Nicotinamide mononucleotide (NMN) is a natural antioxidant approved as a nutritional supplement and food ingredient, but its protective role in silicosis characterized by oxidative damage remains unknown. In this study, we generated a silicosis model by intratracheal instillation of silica, and then performed histopathological, biochemical, and transcriptomic analysis to evaluate the role of NMN in silicosis. We found that NMN mitigated lung damage at 7 and 28 days, manifested as a decreasing coefficient of lung weight and histological changes, and alleviated oxidative damage by reducing levels of reactive oxygen species and increasing glutathione. Meanwhile, NMN treatment also reduced the recruitment of inflammatory cells and inflammatory infiltration in lung tissue. Transcriptomic analysis showed that NMN treatment mainly regulated immune response and glutathione metabolism pathways. Additionally, NMN upregulated the expression of antioxidant genes Gstm1, Gstm2, and Mgst1 by promoting the expression and nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Gene interaction analysis showed that Nrf2 interacted with Gstm1 and Mgst1 through Gtsm2. Promisingly, oxidative damage mediated by these genes occurred mainly in fibroblasts. In summary, NMN alleviates silica-induced oxidative stress and lung injury by regulating the endogenous glutathione metabolism pathways. This study reveals that NMN supplementation might be a promising strategy for mitigating oxidative stress and inflammation in silicosis.
Biomimetic drug delivery systems have attracted much interests as they could accomplish tasks such as precise delivery and biological barrier penetration. Biological membranes often play important functional roles in these systems. We discover that the circulating time and targeting capability of biological membrane-coated nanovehicles could be significantly improved by reducing their cholesterol content with simple (2-hydroxypropyl)-β-cyclodextrin treatment. A proof-of-concept biomimetic nano system using cholesterol-reduced T cell membrane with overexpressed PD-1 to deliver photothermal agent and STING agonist SR-717 is fabricated and assessed. Comparing with non-modified membrane and conventional PEGlaytion modified membranes, these membranes offer remarkably improved performance in immunocompetent mice, with ~ 2-fold increase in tumor accumulation. After intravenous injection and laser irradiation, melanoma tumors are completely eliminated with no recurrence for > 100 days in > 80% treated mice. Mechanistic studies suggest that the treated membranes could efficiently escape the immune surveillance to avoid blood clearance while keeping functional surface molecules exposed. This subtractive strategy does not introduce new substances and appears to be highly safe. In summary, we discover a simple, safe and widely-applicable biological membrane modification strategy that could significantly improve delivery performance. This strategy displays advantages than conventional PEGlaytion in some aspects and has good potential for further development.
To the Editor: Chronic obstructive pulmonary disease (COPD), a clinical syndrome encompassing a spectrum of chronic, progressive, and debilitating respiratory disorders, is increasingly recognized as a multisystemic heterogeneous disease. [1] Because the characteristics of East Asian COPD patients differ from those of Westerners, it would be practical to investigate whether variations in COPD genetic performance exist between East Asian and Western populations. [2]
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.