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The Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2) is the most common motor assessment in Korea. The BOT-2-Short Form (SF) is preferred over the complete form (CF) in settings with limited time. The present study aimed to assess the validity of the BOT-2 SF in Korean school-age children. First, we verified that the BOT-2 SF reflects developmental changes in motor skills. Second, we compared the BOT-2 SF scores to those of the BOT-2 CF. A total of 283 Korean school-age children performed the BOT-2. The differences in the BOT-2 SF point according to age group (7 years, 8-9 years, and 10-12 years) were analyzed. A correlation analysis of the standard scores between the BOT-2 SF and CF was conducted. The sensitivity and specificity of the BOT-2 SF were calculated in reference to its CF. Overall, the BOT-2 SF point scores increased with age. The correlation between the total scores of the BOT-2 SF and CF was strong. The BOT-2 SF had a sensitivity of 83% and specificity of 92%. This study has demonstrated the validity of the BOT-2 SF in Korean school-age children. The BOT2 SF can be useful in screening Korean school-age children with motor skills problems.
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BACKGROUND AND PURPOSE: Mitochondrial dysfunction contributes to the pathogenesis and maintenance of chemotherapy-induced peripheral neuropathy (CIPN), a significant limitation of cancer chemotherapy. Recently, the stimulation of mitophagy, a pivotal process for mitochondrial homeostasis, has emerged as a promising treatment strategy for neurodegenerative diseases, but its therapeutic effect on CIPN has not been explored. Here, we assessed the mitophagy-inducing activity of 3,5-dibromo-2-(2',4'-dibromophenoxy)-phenol (PDE701), a diphenyl ether derivative isolated from the marine sponge Dysidea sp., and investigated its therapeutic effect on a CIPN model. EXPERIMENTAL APPROACH: Mitophagy activity was determined by a previously established mitophagy assay using mitochondrial Keima (mt-Keima). Mitophagy induction was further verified by western blotting, immunofluorescence, and electron microscopy. Mitochondrial dysfunction was analysed by measuring mitochondrial superoxide levels in SH-SY5Y cells and Drosophila larvae. A thermal nociception assay was used to evaluate the therapeutic effect of PDE701 on the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae. KEY RESULTS: PDE701 specifically induced mitophagy but was not toxic to mitochondria. PDE701 ameliorated paclitaxel-induced mitochondrial dysfunction in both SH-SY5Y cells and Drosophila larvae. Importantly, PDE701 also significantly ameliorated paclitaxel-induced thermal hyperalgesia in Drosophila larvae. Knockdown of ATG5 or ATG7 abolished the effect of PDE701 on thermal hyperalgesia, suggesting that PDE701 exerts its therapeutic effect through mitophagy induction. CONCLUSION AND IMPLICATIONS: This study identified PDE701 as a novel mitophagy inducer and a potential therapeutic compound for CIPN. Our results suggest that mitophagy stimulation is a promising strategy for the treatment of CIPN and that marine organisms are a potential source of mitophagy-inducing compounds.
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BACKGROUND/AIM: Gastric cancer, with its high global incidence and mortality rates, poses a significant challenge due to the rapid decline in patient survival upon metastasis. Understanding and combating metastasis are crucial in improving outcomes. The metastasis suppressor gene CD82 has demonstrated efficacy in inhibiting metastasis across various carcinomas but is frequently down-regulated. However, its role and regulatory mechanisms in gastric cancer remain elusive. MATERIALS AND METHODS: Utilizing public data, we assessed patient survival in relation to CD82 expression. CD82 expression in gastric cancer cell lines was evaluated via western blotting, and its impact on cell mobility was assessed through wound healing and Transwell assays. The demethylation of CD82 was induced using 5-aza-deoxycytidine, while methylation levels were detected via methylation-specific PCR. RESULTS: Low CD82 expression correlated with poor prognosis in patients, and down-regulation and over-expression of CD82 significantly affected cell mobility. Treatment with 5-aza-deoxycytidine restored CD82 expression in low-expressing cell lines, highlighting its methylation-dependent regulation. CONCLUSION: CD82 serves as a pivotal regulator of cell mobility in gastric cancer by suppressing metastasis. Its expression is attenuated in gastric cancer cells through promoter hypermethylation.
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Movimiento Celular , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Proteína Kangai-1 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Proteína Kangai-1/genética , Proteína Kangai-1/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Regiones Promotoras Genéticas , Pronóstico , Decitabina/farmacología , Metástasis de la Neoplasia , Regulación hacia Abajo , Genes Supresores de TumorRESUMEN
The epidermis serves as a protective barrier against external threats and is primarily composed of keratinocytes, which ultimately form corneocytes. Involucrin, a protein integral to the cornified envelope, plays a pivotal role in preserving the functional integrity of the skin barrier. Previous studies have shown that Akt plays an important role in keratinocyte differentiation and skin barrier development. This study investigated whether dihydromyrcenol (DHM), a plant-derived terpene, could increase involucrin production in keratinocytes and sought to elucidate the possible underlying mechanisms. To accomplish this objective, we assessed the alterations in involucrin by DHM through quantitative PCR and Western blot on the HaCaT cell line. The changes in the promoter levels were investigated using luciferase assays. Furthermore, upstream mechanisms were explored through the use of siRNA and inhibitors. To strengthen our findings, the results were subsequently validated in primary cells and 3D skin equivalents. DHM significantly increased involucrin mRNA and protein levels in a concentration-dependent manner. In addition, the Fyn-Akt signaling pathway was found to be required for DHM-induced involucrin expression, as inhibition of Fyn or Akt blocked the increase in involucrin mRNA induced by DHM. The transcription factor Sp1, which is recognized as one of the transcription factors for involucrin, was observed to be activated in response to DHM treatment. Moreover, DHM increased epidermal thickness in a 3D human skin model. These findings suggest that the modulation of involucrin expression with DHM could improve skin barrier function and highlight the importance of manipulating the Akt pathway to achieve this improvement.
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Queratinocitos , Monoterpenos , Octanoles , Precursores de Proteínas , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Queratinocitos/metabolismo , Diferenciación Celular/genética , Transducción de Señal , ARN Mensajero/metabolismoRESUMEN
ABSTRACT: Hepatocellular carcinoma (HCC) represents a significant global burden, with management complicated by its heterogeneity, varying presentation, and relative resistance to therapy. Recent advances in the understanding of the genetic, molecular, and immunological underpinnings of HCC have allowed a detailed classification of these tumors, with resultant implications for diagnosis, prognostication, and selection of appropriate treatments. Through the correlation of genomic features with histopathology and clinical outcomes, we are moving toward a comprehensive and unifying framework to guide our diagnostic and therapeutic approach to HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , GenómicaRESUMEN
BACKGROUND: Acetaminophen overdose is one of the leading causes of acute liver failure in the USA. In this study, we investigated the impact of race and gender on the hospital outcomes of patients admitted with acetaminophen-induced acute liver failure. METHODS: From the National Inpatient Sample between the years 2016 and 2019, patients with acetaminophen-induced acute liver failure were selected and stratified based on gender (Male and Female) and race (White, Black and Hispanic). The cases were propensity score-matched to controls (male and Whites) and were compared along the following endpoints: mortality, length of stay, hospitalization costs, and hepatic complications. RESULTS: Among patients with acetaminophen-induced acute liver failure, females experienced higher rates of mortality (16.60% vs. 11.70%, Pâ =â 0.004) and clinical illness, including hypotension (11.80% vs. 7.15%, Pâ =â 0.002) and ventilator use (40.80% vs. 30.00%, Pâ <â 0.001). When stratified by race, Black patients had longer hospital stays (Black vs. White, 8.76 days vs. 7.46 days, Pâ =â 0.03). There were no significant differences in outcomes between Hispanic and White patients. No significant differences in mortality were shown between races. CONCLUSION: We found that females had a higher rate of mortality and incidence of hepatic encephalopathy compared to males. When stratified by race, Blacks were shown to have longer hospital stay. Females and racial minorities were also affected by special healthcare needs after discharge compared to their male and White cohorts, respectively.
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Acetaminofén , Fallo Hepático Agudo , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Acetaminofén/efectos adversos , Puntaje de Propensión , Mortalidad Hospitalaria , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/terapia , Estudios Retrospectivos , BlancoRESUMEN
Glucocorticoid receptors (GRs) play a pivotal role in the stress response of the body, but overactivation can disrupt normal physiological functions. This study explores the role of cyclic adenosine monophosphate (cAMP) in GR activation and the associated mechanisms. We initially used the human embryonic kidney 293 cell line (HEK293) and found that cAMP enhancement, using forskolin and 3-isobutyl-1-methylxanthine (IBMX), did not alter glucocorticoid signaling under normal conditions, as evidenced by glucocorticoid response element (GRE) activity and the translocation of GR. However, in stressful conditions induced by dexamethasone, a synthetic glucocorticoid, cAMP was found to lessen glucocorticoid signaling within a short time frame but amplify it over an extended period in HEK293 cells. Bioinformatic analysis revealed that cAMP upregulation triggers the extracellular signal-regulated kinase (ERK) pathway, which influences GR translocation and ultimately regulates its activity. This stress-modulating function of cAMP was also investigated in the Hs68 dermal fibroblast line, known for its susceptibility to glucocorticoids. We found that cAMP enhancement via forskolin reduces GRE activity and reverses collagen loss in Hs68 cells exposed to dexamethasone. These findings underline the context-specific role of cAMP signaling in managing glucocorticoid signaling and its potential therapeutic application in treating stress-related pathological conditions like skin aging characterized by collagen reduction.
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Glucocorticoides , Receptores de Glucocorticoides , Humanos , Glucocorticoides/farmacología , Receptores de Glucocorticoides/metabolismo , Células HEK293 , Colforsina/farmacología , AMP Cíclico/metabolismo , Dexametasona/farmacología , Adenosina MonofosfatoRESUMEN
Over several decades, excess glucocorticoids (GCs) of endogenous or exogenous origin have been recognized to significantly inhibit collagen synthesis and accelerate skin aging. However, little is known regarding their molecular mechanisms. We hypothesized that the action of GCs on collagen production is at least partially through the glucocorticoid receptor (GR) and its target genes, and therefore aimed to identify GR target genes that potentially inhibit collagen synthesis in Hs68 human dermal fibroblasts. We first confirmed that dexamethasone, a synthetic GC, induced canonical GR signaling in dermal fibroblasts. We then collected 108 candidates for GR target genes reported in previous studies on GR target genes and verified that 17 genes were transcriptionally upregulated in dexamethasone-treated dermal fibroblasts. Subsequently, by individual knockdown of the 17 genes, we identified that six genes, AT-rich interaction domain 5B, FK506 binding protein 5, lysyl oxidase, methylenetetrahydrofolate dehydrogenase (NADP + dependent) 2, zinc finger protein 36, and zinc fingers and homeoboxes 3, are potentially involved in GC-mediated inhibition of collagen synthesis. The present study sheds light on the molecular mechanisms of GC-mediated skin aging and provides a basis for further research on the biological characteristics of individual GR target genes.
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Colágeno , Dermis , Fibroblastos , Glucocorticoides , Receptores de Glucocorticoides , Humanos , Colágeno/biosíntesis , Dermis/citología , Dermis/efectos de los fármacos , Dermis/metabolismo , Dexametasona/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Glucocorticoides/farmacología , Receptores de Glucocorticoides/efectos de los fármacos , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismoRESUMEN
Telehealth has been applied to occupational therapy practice since the COVID-19 pandemic, but no research has been conducted on the use of telehealth to improve the occupational performances of Korean children and parents. This study explored the possibility of tele-coaching parents to improve toddlers' occupational performance and parenting competence in Korea. Three mothers of toddlers received Occupational Performance Coaching (OPC) via videoconference. The Canadian Occupational Performance Measure (COPM) and the Parenting Sense of Competence Scale (PSOC) were used pre- and post-intervention to measure the occupational performances of the toddlers and parents and parenting competence. Post-intervention interviews were conducted to explore the parents' experiences with the tele-coaching and analyzed by content analysis. Most of the COPM scores showed a significant increase. The PSOC scores also increased. The mothers reported their learning, the changes in their children, the appropriateness of the coaching, and the usefulness of the tele-coaching delivery. The findings demonstrate the potential of tele-coaching as a practical intervention for Korean children and parents.
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OBJECTIVE: To determine whether there is laterality predominance in the horizontal dimensions of the periocular region. DESIGN: Retrospective study. PARTICIPANTS: Patients >18 years of age who presented to a single academic ophthalmology department. Exclusion criteria included history of facial trauma or surgery, aesthetic injections, or other periocular-altering processes. METHODS: Standardized digital photographs were obtained, and periocular structures were measured with Image J software. The midline was defined as the midpoint between the medial canthi, and the distances measured include midline to medial canthus, pupil centre, lateral canthus, and lateral zygoma. The palpebral fissure width was calculated as the distance between the lateral canthus and medial canthus. Data analysis was done for the full cohort and subsequently according to patient-identified gender. RESULTS: Periocular structures were measured in 83 patients (50 female and 33 male) with a mean age of 57.0 ± 16.2 years (range, 22-84 years). Right-sided predominance was found to be increasingly significant for the following variables: midline to pupil centre (31.34 mm vs 31.08 mm, p < 0.01), midline to lateral canthus (42.57 mm vs 42.23 mm, p < 0.005), and midline to lateral zygoma (65.70 mm vs 64.01 mm, p < 0.001). CONCLUSIONS: Photographic analysis of adults with no periocular-altering history demonstrates that there is a right-sided predominance in the horizontal dimension of the midline to the pupil, lateral canthus, and zygoma with increasing significance. Asymmetry of horizontal periocular measurements was more prevalent in males.
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Párpados , Aparato Lagrimal , Adulto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Cara , PupilaRESUMEN
In recent years, there has been a great deal of interest in the ectopic roles of olfactory receptors (ORs) throughout the human body. Especially, the ectopic function of OR in the skin is one of the most actively researched areas. Suberic acid, a scent compound, was hypothesized to increase collagen synthesis in the ultraviolet B (UVB)-irradiated human dermal fibroblasts (Hs68) through a specific olfactory receptor. Suberic acid ameliorated UVB-induced decreases in collagen production in Hs68 cells. Using in silico docking to predict the binding conformation and affinity of suberic acid to 15 ectopic ORs detectable in Hs68, several ORs were identified as promising candidates. The effect of suberic acid on collagen synthesis in UVB-exposed dermal fibroblasts was nullified only by a reduction in OR10A3 expression via specific siRNA. In addition, using the cells transiently expressing OR10A3, we demonstrated that suberic acid can activate OR10A3 by assessing the downstream effector cAMP response element (CRE) luciferase activity. We examined that the activation of OR10A3 by suberic acid subsequently stimulates collagen synthesis via the downstream cAMP-Akt pathway. The findings support OR10A3 as a promising target for anti-aging treatments of the skin.
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Receptores Odorantes , Envejecimiento de la Piel , Humanos , Colágeno/metabolismo , Fibroblastos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/genética , Envejecimiento de la Piel/fisiología , Receptores Odorantes/genética , Receptores Odorantes/metabolismoRESUMEN
Dermal papilla cells (DPCs) are growth factor reservoirs that are specialized for hair morphogenesis and regeneration. Due to their essential role in hair growth, DPCs are commonly used as an in vitro model to investigate the effects of hair growth-regulating compounds and their molecular mechanisms of action. Cyclic adenosine monophosphate (cAMP), an intracellular second messenger, is currently employed as a growth-promoting target molecule. In a pilot test, we found that α-phellandrene, a naturally occurring phytochemical, increased cAMP levels in DPCs. Therefore, we sought to determine whether α-phellandrene increases growth factors and proliferation in human DPCs and to identify the underlying mechanisms. We demonstrated that α-phellandrene promotes cell proliferation concentration-dependently. In addition, it increases the cAMP downstream effectors, such as protein kinase A catalytic subunit (PKA Cα) and phosphorylated cAMP-responsive element-binding protein (CREB). Also, among the CREB-dependent growth factor candidates, we identified that α-phellandrene selectively upregulated vascular endothelial growth factor (VEGF) mRNA expression in DPCs. Notably, the beneficial effects of α-phellandrene were nullified by a cAMP inhibitor. This study demonstrated the cAMP-mediated growth effects in DPCs and the therapeutic potential of α-phellandrene for preventing hair loss.
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Folículo Piloso , Factor A de Crecimiento Endotelial Vascular , Proliferación Celular , Células Cultivadas , AMP Cíclico/metabolismo , Monoterpenos Ciclohexánicos , Folículo Piloso/metabolismo , Humanos , Factor A de Crecimiento Endotelial Vascular/farmacologíaRESUMEN
Particulate matter (PM), a component of air pollution, has been epidemiologically associated with a variety of diseases. Recent reports reveal that PM has detrimental effects on the brain. In this study, we aimed to investigate the biological effects of ambient particles on the neurodegenerative disease Parkinson's disease (PD). We exposed mice to coarse particles (PM10: 2.5-10 µm) for short (5 days) and long (8 weeks) durations via intratracheal instillation. Long-term PM10 exposure exacerbated motor impairment and dopaminergic neuron death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. Short-term PM10 exposure resulted in both pulmonary and systemic inflammatory responses in mice. We further investigated the mechanism underlying PM10-induced neurotoxicity in cocultures of lung LA-4 epithelial cells and RAW264.7 macrophages. PM10 treatment elicited a dramatic increase in proinflammatory mediators in LA-4/RAW264.7 coculture. Treating BV2 microglial cells with PM10-treated conditioned medium induced microglial activation. Furthermore, 1-methyl-4-phenylpyridinium (MPP+) treatment caused notable cell death in N2A neurons cocultured with activated BV2 cells in PM10-conditioned medium. Altogether, our results demonstrated that PM10 plays a role in the neurodegeneration associated with PD. Thus, the impact of PM10 on neurodegeneration could be related to detrimental air pollution-induced systemic effects on the brain.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , 1-Metil-4-fenilpiridinio/farmacología , Animales , Medios de Cultivo Condicionados/farmacología , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/metabolismo , Material Particulado/toxicidadRESUMEN
OBJECTIVE: The study aimed to examine the relationship on attitudes toward suicide, frustrated interpersonal needs, and non-suicidal self-injury (NSSI) of the university students. METHODS: The participants included 175 university students. Data were analyzed using the SPSS PROCESS macro (Model 4). RESULTS: Depression showed a fully mediating effect on the relationship between one's attitude toward suicide and NSSI behaviors. Furthermore, depression showed a full mediating impact on the relationship between frustrated interpersonal needs and NSSI behaviors. CONCLUSIONS: These findings indicate that suicidal attitudes and frustrated interpersonal needs should be considered significant factors for developing NSSI preventions and intervention among university students.
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COVID-19 , Conducta Autodestructiva , Suicidio , Actitud , Depresión , Humanos , Pandemias , Estudiantes , Intento de Suicidio , UniversidadesRESUMEN
This study investigated the relationship between the Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07) and the Bruininks-Oseretsky Test of Motor Proficiency Second Edition (BOT-2) in Korea. This study also adjusted the cutoff score of the DCDQ'07 based on the BOT-2 for Korean children. A total of 256 children were recruited from communities in Korea. They were divided into two age groups: 8 to 9 years old and 10 to 12 years old. Children performed the BOT-2, and their parents completed the DCDQ'07. The correlation between the DCDQ'07 and the BOT-2 was analyzed. The adjusted DCDQ'07 cutoff score for Korean children was calculated using the BOT-2 as the criterion through a receiver operating characteristic curve. A significant correlation between the DCDQ'07 and the BOT-2 was found, indicating that Korean parents' perception of children's motor skills was related to their children's actual motor proficiency. The adjusted cutoff score of the DCDQ'07 had a sensitivity of 72.7-85.7% and a specificity of 62.5-64.0%. This study demonstrated that children's motor skills reported by Korean parents on the DCDQ'07 were valid based on a community sample. The adjusted cutoff score of the DCDQ'07 could be used to identify children suspected of having a developmental coordination disorder.
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PURPOSE: To investigate the relationship between sleep position preference and eyebrow and eyelid position and degree of upper eyelid dermatochalasis. METHODS: A prospective study evaluating the impact of sleep position on facial asymmetry was conducted at an academic ophthalmology department. Eligibility criteria included the absence of periocular-altering trauma or surgery, contact lens use, or other periorbital disease processes. Patients reported their sleep position preference on a questionnaire. Standardized digital photographs of patients were obtained, and Image J software was used for measurements and converted into millimeters based on a standard corneal limbus-to-limbus ratio. Upper and lower eyelid position, upper eyelid dermatochalasis, and eyebrow position were assessed by the following image-derived measurements: marginal reflex distance 1 (iMRD1), marginal reflex distance 2 (iMRD2), tarsal platform show (iTPS), and central brow position (iBP). These results were compared with the patient reported sleep position preference to determine correlation. RESULTS: Seventy-one patients were enrolled and reported the following sleep position preferences: 28 (right), 24 (left), 13 (both), and 6 (supine). Patients with a right- or left-sided preference demonstrated lower iMRD1 measurements for the preferred sleep side (p < 0.0004) with no other significant difference in periorbital measurements. A larger degree of upper eyelid height (iMRD1) asymmetry was observed among patients with a sleep side preference. CONCLUSION: Patients with a predominant sleep side preference demonstrate a significant increase in ipsilateral upper eyelid asymmetry and an inferior upper eyelid position on the sleep side. There were no differences noted in lower eyelid position, central eyebrow position, or amount of upper eyelid dermatochalasis.
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Blefaroplastia , Lesiones Oculares , Blefaroplastia/métodos , Cejas , Párpados , Humanos , Estudios Prospectivos , SueñoRESUMEN
Skin dermis comprises extracellular matrix components, mainly collagen fibers. A decrease in collagen synthesis caused by several factors, including ultraviolet (UV) irradiation and stress, eventually causes extrinsic skin aging. Olfactory receptors (ORs) were initially considered to be specifically expressed in nasal tissue, but several ORs have been reported to be present in other tissues, and their biological roles have recently received increasing attention. In this study, we aimed to characterize the role of ORs in cell survival and collagen synthesis in dermal fibroblasts. We confirmed that UVB irradiation and dexamethasone exposure significantly decreased cell survival and collagen synthesis in Hs68 dermal fibroblasts. Moreover, we demonstrated that the mRNA expression of 10 ORs detectable in Hs68 cells was significantly downregulated in aged conditions compared with that in normal conditions. Thereafter, by individual knockdown of the 10 candidate ORs, we identified that only OR51B5 knockdown leads to a reduction of cell survival and collagen synthesis. OR51B5 knockdown decreased cAMP levels and dampened the downstream protein kinase A/cAMP-response element binding protein pathway, downregulating the survival- and collagen synthesis-related genes in the dermal fibroblasts. Therefore, OR51B5 may be an interesting candidate that plays a role in cell survival and collagen synthesis.
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Supervivencia Celular , Colágeno/biosíntesis , Fibroblastos/metabolismo , Línea Celular , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Dexametasona , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Fibroblastos/efectos de la radiación , Humanos , Transducción de Señal , Piel/metabolismo , Rayos UltravioletaRESUMEN
Olfactory receptors (ORs) have diverse physiological roles in various cell types, beyond their function as odorant sensors in the olfactory epithelium. These previous findings have suggested that ORs could be diagnostic markers and promising therapeutic targets in several pathological conditions. In the current study, we sought to characterize the changes in the expression of ORs in the HaCaT human keratinocytes cell line exposed to ultraviolet (UV) light or inflammation, well-recognized stimulus for skin barrier disruption. We confirmed that major olfactory signaling components, including ORs, GNAL, Ric8b, and adenylate cyclase type 3, are highly expressed in HaCaT cells. We have also demonstrated that the 12 ectopic ORs detectable in HaCaT cells are more highly expressed in UV-irradiated or inflamed conditions than in normal conditions. We further assessed the specific OR-mediated biological responses of HaCaT cells in the presence of known odorant ligands of ORs and observed that specific ligand-activated ORs downregulate skin barrier genes in HaCaT cells. This study shows the potential of OR as a marker for skin barrier abnormalities. Further research is needed to explore how OR is implicated in the development and progression of barrier dysfunction.
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Regulación de la Expresión Génica/efectos de la radiación , Inflamación/genética , Queratinocitos/efectos de la radiación , Receptores Odorantes/genética , Piel/efectos de la radiación , Rayos Ultravioleta , Adenilil Ciclasas/genética , Adenilil Ciclasas/metabolismo , Línea Celular , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Humanos , Inflamación/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Receptores Odorantes/metabolismo , Transducción de Señal/genética , Transducción de Señal/efectos de la radiación , Piel/metabolismo , Piel/patologíaRESUMEN
Stress is a major contributing factor of skin aging, which is clinically characterized by wrinkles, loss of elasticity, and dryness. In particular, glucocorticoids are generally considered key hormones for promoting stress-induced skin aging through binding to glucocorticoid receptors (GRs). In this work, we aimed to investigate whether ß-ionone (a compound occurring in various foods such as carrots and almonds) attenuates dexamethasone-induced suppression of collagen and hyaluronic acid synthesis in human dermal fibroblasts, and to explore the mechanisms involved. We found that ß-ionone promoted collagen production dose-dependently and increased mRNA expression levels, including collagen type I α 1 chain (COL1A1) and COL1A2 in dexamethasone-treated human dermal fibroblasts. It also raised hyaluronic acid synthase mRNA expression and hyaluronic acid levels. Notably, ß-ionone inhibited cortisol binding to GR, subsequent dexamethasone-induced GR signaling, and the expression of several GR target genes. Our results reveal the strong potential of ß-ionone for preventing stress-induced skin aging and suggest that its effects are related to the inhibition of GR signaling in human dermal fibroblasts.
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Norisoprenoides/metabolismo , Norisoprenoides/farmacología , Piel/metabolismo , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Línea Celular , Células Cultivadas , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Colágeno Tipo I/efectos de los fármacos , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Dexametasona/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/fisiología , Humanos , Ácido Hialurónico/metabolismo , Transducción de Señal/efectos de los fármacos , Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Rayos UltravioletaRESUMEN
Melanin, which determines the color of the skin and hair, is initially synthesized to protect the skin from ultraviolet light; however, excessive melanin pigmentation caused by abnormal cell proliferation can result in various melanocytic lesions. Cyclic adenosine monophosphate (cAMP) is known to regulate cell cycle progression and consequently to inhibit the division of abnormally proliferating cells. In this work, we aimed to test whether carvone, a scent compound from plants, inhibits proliferation and subsequently reduces melanin content of melanoma cells and to determine whether its beneficial effects are mediated by the cAMP pathway. We found that carvone decreases melanin content and inhibits melanoma cell proliferation in a concentration-dependent manner. Meanwhile, it inhibited the activation of cell cycle-associated proteins such as cyclin-dependent kinase 1 (CDK1). Of note, the beneficial effects of carvone were abrogated by cAMP inhibition. Our findings indicate potential benefits of carvone for the treatment of melanomas and presumably other hyperpigmentation-related dermatological disorders such as melasmas, lentigines, and excessive freckles.