Effects of T2DM on cancer progression: pivotal precipitating factors and underlying mechanisms.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting people worldwide. It is characterized by several key features, including hyperinsulinemia, hyperglycemia, hyperlipidemia, and dysbiosis. Epidemiologic studies have shown that T2DM is closely associated with the development and progression of cancer. T2DM-related hyperinsulinemia, hyperglycemia, and hyperlipidemia contribute to cancer progression through complex signaling pathways. These factors increase drug resistance, apoptosis resistance, and the migration, invasion, and proliferation of cancer cells. Here, we will focus on the role of hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with T2DM in cancer development. Additionally, we will elucidate the potential molecular mechanisms underlying their effects on cancer progression. We aim to identify potential therapeutic targets for T2DM-related malignancies and explore relevant directions for future investigation.

Microfluidic characterization of single-cell biophysical properties and the applications in cancer diagnosis.

Single-cell biophysical properties play a crucial role in regulating cellular physiological states and functions, demonstrating significant potential in the fields of life sciences and clinical diagnostics. Therefore, over the last few decades, researchers have developed various detection tools to explore the relationship between the biophysical changes of biological cells and human diseases. With the rapid advancement of modern microfabrication technology, microfluidic devices have quickly emerged as a promising platform for single-cell analysis offering advantages including high-throughput, exceptional precision, and ease of manipulation. Consequently, this paper provides an overview of the recent advances in microfluidic analysis and detection systems for single-cell biophysical properties and their applications in the field of cancer. The working principles and latest research progress of single-cell biophysical property detection are first analyzed, highlighting the significance of electrical and mechanical properties. The development of data acquisition and processing methods for real-time, high-throughput, and practical applications are then discussed. Furthermore, the differences in biophysical properties between tumor and normal cells are outlined, illustrating the potential for utilizing single-cell biophysical properties for tumor cell identification, classification, and drug response assessment. Lastly, we summarize the limitations of existing microfluidic analysis and detection systems in single-cell biophysical properties, while also pointing out the prospects and future directions of their applications in cancer diagnosis and treatment.

A high-throughput microfluidic device inspired by the Wheatstone bridge principle for characterizing the mechanical properties of single cells.

The mechanical properties of single cells have been recognized as biomarkers for identifying individual cells and diagnosing human diseases. Microfluidic devices based on the flow cytometry principle, which are not limited by the vision field of a microscope and can achieve a very high throughput, have been extensively adopted to measure the mechanical properties of single cells. However, these kinds of microfluidic devices usually required pressure-driven pumps with a very low flow rate and high precision. In this study, we developed a high-throughput microfluidic device inspired by the Wheatstone bridge principle for characterizing the mechanical properties of single cells. The microfluidic analogue of the Wheatstone bridge not only took advantage of flow cytometry, but also allowed precise control of a very low flow rate through the constricted channel with a higher input flow rate generated by a commercially available pressure-driven pump. Under different input flow rates of the pump, the apparent elastic moduli and the fluidity of osteosarcoma (U-2OS) cells and cervical carcinoma (HeLa) cells were measured by monitoring their dynamic deformations passing through the bridge-channel with different sizes of rectangular constrictions. The results showed that the input flow rate had little effect on measuring the mechanical properties of the cells, while the ratio of cell radius to effective constriction radius was different, i.e., for U-2OS cells it was 1.20 and for HeLa cells it was 1.09. Under this condition compared with predecessors, our statistic results of cell mechanical properties exhibited minimal errors. Furthermore, the cell viability after measurements was kept above 90% that demonstrated the non-destructive property of our proposed method.

The intracellular calcium dynamics in a single vascular endothelial cell being squeezed through a narrow microfluidic channel.

Revealing the mechanisms underlying the intracellular calcium responses in vascular endothelial cells (VECs) induced by mechanical stimuli contributes to a better understanding for vascular diseases, including hypertension, atherosclerosis, and aneurysm. Combining with experimental measurement and Computational Fluid Dynamics simulation, we developed a mechanobiological model to investigate the intracellular [Ca2+] response in a single VEC being squeezed through narrow microfluidic channel. The time-dependent cellular surface tension dynamics was quantified throughout the squeezing process. In our model, the various Ca2+ signaling pathways activated by mechanical stimulation is fully considered. The simulation results of our model exhibited well agreement with our experimental results. By using the model, we theoretically explored the mechanism of the two-peak intracellular [Ca2+] response in single VEC being squeezed through narrow channel and made some testable predictions for guiding experiment in the future.

Sheathless Focusing and Separation of Diverse Nanoparticles in Viscoelastic Solutions with Minimized Shear Thinning.

Viscoelastic microfluidics becomes an efficient and label-free hydrodynamic technology to enrich and separate micrometer-scale particles, including blood cells, circulating tumor cells, and bacteria. However, the manipulation of nanoscale particles by viscoelastic microfluidics remains a major challenge, because the viscoelastic force acting on the smaller particle decreases dramatically. In contrast to the commonly used polymer solutions of high molecular weight, herein we utilize the aqueous solutions of poly(ethylene oxide) (PEO) of low molecular weight with minimized shear thinning but sufficient elastic force for high-quality focusing and separation of various nanoparticles. The focusing efficiencies of 100 nm polystyrene (PS) nanoparticles and λ-DNA molecules are 84% and 85%, respectively, in a double spiral microchannel, without the aid of sheath flows. Furthermore, we demonstrate the size-based viscoelastic separation of two sets of binary mixtures-100/2000 nm PS particles and λ-DNA molecules/blood platelets-all achieving separation efficiencies of >95% in the same device. Our proposal technique would be a promising approach for enrichment/separation of the nanoparticles encountered in applications of analytical chemistry and nanotechnology.

Size-Based Separation of Particles and Cells Utilizing Viscoelastic Effects in Straight Microchannels.

Viscoelasticity-induced particle migration has recently received increasing attention due to its ability to obtain high-quality focusing over a wide range of flow rates. However, its application is limited to low throughput regime since the particles can defocus as flow rate increases. Using an engineered carrier medium with constant and low viscosity and strong elasticity, the sample flow rates are improved to be 1 order of magnitude higher than those in existing studies. Utilizing differential focusing of particles of different sizes, here, we present sheathless particle/cell separation in simple straight microchannels that possess excellent parallelizability for further throughput enhancement. The present method can be implemented over a wide range of particle/cell sizes and flow rates. We successfully separate small particles from larger particles, MCF-7 cells from red blood cells (RBCs), and Escherichia coli (E. coli) bacteria from RBCs in different straight microchannels. The proposed method could broaden the applications of viscoelastic microfluidic devices to particle/cell separation due to the enhanced sample throughput and simple channel design.