RESUMEN

Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.

Asunto(s)

Apoptosis , Telómero , Telómero/metabolismo , Apoptosis/efectos de los fármacos , Humanos , Animales , Línea Celular Tumoral , Ratones , G-Cuádruplex/efectos de los fármacos , Ratones Desnudos , Polietilenglicoles/química , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Neoplasias/patología , Neoplasias/tratamiento farmacológico , Femenino , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/farmacología , Nanoestructuras/química

RESUMEN

Objective: Using meta-analysis, we evaluate circulating tumor cells(CTCs) as a potential diagnostic tool for breast cancer. Methods: A document search was conducted using publicly available databases up to May 2021. Specific inclusion and exclusion criteria were formulated and summarize relevant data through literature types, research types, case populations, samples, etc. Subgroup analysis of documents based on regions, enrichment methods, and detection methods. The included research projects were evaluated using DeeKs' bias, and evaluation indicators such as specificity (SPE), sensitivity (SEN), diagnosis odds ratio (DOR) were used as evaluation indicators. Results: 16 studies on the use of circulating tumor cells to diagnose breast cancer were included in our meta-analysis. Overall sensitivity value was 0.50 (95%CI:0.48-0.52), specificity value was 0.93 (95%CI:0.92- 0.95), DOR value was 33.41 (95%CI:12.47-89.51), and AUC value was 0.8129. Conclusion: In meta-regressions and subgroup analysis, potential heterogeneity factors were analyzed, but the source of heterogeneity is still unclear. CTCs, as a novel tumor marker, have a good diagnostic value, but its enrichment and detection methods still need to continue to be developed to improve detection accuracy. Therefore, CTCs can be used as an auxiliary means of early detection, which is helpful to the diagnosis and screening of breast cancer.

RESUMEN

High concentrations of heavy metals in the environment will cause serious harm to ecosystems and human health. It is urgent to develop effective methods to control soil heavy metal pollution. Phytoremediation has advantages and potential for soil heavy metal pollution control. However, the current hyperaccumulators have the disadvantages of poor environmental adaptability, single enrichment species and small biomass. Based on the concept of modularity, synthetic biology makes it possible to design a wide range of organisms. In this paper, a comprehensive strategy of "microbial biosensor detection - phytoremediation - heavy metal recovery" for soil heavy metal pollution control was proposed, and the required steps were modified by using synthetic biology methods. This paper summarizes the new experimental methods that promote the discovery of synthetic biological elements and the construction of circuits, and combs the methods of producing transgenic plants to facilitate the transformation of constructed synthetic biological vectors. Finally, the problems that should be paid more attention to in the remediation of soil heavy metal pollution based on synthetic biology were discussed.