MicroRNAs (miRNAs) involve in destabilising messenger RNA or repressing translation of target molecules. Ginger-derived exosome-like nanoparticles (GELNs) play a crucial role in modulating intestinal inflammation. Moreover, GELNs contain highly heterogeneous miRNA. However, the role of miRNAs derived from GELNs in immunomodulation remains unclear. This study aimed to elucidate the molecular basis of the unique biological effects mediated by miRNA derived from GELNs on macrophages. GELNs were isolated using a combination of commercial exosome isolation kits and the differential centrifugation method, and the lipid composition of GELNs was determined using liquid chromatography-mass spectrometry. Subsequently, PKH26 labelled GELNs were taken up by macrophages. Furthermore, the modulation of inflammatory and immune responses by GELNs or osa-miR164d was assessed through the RNA-seq, RT-qPCR, online databases, and dual luciferase reporter assays to explore the underlying mechanisms of osa-miR164d. Biomimetic exosomes loaded with osa-miR164d were prepared using a microfluidic mixing device and systematically characterized. The therapeutic effects of osa-miR164d on relieving colitis were evaluated. We report for the first time that GELNs-derived osa-miR164d is a regulatory factor of reprogramming macrophage polarization, thereby inhibiting the intestinal inflammatory response. Mechanistically, osa-miR164d directly targets the 3'-UTRs of TAB1, which regulates macrophage polarization through the downregulation of NF-κB expression. In addition, We have designed a biomimetic exosome mimicking GELNs to deliver osa-miR164d (osa-miR164d-MGELNs). Notably, the osa-miR164d-MGELNs can efficiently reprogram macrophages to alleviate colitis-related symptoms. Our findings enhance the systematic understanding of how GELNs-derived osa-miR164d mediates cross-kingdom communication and provide an original engineering paradigm for mimicking GELNs to transfer miRNA.

Inflammatory bowel disease (IBD) is associated with the microbial composition of the gut and its metabolites. Akkermansia muciniphila is a probiotic that exerts a significant alleviative or therapeutic effect on host enteritis. This study was designed to determine the protective effect and potential mechanism underlying the secretion of β-acetylaminohexosidase (Amuc_2109) by A. muciniphila against dextran sulfate sodium (DSS)-induced colitis in mice. C57BL/6 mice were gavaged with Amuc_2109 for 21 days, and during the last seven days of treatment, they drank DSS dissolved in their drinking water to induce colitis. Our results showed that supplementation with Amuc_2109 improved DSS-induced colitis as evidenced by lowered disease activity index (DAI) scores, reduced weight loss, increased colon length, and inhibited oxidative stress. In addition, Amuc_2109 inhibited the overexpression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and the NLR family pyrin domain containing 3 (NLRP3) inflammasome in DSS-induced colitis. Furthermore, supplementation with Amuc_2109 also restored the mRNA expression of tight junction proteins (ZO-1, occludin, claudin-1). Further analysis of fecal microbial 16S rRNA sequences showed that Amuc_2109 reshaped the intestinal microbiota. While the anti-inflammatory effects of Amuc_2109 were only manifested with the wild-type protein, the anti-inflammatory effects were completely lost after the mutation of its key catalytic amino acids rendered Amuc_2109 inactive. In summary, these findings demonstrate the potential of Amuc_2109, as a therapeutic agent for ulcerative colitis. We posit that it will provide additional assistance in the prevention and treatment of mucus layer-related diseases such as ulcerative colitis.

Grape seed proanthocyanidin extract (GSPE) that prevents and alleviates the degenerative changes associated with aging has been receiving extensive attention. In our present work, the ageing model was induced by injection of 500 mg kg⁻¹ D-galactose daily for a period of eight weeks. The D-galactose-induced ageing mice model was used for evaluating the effect of GSPE on oxidative stress, inflammation levels and gut microbiota composition. D-Galactose induced oxidative damage and inflammation with a significant increase in malondialdehyde contents, myeloperoxidase activities and the levels of TNF-α and IL-1β, as well as a reduction in the activities of glutathione peroxidase and reduced glutathione. Treatment with different doses of GSPE could significantly improve the antioxidant capacity and inflammation levels in the liver and brain, which is accompanied by increased Lachnospiraceae_NK4A136, Lactobacillus, Bifidobacterium, and Akkermansia, as well as decreased Helicobacter and Alistipes. In addition, the high-dose GSPE group exhibited greater potential to delay the ageing process than the low-dose group. Our results also showed that GSPE administration could downregulate the NLRP3 inflammasome signaling pathway for inhibiting inflammation levels in the brain tissue. This study provided a novel strategy to target the gut microbiota with regard to the effect of GSPE administration on alleviating aging-induced alterations via the gut microbiota–liver axis and gut microbiota–brain axis.

Vanadium, a transition metal, has emerged as a promising element in the development of therapeutic drugs. While not an essential element for life, vanadium compounds have demonstrated significant potential as anticancer agents. Current evidence suggests that these compounds exert their anti-tumor effects through multiple mechanisms, including DNA damage, cell cycle regulation, induction of apoptosis and autophagy, inhibition of metastasis and invasion, and disruption of mitochondrial function. Furthermore, vanadium compounds have shown efficacy against a wide range of cancers, such as melanoma, breast, colorectal, pancreatic, liver, and central nervous system tumors, as well as oral squamous cell carcinoma. This review aims to comprehensively examine the anti-tumor properties and underlying mechanisms of various vanadium compounds while also providing an overview of their current biological applications.