RESUMEN
OBJECTIVES: Glioblastoma multiforme (GBM) is considered the most assailant subtype of gliomas, presenting a formidable obstacle because of its inherent resistance to temozolomide (TMZ). This study aimed to characterize the function of lncRNA NEAT1 in facilitating the advancement of gliomas. METHODS: The expression level of NEAT1 in glioma tissues and cells was detected by qRT-PCR. RNA interference experiment, cell proliferation assay, FITC/PI detection assay, immunoblotting, bioinformatics prediction, a double luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay, SLDT assay and correlation analysis of clinical samples were performed to explore the regulatory effects of NEAT1, miR-454-3p and Cx43 and their role in malignant progression of GBM. The role of NEAT1 in vivo was investigated by an intracranial tumor formation experiment in mice. RESULTS: The results showed that recurring gliomas displayed elevated levels of NEAT1 compared to primary gliomas. The suppression of NEAT1 led to a restoration of sensitivity in GBM cells to TMZ. NEAT1 functioned as a competitive endogenous RNA against miR-454-3p. Connexin 43 was identified as a miR-454-3p target. NEAT1 was found to regulate gap junctional intercellular communication by modulating Connexin 43, thereby impacting the response of GBM cells to TMZ chemotherapy. Downregulation of NEAT1 resulted in enhanced chemosensitivity to TMZ and extended the survival of mice. CONCLUSIONS: Overall, these results indicated that the NEAT1/miR-454-3p/Connexin 43 pathway influences GBM cell response to TMZ and could offer a potential new strategy for treating GBM.
Asunto(s)
Neoplasias Encefálicas , Proliferación Celular , Conexina 43 , Regulación Neoplásica de la Expresión Génica , Glioblastoma , MicroARNs , ARN Largo no Codificante , Temozolomida , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , ARN Largo no Codificante/genética , Humanos , Conexina 43/genética , Conexina 43/metabolismo , Animales , Ratones , Temozolomida/farmacología , Temozolomida/uso terapéutico , MicroARNs/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Masculino , FemeninoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. AIM OF THE STUDY: The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. METHODS: To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. RESULTS: Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. CONCLUSION: According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.
Asunto(s)
Neoplasias Colorrectales , Necroptosis , Animales , Simulación del Acoplamiento Molecular , Sincalida , Neoplasias Colorrectales/tratamiento farmacológico , CarcinogénesisRESUMEN
Metal-organic frameworks (MOFs) are a class of crystalline porous materials with simple synthesis conditions, large specific surface area, structural diversity, and a wide range of interesting properties. The integration of MOFs with other materials can provide new multifunctional composites that exhibit both component properties and new characteristics. In recent years, the integration of carbon dots (CDs) into MOFs to form composites has shown improved optical properties and fascinating new characteristics. This review focuses on the design and synthesis strategies of CDs@MOFs composites (including pore-confined synthesis, inâ situ encapsulation, post-synthesis modification and impregnation method) and their recent research progress in photocatalysis and detection of environmental pollutants. Both the achievements and problems are evaluated and proposed, and the opportunities and challenges of CDs@MOF composite are discussed.
Asunto(s)
Contaminantes Ambientales , Estructuras Metalorgánicas , Carbono , Estructuras Metalorgánicas/química , PorosidadRESUMEN
Controllable encapsulation of sulfur quantum dots (SQDs) into metal-organic frameworks (ZIF-8) by a surface-bound zinc ion-induced growth strategy, and SQDs@ZIF-8 was successfully prepared for alkaline phosphatase (ALP) detection. The new synthesis procedure involves first binding Zn2+ to the surface of SQDs to form SQDs/Zn, and then via zinc ion-induced in situ ZIF-8 growth to obtain SQDs@ZIF-8, which greatly improved the luminous efficiency of SQDs. The specific process of detecting ALP using pH-triggered fluorescence quenching of SQDs@ZIF-8: firstly ALP hydrolyzes 2-phosphate-l-ascorbic acid trisodium salt (AAP) to ascorbic acid (AA), and then the leakage of SQDs in the SQDs@ZIF-8 leads to a decrease in fluorescence intensity based on the destruction of ZIF-8 skeleton by H+ released by AA. A linear relationship was obtained between the fluorescence intensity and the ALP concentration in the range of 0.15-50 U/L, and the detection limit was 0.044 U/L. Moreover, it was found that free SQDs can be complexed with Fe2+ to produce wine red complexes, and the obtained UV absorbance and ALP concentration have a linear relationship in the range of 10-200 U/L. The detection range of ALP is significantly broadened based on the combination of the above two detection methods. Furthermore, SQDs@ZIF-8 exhibited excellent stability in water and was successfully applied to the fluorescence and colorimetric detection of ALP in human serum.