内容: Ganoderma sinense is a traditional and protein-rich edible fungus with outstanding immunoregulatory activity. However, the mechanism through which G. sinense protein hydrolysates and peptides exert their immunomodulatory effects is unclear. The objective of this study was to prepare and isolate immunologically active peptides from G. sinense protein hydrolysates (GSP) and to investigate their impact on the activation of macrophages. G. sinense peptides with low molecular weights (< 1 kDa, 87.76%) markedly promoted RAW264.7 cell proliferation; increased their phagocytic capacity, nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and IL-6 secretion and reactive oxygen species (ROS) production; and upregulated Tlr2 mRNA expression. In addition, GSP promoted nuclear factor kappa-B (NF-κB) activation and translocation through the upregulation of p65 and p-p65 protein expression. Virtual molecular screening technology revealed that compared with other peptides, the SFAGNIPVNR, YGDAFIR and TVSYLPAPQR peptides derived from GSP showed stronger binding affinities. Interaction site map analysis indicated that the SFAGNIPVNR and YGDAFIR peptides formed stable hydrogen bonds with toll-like receptor 2 (TLR2). Together, these results suggested that G. sinense peptides can serve as important ingredients in nutraceuticals or functional foods.

内容: Hypercholesteremia results in cognitive decline, while higher intakes of marine n-3 polyunsaturated fatty acids (PUFA) can ameliorate mild cognitive impairment (MCI). However, whether individual n-3 PUFA, notably docosahexaenoic acid (DHA, C22:6n-3) and eicosapentaenoic acid (EPA, C20:5n-3) have different efficiency to ameliorate MCI remain ambiguous. This study aimed to investigate the underlying mechanism why DHA had superior functions to ameliorate MCI. Here, a case-control study with 1:2 case-to-control ratio was implemented. It showed that serum ceramide concentrations were significantly higher in MCI patients compared with healthy controls, and were negatively associated with DHA composition in erythrocyte phospholipids. The MCI model was established with male C57BL/6J wild-type mice fed a high-fat and high-cholesterol diet (HFD), and administration of DHA led to ameliorated cognitive behavior abnormalities and neuronal apoptosis. The improvement of MCI phenotype was further recapitulated in low-density lipoprotein receptor knockout (LDLR−/−) mice treated with DHA. Mechanistically, DHA could remodel composition of phospholipid membranes, leading to reduced endocannabinoid ligands and inhibited cannabinoid receptor 1 (CB1). The restrained endocannabinoid system was bound up with inhibited ceramide-induced apoptosis of neurons. This work reveals a novel mechanism, namely CB1-ceramide axis, through which DHA exhibits an alleviation in HFD-induced MCI.

内容: Digestive properties of starch can be significantly modified by its interaction with polyphenols. This study focused on the modulatory effect of tea polyphenol-fortified parboiled rice (TP) on high-fat diet (HFD)-induced obesity in mice through the regulation of gut microbiota. TP was prepared with parboiled rice (PR) by soaking with tea polyphenols (TPs). The results showed that average body weight of mice fed with an HFD containing PR (PR-H) or TP (TP-H) decreased by 24.5% and 48.7%, compared with the group of an HFD containing white rice (WR-H), respectively. The levels of total triglyceride and total cholesterol were ranked as WR-H > PR-H > TP-H. Histological sections of the liver and epididymal adipose tissue showed that TP reduced lipid accumulation in mice fed with an HFD. Additionally, TP enhanced the liver antioxidant capacity and reduced oxidative damage in mice, thereby ameliorating liver oxidative stress caused by the HFD. Besides, TP modified the microbial community of mice by improving the gut microbiota diversity with the abundance of Akkermansiaceae, Muribaculaceae, and Bacteroidaceae increased. These findings suggested that TP can improve the intestinal microecological environment of mice, regulate lipid metabolism levels, and thereby exert a certain anti-obesity effect.

内容: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that has long been hampered by limited treatment efficacy and significant side effects. Tumor necrosis factor-α (TNF-α) plays a pivotal role in RA pathogenesis by binding to its receptor (TNFR) and activating the downstream nuclear factor-kappa B (NF-κB) signaling pathway, which promotes the transcription of pro-inflammatory genes and perpetuates disease progression. Blocking the TNF-α–TNFR interaction thus represents a promising therapeutic strategy for RA. In this study, we identified a natural compound, 1-norbetulonic acid (DOCA), that disrupts the binding between TNF-α and TNFR, leading to therapeutic benefits in RA. Our results show that DOCA inhibits TNF-α-induced activation of the NF-κB pathway in human fibroblast-like synoviocytes and MH7A cells, and prevents nuclear translocation of the p65 subunit. Notably, DOCA demonstrated significant therapeutic efficacy in a mouse model of RA. Together, these findings support the hypothesis that DOCA alleviates RA by blocking TNF-α–TNFR signaling, underscoring its potential as a natural product-derived inhibitor of this interaction and highlighting a viable approach for the discovery of TNF-α/TNFR-targeted natural therapeutics.

内容: Akkermansia, a next-generation probiotic candidate, exhibits a reduced abundance in obesity yet persists in the gut, suggesting unique adaptive mechanisms for survival in this adverse metabolic environment. To elucidate these mechanisms, a comparative pan-genome analysis of 494 Akkermansia metagenome-assembled genomes from hosts with diverse body mass indices was conducted. It was found that the genus possesses high genetic diversity, with Akkermansia muciniphila as the dominant species (80%), though species distribution itself was not correlated with BMI. There were 15 genes significantly enriched in obese individuals. These genes may potentially be involved in pathways such as nutrient acquisition, antioxidant stress response, energy metabolism, translational fidelity, and viral defense. Co-occurrence network analysis showed that these genes are associated with pathways including the tricarboxylic acid cycle and lipoic acid metabolism. These findings suggest potential adaptive functional mechanisms of Akkermansia for survival in the obese gut environment, providing novel insights for the development of targeted probiotics addressing obesity-related conditions.