Anti-Inflammatory and Proangiogenic Metabolites from the Hadal Trench-Derived Fungus Acremonium dichromosporum YP-213.

Four new compounds, including two ascochlorin-type meroterpenoids acremocholrins A (1) and B (2), one pyridone alkaloid acremopyridone A (7), and one cyclopentenone derivative acremoketene A (12), together with eight known compounds (3-6 and 8-11), were isolated and identified from the hadal trench-derived fungus Acremonium dichromosporum YP-213. Their structures were determined with a detailed spectroscopic analysis of NMR and MS data, NOE analysis, octant rule and quantum chemical calculations of ECD, and NMR (with DP4+ probability analysis). Among the compounds, 7 represent a novel scaffold derived from a pyridone alkaloid by cleavage of the C-16-C-17 bond following oxidation to give a ketone. Compounds 9, 11, and 12 showed potent in vivo anti-inflammatory activity in transgenic zebrafish, while compound 8 exhibited significant proangiogenic activity in transgenic zebrafish.

Endothelial injury and inflammation in patients with hyperuricemic nephropathy at chronic kidney disease stages 1-2 and 3-4.

BACKGROUND: Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy (HN); however, they have not been assessed in patients in the early, middle, and late phases of HN. AIM: To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease (CKD) stages 3-4 and CKD 1-2. METHODS: This study enrolled 80 patients (49 and 31 with HN at CKD stage 1-2 and 3-4, respectively) from the Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022. Plasma levels of heparan sulfate, endocan, oxidized low-density lipoprotein (Ox-LDL), E-selectin, soluble intercellular adhesion molecule-1 (slCAM1), interleukin (IL)-1ß, and IL-6 and urine levels of lipocalin-type prostaglandin D synthase (L-PGDS), IL-1ß, and IL-6 were measured using enzyme-linked immunosorbnent assay. RESULTS: Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors (P < 0.001 and P < 0.010, respectively). There were no statistical differences in sex, heart rate, body mass index, and systolic and diastolic blood pressures. The incidence of hypertension was also significant (P = 0.03). Plasma levels of heparin sulfate (P < 0.001), endocan (P = 0.034), E-selectin (P < 0.001), slCAM1 (P < 0.001), IL-1ß (P = 0.006), and IL-6 (P = 0.004) and the urine levels of L-PGDS (P < 0.001), IL-1ß (P = 0.003), and IL-6 (P < 0.001) were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2. The difference in plasma Ox-LDL levels was not significant (P = 0.078). CONCLUSION: Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2. Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.