Phytochemical investigation of the leaves of Lansium domesticum (Meliaceae) resulted in the isolation of 10 glycosides, including three previously undescribed glycosides, designated as landomsides A-C (1-3). The structures of these glycosides were elucidated using extensive spectroscopic analyses (HRESIMS, 1D/2D NMR, and ECD data). All isolated glycosides were evaluated for their inhibitory effects on LPS-induced NO production in RAW264.7 macrophages. Glycosides 1-7 and 10 exhibited inhibitory activities, with IC50 values ranging from 19.36 ± 1.60 to 52.18 ± 2.21 μM. Among them, glycosides 1, 2, and 10 showed the strongest activities, with IC50 values of 19.36 ± 1.60, 20.06 ± 1.56, and 22.03 ± 1.81 μM, respectively. These compounds also inhibited TNF-α production, with glycoside 1 displaying the greatest activity (IC50 = 13.96 ± 1.19 μM), followed by glycosides 10 (IC50 = 19.82 ± 1.52 μM) and 2 (IC50 = 26.77 ± 1.64 μM). Integrated network pharmacology and molecular docking analyses suggested that the active glycosides may exert their anti-inflammatory effects through the modulation of multiple inflammation-related targets and signaling pathways, providing a plausible mechanistic basis for their observed anti-inflammatory activity.
H. Q. Nguyen, Hien Thi Tran, L. T. Thao et al.· Carbohydrate Research· 0 citations
BACKGROUND AND AIMS
Atherothrombotic cardiovascular disease (CVD) risk prediction in older adults remains suboptimal. The relative contributions of circulating protein biomarkers and polygenic scores (PGS) are uncertain.
METHODS
In 10,433 older individuals aged ≥70 years without prior CVD events, we evaluated traditional risk factors alongside three circulating biomarkers (high-sensitivity C-reactive protein, hsCRP; N-terminal pro-b-type natriuretic peptide, NT proBNP; and high-sensitivity troponin I, hsTnI), and two PGSs (coronary artery disease, ischemic stroke) for prediction of major adverse cardiovascular events (MACE). Associations were assessed using Cox proportional hazards models. Model performance was evaluated using the C-index, calibration, and continuous net reclassification improvement (NRI).
RESULTS
Over a median follow-up of 4.5 years (interquartile range 3.4-5.5), 359 MACE occurred. Each biomarker and both PGSs were independently associated with MACE, with NT-proBNP showing the strongest association (adjusted HR per SD 1.50, 95% CI 1.36-1.65). Compared with the base clinical model, the addition of the three circulating biomarkers (hsCRP, NT-proBNP, and hsTnI) resulted in a greater improvement in discrimination than the addition of the two PGSs (ΔC-index +0.041 vs. +0.016). The fully combined model achieved the highest discrimination (C-index 0.734) with good calibration. Circulating biomarkers improved reclassification primarily through correct identification of non-cases (NRI 0.34), whereas PGSs contributed relatively more to identification of cases (NRI 0.31).
CONCLUSIONS
In older adults, circulating biomarkers and PGSs provide cumulative information for CVD risk prediction, contributing differently to discrimination and risk reclassification. Integrating biomarkers and genetic risk may improve CVD risk prediction in older people beyond traditional risk factors.
Cheng-Long Yu, C. Tran, J. Neumann et al.· Atherosclerosis· 0 citations
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