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Lester Packer was an exceptional scientific leader, whose radiant personality inspired and encouraged generations of students and scientists for research to pursue oxidants and antioxidants in biology and medicine. For the FORUM dedicated to Professor Packer, we here describe key aspects of his professional career, from the early years at Brooklyn College, Yale University, and the Johnson Research Foundation at Philadelphia to his long-term base at the University of California, at UC Berkeley. The concept of the "Antioxidant Network" formed the core of his activities in later years. His welcoming and integrative personality led to a worldwide network of colleagues, starting with the Bay Area Oxygen Club, which turned into the Oxygen Club of California, and his leadership in the Society for Free Radical Research-International. To illustrate his warmth and outreach, which enabled him to form borderless global collaborations, we conclude with words from some of his many friends also from outside academia: Lester Packer's legacy. Antioxid. Redox Signal. 38, 768–774. [ABSTRACT FROM AUTHOR]

Aims Endothelial function is essential for cardiovascular health, and flow-mediated dilation (FMD) is an established technique to measure it. This paper aims to assess FMD values in apparently healthy individuals and provides reference values to facilitate wider clinical use. Methods and results In 1,579 apparently healthy individuals (aged 18–76), fasted FMD values (data from 44 studies, 6 institutions, 22 operators) were normally distributed and inversely univariately correlated with age, body mass index, glucose, cholesterol, blood pressure, and brachial artery (BA) diameter. Significant multivariate predictors of FMD were age (−0.4%/decade), BMI (0.04%/kg/m2), smoking (−0.7%), and BA diameter (−0.44%/mm) that together explained 19% of the variability independent of operator, institution or ultrasound machine. Individuals in the high FMD tertile (>6.8%) were younger, had smaller BA diameter, lower blood pressure and cholesterol. In individuals with low- and intermediate fatal cardiovascular risk (SCORE), 26% and 53% of individuals, respectively, had FMD values in the low tertile (<5.4%). After adding data from 385 patients with stable coronary artery disease (CAD), ROC analysis (c = 0.841 , P < 0.001) showed that FMD of >6.5% excluded CAD (95% sensitivity; 60% specificity) and FMD <3.1% excluded 95% healthy individuals (95% specificity, 31% sensitivity). A meta-analysis and meta-regression of 82 clinical trials (11 countries, n = 3,509) using similar FMD methodology showed that despite considerable heterogeneity (I 2 = 0.97) FMD in healthy individuals was on average 6.4% (95%CI: 6.2%, 6.7%) with no significant differences between countries but a significant age-dependent decline (−0.3%/decade, R 2 = 0.13). Conclusions We provide an age-adapted frame of FMD reference intervals in apparently healthy individuals for use as a biomarker of cardiovascular health. As the degree of vascular endothelial function integrates environmental and genetic factors with classical CV risk factors, FMD may more comprehensively classify individuals with and without standard modifiable cardiovascular risk factors and serve as a target for cardiovascular prevention. [ABSTRACT FROM AUTHOR]

Redox reactions are linked to fundamental life processes. Recent research revealed a central role of hydrogen peroxide (H2O2) in redox regulation and oxidative stress responses. A physiological low level of H2O2 is essential in redox signaling, "oxidative eustress", whereas supraphysiological H2O2 is detrimental, causing molecular damage, "oxidative distress". Fine-tuning H2O2 steady-states in specific cell-types and subcellular organelles represents a challenge for a future redox medicine. [ABSTRACT FROM AUTHOR]

Research on oxidants and electrophiles has shifted from focusing on damage to biomolecules to the more fine‐grained physiological arena. Redox transitions as excursions from a steady‐state redox set point are continually ongoing in maintenance of redox balance. Current excitement on these topics results from the fact that recent research provided mechanistic insight, which gives rise to more concrete and differentiated questions. This Commentary focuses on redox eustress and the feedback restoration of steady state as concepts in active maintenance of physiological health, with brief discussion of redox stress response to viral infection, exemplified by COVID‐19. [ABSTRACT FROM AUTHOR]

Cell and organ metabolism is organized through various signaling mechanisms, including redox, Ca 2+ , kinase and electrochemical pathways. Redox signaling operates at multiple levels, from interactions between individual molecules in their microenvironment to communication among subcellular organelles, single cells, organs, and the entire organism. Redox communication is a dynamic and ongoing spatiotemporal process. This article focuses on hydrogen peroxide (H 2 O 2 ), a key second messenger that targets redox-active protein cysteine thiolates. H 2 O 2 gradients across cell membranes are controlled by peroxiporins, specialized aquaporins. Redox-active endosomes, known as redoxosomes, form at the plasma membrane. Cell-to-cell redox communication involves direct contacts, such as per gap junctions that connect cells for transfer of molecules via connexons. Moreover, signaling occurs through the release of redox-active molecules and enzymes into the surrounding space, as well as through various extracellular vesicles (EVs) that transport these signals to nearby or distant target cells., Competing Interests: Declaration of Competing Interest I declare that there is no competing interest., (Copyright © 2024. Published by Elsevier Inc.)