RESUMO
Glioma is the most common malignant tumor of the central nervous system with poor survival. Temozolomide (TMZ) is the first-line chemotherapy drug for initial and recurrent glioma treatment with a relatively good efficacy, which exerts its antitumor effects mainly through cell death induced by DNA double-strand breaks in the G1 and S phases. However, endogenous or acquired resistance to TMZ limits glioma patients' clinical outcome and is also an important cause of glioma replase. MicroRNA-195 (miR-195) plays an important role in the regulation of G1-phase/S-phase transition, DNA damage repair, and apoptosis of tumor cells. We found that miR-195 expression was significantly decreased in TMZ-resistant glioma cells induced with TMZ and correlated to the resistance index negatively. Also, the exogenous expression of miR-195 reversed TMZ resistance and induced the apoptosis of TMZ-resistant glioblastoma cells. Further bioinformatics analysis showed cyclin E1 (CCNE1) was a potential target gene of miR-195. Knockdown of CCNE1 partially reversed the effect of decreased miR-195 on TMZ resistance. The data from The Cancer Genome Atlas - Cancer Genome further suggested that hsa-miR-195 could negatively regulate the expression of CCNE1 in glioma. In conclusion, miR-195 reverses the resistance to TMZ by targeting CCNE1 in glioma cells and it could act as a potential target for treatment in glioma with TMZ resistance.
Assuntos
Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Ciclina E/genética , Ciclina E/metabolismo , Glioblastoma/tratamento farmacológico , MicroRNAs/biossíntese , MicroRNAs/genética , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Temozolomida/farmacologia , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/metabolismo , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismoRESUMO
A novel porous polydimethylsiloxane/bimetallic ZnCo-MOF carbonization (PDMS/ZnCo-MOF@C) sponge was successfully fabricated, followed by its utilization in GC-MS for the high efficiency extraction and determination of volatile compounds in cumin. The PDMS/ZnCo-MOF@C sponge exhibits outstanding properties with a considerable adsorption capacity, high surface area, and large pore volume and has shown potential as an ideal adsorbent for the separation and preconcentration of trace volatile compounds. The effect of different parameters on the extraction efficiency were investigated. Excellent analytical performances were achieved for the representative compounds (ß-pinene, p-cymene, γ-terpinene, cuminaldehyde, and linalyl acetate), including wide linearity (2.31-440.1 ng) with high correlation coefficients (R2 ≥ 0.9979), low LODs (1.02-3.11 ng) and LOQs (2.45-7.08 ng), and satisfactory precision (intra-day RSDs ≤ 2.89% and inter-day RSDs ≤ 4.14%). The optimal method was applied for the analysis of cumin from different regions and 44 volatile compounds were identified. The correlation between the different regions of cumin and volatile compounds was explored using multivariate statistical analysis. These results demonstrated that PDMS/ZnCo-MOF@C is an efficient, simple and sensitive material for use in the pretreatment technique for the determination of the volatile compounds in aromatic plants.
Assuntos
Cuminum , Cromatografia Gasosa-Espectrometria de Massas , DimetilpolisiloxanosRESUMO
Surface-enhanced Raman scattering (SERS) enables pesticide residue monitoring to become facile and efficient. In this study, a core-shell structured gold nanoparticles@ZnCo metal-organic framework (AuNPs@ZnCo-MOF) SERS substrate was designed and successfully synthesized for efficient and selective detection of thiram. The bimetallic ZnCo-MOF shell can not only enrich the targeted molecules in the electromagnetic field because of its excellent absorptive capacity, but also act as a stabilized matrix for protecting the AuNPs from aggregation. The AuNPs@ZnCo-MOFs exhibited a high enhancement factor (EF) of 3.51 × 106 and a low detection limit of 1 × 10-7 mol L-1. Besides, the substrate material showed exceptional stability for up to 28 days at room temperature. The AuNPs@ZnCo-MOFs were used to detect thiram which displayed wide linearity (1 × 10-7 to 1 × 10-4 mol L-1) and high recoveries (83.45-99.61%). Moreover, the AuNPs@ZnCo-MOF SERS substrate exhibited excellent anti-interference ability and size selectivity for the target molecules. These indicate that the AuNPs@ZnCo-MOF substrate has great potential for the detection of thiram residues in practical applications.
RESUMO
Aim: The rational design of a fluorescence imaging-guided, highly efficient multiresponsive delivery system is important for improving drug delivery efficiency. Materials and methods: Herein, pH/H2O2-responsive polyhedral oligomeric silsesquioxane (POSS) molecule functionalized 4-(phenyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)amino)benzaldehyde (OTB) copolymer (PEG-POSS-OTB) was synthesized to encapsulate doxorubicin (DOX) for precise drug delivery. Results: The self-assembly fluorescent vesicles exhibited excellent pH/H2O2-responsive drug release properties under physiological conditions and efficient drug-targeting ability. In vitro, compared with the DOX group, PEG-POSS-OTB fluorescent vesicles exhibited improved drug delivery and reduced toxicity. Importantly, we performed a proof-of-concept study demonstrating that PEG-POSS-OTB fluorescent vesicles were a high-efficiency nanoassembly drug-delivery platform for improving drug delivery efficiency. In vivo studies demonstrated that PEG-POSS-OTB vesicles with enhanced stability could be used in targeted drug delivery and controlled intelligent release.