Harnessing Metformin's Immunomodulatory Effects on Immune Cells to Combat Breast Cancer.

Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin's impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ+ NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1+, FoxP3+, and IL-10+ NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46+ NKT cells and increased FasL expression, while lowering the percentages of FoxP3+, PD-1+, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10+ and FoxP3+ Tregs, along with Gr-1+ myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10+ and FoxP3+ Tregs, Gr-1+, NF-κB+, and iNOS+ MDSCs, and iNOS+ dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin's broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types.

Driving Sustainability: Carbon Footprint, 3D Printing, and Legislation concerning Electric and Autonomous Vehicles.

In recent years, there has been a remarkable development in the technology and legislation related to electric and autonomous vehicles (i.e., EVs/AVs). This technological advancement requires the deployment of the most up-to-date supporting infrastructure to achieve safe operation. Further infrastructure is needed for Level 5 vehicles, namely the introduction of super-fast wireless 5G technology. To achieve harmony between the rapid technological advancement of EVs/AVs and environmental preservation, enacting legislation related to their sustainable use is vital. Thus, this manuscript provides a review of the technological development of EVs/AVs, with a special focus on carbon footprints and the implementation of additive manufacturing using recycled materials. While EVs have a 12.13% increased carbon footprint compared to conventional vehicles, AVs with basic and advanced intelligence features have an increased carbon footprint of 41.43% and 99.65%, respectively. This article emphasizes that the integration of 3D-printed components has the potential to offset this impact with a substantial 60% reduction. As a result, custom-made solutions involving 3D printing are explored, leading to greater speed, customization, and cost-effectiveness for EVs/AVs. This article also lists the advantages and disadvantages of the existing legislation in Spain, the United Kingdom, and the western Balkans, demonstrating various approaches to promoting electric mobility and the development of autonomous vehicles. In Spain, initiatives like the MOVES program incentivize EV adoption, while the UK focuses on expanding the EV market and addressing concerns about EVs' quiet operation. In the western Balkans, the adoption of legislation lags behind, with limited incentives and infrastructure for EVs. To boost sales, legal mechanisms are necessary to reduce costs and improve accessibility, in addition to offering subsidies for the purchase of EVs. To this end, an analysis of the incentive measures proposed for the development and use of renewable power sources for the supply of energy for EVs/AVs is presented.

The Influence of Myopia on the Foveal Avascular Zone and Density of Blood Vessels of the Macula-An OCTA Study.

Background and Objectives: Myopia is the most common refractive eye anomaly with a prevalence that is constantly increasing. High myopia is associated with numerous complications that can lead to permanent vision loss. It is believed that the basis of these complications lies in changes in the microvasculature of the retina caused by an increase in the longitudinal axis of the eye. Materials and Methods: Optical coherence tomography angiography (OCTA) was used to analyze differences in macular zone vascular and perfusion density and foveal avascular zone (FAZ) parameters in myopic subjects. The following OCTA parameters were analyzed: the vessel and perfusion density of retinal blood vessels in the superficial plexus; the area, perimeter, and index of circularity of the foveal avascular zone (FAZ); and foveal and ganglion cell complex (GCC) thickness. Results: Subjects with low myopia did not show statistically significant differences compared to the control for any of the analyzed parameters. Groups with moderate and high myopia showed a significant decrease in vessel and perfusion density in the parafoveal and the entire 3 × 3 mm analyzed field. Foveal vessel and perfusion densities in the myopic groups were similar to those of the control regardless of the degree of myopia. The area and perimeter of the FAZ, as well as foveal and mean GCC thickness, did not differ significantly no matter the degree of myopia, while the index of circularity was lower in highly myopic subjects. The minimal thickness of the GCC was also lower in the high myopia group. Conclusions: High and moderate myopia led to a loss of blood vessels in the macular region. Perfusion and vascular densities were preserved in the foveal region and were not affected by different degrees of myopia. The FAZ was not significantly larger in myopic subjects, but its circularity was lower in subjects with high myopia.