利用 Verapamil 引發斑馬魚胚胎心衰竭模式並探討臨床心衰竭用藥 Dapagliflozin 和 Valsartan 之成效與機制
本研究利用 Verapamil 誘導斑馬魚胚胎心衰竭模式,並探討 Dapagliflozin 對斑馬魚胚胎表皮離子細胞的調控機制,以加深對 SGLT2 inhibitors 機制的了解。受精後第四天的斑馬魚在暴露於Verapamil 24小時後,除了抑制卵黃囊吸收以及造成心包膜水腫以外,對心臟整體功能(HR, EDV,ESV, SV, EF, CO)具負面影響。以粒線體染劑標記離子細胞,發現Verapamil使其密度上升,使用掃描式電子顯微鏡觀察,則可看到離子細胞頂端開口有明顯的萎縮,影響到正常功能。以抗體標記染色的方式檢測不同離子細胞亞型,顯示 Dapagliflozin 使富含 Na⁺-K⁺ ATPase 的 HR 細胞和富含 H⁺-ATPase 的 NaR 細胞密度上升。同時,心臟功能診斷標誌物的 mRNA 水平(naap, nppb,gata4, vmhc)暴露於Verapamil後上升,促進離子細胞代償性上調。
橡實代謝物與飛鼠小腸內生菌共發酵產物之應用
This study primarily investigates the components of food residues in the stomach of flying squirrels and the metabolism of the intestinal bacteria Floricoccus tropicus. Using nuclear magnetic resonance (NMR) hydrogen spectrum analysis, the signals of long-chain fatty acids were detected in both n-hexane and 75% ethanol extracts of flying squirrel gastric residues and acorns, suggesting that acorns may be a primary food source for the flying squirrels. The study also identified Floricoccus tropicus, one of the lactic acid bacteria, from the intestines of flying squirrels and discovered its role in the metabolism of fatty acids in acorns. Results showed that polyunsaturated fatty acids significantly decreased during fermentation, indicating that they were converted into short-chain fatty acids with anti-inflammatory properties. In the antibacterial activity experiments, the acorn grease showed no inhibitory effects before fermentation, but after fermentation, the acorn grease exhibited inhibitory effects against E. coli. Furthermore, in anti-inflammatory tests, fermented acorn grease samples significantly suppressed the production of NO and TNF-α in LPSinduced RAW 264.7 cells, with greater inhibition at higher concentrations. In conclusion, the lactic acid bacteria Floricoccus tropicus was found to metabolize fatty acids of acorns into compounds with antibacterial and anti-inflammatory effects.
Revolutionizing Metabolic Health: The Therapeutic Potential of Next-Generation Probiotic Akkermansia Strains (Z62, IR119) for Metabolic Syndromes
The human gut microbiome is integral to digestion, overall health, and metabolic disorder imbalances. Recent advancements in fecal microbiota transplantation (FMT) have highlighted the therapeutic promise of restoring healthy gut microbiota in populations with high incidences of diseases. Focusing on fecal DNA samples from healthy Asian individuals, this study examines the potential of novel Akkermansia strains, specifically Akkermansia muciniphila (Z62) and Akkermansia massiliensis (IR119), as next-generation probiotics for mitigating metabolic syndrome. A key aspect of the study is the investigation of short-chain fatty acids (SCFAs), which are produced and play a crucial role in regulating metabolic processes. SCFAs such as butyrate, acetate, and propionate are essential for energy provision to colon cells and exerting anti-inflammatory effects. The methodology involves selecting two Akkermansia strains, analyzing them through 16S rRNA and WGS, evaluating their growth and survival rates under acidic and bile-salt conditions, alongside their cell adhesion capabilities. The study focuses on the production of key short-chain fatty acids (SCFAs) and tryptophan derivatives by bacteria in regulating metabolic processes, as well as their anti-inflammatory effects on colon cells. Through in vitro assays, both strains exhibited survival in acidic/bile-rich conditions, though Z62 demonstrated superior adhesion to Caco-2 cells, suggesting a higher colonization potential. Metabolomic analysis revealed both strains produce SCFAs, including propionic and acetic acids, and indole metabolites, such as indole-3-propionic acid and indole-3-acetic acid, which are known to influence lipid metabolism and insulin sensitivity. In adipocyte cell models, IR119 significantly reduced lipid accumulation, while Z62 increased lipid presence. Furthermore, IR119 reduced pro-inflammatory cytokine levels, including IL-6 and TNF-α, suggesting potential for inflammation mitigation. The future potential of IR119 as a therapeutic probiotic is extraordinary in addressing complex metabolic and inflammatory diseases, which open new avenues for managing chronic inflammatory conditions like type 2 diabetes and cardiovascular disease. Future clinical trials could refine IR119’s efficacy, positioning it as a leading probiotic in preventive and therapeutic contexts.