Accumulation and aggregation of misfolded proteins is a hallmark of several diseases collectively known as proteinopathies. Autophagy has a cytoprotective role in diseases associated with protein aggregates. Age-related macular degeneration (AMD) is the most common neurodegenerative eye disease that evokes blindness in elderly. AMD is characterized by degeneration of retinal pigment epithelial (RPE) cells and leads to loss of photoreceptor cells and central vision. The initial phase associates with accumulation of intracellular lipofuscin and extracellular deposits called drusen. Epidemiological studies have suggested an inverse correlation between dietary intake of marine n-3 polyunsaturated fatty acids (PUFAs) and the risk of developing neurodegenerative diseases, including AMD. However, the disease-preventive mechanism(s) mobilized by n-3 PUFAs is not completely understood. In human retinal pigment epithelial cells we find that physiologically relevant doses of the n-3 PUFA docosahexaenoic acid (DHA) induce a transient increase in cellular reactive oxygen species (ROS) levels that activates the oxidative stress response regulator NFE2L2/NRF2 (nuclear factor, erythroid derived 2, like 2). Simultaneously, there is a transient increase in intracellular protein aggregates containing SQSTM1/p62 (sequestosome 1) and an increase in autophagy. Pretreatment with DHA rescues the cells from cell cycle arrest induced by misfolded proteins or oxidative stress. Cells with a downregulated oxidative stress response, or autophagy, respond with reduced cell growth and survival after DHA supplementation. These results suggest that DHA both induces endogenous antioxidants and mobilizes selective autophagy of misfolded proteins. Both mechanisms could be relevant to reduce the risk of developing aggregate-associate diseases such as AMD.

Carotenoids are a large group of health-promoting compounds used in many industrial sectors, such as foods, feeds, pharmaceuticals, cosmetics, nutraceuticals, and colorants. Considering the global population growth and environmental challenges, it is essential to find new sustainable sources of carotenoids beyond those obtained from agriculture. This review focuses on the potential use of marine archaea, bacteria, algae, and yeast as biological factories of carotenoids. A wide variety of carotenoids, including novel ones, were identified in these organisms. The role of carotenoids in marine organisms and their potential health-promoting actions have also been discussed. Marine organisms have a great capacity to synthesize a wide variety of carotenoids, which can be obtained in a renewable manner without depleting natural resources. Thus, it is concluded that they represent a key sustainable source of carotenoids that could help Europe achieve its Green Deal and Recovery Plan. Additionally, the lack of standards, clinical studies, and toxicity analysis reduces the use of marine organisms as sources of traditional and novel carotenoids. Therefore, further research on the processing of marine organisms, the biosynthetic pathways, extraction procedures, and examination of their content is needed to increase carotenoid productivity, document their safety, and decrease costs for their industrial implementation.

Inflammation is crucial in the defense against infections but must be tightly controlled to limit detrimental hyperactivation. Our diet influences inflammatory processes and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have known anti-inflammatory effects. The balance of pro- and anti-inflammatory processes is coordinated by macrophages and macroautophagy/autophagy has recently emerged as a cellular process that dampens inflammation. Here we report that the n-3 PUFA docosahexaenoic acid (DHA) transiently induces cytosolic speckles of the autophagic receptor SQSTM1/p62 (sequestosome 1) (described as SQSTM1/p62-bodies) in macrophages. We suggest that the formation of SQSTM1/p62-bodies represents a fast mechanism of NFE2L2/Nrf2 (nuclear factor, erythroid 2 like 2) activation by recruitment of KEAP1 (kelch like ECH associated protein 1). Further, the autophagy receptor TAX1BP1 (Tax1 binding protein 1) and ubiquitin-editing enzyme TNFAIP3/A20 (TNF α induced protein 3) could be identified in DHA-induced SQSTM1/p62-bodies. Simultaneously, DHA strongly dampened the induction of pro-inflammatory genes including CXCL10 (C-X-C motif chemokine ligand 10) and we suggest that formation of SQSTM1/p62-bodies and activation of NFE2L2 leads to tolerance towards selective inflammatory stimuli. Finally, reduced CXCL10 levels were related to the improved clinical outcome in n-3 PUFA-supplemented heart-transplant patients and we propose CXCL10 as a robust marker for the clinical benefits mobilized by n-3 PUFA supplementation.

Significance: Inflammatory signaling is a central mechanism controlling host defenses to pathogens. Members of Mycobacterium avium complex cause disease in immunocompromised patients and in individuals with predisposing lung abnormalities. We provide evidence of a mechanism in human primary macrophages whereby the oxidative stress sensor Kelch-like ECH-associated protein 1 (Keap1) negatively regulates inflammatory responses and thus facilitates intracellular growth of M. avium . Our findings are of high biological and clinical significance, as opportunistic infections with nontuberculous mycobacteria are receiving renewed attention because of increased incidence and difficulties in treatment. Altered Keap1 gene expression may also have vital clinical implications for other inflammation-associated conditions, opening novel research venues for translational research, for instance in the expanding field of host-targeted therapy for infectious diseases.

Macroalgae are considered healthy food ingredients due to their content in numerous bioactive compounds, and the traditional use of whole macroalgae in Asian cuisine suggests a contribution to longevity. Although much information is available about the bioactivity of pure algal compounds, such as different polyphenols and polysaccharides, documentation of potential effects of whole macroalgae as part of Western diets is limited. Lifestyle‐ and age‐related diseases, which have a high impact on population health, are closely connected to underlying chronic inflammation. Therefore, we have studied crude extracts of green (Ulva fenestrata) and brown (Saccharina latissima) macroalgae, as two of the most promising food macroalgae in the Nordic countries for their effect on inflammation in vitro. Human macrophage‐like reporter THP‐1 cells were treated with macroalgae extracts and stimulated with lipopolysaccharide (LPS) to induce inflammatory signalling. Effects of the macroalgae extracts were assessed on transcription factor activity of NF‐κB and IRF as well as secretion and/or expression of the cytokines TNF‐α and IFN‐β and chemokines IL‐8 and CXCL10. The crude macroalgae extracts were further separated into polyphenol‐enriched and polysaccharide‐enriched fractions, which were also tested for their effect on transcription factor activity. Interestingly, we observed a selective activation of NF‐κB, when cells were treated with macroalgae extracts. On the other hand, pretreatment with macroalgae extracts selectively repressed IRF activation when inflammatory signaling was subsequently induced by LPS. This effect was consistent for both tested species as well as for polyphenol‐ and polysaccharide‐enriched fractions, of which the latter had more pronounced effects. Overall, this is the first indication of how macroalgae could modulate inflammatory signaling by selective activation and subsequent repression of different pathways. Further in vitro and in vivo studies of this mechanism would be needed to understand how macroalgae consumption could influence the prevention of noncommunicable, lifestyle‐ and age‐related diseases that are highly related to unbalanced inflammatory processes.