An Overview of Three Promising Mechanical, Optical, and Biochemical Engineering Approaches to Improve Selective Photothermolysis of Refractory Port Wine Stains

During the last three decades, several laser systems, ancillary technologies, and treatment modalities have been developed for the treatment of port wine stains (PWSs). However, approximately half of the PWS patient population responds suboptimally to laser treatment. Consequently, novel treatment modalities and therapeutic techniques/strategies are required to improve PWS treatment efficacy. This overview therefore focuses on three distinct experimental approaches for the optimization of PWS laser treatment. The approaches are addressed from the perspective of mechanical engineering (the use of local hypobaric pressure to induce vasodilation in the laser-irradiated dermal microcirculation), optical engineering (laser-speckle imaging of post-treatment flow in laser-treated PWS skin), and biochemical engineering (light- and heat-activatable liposomal drug delivery systems to enhance the extent of post-irradiation vascular occlusion)

Lunar Volatiles and Solar System Science

Understanding the origin and evolution of the lunar volatile system is not only compelling lunar science, but also fundamental Solar System science. This white paper (submitted to the US National Academies' Decadal Survey in Planetary Science and Astrobiology 2023-2032) summarizes recent advances in our understanding of lunar volatiles, identifies outstanding questions for the next decade, and discusses key steps required to address these questions

Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer

Human epidermal growth factor receptor-2 (HER2)-targeting therapies provide clinical benefits for patients with HER2-positive breast cancer. However, the resistance to monotherapies invariably develops and leads to disease relapse and treatment failure. Previous studies have demonstrated a link between the potency of HER2-targeting tyrosine kinase inhibitors (TKIs) and their ability to induce an iron-dependent form of cell death called ferroptosis. The aim of this study was to understand the mechanisms of resistance to TKI-induced ferroptosis and identify novel approaches to overcome treatment resistance. We used mouse and human HER2-positive models of acquired TKI resistance to demonstrate an intimate link between the resistance to TKIs and to ferroptosis and present the first evidence that the cell adhesion receptor αvβ3 integrin is a critical mediator of resistance to TKI-induced ferroptosis. Our findings indicate that αvβ3 integrin-mediated resistance is associated with the re-wiring of the iron/antioxidant metabolism and persistent activation of AKT signalling. Moreover, using gene manipulation approaches and pharmacological inhibitors, we show that this “αvβ3 integrin addiction” can be targeted to reverse TKI resistance. Collectively, these findings provide critical insights into new therapeutic strategies to improve the treatment of advanced HER2-positive breast cancer patients

Social regulation of inflammation related gene expression in the multi-ethnic study of atherosclerosis

BackgroundExposure to adverse social factors has been associated with an altered inflammatory profile, a risk factor for several acute and chronic diseases. Differential gene expression may be a biological mediator in the relationship. In this study, associations between a range of social factors and expression of inflammation-related genes were investigated.MethodsSocial factor and gene expression data were collected from 1,264 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA). Inflammation-related genes were identified from the Gene Ontology database. The associations between social factors and gene expression were first assessed using the Global Analysis of Covariance (Global ANCOVA) gene set enrichment test. When the global test was significant, linear regression and elastic net penalized regression were employed to identify the individual gene transcripts within each gene set associated with the social factor.ResultsLoneliness (p = 0.003), chronic burden (p = 0.002), and major or lifetime discrimination (p = 0.045) were significantly associated with global expression of the chronic inflammatory gene set. Of the 20 transcripts that comprise this gene set, elastic net selected 12 transcripts for loneliness, 8 for chronic burden, and 3 for major or lifetime discrimination. Major or lifetime discrimination was also associated with the inflammatory response (p = 0.029), regulation of the inflammatory response (p = 0.041), and immune response (p = 0.025) gene sets in global analyses, and 53, 136, and 26 transcripts were selected via elastic net for these gene sets respectively. There were no significant associations in linear regression analyses after adjustment for multiple testing.ConclusionsThis study highlights gene expression as a biological mechanism through which social factors may affect inflammation