The challenge and opportunity of gut microbiota-targeted nanomedicine for colorectal cancer therapy.

The gut microbiota is an integral component of the colorectal cancer (CRC) microenvironment and is intimately associated with CRC initiation, progression, and therapeutic outcomes. We reviewed recent advancements in utilizing nanotechnology for modulating gut microbiota, discussing strategies and the mechanisms underlying their design. For future nanomedicine design, we propose a 5I principle for individualized nanomedicine in CRC management.

A NSC-34 cell line-derived spheroid model: Potential and challenges for in vitro evaluation of neurodegeneration.

Three-dimensional (3D) spheroid models aim to bridge the gap between traditional two-dimensional (2D) cultures and the complex in vivo tissue environment. These models, created by self-clustering cells to mimic a 3D environment with surrounding extracellular framework, provide a valuable research tool. The NSC-34 cell line, generated by fusing mouse spinal cord motor neurons and neuroblastoma cells, is essential for studying neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), where abnormal protein accumulation, such as TAR-DNA-binding protein 43 (TDP-43), occurs in affected nerve cells. However, NSC-34 behavior in a 3D context remains underexplored, and this study represents the first attempt to create a 3D model to determine its suitability for studying pathology. We generated NSC-34 spheroids using a nonadhesive hydrogel-based template and characterized them for 6 days. Light microscopy revealed that NSC-34 cells in 3D maintained high viability, a distinct round shape, and forming stable membrane connections. Scanning electron microscopy identified multiple tunnel-like structures, while ultrastructural analysis highlighted nuclear bending and mitochondria alterations. Using inducible GFP-TDP-43-expressing NSC-34 spheroids, we explored whether 3D structure affected TDP-43 expression, localization, and aggregation. Spheroids displayed nuclear GFP-TDP-43 expression, albeit at a reduced level compared with 2D cultures and generated both TDP-35 fragments and TDP-43 aggregates. This study sheds light on the distinctive behavior of NSC-34 in 3D culture, suggesting caution in the use of the 3D model for ALS or TDP-43 pathologies. Yet, it underscores the spheroids' potential for investigating fundamental cellular mechanisms, cell adaptation in a 3D context, future bioreactor applications, and drug penetration studies. RESEARCH HIGHLIGHTS: 3D spheroid generation: NSC-34 spheroids, developed using a hydrogel-based template, showed high viability and distinct shapes for 6 days. Structural features: advanced microscopy identified tunnel-like structures and nuclear and mitochondrial changes in the spheroids. Protein dynamics: the study observed how 3D structures impact TDP-43 behavior, with altered expression but similar aggregation patterns to 2D cultures. Research implications: this study reveals the unique behavior of NSC-34 in 3D culture, suggests a careful approach to use this model for ALS or TDP-43 pathologies, and highlights its potential in cellular mechanism research and drug testing applications.

Biological Effects of Small Sized Graphene Oxide Nanosheets on Human Leukocytes.

Since the discovery of graphene, there has been a wide range of the literature dealing with its versatile structure and easy binding of biomolecules as well as its large loading capacity. In the emerging field of immunotherapy, graphene and its derivatives have potential uses as drug delivery platforms directly into tumour sites or as adjuvants in cancer vaccines, as they are internalized by monocytes which in turn may activate adaptive anti-tumoral immune responses. In this study, we expose cells of the innate immune system and a human acute monocytic leukemia cell line (THP-1) to low doses of small-sized GO nanosheets functionalized with bovine serum albumin (BSA) and fluorescein isothiocyanate (FITC), to study their acute response after internalization. We show by flow cytometry, uptake in cells of GO-BSA-FITC reaches 80% and cell viability and ROS production are both unaffected by exposure to nanoparticles. On the contrary, GO-BSA nanosheets seem to have an inhibitory effect on ROS production, probably due to their antioxidant properties. We also provided results on chemotaxis of macrophages derived from peripheral blood monocytes treated with GO-BSA. In conclusion, we showed the size of nanosheets, the concentration used and the degree of functionalization were important factors for biocompatibility of GO in immune cells. Its low cytotoxicity and high adaptability to the cells of the innate immune system make it a good candidate for deployment in immunotherapy, in particular for delivering protein antigens to monocytes which activate adaptive immunity.

In Vitro Evaluation of a Recently Developed Rotary File: AF Rotary / Avaliação in vitro de um arquivo rotativo desenvolvido recentemente: AF Rotary

Objective: Aim of the present study is to evaluate mechanical properties of a newly developed rotary file, AF Rotary (Fanta Dental, Shanghai, China), and to compare these features with a worldwide spread rotary file, Protaper Gold F2 (PTG F2; Dentsply Maillefer, Ballaigues, Switzerland). Material and Methods: 60 AF Rotary 25.06 and 60 PTG F2 were divided in three groups of 20 files each. A group underwent to cyclic fatigue resistance tests, second group underwent to torsional resistance tests, third group underwent to bending tests. The statistical analysis was performed using t student test with significance level set at 95% (p < 0.05). Results: AF Rotary showed significantly higher torsional resistance and cyclic fatigue resistance (p < 0.05) when compared to the PTG F2. AF Rotary also showed significantly lower bending resistance (p < 0.05) when compared to the PTG F2. Conclusion: Therefore, within the limitations of this study, the results show better performances for AF Rotary compared to PTG F2 regarding the cyclic fatigue test, the torsional test and the bending test. Since the PTG F2 is a commonly used and widely investigated instrument it could be possible to state that the AF Rotary exhibits remarkable in vitro performances. (AU)

Objetivo: O objetivo do presente estudo é avaliar as propriedades mecânicas de uma lima rotativa recém-desenvolvida, AF Rotary (Fanta Dental, Shanghai, China), e comparar essas características com uma lima rotativa mundialmente difundida, Protaper Gold F2 (PTG F2; Dentsply Maillefer, Ballaigues, Suíça). Material e Métodos: 60 AF Rotary 25.06 e 60 PTG F2 foram divididos em três grupos de 20 arquivos cada. Um grupo foi submetido a testes de resistência à fadiga cíclica, o segundo grupo foi submetido a testes de resistência à torção, o terceiro grupo foi submetido a testes de flexão. A análise estatística foi realizada por meio do teste t student com nível de significância de 95% (p <0,05). Resultados: AF Rotary apresentou resistência torcional e resistência à fadiga cíclica significativamente maiores (p <0,05) quando comparado ao PTG F2. AF Rotary também apresentou resistência à flexão significativamente menor (p <0,05) quando comparado ao PTG F2. Conclusão: Portanto, dentro das limitações deste estudo, os resultados mostram melhores desempenhos do AF Rotary em relação ao PTG F2 no que diz respeito ao teste de fadiga cíclica, ao teste de torção e ao teste de flexão. Uma vez que o PTG F2 é um instrumento comumente usado e amplamente investigado, pode-se afirmar que o AF Rotary exibe desempenhos in vitro notáveis. (AU)