內(nèi)容: Atherosclerosis remains a great threat to human health worldwide. Previous studies found that tetramethylpyrazine (TMP) and paeoniflorin (PF) combination (TMP-PF) exerts anti-atherosclerotic effects in vitro. However, whether TMP-PF improves atherosclerosis in vivo needs further exploration. The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE-/- mice and explore the related molecule mechanisms. Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels, suppressed vascular endothelial growth factor receptor 2 (VEGFR2) and nuclear receptor subfamily 4 group A member 1 (NR4A1) expression in aortic tissues, inhibited plaque angiogenesis, reduced plaque areas, and alleviated atherosclerosis in ApoE-/- mice. Also, TMP-PF exhibited a better modulation effect than TMP or PF alone. However, NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF. In conclusion, TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway, indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

內(nèi)容: Trastuzumab resistance is one of the causes of poor prognosis in patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer (BC). The truncated isoform of dopamine- and cAMP-regulated phosphoprotein (t-DARPP) has been reported to be involved in trastuzumab therapy resistance and promoting tumor progression. To evaluate the t-DARPP expression in BC, paired tumors and surrounding normal tissues were analyzed by real-time polymerase chain reaction and confirmed higher DARPP-32 kDa family mRNA expression in HER2+ BC tumor tissues. We established 2 patient-derived xenografts (PDX) mice models to test the efficacy of trastuzumab, named model 1 (non-responder) and model 2 (responder). t-DARPP and p95-HER2 protein-protein interactions were detected in PDX tumor tissue from non-responders using F?rster resonance energy transfer assays. Instead, there is no response from the responder. Furthermore, mechanistic studies using transwell and western blot assays demonstrated that t-DARPP could upregulate epithelial-mesenchymal transition signaling proteins, enhance p95-HER2 expression and promote cell migration. We found that quercetin effectively reduced t-DARPP expression in HER2+ BC cells. In t-DARPP ShRNA-suppressed cells, quercetin synergistically enhanced trastuzumab-induced apoptotic cell death and G2/M phase arrest. In conclusion, the combination of quercetin and trastuzumab treatment by targeting t-DARPP in HER2+ BC patients has the potential as a biomarker for mitigating drug resistance.

內(nèi)容: This cohort study was designed to explore the relationship between maternal dietary patterns (DPs) and bone health in Chinese lactating mothers and infants. We recruited 150 lactating women at 1-month postpartum. The estimated bone mineral density (eBMD) of subjects’ calcanei and the information on dietary intake were collected. After 5-month follow-up, the eBMD of mothers and their infants were measured again. Factor analysis was applied to determine maternal DPs. General linear models were used to evaluate the association between maternal DPs and maternal eBMD loss or infants’ eBMD. With all potential covariates adjusted, Factor 2 (high intake of whole grains, tubers, mixed beans, soybeans and soybean products, seaweeds, and nuts) showed a positive association with the changes of maternal eBMD (β = 0.16, 95% CI: 0.005, 0.310). Factor 3 (high intake of soft drinks, fried foods, and puffed foods) was inversely correlated with the changes of maternal eBMD (β = -0. 22, 95% CI: -0.44, 0.00). The changes of maternal eBMD were positively associated with 6-month infants’ eBMD (β = 0.34, 95% CI: 0.017, 0.652). In conclusion, Factor 2 might contribute to the maintenance of eBMD in lactating women, while Factor 3 could exacerbate maternal eBMD loss. Additionally, the changes of maternal eBMD presented a positive correlation with 6-month infants’ eBMD.

內(nèi)容: Akkermansia muciniphila is one of the commensals residing within the mammalian gut and co-evolving with the host. Numerous studies have demonstrated the benefits of A. muciniphila in ameliorating metabolic disorders, while little is known about the antimicrobial potential of A. muciniphila against pathogens. Here, we examined the antimicrobial and anti-virulence properties of cell free supernatant (CFS) of A. muciniphila against Salmonella Typhimurium. CFS retarded bacterial growth and inhibited the motility of S. Typhimurium SL1344 and S. Typhimurium 14028. CFS dose-dependently reduced cell hydrophobicity and auto-aggregation of both strains. Also, CFS from A. muciniphila significantly attenuated biofilm formation. Compared with untreated bacteria, CFS-treated bacteria significantly decreased adhesion and invasion to Caco-2 cells, and reduced intracellular survival in macrophages. CFS maintained antimicrobial properties after treatment with high temperatures and various proteases, while it lost its antimicrobial activity after pH neutralization. Gas chromatography-mass spectrometry (GC-MS) confirmed that A. muciniphila produced a certain amount of acetate and propionate, and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) identified other organic acids and metabolites in CFS. In summary, CFS from A. muciniphila exhibited anti-biofilm and anti-virulence properties against Salmonella and could be potentially utilized in the food industry for controlling Salmonella contamination and reducing infection.

內(nèi)容: Conventional filling therapy fails to fundamentally reduce oral cariogenic bacteria. Thus, oral microbiota follow-up intervention after filling would be necessary for improving dental caries prognosis. We recruited 9 caries-free individuals, and 89 dental caries subjects (5 dropouts). Eighty-nine patients were randomized into three groups: caries (n = 8; no treatment), control (n = 40; filling), and postbiotics (n = 41; filling and 14-day Probio-Eco? intervention). Salivary samples were collected at 0 day (after filling) and 14 days. Our results showed that the diversity of dental caries oral microbiota was significantly increased compared with healthy subjects, and filling could restore a healthier oral microbiota partially and temporarily. Thepostbiotics intervention keeps a low alpha-diversity. Co-occurrence network analysis showed that a more stable oral microbiota structure after postbiotics intervention. Taxonomic and functional annotation of the microbiota revealed that postbiotics co-treatment significantly: increased the relative abundance of Pseudomonas and P. reactans, decreased the relative abundance of Prevotella shahii, and enriched the energy metabolism-related pathways. BugBase-predicted phenotypes inferred to an oral microbiota with decreased potential pathogenic bacteria and increased oxidative stress-tolerant bacteria after postbiotics intervention. Collectively, it suggested that postbiotics co-treatment could be a promising strategy that restores the oral microecological balance for dental caries.

內(nèi)容: Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide. Bupleurum is widely used in the treatment of non-alcoholic fatty liver, and saikosaponin D (SSD) is one of the main active components of Bupleurum. The purpose of this study was to investigate the efficacy of SSD in the treatment of NAFLD and to explore the mechanism of SSD in the improvement of NAFLD based on “gut-liver axis”. Our results showed that SSD dose-dependently alleviated high fat diet-induced weight gain in mice, improved insulin sensitivity, and also reduced liver lipid accumulation and injury-related biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Further exploration found that SSD inhibited the mRNA expression levels of farnesoid X receptor (Fxr), small heterodimer partner (Shp), recombinant fibroblast growth factor 15 (Fgf15) and apical sodium dependent bile acid transporter (Asbt) in the intestine, suggesting that SSD improved liver lipid metabolism by inhibiting intestinal FXR signaling. SSD can significantly reduce the gut microbiota associated with bile salt hydrolase (BSH) expression, such as Clostridium. Decreased BSH expression reduced the ratio of unconjugated to conjugated bile acids, thereby inhibiting the intestinal FXR. These data demonstrated that SSD ameliorated NAFLD potentially through the gut microbiota-bile acid-intestinal FXR pathway and suggested that SSD is a promising therapeutic agent for the treatment of NAFLD.

內(nèi)容: Chinese yam (Dioscorea opposita Thunb.), as one of the medicinal and edible homologous plants, is rich in various nutrients and functional factors. In this study, Chinese yam fermented by Saccharomyces boulardii was performed to investigate its bioactive components and metabolic profile. And then, the main bioactive components and biological activities of fermented Chinese yam ethanol extract (FCYE) were evaluated. Results showed that there were 49 up-regulated metabolites and 52 down-regulated metabolites in fermented Chinese yam compared to unfermented Chinese yam. Besides, corresponding metabolic pathways analysis initially revealed that the distribution of bioactive substances was concentrated on alcohol-soluble small molecular substances. Ulteriorly, the total polyphenol content and the total flavonoid content in FCYE were significantly increased, and the corresponding antioxidant and immunomodulatory activities in vitro were also significantly enhanced. Our study provided a new reference for the comprehensive utilization of Chinese yam and laid a theoretical foundation for the development and application of natural probiotic-fermented products.

內(nèi)容: Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health. However, to date, no approved therapeutic drugs have been developed. Dietary interventions with natural products have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompound with antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN can ameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying these beneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipid accumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis (NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line and the liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type and the regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophage M2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovered a new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFN might be protective against NASH.

內(nèi)容: This study investigated the effects of a xylitol-casein non-covalent complex (XC) on parameters related to type 2 diabetes mellitus (T2DM), in addition to related changes in gut microbiome composition and functions. High-fat-diet (HFD) + streptozotocin (STZ)-induced T2DM mice were treated with xylitol (XY), casein (CN), and XC, after which fecal samples were collected for gut microbiota composition and diversity analyses based on 16S rRNA high-throughput sequencing and multivariate statistics. XC decreased body weight and improved glucose tolerance, insulin sensitivity, pancreas impairment, blood lipid levels, and liver function in T2DM mice compared to XY- and CN-treated mice. Furthermore, XC modulated the α-diversity, β-diversity and gut microbiota composition. Based on Spearman’s correlation analysis, the relative abundances of Alistipes, Bacteroides, and Faecalibaculum were positively correlated and those of Akkermansia, Lactobacillus, Bifidobacterium, and Turicibacter were negatively correlated with the phenotypes related to the improvement of T2DM. In conclusion, we found that XC alleviated insulin resistance by restoring the gut microbiota of T2DM mice. Our results provide strong evidence for the beneficial effects of XC on T2DM and motivation for further investigation in animal models and, eventually, human trials.

內(nèi)容: A novel and reactive oxygen species (ROS) responsive astaxanthin phenylboronic acid derivative (AstaD-PBA) was constructed by grafting phenylboronic acid (PBA) onto astaxanthin succinate diester (AstaD), and its chemical structure and physicochemical property were identified. AstaD-PBA could effectively improve the ROS quenching ability in the lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model. Then, the bioactivity of AstaD-PBA was studied by 4 zebrafish ROS-responsive inflammatory models induced by LPS, copper (Cu2+), high-fat diet, and dextran sodium sulfate (DSS). The results suggest that AstaD-PBA might have high biosafety and the best effect on ulcerative colitis (UC) induced by DSS. Furtherly, AstaD-PBA significantly alleviated and treated weight loss and colonic shrinkage, inhibited inflammatory cytokines, and maintained microbiota homeostasis to improve UC in C57BL/6J mice. Alistipes and Oscillibacter were expected to be considered UC marker flora according to the Metastats analysis and Pearson correlation Mantel test (P < 0.01) of 16S rRNA gene sequencing data. In conclusion, AstaD-PBA has been promised to be a functional compound to improve UC and maintain intestinal microbiota homeostasis.