Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Sci Rep ; 14(1): 12149, 2024 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802416

RESUMEN

Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo-keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan-Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.


Asunto(s)
Miembro B10 de la Familia 1 de las Aldo-Ceto Reductasas , Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/metabolismo , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/metabolismo , Masculino , Femenino , Pronóstico , Miembro B10 de la Familia 1 de las Aldo-Ceto Reductasas/genética , Miembro B10 de la Familia 1 de las Aldo-Ceto Reductasas/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Estimación de Kaplan-Meier , Aldo-Ceto Reductasas/genética , Aldo-Ceto Reductasas/metabolismo , Perfilación de la Expresión Génica , Biología Computacional/métodos
2.
Sci Rep ; 14(1): 224, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168113

RESUMEN

Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines. Bioinformatics analysis showed that DJ-1 was highly expressed in HCC ((P < 0.001) were closely associated with tumor stage (T), portal vein vascular invasion, OS, DSS, and PFI (P < 0.05); miR-199a/b-3p was lowly expressed in HCC (P < 0.001), which was the upstream regulator of DJ-1. Spearman coefficient r = -0.113, P = 0.031; Dual luciferase gene report verified the negative targeting relationship between them P< 0.001; Western blotting demonstrated that miR-199a/b-3p could inhibit the protein expression of DJ-1, Ras and AKT(P < 0.05); The results of CCK8, cell scratch, Transwell migration and flow cytometry showed that OE + DJ-1 increased the proliferation, migration and invasion ability of HepG2 cells, and decreased the apoptosis process, and the differences were statistically significant (P < 0.05), while miR-199a/b-3p had the opposite effect (P < 0.05).


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Luciferasas/metabolismo , MicroARNs/genética , Procesos Neoplásicos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteómica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/genética
3.
Cell Stress Chaperones ; 15(4): 387-94, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19902381

RESUMEN

It has been demonstrated that hypoxic preconditioning (HP) enhances the survival ability of the organism against the subsequent acute anoxia (AA). However, it is not yet clear whether necrosis induced by AA can be prevented by HP, and what are the underlying mechanisms. In this study, we examined the effect of HP (10% O(2), 48 h) on necrosis induced by AA (0% O(2), 24 h) in PC12 cells. We found that HP delayed the regulatory volume decrease and reduced cell swelling after 24 h of exposure to AA. Since aldose reductase (AR) is involved in cell volume regulation, we detected AR mRNA expression with reverse transcription-polymerase chain reaction (RT-PCR) techniques. The AR mRNA level was dramatically elevated by HP. Furthermore, an HP-induced decrease in cell injury was reversed by berberine chloride (BB), the inhibitor of AR. In addition, sorbitol synthesized from glucose catalyzed by AR is directly related to cell volume regulation. Subsequently, we tested sorbitol content in the cytoplasm. HP clearly elevated sorbitol content, while BB inhibited the elevation induced by HP. Further study showed that a strong inhibitor of sorbitol permease, quinidine, completely reversed the protection induced by HP after AA. These data provide evidence that HP prevents necrosis induced by AA and is mediated by AR and sorbitol pathway.


Asunto(s)
Aldehído Reductasa/metabolismo , Sorbitol/metabolismo , Aldehído Reductasa/genética , Animales , Berberina/farmacología , Hipoxia de la Célula , Necrosis/metabolismo , Células PC12 , ARN Mensajero/metabolismo , Ratas
4.
Neurosignals ; 14(3): 109-16, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16088225

RESUMEN

It is known that hypoxic preconditioning (HP, a brief period of sublethal hypoxia) provides neuroprotection against subsequent severe anoxia, but the mechanisms of this increased tolerance have not been fully elucidated. A hypoxic preconditioning model was established by exposing a 4-day hippocampal culture to 1% O(2) for 20 min/day for 8 days. The preconditioning significantly decreased the number of apoptotic neurons at reoxygenation 24 h after 4 h of severe anoxia (0% O(2)). Further study demonstrated that the degradation of mitochondrial membrane potential (MMP) was greatly inhibited and the expression of B-cell lymphoma protein-2 (Bcl-2) was increased considerably after severe anoxia in the HP groups. These results indicate that the increased anoxic tolerance, which is induced by HP in cultured hippocampal cells, may be correlated with Bcl-2 overexpression and enhanced stability of MMP, which ultimately reduces apoptosis 24 h after reoxygenation.


Asunto(s)
Apoptosis/fisiología , Hipocampo/citología , Hipoxia/fisiopatología , Precondicionamiento Isquémico/métodos , Neuronas/fisiología , Animales , Animales Recién Nacidos , Recuento de Células/métodos , Supervivencia Celular/fisiología , Células Cultivadas , Citometría de Flujo/métodos , Inmunohistoquímica/métodos , Etiquetado Corte-Fin in Situ/métodos , Potenciales de la Membrana/fisiología , Microscopía Confocal/métodos , Mitocondrias/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo
5.
Brain Res ; 999(2): 149-54, 2004 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-14759493

RESUMEN

The effects of hypoxic preconditioning (HP) on changes in mitochondrial membrane potential (MMP) and Bcl-2 expression in cultured hypothalamic neurons after severe anoxia were investigated. In the HP group, hypothalamic neurons, after a 4-day culture, were preconditioned daily under a hypoxic condition (1% O(2), 10 min) for 8 days; subsequently, the HP neurons and those in the control group (similarly cultured, but without HP) were exposed to 6 h of severe anoxia (0% O(2)). The preconditioned neurons had a higher survival rate and a lower lactate dehydrogenase leakage, compared with the control group. Although HP did not prevent the degradation of MMP during severe hypoxia, preconditioned neurons exhibited a higher level of MMP than that of the control group. Increased expression of Bcl-2 was also observed in the preconditioned hypothalamic neurons. These results suggest that HP enhances the hypoxic tolerance of hypothalamic neurons, and the underlying mechanisms may be related to the increased stability of MMP and the overexpression of Bcl-2 induced by HP.


Asunto(s)
Hipotálamo/metabolismo , Hipoxia Encefálica/metabolismo , Precondicionamiento Isquémico , Mitocondrias/metabolismo , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Animales , Animales Recién Nacidos , Hipoxia de la Célula , Supervivencia Celular/fisiología , Células Cultivadas , Hipotálamo/citología , Membranas Intracelulares/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Potenciales de la Membrana/fisiología , Ratas , Ratas Wistar
6.
Artículo en Chino | MEDLINE | ID: mdl-21166218

RESUMEN

AIM: To investigate the effects of oxygen-glucose deprivation on cultured rat hippocampal neurons. METHODS: The hippocampal neurons cultured for 12 d were exposed to combined oxygen-glucose deprivation for 0.5 - 4 h and then cultured with original medium in normoxia for 28 h. Necrotic neurons were identified by 0.4% trypan blue staining and apoptotic neurons were detected by a TUNEL technique. Meanwhile, the area, perimeter and circle diameter of cell bodies were measured respectively by a photography analysis system. RESULTS: The percentage of necrotic cells in cultured hippocampal neurons increased significantly during oxygen-glucose deprivation, but the percentage of apoptotic cells increased significantly after 28 h oxygen-glucose recovery. Photography analysis showed that area, perimeter and circle diameter of the necrotic cell bodies were larger than those of the apoptotic ones. CONCLUSION: Oxygen-glucose deprivation can lead to severe damage of cultured hippocampal neurons. The necrosis is major during acute oxygen-glucose deprivation, while the apoptosis is major 28 h after oxygen-glucose recovery.


Asunto(s)
Glucosa/deficiencia , Hipocampo/citología , Neuronas/citología , Oxígeno/metabolismo , Animales , Hipoxia de la Célula , Células Cultivadas , Ratas , Ratas Wistar
7.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 19(2): 197-200, 2003 May.
Artículo en Chino | MEDLINE | ID: mdl-21207677

RESUMEN

AIM: To establish the model of oxygen-glucose deprivation in vitro rat hippocampal neurons. METHODS: The hippocampal neurons cultured for 12 d were exposed to combined oxygen-glucose deprivation for 0.5-4 h and then cultured with original medium in normoxia for 24 h. Auto-biochemical analyzer determined LDH activity. The change of neuronal morphology and neuron survival were observed by converted contrast microscope and assessed by photography analysis system. Neuron apoptosis was detected by using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL) method. RESULTS: The neurons swelled, LDH release increased and neuron survival decreased after gradually oxygen-glucose deprivation. The percentage of apoptosis increased obviously 24 h after recovering the supply of oxygen and glucose. CONCLUSION: The model of oxygen-glucose deprivation in vitro rat hippocampal neurons is established successfully by using the modified ACSF (artificial cerebral spinal fluid) with serum and glucose free.


Asunto(s)
Glucosa/deficiencia , Hipocampo/citología , Neuronas/citología , Oxígeno/fisiología , Animales , Animales Recién Nacidos , Hipoxia de la Célula , Células Cultivadas , Ratas , Ratas Wistar
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...