Moreover, we found that a decrease in CWH43 expression correlates with poorer prognoses for CRC patients. In vitro experiments demonstrated that the suppression of CWH43 led to increased cell proliferation, migration, and invasiveness, while its overexpression had inhibitory effects. Further evidence from xenograft models showed enhanced tumor growth upon CWH43 silencing. Leveraging data from The Cancer Genome Atlas (TCGA), our Gene Set Enrichment Analysis (GSEA) indicated a positive relationship between low CWH43 expression and the activation of the epithelial-mesenchymal Transition (EMT) pathway. We conducted RNA sequencing to analyze gene expression changes under both silenced and overexpressed CWH43 conditions. By identifying core genes and executing KEGG pathway analysis, we discovered that CWH43 appears to have regulatory influence over the TTK-mediated cell cycle. Importantly, inhibition of TTK counteracted the tumor-promoting effects caused by CWH43 downregulation. Our findings propose that the decreased expression of CWH43 amplifies TTK-mediated cell cycle activities, thus encouraging tumor growth. This newly identified mechanism offers promising avenues for targeted CRC treatment strategies.
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Neoplasias Colorrectales , Humanos , Proteínas de Ciclo Celular/metabolismo , División Celular , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , ARN Mensajero/metabolismoRESUMEN
Oxidative stress-induced melanocyte apoptosis is linked to the immune system and plays a critical role in the pathogenesis of vitiligo. Aquaporin-3 (AQP3), which is downregulated in vitiligo keratinocytes, regulates intracellular H2O2 accumulation. However, the role of AQP3 in oxidative stress is uncertain in vitiligo. This study investigated the effect of downregulated AQP3 on oxidative stress in vitiligo using lesional and non-lesional skin specimen sets from vitiligo patients and primary cultured adult normal human epidermal keratinocytes, with or without downregulation and overexpression of AQP3 in the presence or absence of H2O2 treatment. The levels of nuclear factor E2-related factor 2 (NRF2) and/or its main target, NAD(P)H quinone dehydrogenase 1 (NQO-1), were lower in the lesional keratinocytes and cultured keratinocytes with AQP3 knockdown, but were increased in keratinocytes upon AQP3 overexpression. Ratios of NRF2 nuclear translocation and NQO-1 expression levels were further reduced in AQP3-knockdown keratinocytes following H2O2 treatment. The conditioned media from AQP3-knockdown keratinocytes treated with H2O2 contained higher concentrations of reactive oxygen species (ROS). Moreover, the number of viable melanocytes was reduced when the conditioned media were added to the culture media. Overall, AQP3 downregulation in the keratinocytes of patients with vitiligo can induce oxidative stress in neighboring melanocytes, leading to melanocyte death.
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Aspacochioside C (ACC) is a steroidal saponin isolated from Asparagus cochinchinensis. Steroidal saponins, such as pseudoprotodioscin and dioscin, are known to inhibit melanogenesis, but the role of ACC in melanogenesis remains unknown. Due to the toxic effect of the commonly used skin whitening agents like arbutin, kojic acid and α-lipoic acid alternative plant products are recentlybeen studied for their anti-hypergmentation effect. This study explores the role of ACC in melanogenesis in both in vivo and in vitro models. Here, we for the first time demonstrate that ACC attenuated α-MSH- and UVB-induced eumelanin production by inhibiting tyrosinase-related protein (TRP)-2 protein expression in both murine B16F10 and human melanoma MNT1 cells. However, ACC had no significant effect on pheomelanin concentration. ACC also decreased the pigmentation density in zebrafish embryos, which indicates that ACC targets TRP2 and inhibits eumelanin synthesis. Our results demonstrate that ACC inhibits TRP2, thereby attenuating eumelanin synthesis both in in vitro and in vivo zebrafish model. Therefore, ACC can potentially be used as an anti-melanogenic agent for both aesthetic and pharmaceutical purposes.