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1.
J Med Internet Res ; 26: e57762, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008834

RESUMEN

BACKGROUND: Early detection of cancer and provision of appropriate treatment can increase the cancer cure rate and reduce cancer-related deaths. Early detection requires improving the cancer screening quality of each medical institution and enhancing the capabilities of health professionals through tailored education in each field. However, during the COVID-19 pandemic, regional disparities in educational infrastructure emerged, and educational accessibility was restricted. The demand for remote cancer education services to address these issues has increased, and in this study, we considered medical metaverses as a potential means of meeting these needs. In 2022, we used Metaverse Educational Center, developed for the virtual training of health professionals, to train radiologic technologists remotely in mammography positioning. OBJECTIVE: This study aims to investigate the user experience of the Metaverse Educational Center subplatform and the factors associated with the intention for continuous use by focusing on cases of using the subplatform in a remote mammography positioning training project. METHODS: We conducted a multicenter, cross-sectional survey between July and December 2022. We performed a descriptive analysis to examine the Metaverse Educational Center user experience and a logistic regression analysis to clarify factors closely related to the intention to use the subplatform continuously. In addition, a supplementary open-ended question was used to obtain feedback from users to improve Metaverse Educational Center. RESULTS: Responses from 192 Korean participants (male participants: n=16, 8.3%; female participants: n=176, 91.7%) were analyzed. Most participants were satisfied with Metaverse Educational Center (178/192, 92.7%) and wanted to continue using the subplatform in the future (157/192, 81.8%). Less than half of the participants (85/192, 44.3%) had no difficulty in wearing the device. Logistic regression analysis results showed that intention for continuous use was associated with satisfaction (adjusted odds ratio 3.542, 95% CI 1.037-12.097; P=.04), immersion (adjusted odds ratio 2.803, 95% CI 1.201-6.539; P=.02), and no difficulty in wearing the device (adjusted odds ratio 2.020, 95% CI 1.004-4.062; P=.049). However, intention for continuous use was not associated with interest (adjusted odds ratio 0.736, 95% CI 0.303-1.789; P=.50) or perceived ease of use (adjusted odds ratio 1.284, 95% CI 0.614-2.685; P=.51). According to the qualitative feedback, Metaverse Educational Center was useful in cancer education, but the experience of wearing the device and the types and qualities of the content still need to be improved. CONCLUSIONS: Our results demonstrate the positive user experience of Metaverse Educational Center by focusing on cases of using the subplatform in a remote mammography positioning training project. Our results also suggest that improving users' satisfaction and immersion and ensuring the lack of difficulty in wearing the device may enhance their intention for continuous use of the subplatform.


Asunto(s)
COVID-19 , Humanos , Femenino , COVID-19/prevención & control , Estudios Transversales , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Mamografía/estadística & datos numéricos , Mamografía/métodos , Masculino , Neoplasias de la Mama/diagnóstico por imagen , Adulto , Educación a Distancia/métodos , Persona de Mediana Edad , SARS-CoV-2
2.
JMIR Serious Games ; 12: e58724, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985502

RESUMEN

BACKGROUND: Effective health care services that meet the diverse needs of children and adolescents with cancer are required to alleviate their physical, psychological, and social challenges and improve their quality of life. Previous studies showed that serious games help promote people's health. However, the potential for serious games to be used for successful cancer control for children and adolescents has received less attention. OBJECTIVE: This scoping review aimed to map the use of serious games in cancer prevention and cancer care for children and adolescents, and provide future directions for serious games' development and implementation within the context of cancer control for children and adolescents. METHODS: This study followed a combination of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) and the JBI (Joanna Briggs Institute) framework for the conduct of scoping reviews. PubMed, CINAHL Plus Full Text, Scopus, Web of Science Core Collection, and American Psychological Association (APA) PsycINFO databases were used for the search. RESULTS: From the initial 2750 search results, 63 papers were included in the review, with 28 quantitative, 14 qualitative, and 21 mixed method studies. Most of the studies were cancer care serious game papers (55/63, 87%) and a small number of studies were cancer prevention serious game papers (8/63, 13%). The majority of the included studies were published between 2019 and 2023 (cancer prevention: 5/8, 63%; cancer care: 35/55, 64%). The majority of the studies were conducted in Europe (cancer prevention: 3/8, 38%; cancer care: 24/55, 44%) and North America (cancer prevention: 4/8, 50%; cancer care: 17/55, 31%). Adolescents were the most represented age group in the studies' participants (cancer prevention: 8/8, 100%; cancer care: 46/55, 84%). All (8/8, 100%) cancer prevention serious game papers included healthy people as participants, and 45 out of 55 (82%) cancer care serious game papers included patients with cancer. The majority of cancer prevention serious game papers addressed game preference as a target outcome (4/8, 50%). The majority of cancer care serious game papers addressed symptom management as a target outcome (28/55, 51%). Of the cancer care studies examining serious games for symptom management, the majority of the studies were conducted to treat psychological (13/55, 24%) and physical symptoms (10/55, 18%). CONCLUSIONS: This review shows both the growth of interest in the use of serious games for cancer control among children and adolescents and the potential for bias in the relevant literature. The diverse characteristics of the included papers suggest that serious games can be used in various ways for cancer control among children and adolescents while highlighting the need to develop and implement serious games in underrepresented areas.

3.
Anim Cells Syst (Seoul) ; 28(1): 184-197, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38693921

RESUMEN

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and -140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer.

4.
Sci Rep ; 14(1): 10924, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740866

RESUMEN

Bovine intramuscular fat (IMF), commonly referred to as marbling, is regulated by lipid metabolism, which includes adipogenesis, lipogenesis, glycerolipid synthesis, and lipolysis. In recent years, breeding researchers have identified single nucleotide polymorphisms (SNPs) as useful marker-assisted selection tools for improving marbling scores in national breeding programs. These included causal SNPs that induce phenotypic variation. MicroRNAs (miRNAs) are small highly conserved non-coding RNA molecules that bind to multiple non-coding regions. They are involved in post-transcriptional regulation. Multiple miRNAs may regulate a given target. Previously, three SNPs in the GPAM 3' UTR and four miRNAs were identified through in silico assays. The aim of this study is to verify the binding ability of the four miRNAs to the SNPs within the 3'UTR of GPAM, and to identify the regulatory function of miR-375 in the expression of genes related to lipid metabolism in mammalian adipocytes. It was verified that the four miRNAs bind to the GPAM 3'UTR, and identified that the miR-375 sequence is highly conserved. Furthermore, it was founded that miR-375 upregulated the GPAM gene, C/EBPα, PPARγ and lipid metabolism-related genes and promoted lipid droplet accumulation in 3T3-L1 cells. In conclusion, these results suggest that miR-375 is a multifunctional regulator of multiple lipid metabolism-related genes and may aid in obesity research as a biomarker.


Asunto(s)
Regiones no Traducidas 3' , Células 3T3-L1 , Metabolismo de los Lípidos , MicroARNs , Polimorfismo de Nucleótido Simple , MicroARNs/genética , MicroARNs/metabolismo , Animales , Ratones , Metabolismo de los Lípidos/genética , Bovinos , Regulación de la Expresión Génica , Adipocitos/metabolismo , Adipogénesis/genética
5.
BMC Vet Res ; 20(1): 233, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38807154

RESUMEN

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.


Asunto(s)
Enfermedades de los Perros , Neoplasias Mamarias Animales , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Animales , Perros , Femenino , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Enfermedades de los Perros/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transducción de Señal , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología
6.
J Anim Sci Technol ; 66(1): 204-218, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38618027

RESUMEN

Elsholtzia fruticosa (EF) is present in tropical regions throughout South Asian countries as well as the Himalayas. Although it has been used as a traditional medicine to treat digestive, respiratory, and inflammatory issues, its effect on preadipocyte differentiation is unknown. In this study, we examined the effects of a methanol extract prepared from EF on the differentiation of 3T3-L1 preadipocytes. Cell differentiation was assessed by microscopic observation and oil-red O staining. The expression of adipogenic and lipogenic genes, including PPARγ and C/EBPα, was measured by western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR), to provide insight into adipogenesis and lipogenesis mechanisms. The results indicated that EF promotes the differentiation of 3T3-L1 preadipocytes, with elevated lipid accumulation occurring in a concentration-dependent manner without apparent cytotoxicity. EF enhances the expression of adipogenic and lipogenic genes, including PPARγ, FABP4, adiponectin, and FAS, at the mRNA and protein levels. The effect of EF was more pronounced during the early and middle stages of 3T3-L1 cell differentiation. Treatment with EF decreased C/EBP homologous protein (CHOP) mRNA and protein levels, while increasing C/EBPα and PPARγ expression. Treatment with EF resulted in the upregulation of cyclin E and CDK2 gene expression within 24 h, followed by a decrease at 48 h, demonstrating the early-stage impact of EF. A concomitant increase in cyclin-D1 levels was observed compared with untreated cells, indicating that EF modulates lipogenic and adipogenic genes through intricate mechanisms involving CHOP and cell cycle pathways. In summary, EF induces the differentiation of 3T3-L1 preadipocytes by increasing the expression of adipogenic and lipogenic genes, possibly through CHOP and cell cycle-dependent mechanisms.

7.
Anim Cells Syst (Seoul) ; 28(1): 93-109, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487309

RESUMEN

Myeloid ecotropic virus insertion site 1 (MEIS1) is a HOX co-factor necessary for organ development and normal hematopoiesis. Recently, MEIS1 has been linked to the development and progression of various cancers. However, its role in gliomagenesis particularly on glioma stem cells (GSCs) remains unclear. Here, we demonstrate that MEIS1 is highly upregulated in GSCs compared to normal, and glioma cells and to its differentiated counterparts. Inhibition of MEIS1 expression by shRNA significantly reduced GSC growth in both in vitro and in vivo experiments. On the other hand, integrated transcriptomics analyses of glioma datasets revealed that MEIS1 expression is correlated to cell cycle-related genes. Clinical data analysis revealed that MEIS1 expression is elevated in high-grade gliomas, and patients with high MEIS1 levels have poorer overall survival outcomes. The findings suggest that MEIS1 is a prognostic biomarker for glioma patients and a possible target for developing novel therapeutic strategies against GBM.

8.
Cell Death Discov ; 10(1): 103, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418476

RESUMEN

Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs.

9.
JMIR Serious Games ; 11: e46242, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38032697

RESUMEN

BACKGROUND: As cancer treatment methods have diversified and the importance of self-management, which lowers the dependence rate on direct hospital visits, has increased, effective cancer care education and management for health professionals and patients have become necessary. The metaverse is in the spotlight as a means of digital health that allows users to engage in cancer care education and management beyond physical constraints. However, it is difficult to find a multipurpose medical metaverse that can not only be used in the field but also complements current cancer care. OBJECTIVE: This study aimed to develop an integrated metaverse cancer care platform, Dr. Meta, and examine its usability. METHODS: We conducted a multicenter, cross-sectional survey between November and December 2021. A descriptive analysis was performed to examine users' experiences with Dr. Meta. In addition, a supplementary open-ended question was used to ask users for their suggestions and improvements regarding the platform. RESULTS: Responses from 70 Korean participants (male: n=19, 27% and female: n=51, 73%) were analyzed. More than half (n=37, 54%) of the participants were satisfied with Dr. Meta; they responded that it was an interesting and immersive platform (n=50, 72%). Less than half perceived no discomfort when using Dr. Meta (n=34, 49%) and no difficulty in wearing and operating the device (n=30, 43%). Furthermore, more than half (n=50, 72%) of the participants reported that Dr. Meta would help provide non-face-to-face and noncontact services. More than half also wanted to continue using this platform in the future (n=41, 59%) and recommended it to others (n=42, 60%). CONCLUSIONS: We developed a multidomain metaverse cancer care platform that can support both health professionals and patients in non-face-to-face cancer care. The platform was uniquely disseminated and implemented in multiple regional hospitals and showed the potential to perform successful cancer care.

10.
Am J Cancer Res ; 13(9): 4021-4038, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37818053

RESUMEN

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, with an extremely poor prognosis due to resistance to standard-of-care treatments. Strong evidence suggests that the small population of glioma stem cells (GSCs) contributes to the aggressiveness of GBM. One of the mechanisms that promote GSC progression is the dysregulation of membrane transporters, which mediate the influx and efflux of substances to maintain cellular homeostasis. Here, we investigated the role of multidrug and toxin extrusion transporter gene SLC47A1 in GSCs. Results show that SLC47A1 is highly expressed in GSCs compared to non-stem cell glioma cells, and non-tumor cells. Additionally, in-silico analysis of public datasets showed that high SLC47A1 expression is linked to malignancy and a poor prognosis in glioma patients. Further, SLC47A1 expression is correlated with important biological processes and signaling pathways that support tumor growth. Meanwhile, silencing SLC47A1 by short-hairpin RNA (shRNA) influenced cell viability and self-renewal activity in GSCs. Interestingly, SLC47A1 shRNA knockdown or pharmacological inhibition potentiates the effect of temozolomide (TMZ) in GSC cells. The findings suggest that SLC47A1 could serve as a useful therapeutic target for gliomas.

11.
eNeuro ; 10(8)2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37550059

RESUMEN

As cellular energy powerhouses, mitochondria undergo constant fission and fusion to maintain functional homeostasis. The conserved dynamin-like GTPase, Mitofusin2 (MFN2)/mitochondrial assembly regulatory factor (Marf), plays a role in mitochondrial fusion, mutations of which are implicated in age-related human diseases, including several neurodegenerative disorders. However, the regulation of MFN2/Marf-mediated mitochondrial fusion, as well as the pathologic mechanism of neurodegeneration, is not clearly understood. Here, we identified a novel interaction between MFN2/Marf and microtubule affinity-regulating kinase 4 (MARK4)/PAR-1. In the Drosophila larval neuromuscular junction, muscle-specific overexpression of MFN2/Marf decreased the number of synaptic boutons, and the loss of MARK4/PAR-1 alleviated the synaptic defects of MFN2/Marf overexpression. Downregulation of MARK4/PAR-1 rescued the mitochondrial hyperfusion phenotype caused by MFN2/Marf overexpression in the Drosophila muscles as well as in the cultured cells. In addition, knockdown of MARK4/PAR-1 rescued the respiratory dysfunction of mitochondria induced by MFN2/Marf overexpression in mammalian cells. Together, our results indicate that the interaction between MFN2/Marf and MARK4/PAR-1 is fine-tuned to maintain synaptic integrity and mitochondrial homeostasis, and its dysregulation may be implicated in neurologic pathogenesis.


Asunto(s)
Proteínas de Drosophila , Mitocondrias , Sinapsis , Animales , Humanos , Drosophila , Proteínas de Drosophila/genética , GTP Fosfohidrolasas/genética , Mamíferos , Microtúbulos , Mitocondrias/patología , Proteínas Mitocondriales/genética , Proteínas Serina-Treonina Quinasas , Sinapsis/patología
12.
Adv Sci (Weinh) ; 10(24): e2302483, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37341246

RESUMEN

Antimicrobial peptides (AMPs) are promising therapeutics in the fight against multidrug-resistant bacteria. As a mimic of AMPs, peptoids with N-substituted glycine backbone have been utilized for antimicrobials with resistance against proteolytic degradation. Antimicrobial peptoids are known to kill bacteria by membrane disruption; however, the nonspecific aggregation of intracellular contents is also suggested as an important bactericidal mechanism. Here,structure-activity relationship (SAR) of a library of indole side chain-containing peptoids resulting in peptoid 29 as a hit compound is investigated. Then, quantitative morphological analyses of live bacteria treated with AMPs and peptoid 29 in a label-free manner using optical diffraction tomography (ODT) are performed. It is unambiguously demonstrated that both membrane disruption and intracellular biomass flocculation are primary mechanisms of bacterial killing by monitoring real-time morphological changes of bacteria. These multitarget mechanisms and rapid action can be a merit for the discovery of a resistance-breaking novel antibiotic drug.


Asunto(s)
Antiinfecciosos , Peptoides , Peptoides/farmacología , Peptoides/química , Peptoides/metabolismo , Antiinfecciosos/química , Antibacterianos/farmacología , Antibacterianos/química , Relación Estructura-Actividad , Bacterias/metabolismo , Tomografía
13.
Exp Mol Med ; 55(1): 43-54, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36596853

RESUMEN

Glioblastoma multiforme (GBM), the most aggressive and malignant glioma, has a poor prognosis. Although patients with GBM are treated with surgery, chemotherapy, and radiation therapy, GBM is highly resistant to treatment, making it difficult and expensive to treat. In this study, we analyzed the Gene Expression Profiling Interactive Analysis dataset, the Cancer Genome Atlas dataset, and Gene Expression Omnibus array data. ZBTB7A (also called FBI1/POKEMON/LRF) was found to be highly expressed in low-grade glioma but significantly downregulated in patients with GBM. ZBTB7A is a transcription factor that plays an important role in many developmental stages, including cell proliferation. The activation of epithelial-mesenchymal transition (EMT) is a key process in cancer progression and metastasis. Erythrocyte membrane protein band 4.1 like 5 (EPB41L5) is an essential protein for EMT progression and metastasis in various types of cancer. We found that ZBTB7A depletion in U87 cells induced GBM progression and metastasis. Based on RNA sequencing data, ZBTB7A directly binds to the promoter of the EPB41L5 gene, reducing its expression and inhibiting GBM progression. We demonstrated that ZBTB7A dramatically inhibits GBM tumor growth through transcriptional repression of EPB41L5. Thus, both ZBTB7A and EPB41L5 may be potential biomarkers and novel therapeutic targets for GBM treatment. Overall, we discovered the role of a novel tumor suppressor that directly inhibits GBM progression (ZBTB7A) and identified EPB41L5 as a therapeutic target protein for patients with GBM.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Glioblastoma/metabolismo , Línea Celular Tumoral , Glioma/genética , Transformación Celular Neoplásica/genética , Carcinogénesis/genética , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Proliferación Celular/genética , Proteínas de la Membrana/metabolismo
14.
CNS Neurosci Ther ; 29(2): 682-690, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36514188

RESUMEN

AIMS: Glioblastoma multiforme (GBM) is the most aggressive type of human brain tumor, with a poor prognosis and a median overall survival of fewer than 15 months. Glioma stem cells (GSCs) have recently been identified as a key player in tumor initiation and therapeutic resistance in GBM. ADAMTS family of metalloproteinases is known to cleave a wide range of extracellular matrix substrates and has been linked to tissue remodeling events in tumor development. Here, we investigate that ADAMTS3 regulates GSC proliferation and self-renewal activities, and tumorigenesis in orthotopic xenograft models. METHODS: ADAMTS3 mRNA expression levels in normal human astrocyte (NHA), glioma, and GSCs cell lines were compared. After knockdown of ADAMTS3, alamarBlue assay, in vitro limiting dilution, and orthotopic xenograft assays were performed. To investigate the tumor-associated roles of ADAMTS3, several statistical assays were conducted using publicly available datasets. RESULTS: ADAMTS3 level was remarkably higher in GSCs than in NHA, glioma cell lines, and their matched differentiated tumor cells. Interestingly, knockdown of ADAMTS3 disrupted GSC's proliferation, self-renewal activity, and tumor formation in vivo. Furthermore, ADAMTS3 could be used as an independent predictor of malignancy progression in GBM. CONCLUSION: We identified ADAMTS3 as a potential therapeutic target for GBM.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Regulación hacia Abajo , Células Madre Neoplásicas/metabolismo , Glioma/metabolismo , Glioblastoma/patología , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Proteínas ADAMTS/genética , Proteínas ADAMTS/metabolismo , Procolágeno N-Endopeptidasa/genética , Procolágeno N-Endopeptidasa/metabolismo , Procolágeno N-Endopeptidasa/uso terapéutico
15.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36499416

RESUMEN

SMILE (small heterodimer partner-interacting leucine zipper protein) is a transcriptional corepressor that potently regulates various cellular processes such as metabolism and growth in numerous tissues. However, its regulatory role in skin tissue remains uncharacterized. Here, we demonstrated that SMILE expression markedly decreased in human melanoma biopsy specimens and was inversely correlated with that of microphthalmia-associated transcription factor (MITF). During melanogenesis, α-melanocyte-stimulating hormone (α-MSH) induction of MITF was mediated by a decrease in SMILE expression in B16F10 mouse melanoma cells. Mechanistically, SMILE was regulated by α-MSH/cAMP/protein kinase A signaling and suppressed MITF promoter activity via corepressing transcriptional activity of the cAMP response element-binding protein. Moreover, SMILE overexpression significantly reduced α-MSH-induced MITF and melanogenic genes, thereby inhibiting melanin production in melanocytes. Conversely, SMILE inhibition increased the transcription of melanogenic genes and melanin contents. These results indicate that SMILE is a downstream effector of cAMP-mediated signaling and is a critical factor in the regulation of melanogenic transcription; in addition, they suggest a potential role of SMILE as a corepressor in skin pigmentation.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Melanoma , Factor de Transcripción Asociado a Microftalmía , Animales , Humanos , Ratones , alfa-MSH/farmacología , alfa-MSH/metabolismo , Línea Celular Tumoral , AMP Cíclico/metabolismo , Melaninas/metabolismo , Melanocitos/metabolismo , Melanoma/metabolismo , Factor de Transcripción Asociado a Microftalmía/genética , Factor de Transcripción Asociado a Microftalmía/metabolismo , Monofenol Monooxigenasa/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética
16.
J Med Internet Res ; 24(11): e39501, 2022 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-36449344

RESUMEN

BACKGROUND: Mindfulness has emerged as a promising approach toward improving mental health. Interest in mindfulness mobile app services has also increased in recent years. Understanding the determinants of mindfulness behavior is essential to predict people's utilization of mindfulness mobile apps and beneficial for developing and implementing relevant intervention strategies. Nevertheless, little has been done to determine the predictors of mindfulness behavior. OBJECTIVE: This study investigates the association between the Big Five personality traits and the Theory of Planned Behavior (TPB) variables in the context of using mindfulness mobile apps to explore the potential indirect effects of conscientiousness and neuroticism on people's behavioral intention for mindfulness, mediated by their attitude toward mindfulness, subjective norm about mindfulness, and perceived behavior control over mindfulness. METHODS: The authors conducted an online, cross-sectional survey in December 2021. Structural equation modeling was conducted to evaluate the overall model fit and test possible linkages among conscientiousness, neuroticism, attitude toward mindfulness, subjective norm about mindfulness, perceived behavior control over mindfulness, and behavioral intention for mindfulness. Bootstrapping mediation analyses were also conducted to test the potential mediating effect in the model. RESULTS: A total of 297 Korean participants' responses (153 males and 144 females) were analyzed. The proposed model had a good fit. Conscientiousness was correlated with attitude toward mindfulness (ß=.384, P<.001), subjective norm about mindfulness (ß=.249, P<.001), and perceived behavior control over mindfulness (ß=.443, P<.001). Neuroticism was not correlated with attitude toward mindfulness (ß=-.072, P=.28), but was correlated with subjective norm about mindfulness (ß=.217, P=.003) and perceived behavior control over mindfulness (ß=-.235, P<.001). Attitude toward mindfulness (ß=.508, P<.001), subjective norm about mindfulness (ß=.132, P=.01), and perceived behavior control over mindfulness (ß=.540, P<.001) were separately correlated with behavioral intention for mindfulness. Conscientiousness was not directly correlated with behavioral intention for mindfulness (ß=-.082, P=.27), whereas neuroticism was directly correlated with behavioral intention for mindfulness (ß=.194, P=.001). Conscientiousness was indirectly linked with behavioral intention for mindfulness through attitude toward mindfulness (B=0.171, 95% CI 0.103-0.251) and perceived behavior control over mindfulness (B=0.198, 95% CI 0.132-0.273) but not through subjective norm about mindfulness (B=0.023, 95% CI -0.002 to 0.060). Neuroticism was indirectly linked with behavioral intention for mindfulness via perceived behavior control over mindfulness (B=-0.138, 95% CI -0.197 to -0.088) but not via subjective norm about mindfulness (B=0.021, 95% CI -0.002 to 0.059). CONCLUSIONS: The results show that the integration of the Big Five personality traits and TPB constructs is useful in predicting the use of mindfulness mobile apps. Focusing on conscientiousness and neuroticism in developing information dissemination and implementation strategies for enhancing mindfulness behavior using mobile apps may lead to the successful promotion of mindfulness mobile apps and adherence to mindfulness techniques.


Asunto(s)
Atención Plena , Aplicaciones Móviles , Femenino , Masculino , Humanos , Estudios Transversales , Intención , Personalidad
17.
Cell Rep ; 41(8): 111626, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36417870

RESUMEN

Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, like formation of the NOTCH1 intracellular domain (NICD1); however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Here we show that JICD1 induces astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to anticancer therapy. The transcriptome, chromatin immunoprecipitation sequencing (ChIP-seq), and proteomics analyses show that JICD1 increases SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. JICD1-driven tumorigenicity is directly regulated by SOX2. Our results demonstrate that, like NICD1, JICD1 acts as a transcriptional cofactor in formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.


Asunto(s)
Receptores Notch , Transducción de Señal , Transducción de Señal/fisiología , Receptores Notch/metabolismo , Oncogenes , Células Madre Neoplásicas/metabolismo , Unión Proteica
18.
Onco Targets Ther ; 15: 1375-1383, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36411942

RESUMEN

Background: Glioma stem cells (GSCs) have been reported to contribute to tumor initiation and relapse, therapy resistance, and intra-tumoral heterogeneity of glioblastoma multiforme. Therefore, inhibiting GSCs presents a critical therapeutic tactic to suppress the aggressiveness of tumors. Methods: In this study, we examined the effects of 7ß-22 dihydroxyhopane (AP 18), isolated from the sub-Antarctic lichen, Pseudocyphellaria freycinetii. The cytotoxic effect of AP 18 and its effects on cell proliferation were assessed by alamarBlue assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Real-time confluence analysis was performed with a Celloger automatic live cell imaging system. Western Blotting and 3-D optical diffraction tomography (ODT) imaging were performed to determine whether apoptosis was triggered by AP 18. A Limiting dilution assay and qRT-PCR were performed to investigate the impact of AP 18 on GSC stemness. Results: AP 18 significantly reduced GSCs viability and proliferation, inducing programmed cell death identified by Annexin V/PI staining and had effects on morphologic features determined by 3-D ODT. Interestingly, treatment with AP 18 suppressed stemness features. Conclusion: Taken together, our results suggest that AP 18 might be a potential therapeutic agent to target GSCs.

19.
Artículo en Inglés | MEDLINE | ID: mdl-36397994

RESUMEN

Colorectal cancer (CRC) is a deadly disease regardless of sex, and a few therapeutic approaches have been fully developed at advanced stages, even if some strategies have durable clinical benefits, such as immunotherapy and chemotherapy. Ganoderma lucidum has been recognized as an organism that suppresses tumors and inflammation; however, the molecular mechanisms induced by a triterpenoid in Ganoderma lucidum, Lucidumol A, have not yet been fully explored in CRC and inflammatory responses. To this end, we extracted Lucidumol A from Ganoderma lucidum and analyzed its anticancer effect and anti-inflammatory potential in CRC cell lines and RAW264.7 macrophage-derived cell lines, respectively. A series of in vitro experiments including cell survival, wound healing, and migration assays were performed to determine the role of Lucidumol A in the CRC cell line. We also analyzed inflammatory responses using qRT-PCR, Western Blot, and ELISA in RAW 264.7 macrophaged-derived cell lines exposed to various concentrations of Lucidumol A. Lucidumol A efficiently suppressed the metastatic potential of CRC at very low concentrations. Furthermore, significant anti-inflammatory activities were observed in Lucidumol A-treated RAW264.7 cells through modulation of inflammation-associated marker genes and cytokines. In conclusion, Lucidumol A plays an important role in Ganoderma lucidum-dependent tumor suppression and anti-inflammation, suggesting different strategies to treat CRC patients, and other diseases evoked by proinflammatory cytokines, despite the need to explore further its mechanism of action.

20.
J Med Food ; 25(10): 963-970, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36260138

RESUMEN

Glioblastoma (GBM) is one of the most dangerous brain tumors in humans. The median survival of patients with GBM is <18 months. Glioma stem-like cells (GSCs), a small subpopulation of cells with stem cell-like characteristics found within GBM, are regarded as the main cause of GBM malignancy. Therefore, targeting GSCs presents an important therapeutic strategy for reducing the aggressiveness of tumors. In this study, we examined effects of (9Z,16S)-16-O-acetyl-9,17-octadecadiene-12,14-diynoic acid (AODA), a diacetylenic carboxylic acid isolated from leaves of Dendropanax morbiferus, on viability and self-renewal activity of GSCs. AODA substantially decreased GSC growth, causing apoptotic cell death as assessed by Annexin V/PI staining and morphological alterations by optical diffraction tomography. Interestingly, treatment with AODA suppressed ''stem-like features'' in vitro by limiting dilution assays and real-time polymerase chain reaction analysis. In addition, Western blotting revealed that AODA treatment decreased expression levels of phosphorylated AKT and phosphorylated ERK in GSC11 cells. Taken together, our results indicate that AODA could be considered a new therapeutic candidate to target GSCs.


Asunto(s)
Glioblastoma , Glioma , Humanos , Anexina A5 , Proteínas Proto-Oncogénicas c-akt , Glioma/tratamiento farmacológico , Células Madre , Ácidos Carboxílicos , Línea Celular Tumoral , Proliferación Celular
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