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A definitive understanding of the interplay between protein binding/migration and membrane curvature evolution is emerging but needs further study. The mechanisms defining such phenomena are critical to intracellular transport and trafficking of proteins. Among trafficking modalities, exosomes have drawn attention in cancer research as these nano-sized naturally occurring vehicles are implicated in intercellular communication in the tumor microenvironment, suppressing anti-tumor immunity and preparing the metastatic niche for progression. A significant question in the field is how the release and composition of tumor exosomes are regulated. In this perspective article, we explore how physical factors such as geometry and tissue mechanics regulate cell cortical tension to influence exosome production by co-opting the biophysics as well as the signaling dynamics of intracellular trafficking pathways and how these exosomes contribute to the suppression of anti-tumor immunity and promote metastasis. We describe a multiscale modeling approach whose impact goes beyond the fundamental investigation of specific cellular processes toward actual clinical translation. Exosomal mechanisms are critical to developing and approving liquid biopsy technologies, poised to transform future non-invasive, longitudinal profiling of evolving tumors and resistance to cancer therapies to bring us one step closer to the promise of personalized medicine.

Background and Aims: Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D). Methods: Using a nationally representative sample from the Korean National Health Insurance Service database, 1 528 108 adults aged 30–64 with T2D and no history of CVD were included from 2009 to 2012 (mean follow-up of 7.3 years). Using monthly health insurance premium information, income levels were assessed annually for the baseline year and the four preceding years. Income variability was defined as the intraindividual standard deviation of the percent change in income over 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, heart failure, and stroke) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders. Results: High-income variability was associated with increased CVD risk (HRhighest vs. lowest quartile 1.25, 95% CI 1.22–1.27; Ptrend <.001). Individuals who experienced an income decline (4 years ago vs. baseline) had increased CVD risk, which was particularly notable when the income decreased to the lowest level (i.e. Medical Aid beneficiaries), regardless of their initial income status. Sustained low income (i.e. lowest income quartile) over 5 years was associated with increased CVD risk (HRn = 5 years vs. n = 0 years 1.38, 95% CI 1.35–1.41; Ptrend <.0001), whereas sustained high income (i.e. highest income quartile) was associated with decreased CVD risk (HRn = 5 years vs. n = 0 years 0.71, 95% CI 0.70–0.72; Ptrend <.0001). Sensitivity analyses, exploring potential mediators, such as lifestyle-related factors and obesity, supported the main results. Conclusions: Higher income variability, income declines, and sustained low income were associated with increased CVD risk. Our findings highlight the need to better understand the mechanisms by which income dynamics impact CVD risk among individuals with T2D. Structured Graphical Abstract This study investigates the association between income dynamics over five years and incident composite cardiovascular outcomes in non-elderly individuals with type 2 diabetes. Our graphical abstract highlights significant associations between cardiovascular risk and income metrics, including income variability (standard deviation of percent change), changes in income status (rise and decline), and cumulative number of years in low- or high-income status. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We investigated the association of polyneuropathy (PN) with all‐cause and cardiovascular (CV) mortality and with cardiovascular disease (CVD) events stratified by diabetes status. Materials and Methods: This prospective cohort study used the UK Biobank. Polyneuropathy was defined based on nurse‐led interviews or ICD codes for polyneuropathy. Cox proportional hazards models were used to investigate the association of polyneuropathy with clinical outcomes. Results: A total of 459,127 participants were included in the analysis. Polyneuropathy was significantly associated with all‐cause and cardiovascular mortality, and with CVD events even after adjusting for CVD risk factors across all diabetes statuses. Metabolic parameters HbA1c, waist circumference, BMI and the inflammatory parameter C‐reactive protein showed significant mediation effects for the association between polyneuropathy and CVD. Adherence to a favorable lifestyle was associated with a lower risk of all‐cause and cardiovascular mortality regardless of polyneuropathy status. Conclusions: Polyneuropathy was associated with all‐cause and cardiovascular mortality, and with CVD events in subjects with diabetes or prediabetes, even those having normal glucose tolerance. This study suggests the importance of polyneuropathy as a risk factor for death and highlights the necessity of early diagnosis and lifestyle intervention for those with type 2 diabetes and polyneuropathy. [ABSTRACT FROM AUTHOR]