Nicotinamide adenine dinucleotide (NAD⁺) is an essential metabolite that plays a crucial role in diverse biological processes, including energy metabolism, gene expression, DNA repair, and mitochondrial function. An aberrant NAD⁺ level mediates the development of cardiovascular dysfunction and diseases. Both in vivo and in vitro studies have demonstrated that nicotinamide mononucleotide (NMN), as a NAD⁺ precursor, alleviates the development of cardiovascular diseases such as heart failure, atherosclerosis, and myocardial ischemia/reperfusion injury. Importantly, NMN has suggested pharmacological activities mostly through its involvement in NAD⁺ biosynthesis. Several clinical studies have been conducted to investigate the efficacy and safety of NMN supplementation, indicating its potential role in cardiovascular protection without significant adverse effects. In this review, we systematically summarize the impact of NMN as a nutraceutical and potential therapeutic drug on cardiovascular diseases and emphasize the correlation between NMN supplementation and cardiovascular protection.

Microglia-mediated chronic neuroinflammation is a common pathological feature of Parkinson’s disease (PD). Strong evidence suggests that activated microglia can lesion neurons by releasing exosomes. However, the mechanisms of exosome release from activated microglia remain unclear. We recently revealed a key role of complement receptor 3 (CR3) in regulating microglial activation in the process of progressive neurodegeneration. This study aimed to investigate whether CR3 can regulate exosome release from activated microglia, as well as the underlying mechanisms. We found that LPS, an inducer of microglial M1 activation, induced exosome release from activated microglia. Inhibition of exosome synthesis suppressed LPS-induced microglial activation, gene expression of proinflammatory factors, and related neurotoxicity. Silencing or knocking out CR3 attenuated LPS-induced exosome release in microglia. NADPH oxidase (NOX2) was further identified as a downstream signal of CR3, mediating microglial exosome release and related neurotoxicity. CR3 silencing blocked LPS-induced NOX2 activation and superoxide production through inhibition of p47^phox phosphorylation and membrane translocation. Moreover, NOX2 activation elicited by PMA or supplementation of H₂O₂ recovered exosome release from CR3-silenced microglia. Subsequently, we demonstrated that the CR3-NOX2 axis regulates syntenin-1 to control microglial exosome release. Finally, we observed that the expression of CR3 was increased in the brain of LPS-treated mice, and genetic ablation of CR3 significantly reduced LPS-induced NOX2 activation, microglial M1 polarization, and exosome production in mice. Overall, our findings revealed a critical role of the CR3-NOX2 axis in controlling microglial exosome release and related neurotoxicity through syntenin-1, providing a novel target for the development of a therapeutic strategy for neuroinflammation-mediated neurodegeneration.

The exact mechanisms through which chronic, low-concentration exposure to Cr(VI) facilitates the development of related pathological conditions remain to be fully elucidated. Senescence-associated secretory phenotype (SASP) exhibits a bidirectional regulatory function in biological processes. Consequently, it is essential to identify the formulation and functional characteristics of the SASP released by Cr(VI)-triggered senescent L02 hepatocytes (S-L02). In this study, exosomes were extracted from the conditioned media of both normal L02 cells and their senescent counterparts (Senescent L02, S-L02 cells). Among the miRNAs identified in the exosomes, miR-10b-3p was found to be the most abundantly expressed in the exosomes derived from S-L02 cells. As part of the SASP, miR-10b-3p was shown to suppress the proliferation of both L02 and S-L02 cells. Simultaneously, it promoted the growth, migration, and invasive capabilities of hepatocellular carcinoma (HCC) cells. The next mechanistic analysis showed that miR-10b-3p reduces the regulatory influence of the protein PHLPP2 on Akt by downregulating its target gene, PHLPP2. This suppression led to lower levels of p27, FOXO3a and p21, thereby enhancing the proliferation of HCC cells by relieving the negative regulatory mechanisms of the cell cycle. This research offers significant understanding into the oncogenic pathways induced by Cr(VI), and provides laboratory evidence for mechanistic studies targeting hepatic carcinoma associated with Cr(VI) exposure.