Design and semisynthesis of oleanolic acid derivatives as VEGF inhibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs / 中国天然药物

Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,β-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.

Coronary angiography or not after cardiac arrest without ST segment elevation: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to review the available evidence and evaluate the necessity of immediate coronary angiography (CAG) to obtain positive outcomes for out-of-hospital cardiac arrest (OHCA) patients without ST segment elevation. DATA SOURCES: Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases. STUDY SELECTION: We included observational and case-control studies of outcomes among individuals without ST segment elevation experiencing OHCA who had immediate, delayed, or no CAG. DATA EXTRACTION: We extracted study details, as well as patient characteristics and outcomes. DATA SYNTHESIS: Six studies (n = 2665) investigating mortality until discharge demonstrated a significant increase in survival benefit with early CAG (odds ratio [OR] = 1.78; 95%CI = 1.51-2.11; I = 81%; P < .0001). Seven studies (n = 2909) showed a significant preservation of neurological functions with early CAG at discharge (OR = 1.66; 95%CI = 1.37-2.02; P < .00001). Four studies (n = 1357) investigating survival outcomes with middle-term follow-up revealed no significant benefit with early CAG (OR = 1.21; 95%CI = 0.93-1.57; I = 66%; P = .15). CONCLUSIONS: Our meta-analysis demonstrates that there may be significant benefits in performing immediate CAG on patients who experience OHCA without ST segment elevation.