內容: Tumor necrosis factor-α (TNF-α) is a key player in the pathogenesis of rheumatoid arthritis (RA) and considered a promising target for therapeutic drug development. Activation of the nuclear factor-kappa B (NF-κB) pathway upon TNF-α binding to its receptor is crucial for progression of RA. Stephanine (SA), an isoquinoline aporphine-type alkaloid recently identified in Stephania plants, exhibits anti-inflammatory properties, but its underlying mechanisms of action are unknown at present. In this study, we explored whether SA could ameliorate RA through inhibition of the NF-κB signaling pathway in association with TNF-α activity. Our experiments revealed a binding affinity (KD) of SA for TNF-α of 2.934 × 10?6 mol/L. Additionally, SA at a concentration of 10 μmol/L effectively hindered the binding of TNF-α to its receptors tumor necrosis factor receptor 1 (TNFR1) and TNFR2. In vitro, SA prevented TNF-α-induced death of L929 cells and blocked NF-κB activation triggered by TNF-α in 293-TNF-α responsive, as well as human fibroblast-like synoviocytes (HFLS) and human RA fibroblast-like synoviocytes (MH7A) cell lines. Furthermore, in a collagen-induced arthritis (CIA) mouse model, SA alleviated the symptoms of RA through suppression of NF-κB signaling. Our collective findings support the therapeutic efficacy of SA, a natural compound targeting TNF-α, in the management of RA.

內容: Umami peptides play important roles in the flavor of fermented broad bean paste (FBBP), and proteases produced by microorganisms contributed to the production of umami peptides. In order to reveal the formation of umami peptides and their relationships with protease-producing microorganisms during the natural fermentation of FBBP, peptidomics and virtual screening were used to identify and screen umami peptides. Meanwhile, macrogenomics was used to analyze the abundance of microbial-derived protease genes during FBBP fermentation. Then, based on the Pearson correlation coefficient, the correlation network diagram of each protease-producing microorganism with umami peptides was constructed. The results showed that a total of two exopeptidases and four endopeptidases were annotated from FBBP. Staphylococcus, Lactobacillus, Aspergillus, and Weissella can produce most proteases. The species Lactobacillus curvatus, Dyella jiangningensis, Erythrobacter sp., and unclassified_g_Pantoea had strong correlation with umami peptides, and they may contribute to the process of protein hydrolysis to produce umami peptides. This study is expected to reveal the formation mechanism of umami peptides in FBBP, and the results of this study provided a better understanding of the relationship between proteases, microbiota, and core umami peptides in FBBP, which could help to improve the umami taste of Pixian Douban paste during fermentation.

內容: Acrylamide (AA) is a harmful substance widely found in infant and child biscuits; however, the health hazards of AA, especially endogenous AA, in the biscuit matrix is poorly understood. This study aimed to determine the effects of endogenous (0.11 mg/(kg bw·day)) and exogenous (1.31, 5.23, and 10.13 mg/(kg bw·day)) AA exposure from biscuit diet on the hematology, hormone levels, immune function, and liver and kidney damage in growing female rat pups. For the hematological indices, a quadratic reduction was observed in percentage of neutrophils (Neu%) and percentage of eosinophils (Eos%) in the leukograms and in mean corpuscular hemoglobin concentration and platelet in the erythrograms in all the AA-exposed groups. In terms of hormones, extremely remarkably elevations in estradiol (E2) and growth hormone (GH) levels were associated with exogenous AA, and a significant increase in GH levels was noted in the endogenous AA group. Regarding immune function, endogenous and exogenous AA showed a dose-dependent immunotoxic effect on lysozyme (LYSO), nitric oxide (NO), immunoglobulin (Ig)G, and IgM. In particular, the lactate dehydrogenase (LDH) activity was significantly high in the exogenous medium dose (Exo-M) and exogenous high dose (Exo-H) groups, and the percentage of CD3+ T cells in the blood and CD8+ expression levels in the spleen were significantly elevated in the Exo-H group. For liver and kidney function, exogenous AA had a dose-dependent effect on alanine aminotransferases (ALT), aspartate transferases (AST), alkaline phosphatase (ALP), urea nitrogen (UREA), and creatinine (CREA-S). In addition to the dose-dependent effect on the pathological changes in the liver and kidneys, the endogenous AA group presented with hepatocellular steatosis, kidney inflammatory infiltrates, and glomerular and tubular atrophy. Overall, our findings suggested the dose-dependent harmful effect of endogenous and exogenous AA. Special attention should be paid to the damage caused by exposure to endogenous AA. Stringent AA intake guidelines and measures are required to minimize AA levels in the food matrix.