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BACKGROUND/AIM: Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial. MATERIALS AND METHODS: This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response. RESULTS: Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears. CONCLUSION: Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments.
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Modelos Animales de Enfermedad , Prurito , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratones , Ratas , Prurito/tratamiento farmacológico , Masculino , Piel/efectos de los fármacos , Piel/patología , Piel/lesiones , Pomadas , Crema para la Piel , Productos Biológicos/farmacología , Productos Biológicos/uso terapéuticoRESUMEN
BACKGROUND/AIM: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and a multifactorial etiology. While imatinib has demonstrated efficacy in the treatment of immune-related diseases, its potential effects in IBD treatment remain underexplored. MATERIALS AND METHODS: This study aimed to investigate the therapeutic effects of imatinib in colitis treatment. A dextran sulfate sodium (DSS)-induced colitis model was used to mimic IBD in mice. Imatinib was administered orally to mice simultaneously with DSS treatment. The effects of imatinib on DSS-induced colitis were evaluated by analyzing colitis-related pathology, including the disease activity index (DAI), histological lesions, inflammatory markers, and tight junction integrity. Additionally, western blot analysis and quantitative real-time polymerase chain reaction were used to assess inflammatory markers, tight-junction proteins, and cell death. RESULTS: In the DSS-induced colitis model, imatinib treatment exerted protective effects by attenuating weight loss, restoring colon length, reducing spleen weight, and improving the DAI score and histological lesions. Additionally, imatinib reduced the level of proinflammatory cytokines, including TNF-α, IL-6, and IL-1ß. Furthermore, imatinib treatment restored tight-junction integrity and decreased the expression of apoptosis marker proteins. CONCLUSION: Overall, imatinib treatment significantly alleviated the symptoms of DSS-induced colitis by influencing the expression of proinflammatory cytokines, tight junction proteins, and apoptotic markers in mice. These findings highlight imatinib as a potential therapeutic candidate for IBD.
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Apoptosis , Colitis , Citocinas , Sulfato de Dextran , Modelos Animales de Enfermedad , Mesilato de Imatinib , Animales , Mesilato de Imatinib/farmacología , Sulfato de Dextran/efectos adversos , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/patología , Colitis/metabolismo , Ratones , Apoptosis/efectos de los fármacos , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Masculino , Mediadores de Inflamación/metabolismo , BiomarcadoresRESUMEN
In this study, physicochemical and antioxidant properties, and storage stability (1, 3, and 7 days) of pork patties added with edible insect powders (EIP) of four species (Larvae of Tenenbrio molitor, Protaetia brevitarsis seulensis, Allomyrina dichotoma, and Gryllus bimaculatus) as meat partial substitutes were investigated. Twenty percent of each EIP was added to pork patties, and four treatments were prepared. On the other hand, two control groups were set, one with 0.1 g of ascorbic acid and the other without anything. Adding EIP decreased water content but increased protein, fat, carbohydrate, and ash contents. In addition, the use of EIP increased the water holding capacity and texture properties as well as decreased the cooking loss. However, the sensory evaluation and storage stability were negatively affected by the addition of EIP. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity had a positive effect on storage stability. It is believed that the addition of EIP resulted in high antioxidants due to the presence of polyphenol compounds in EIP. These results indicate that EIP has great potential to be used as meat partial substitute to improve the quality improvement and antioxidant in pork patties. However, in order to improve storage stability and consumer preference, further research is needed to apply it to patties by reducing the amount of EIP or adding auxiliary ingredients.
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Primary cilia are crucial for cellular balance, serving as sensors for external conditions. Nephronophthisis and related ciliopathies, which are hereditary and degenerative, stem from genetic mutations in cilia-related genes. However, the precise mechanisms of these conditions are still not fully understood. Our research demonstrates that downregulating PDIA6, leading to cilia removal, makes cells more sensitive to ferroptotic death caused by endoplasmic reticulum (ER) stress. The reduction of PDIA6 intensifies the ER stress response, while also impairing the regulation of primary cilia in various cell types. PDIA6 loss worsens ER stress, hastening ferroptotic death in proximal tubule epithelial cells, HK2 cells. Counteracting this ER stress can mitigate PDIA6 depletion effects, restoring both the number and length of cilia. Moreover, preventing ferroptosis corrects the disrupted primary ciliogenesis due to PDIA6 depletion in HK2 cells. Our findings emphasize the role of PDIA6 in primary ciliogenesis, and suggest its absence enhances ER stress and ferroptosis. These insights offer new therapeutic avenues for treating nephronophthisis and similar ciliopathies.
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BACKGROUND/AIM: Human melanoma-associated antigen A2 (hMAGEA2) family members play several roles in many types of cancer and have been explored as potential prognostic markers. In this study, we investigated the molecular mechanism underlying hMAGEA2-mediated tumorigenesis of prostate cancer. MATERIALS AND METHODS: Immunohistochemistry and western blot were used to assess protein expression whereas microarray and quantitative reverse transcription-PCR determined mRNA expression. CCK-8 assay was used to determine cell proliferation. Colony formation assay was used to examine tumorigenesis. Migration and invasion were examined using a transwell assay. Propidium iodide (PI)/Annexin V double staining was performed to measure apoptosis. Transcriptional activity was measured using Dual-luciferase reporter assay. RESULTS: hMAGEA2 was highly over-expressed in human prostate cancer tissues compared to benign prostatic hyperplasia tissues. To elucidate its biological function in prostate cancer, we established two stable hMAGEA2-knockdown prostate cancer cell lines, PC3M and 22RV1, and found that they presented significantly decreased proliferation, anchorage-independent colony formation, migration, and invasion. As hMAGEA2 knockdown suppressed prostate cancer cell growth, we examined its potential influence on tumor apoptosis. hMAGEA2-knockdown cell lines displayed early apoptosis. Moreover, knockdown of hMAGEA2 resulted in the down-regulation of EFNA3 expression. Luciferase assay showed that hMAGEA2 bound to the EFNA promoter region and regulated its transcription. Down-regulation of EFNA3 expression led to decreased Ras/Braf/MEK/Erk1/2 phosphorylation and, consequently, inhibited prostate cancer progression. CONCLUSION: hMAGEA2 promotes prostate cancer growth, metastasis, and tumorigenesis by regulating the EFNA3-Erk1/2 signaling pathway, indicating its potential as a therapeutic marker for prostate cancer.
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Apoptosis , Proliferación Celular , Progresión de la Enfermedad , Sistema de Señalización de MAP Quinasas , Neoplasias de la Próstata , Humanos , Masculino , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Sistema de Señalización de MAP Quinasas/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Factores de TranscripciónRESUMEN
Maintaining epidermal homeostasis relies on a tightly organized process of proliferation and differentiation of keratinocytes. While past studies have primarily focused on calcium regulation in keratinocyte differentiation, recent research has shed light on the crucial role of lysosome dysfunction in this process. TLR adaptor interacting with SLC15A4 on the lysosome (TASL) plays a role in regulating pH within the endo-lysosome. However, the specific role of TASL in keratinocyte differentiation and its potential impact on proliferation remains elusive. In our study, we discovered that TASL deficiency hinders the proliferation and migration of keratinocytes by inducing G1/S cell cycle arrest. Also, TASL deficiency disrupts proper differentiation process in TASL knockout human keratinocyte cell line (HaCaT) by affecting lysosomal function. Additionally, our research into calcium-induced differentiation showed that TASL deficiency affects calcium modulation, which is essential for keratinocyte regulation. These findings unveil a novel role of TASL in the proliferation and differentiation of keratinocytes, providing new insights into the intricate regulatory mechanisms of keratinocyte biology.
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Calcio , Diferenciación Celular , Proliferación Celular , Péptidos y Proteínas de Señalización Intracelular , Queratinocitos , Lisosomas , Humanos , Calcio/metabolismo , Línea Celular , Movimiento Celular , Queratinocitos/metabolismo , Queratinocitos/citología , Lisosomas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismoRESUMEN
Inflammatory bowel disease (IBD) is a chronic inflammatory condition that is influenced by various factors, including environmental factors, immune responses, and genetic elements. Among the factors that influence IBD progression, macrophages play a significant role in generating inflammatory mediators, and an increase in the number of activated macrophages contributes to cellular damage, thereby exacerbating the overall inflammatory conditions. HSPA9, a member of the heat shock protein 70 family, plays a crucial role in regulating mitochondrial processes and responding to oxidative stress. HSPA9 deficiency disrupts mitochondrial dynamics, increasing mitochondrial fission and the production of reactive oxygen species. Based on the known functions of HSPA9, we considered the possibility that HSPA9 reduction may contribute to the exacerbation of colitis and investigated its relevance. In a dextran sodium sulfate-induced colitis mouse model, the downregulated HSPA9 exacerbates colitis symptoms, including increased immune cell infiltration, elevated proinflammatory cytokines, decreased tight junctions, and altered macrophage polarization. Moreover, along with the increased mitochondrial fission, we found that the reduction in HSPA9 significantly affected the superoxide dismutase 1 levels and contributed to cellular death. These findings enhance our understanding of the intricate mechanisms underlying colitis and contribute to the development of novel therapeutic approaches for this challenging condition.
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Colitis , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Muerte Celular , Colitis/metabolismo , Colon/metabolismo , Citocinas/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Enfermedades Inflamatorias del Intestino/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Estrés OxidativoRESUMEN
This study investigated the antioxidant activity of radish seed oil (RSO) and its effects on the quality and storage characteristics of pork patties. To assess the antioxidant capacity of RSO, this study analyzed fatty acid composition, peroxide value (PV), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Pork patties were manufactured with the addition of RSO-0.4%, 0.8%, 1.6%, and 2.4%-and measured in terms of proximate composition, pH, water holding capacity (WHC), cooking loss (CL), color, texture profile analysis, and a sensory evaluation. Total microbial count (TMC), volatile basic nitrogen (VBN), thiobarbituric acid reactive substances (TBARS), and PV were measured at 1, 3, and 7 days of refrigerated storage. The DPPH radical scavenging activity of RSO was found to be 75.46%. In the cases of WHC and CL, there was no significant differences observed between RSO0.4%, RSO0.8%, and positive control (PC; p>0.05). Meanwhile, RSO2.4% showed significantly lower hardness, springiness, gumminess, and chewiness than PC (p<0.05), and these values tended to decrease with the addition of increasing RSO. In terms of storage characteristics, with an increase in the amount of RSO added, TMC, VBN, TBARS, and PV all decreased; among the treatment groups, RSO2.4% showed the lowest values. In conclusion, RSO exhibits antioxidant activity, but when added in large amounts, it negatively affects the quality characteristics of patties while positively impacting their storage properties, thus necessitating a balanced consideration of both outcomes. Therefore, adding 1.6% RSO is considered to be the most appropriate level for formulations to be used in practice.
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Oral cancer remains the leading cause of death worldwide. Rhein is a natural compound extracted from the traditional Chinese herbal medicine rhubarb, which has demonstrated therapeutic effects in various cancers. However, the specific effects of rhein on oral cancer are still unclear. This study aimed to investigate the potential anticancer activity and underlying mechanisms of rhein in oral cancer cells. The antigrowth effect of rhein in oral cancer cells was estimated by cell proliferation, soft agar colony formation, migration, and invasion assay. The cell cycle and apoptosis were detected by flow cytometry. The underlying mechanism of rhein in oral cancer cells was explored by immunoblotting. The in vivo anticancer effect was evaluated by oral cancer xenografts. Rhein significantly inhibited oral cancer cell growth by inducing apoptosis and S-phase cell cycle arrest. Rhein inhibited oral cancer cell migration and invasion through the regulation of epithelial-mesenchymal transition-related proteins. Rhein induced reactive oxygen species (ROS) accumulation in oral cancer cells to inhibit the AKT/mTOR signaling pathway. Rhein exerted anticancer activity in vitro and in vivo by inducing oral cancer cell apoptosis and ROS via the AKT/mTOR signaling pathway in oral cancer. Rhein is a potential therapeutic drug for oral cancer treatment.
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Neoplasias de la Boca , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis , Proliferación Celular , Neoplasias de la Boca/tratamiento farmacológico , Línea Celular TumoralRESUMEN
The primary cilium, an antenna-like structure on the cell surface, acts as a mechanical and chemical sensory organelle. Primary cilia play critical roles in sensing the extracellular environment to coordinate various developmental and homeostatic signaling pathways. Here, we showed that the depletion of heat shock protein family A member 9 (HSPA9)/mortalin stimulates primary ciliogenesis in SH-SY5Y cells. The downregulation of HSPA9 enhances mitochondrial stress by increasing mitochondrial fragmentation and mitochondrial reactive oxygen species (mtROS) generation. Notably, the inhibition of either mtROS production or mitochondrial fission significantly suppressed the increase in primary ciliogenesis in HSPA9-depleted cells. In addition, enhanced primary ciliogenesis contributed to cell survival by activating AKT in SH-SY5Y cells. The abrogation of ciliogenesis through the depletion of IFT88 potentiated neurotoxicity in HSPA9-knockdown cells. Furthermore, both caspase-3 activation and cell death were increased by MK-2206, an AKT inhibitor, in HSPA9-depleted cells. Taken together, our results suggest that enhanced primary ciliogenesis plays an important role in preventing neurotoxicity caused by the loss of HSPA9 in SH-SY5Y cells.
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Neuroblastoma , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Apoptosis , Estrés Oxidativo , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas Mitocondriales/metabolismoRESUMEN
BACKGROUND: Although the number of older women living alone (OWLA) has risen steadily in aging societies, and research has been conducted on depression and health-related quality of life (HRQoL) among older adults, research is scarce on the health behaviors of OWLA, including their sleep, physical activity, and sedentary behaviors. Hence, we aimed to identify factors related to depression and HRQoL among this subset of the population, focusing on their health behaviors, using Andersen's model as a research framework. METHODS: Data for secondary analysis were from the Korean National Health and Nutritional Examination Survey (2014, 2016, 2018, and 2020). The inclusion criteria were (1) women aged 65 and older and (2) those living alone. We included 794 older South Korean women living alone from 31,051 respondents. We used hierarchical regression analysis, considering sampling weight and a complex sample design, to identify factors related to depression and HRQoL. RESULTS: Among the health behavior factors of Andersen's model as a research framework, sleep was associated with depression, whereas physical activity and sedentary behaviors were related to HRQoL. Subjective health status, limited activity, and perceived stress were associated with both depression and HRQoL. Household income, as an enabling factor, was only associated with HRQoL. The final regression model explained 39% of the variance in depression (p < 0.001) and 37% of the variance in HRQoL (p < 0.001). CONCLUSIONS: Our study highlights the importance of strategies to improve specific healthy behaviors that affect depression and HRQoL in OWLA. Appropriate interventions that target increasing physical activity and quality of sleep, and decreasing sedentary behaviors, will be effective to enhance the well-being of OWLA. Healthcare providers should comprehensively understand the characteristics of OWLA and pay more attention to enabling, need, and health behavior factors.
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To ensure that older adults (aged 65 years or older) can experience a healthy life, they should use medical services that are appropriate, both quantitatively and qualitatively. This study aimed to identify the factors affecting outpatient service use by older adult women with degenerative arthritis using Andersen's model. A survey was conducted among 232 older adult women with degenerative arthritis in two university hospitals in Seoul. The Korean Activities of Daily Living, Korean Instrumental Activities of Daily Living, and the Geriatric Depression Scale Short Form were used. Data were analyzed using descriptive statistics, χ2-test, t-test, and multiple logistic regression analysis. Among the participants, 69.8% used outpatient services and 30.2% did not. In the univariate analyses, age, marital status, residency, household income, chronic diseases, subjective health status, and disability were significant. Age (odds ratio [OR] = 5.53, p < 0.001), annual household income (OR = 5.64, p < 0.001), chronic diseases (OR = 11.06, p < 0.001), and disability (OR = 3.56, p = 0.016) significantly affected outpatient service use. The results suggest that health promotion interventions for Korean older adult women should focus on predicting outpatient service use according to the patient's characteristics.
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OBJECTIVE: This review presents a list of developmental screening tests used in clinical settings worldwide and provides a broad estimate of their accuracy (PROSPERO: CRD42021236474). METHOD: Following the PRISMA Diagnostic Test Accuracy (DTA) guidelines, this review involved searching PubMed, PsycINFO, Cochrane, EMBASE, CINAHL, and Google Scholar (for manual searching). Inclusion criteria included studies published in English through 2020 that compared the accuracy of developmental screening tests against developmental diagnostic tests among children under 13 years of age. Six researchers, in pairs, independently selected the studies and extracted the data. A hierarchical model was applied to meta-analyze the diagnostic accuracy of the tests, and meta-regression was used to identify the moderators using R 4.1.3 software. RESULTS: The meta-analysis included 56 studies (17 screening tests and 61 outcomes). The most frequently used screening tests were the Ages and Stages Questionnaire (ASQ), Denver Developmental Screening Test (DDST), and Parent's Evaluation of Developmental Status (PEDS). The pooled sensitivity and specificity were 0.75 (95% CI = 0.69-0.80) and 0.76 (95% CI = 0.71-0.80), and the overall diagnostic accuracy of the total outcomes (area under the curve) was 0.80. High heterogeneity was observed between the included studies with various thresholds of the tests. Participants' developmental concerns at the baseline significantly moderated the accuracy of the screening tests, resulting in double the positive predictive value and prevalence compared to those without the concerns. CONCLUSION: We recommend a standardized process of validation studies for diagnostic accuracy, to ensure the effectiveness of developmental screening tests in clinical settings. STUDY PREREGISTRATION INFORMATION: Accuracy of Developmental Screening Tools among Children in Real World: a Systematic Review and Meta Analysis; https://www.crd.york.ac.uk/; CRD42021236474.
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Sensibilidad y Especificidad , Humanos , Niño , Valor Predictivo de las Pruebas , Encuestas y CuestionariosRESUMEN
AIM: To develop a mobile-based multimedia Nursing Competency Evaluation (NCE) system based on the Attention, Relevance, Confidence, Satisfaction model and verify its effectiveness. BACKGROUND: In education, mobile devices can enable the delivery of learning content without time and spatial constraints. Mobile-based test is emerging as a novel method using technologies to appraise students' performance on practicum. This mobile-based test go beyond the simple evaluation of memorised knowledge, a limitation common to paper-based tests. They are useful because they can include multimedia items such as videos, animations and pictures to comprehensively evaluate students' clinical competencies. METHODS: This study was conducted in a nursing university in Seoul, South Korea in September 2021. A mixed method randomised controlled design was employed to evaluate its usability. The participants in the experimental group used the Nursing Competency Evaluation system and joined in focus group interviews for verifying the effects of the Nursing Competency Evaluation system qualitatively. Those in the control group responded to the mobile-based test, but which has only text-based test items. The system usability, effectiveness and learning satisfaction in both groups were measured after the mobile-based test experience. Quantitative and qualitative data were analysed using t-tests and thematic analysis using focus group interviews, respectively. RESULTS: Sixty nursing students participated, with 30 each in the experimental and control groups. There were no significant differences in nursing competency scores between the two groups. However, average scores for effectiveness and learning satisfaction were significantly higher in the experimental than in the control group. Nineteen experimental group participants partook in the interviews, with many describing that the Nursing Competency Evaluation system allowed them to experience new learning contents and efficiently learn practical nursing skills that can be useful in clinical settings. CONCLUSIONS: The Nursing Competency Evaluation system is a promising method because it used mobile technologies and multimedia to appraise students' performance on nursing practicum. It was found that the Nursing Competency Evaluation system with multimedia items is more realistic, interactive and satisfactory compared with text-based mobile test. Thus, we expect it to be used in future nursing curriculums to improve students' nursing competencies.
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Bachillerato en Enfermería , Estudiantes de Enfermería , Competencia Clínica , Curriculum , Bachillerato en Enfermería/métodos , Humanos , Aprendizaje , MultimediaRESUMEN
BACKGROUND/OBJECTIVES: Adolescents who skip breakfast have an increased prevalence of chronic diseases. Thus, we aimed to evaluate whether the intake of rice-based breakfast had positive effects on blood glucose indices and to determine the possibility of diabetes prevalence in Korean youths who habitually skip breakfast. SUBJECTS/METHODS: In this randomized parallel-group controlled trial, 81 subjects who were suitable for compliance among 105 middle-and high-school students aged 12-18 years who usually skipped breakfast were included in this study (rice-meal group [RMG], n = 26; wheat-meal group [WMG], n = 29; general-meal group [GMG], n = 26). The RMG and WMG received a rice-based breakfast and a wheat-based breakfast for 12 weeks, respectively. The anthropometric indices, blood glucose indices, and metabolites were measured at baseline and the endpoint, respectively. RESULTS: The mean body weights in the RMG, WMG, and GMG groups at the endpoint were 62.44 kg, 61.80 kg, and 60.28 kg, respectively, and the mean body weights of the WMG and GMG groups at the endpoint were significantly higher than that at baseline (P < 0.05). The levels of fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly decreased in the RMG group at the endpoint compared to baseline (P < 0.05, P < 0.05, respectively). The levels of tryptophan and tyrosine in the WMG group at the endpoint were significantly higher than that those at baseline (P < 0.01, P < 0.05, respectively). CONCLUSIONS: Rice-based breakfast has positive effects on fasting insulin levels and HOMA-IR in Korean adolescents who skip breakfast. Additionally, it was found that a skipping breakfast could increase the prevalence of diabetes in adolescents who skip breakfast. Therefore, in addition to reducing breakfast skipping, it is vital to develop a rice-based menu that fits teenage preferences to prevent chronic diseases such as diabetes. Trial Registration: Clinical Research Information Service Identifier: KCT0004089.
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Background: Colorectal cancer (CRC) has a high morbidity and mortality worldwide. 20 (S)-ginsenoside Rh2 (G-Rh2) is a natural compound extracted from ginseng, which exhibits anticancer effects in many cancer types. In this study, we demonstrated the effect and underlying molecular mechanism of G-Rh2 in CRC cells in vitro and in vivo. Methods: Cell proliferation, migration, invasion, apoptosis, cell cycle, and western blot assays were performed to evaluate the effect of G-Rh2 on CRC cells. In vitro pull-down assay was used to verify the interaction between G-Rh2 and Axl. Transfection and infection experiments were used to explore the function of Axl in CRC cells. CRC xenograft models were used to further investigate the effect of Axl knockdown and G-Rh2 on tumor growth in vivo. Results: G-Rh2 significantly inhibited proliferation, migration, and invasion, and induced apoptosis and G0/G1 phase cell cycle arrest in CRC cell lines. G-Rh2 directly binds to Axl and inhibits the Axl signaling pathway in CRC cells. Knockdown of Axl suppressed the growth, migration and invasion ability of CRC cells in vitro and xenograft tumor growth in vivo, whereas overexpression of Axl promoted the growth, migration, and invasion ability of CRC cells. Moreover, G-Rh2 significantly suppressed CRC xenograft tumor growth by inhibiting Axl signaling with no obvious toxicity to nude mice. Conclusion: Our results indicate that G-Rh2 exerts anticancer activity in vitro and in vivo by suppressing the Axl signaling pathway. G-Rh2 is a promising candidate for CRC prevention and treatment.
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The effect of glucose-dependent insulinotropic polypeptide (GIP) on cells under oxidative stress induced by glutamate, a neurotransmitter, and the underlying molecular mechanisms were assessed in the present study. We found that in the pre-treatment of HT-22 cells with glutamate in a dose-dependent manner, intracellular ROS were excessively generated, and additional cell damage occurred in the form of lipid peroxidation. The neurotoxicity caused by excessive glutamate was found to be ferroptosis and not apoptosis. Other factors (GPx-4, Nrf2, Nox1 and Hspb1) involved in ferroptosis were also identified. In other words, it was confirmed that GIP increased the activity of sub-signalling molecules in the process of suppressing ferroptosis as an antioxidant and maintained a stable cell cycle even under glutamate-induced neurotoxicity. At the same time, in HT-22 cells exposed to ferroptosis as a result of excessive glutamate accumulation, GIP sustained cell viability by activating the mitogen-activated protein kinase (MAPK) signalling pathway. These results suggest that the overexpression of the GIP gene increases cell viability by regulating mechanisms related to cytotoxicity and reactive oxygen species production in hippocampal neuronal cell lines.
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6-Shogaol (SHO) and 6-gingerol (GIN), naturally derived compounds of ginger (Zingiber officinale Roscoe), have been found to have anti-allergic effects on dermatitis-like skin lesions and rhinitis. Although SHO and GIN have demonstrated a potential in various inflammatory diseases, their efficacy and mechanism in asthma have not been largely examined. Therefore, the present study demonstrated the anti-asthmatic effects of SHO and GIN on the T-helper (Th) 2 cell-mediated allergic response pathway in an ovalbumin (OVA)-induced asthma mouse model. The asthma mouse model was established with an intraperitoneal (i.p.) injection of 50 µg OVA and 1 mg aluminum hydroxide with or without an i.p. injection of SHO and GIN (10 mg/kg) before treatment with OVA. In addition, the current study assessed mast cell degranulation in antigen-stimulated RBL-2H3 cells under different treatment conditions (SHO or GIN at 0, 10, 25, 50 and 100 nM) and determined the mRNA and protein levels of anti-oxidative enzymes [superoxide dismutase (SOD)1, SOD2, glutathione peroxidase-1/2, catalase] in lung tissues. SHO and GIN inhibited eosinophilia in the bronchoalveolar lavage fluids and H&E-stained lung tissues. Both factors also decreased mucus production in periodic acid-Schiff-stained lung tissues and the levels of Th2 cytokines in these tissues. GIN attenuated oxidative stress by upregulating the expression levels of anti-oxidative proteins. In an in vitro experiment, the degranulation of RBL-2H3 rat mast cells was significantly decreased. It was found that SHO and GIN effectively suppressed the allergic response in the mouse model by inhibiting eosinophilia and Th2 cytokine production. Collectively, it was suggested that SHO can inhibit lung inflammation by attenuating the Th2 cell-mediated allergic response signals, and that GIN can inhibit lung inflammation and epithelial cell remodeling by repressing oxidative stress. Therefore, SHO and GIN could be used therapeutically for allergic and eosinophilic asthma.
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Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by PMP22 overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol's effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.
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Enfermedades Desmielinizantes/metabolismo , Farnesol/farmacología , Fenotipo , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Animales , Biomarcadores , Enfermedad de Charcot-Marie-Tooth/tratamiento farmacológico , Enfermedad de Charcot-Marie-Tooth/etiología , Enfermedad de Charcot-Marie-Tooth/metabolismo , Enfermedad de Charcot-Marie-Tooth/patología , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/etiología , Enfermedades Desmielinizantes/patología , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Expresión Génica , Masculino , Ratones , Proteínas de la Mielina/genética , Proteínas de la Mielina/metabolismoRESUMEN
AIM: This study evaluated a practical competency evaluation for nursing students in three Asian countries using tablet PC-based tests. The need to evaluate practical competencies in a non-face-to-face manner continues to pose challenges in nursing education. DESIGN: This study presents descriptive comparative research on a tablet PC-based evaluation of practical competencies in three countries. METHODS: tablet PC-based clinical practice competency evaluation was conducted among nursing college students in Korea, Vietnam and Mongolia. In total, 124 students answered 65 questions for practical competency evaluation and items on its usefulness. RESULTS: Students from Korea had the highest score of nursing competencies (41.6 points; n = 59, SD 6.02), followed by those from Vietnam (26.3 points; n = 30, SD 4.97) and Mongolia (18.4 points; n = 35, SD 5.36). Scores for usability showed an inverse relationship with competency scores. Questions incorporating video showed the lowest proportion of low-discrimination items. CONCLUSIONS: This research recognized that using video which provides contextual elements can increase item discrimination. These findings suggest that incorporating video into evaluation items in tablet-PC-based tests is useful for international comparison.