内容: Although coagulase-negative Staphylococcus (CNS), along with technological activities, plays a key role in fermented sausage flavour and nutrient production, the molecular mechanism of these activities remains elusive. In this study, 18 CNS strains with high proteolytic activity were isolated from Chinese Dong fermented pork (Nanx Wudl), and their technological and transcriptomic properties were investigated. After biochemical identification and genetic analysis, their technological properties, including nitrate reductase, catalase, antioxidant, and lipolytic activities and their growth under varying temperatures, salt concentrations, and pH levels were evaluated. Their aroma-producing potential was also determined in a model medium resembling fermented sausages. Transcriptomic analysis was performed using the most promising isolates. Biochemical identification and 16S rDNA sequencing revealed that the 18 Staphylococcus strains belonged to Staphylococcus xylosus, Staphylococcus saprophyticus, Staphylococcus carnosus, Staphylococcus sciuri, and Staphylococcus equorum. In terms of technological properties, 16 strains showed a nitrate-reducing ability, while 11 strains had a lipolytic activity. All strains exhibited superoxide dismutase (SOD) and catalase activities; four strains displayed an SOD activity of > 50%. They also tolerated 10% NaCl and 150 mg/kg of nitrite. They showed significant differences in ketone and acid production. The transcriptomic analysis of S. xylosus strains Sx3 and Sx6, which were selected because of their excellent enzymatic activities and aroma-producing ability, revealed the remarkable effect of genes related to pyruvate catabolism and amino acid metabolism on aroma generation. Therefore, this study provided valuable insights into the metabolic mechanisms underlying the technological properties of CNS and identified promising candidates as starter cultures in fermented sausage manufacturing.

内容: β-Amyloid (1-42) (Aβ42) can induce excessive activation of microglia, resulting in exacerbated neuroinflammation and neuronal damage. Milk fat globule-epidermal growth factor-8 (MFG-E8) is known to regulate Aβ42-induced neurotoxicity and inflammatory responses via multiple signaling pathways. However, insufficient secretion of endogenous MFG-E8 may lead to autoimmunity in the central nervous system and the accumulation of apoptotic cells. In this study, we systematically investigated the inhibitory effects and potential mechanisms of exogenously administered milk-derived MFG-E8 (M-MFG-E8) on Aβ42-induced inflammation in BV-2 microglia using various techniques, including cell morphology analysis, immunofluorescence staining, ELISA, qRT-PCR, and Western blot assays. The results demonstrated that Aβ42 significantly increased the expression levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in BV-2 microglia, whereas treatment with M-MFG-E8 effectively reversed these inflammatory responses. Furthermore, Aβ42 stimulation increased the secretion of pro-inflammatory cytokines (TNF-α, IL-1β) and the expression of the M1 marker cluster of differentiation 86 (CD86), while suppressing the anti-inflammatory factors (arginase-1 (Arg-1), interleukin-10 (IL-10)) and the M2 marker cluster of differentiation 206 (CD206) in microglia. In contrast, M-MFG-E8 treatment promoted the polarization of microglia from the M1 to the M2 phenotype. Notably, M-MFG-E8 also inhibited the Aβ42-induced upregulation of CD68, whereas M-MFG-E8 alone did not elicit this effect. Finally, our findings suggest that exogenous M-MFG-E8 may exert anti-inflammatory actions through the modulation of the NF-κB and PI3K/Akt pathways, providing new insights into neuronal cell repair and the development of functional foods.

内容: The present study investigated the potential therapeutic potential of Ficus carica polysaccharides (FCPS) in type 2 diabetic mellitus (T2DM) mice, focusing on elucidating the underlying molecular mechanisms. Network pharmacology analysis identified 37 shared targets between FCPS and T2DM, including perixisome proliferator activated receptor alpha (PPARα), highlighting the significance of PPAR signaling pathways in FCPS-mediated T2DM treatment. The results demonstrated that FCPS treatment significantly reduced markers of glucose and lipid metabolism (fasting blood glucose (FBG), nonestesterified fatty acid (NEFA), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C)), inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1)), and liver damage (glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT)) in T2DM mice. Additionally, FCPS ameliorated hepatic lipid droplet accumulation, fatty degeneration, and hepatocyte structural abnormalities. Western blot analysis confirmed FCPS-induced upregulation of key proteins in the IRS-1/AKT/PPARα signaling pathway, (insulin receptor substrate 1 (IRS-1), phosphatidyqinositol-3 kinase (PI3K), phospho-protein kinase B (p-AKT), glucose transporter 2 (GLUT2), phospho-glycogen synthase kinase 3 beta (p-GSK-3β), phospho-adenosine 5′-monophosphate-activated protein kinase alpha (p-AMPKα), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), PPARα, peroxisome proliferator-activated receptor gamma (PPARγ)) and downregulation of GSK-3β, sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). 16S rRNA sequencing results revealed FCPS's ability to modulate gut microbiota dysbiosis in T2DM mice by promoting beneficial bacteria (e.g., Lactobacillus_reuteri, Candidatus_Saccharimonas) and suppressing opportunistic pathogens (e.g., Proteobacteria, Gammaproteobacteria, Escherichia-Shigella). These findings collectively suggest that FCPS has a marked effectiveness in improving glucose and lipid metabolism, decreasing inflammatory responses, as well as modulating the gut microbiota in T2DM mice via the gut-hepatic axis, demonstrating its potential as a functional food for diabetes prevention and management.

内容: Epidemiological studies have indicated that branched-chain amino acids (BCAAs) increased and gut microbiota disordered in type 2 diabetes mellitus (T2DM). This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3 (Lp84-3) combined with Staphylococcus aureus bacteriophage on ameliorating T2DM. Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose (FBG). It revealed that Lp84-3 could inhibit the growth of S. aureus, and Lp84-3 contains BCAAs degradation enzymes in its genome. Furthermore, Lp84-3 alone or combined with S. aureus bacteriophage interventions can improve blood glucose, insulin resistance, triglycerides, interleukin-1β, tumor necrosis factor-α (TNF-α), BCAAs, and acetyllactate synthase (ALS) in db/db mice. Lp84-3 and S. aureus bacteriophage decreased S. aureus, Malacoplasma iowae, and Oscillibacter sp., and increased some beneficial such as L. plantarum and Muribaculaceae bacterium. Transcriptomic analyses revealed that Lp84-3 and S. aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22, Hgf, Col6a1, Gh, Itga10, Fgf23, and Prl involved in glucose metabolism in hypothalamus. Collectively, Lp84-3 and S. aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus, supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.

内容: Prenatal caffeine exposure (PCE) leads to intrauterine growth retardation and altered glucose homeostasis after birth, but the underlying mechanism remains unclear. This study aims to investigate the alteration of pancreatic development and insulin biosynthesis in the PCE female offspring and explore the intrauterine programming mechanism. Pregnant rats were orally treated with 120 mg/(kg∙day) of caffeine from gestational day (GD) 9 to 20. Results showed that fetal pancreatic β-cells in the PCE group exhibited reduced mass and impaired insulin synthesis function, as evidenced by decreased expression of developmental and functional genes and reduced pancreatic insulin content. At postnatal week (PW) 12, the PCE offspring exhibited glucose intolerance, diminished β-cell mass, and lower blood insulin levels. However, by PW28, glucose tolerance showed some improvement. Both in vivo and in vitro findings collectively indicated that excessive serum corticosterone (CORT) levels of the PCE fetuses may act through the activation of the pancreatic glucocorticoid receptor (GR) and recruitment of histone deacetylase 9 (HDAC9), leading to H3K9 deacetylation in promoter and downregulation of insulin-like growth factor 1 (IGF1), thereby inhibiting pancreatic islet morphogenesis and insulin synthesis in fetal rats. Furthermore, the PCE offspring after birth exhibited decreased blood CORT levels, increased H3K9 acetylation in promoter and upregulated gene expression of the pancreatic IGF1 promoter region, accompanied by elevated insulin biosynthesis. However, when exposed to chronic stress, the above changes were totally reversed. Conclusively, "glucocorticoid-insulin like growth factor 1 (GC-IGF1) axis" programming may be involved in pancreatic β-cell dysplasia and dysfunction in the PCE female offspring.