BMB Reports最新文献

Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway. [BMB Reports 2024; 57(5): 244-249].

The gut microbiota, an intricate community of bacteria residing in the gastrointestinal system, assumes a pivotal role in various physiological processes. Beyond its function in food breakdown and nutrient absorption, gut microbiota exerts a profound influence on immune and metabolic modulation by producing diverse gut microbiota-generated metabolites (GMGMs). These small molecules hold potential to impact host health via multiple pathways, which exhibit remarkable diversity, and have gained increasing attention in recent studies. Here, we elucidate the intricate implications and significant impacts of four specific metabolites, Urolithin A (UA), equol, Trimethylamine N-oxide (TMAO), and imidazole propionate, in shaping human health. Meanwhile, we also look into the advanced research on GMGMs, which demonstrate promising curative effects and hold great potential for further clinical therapies. Notably, the emergence of positive outcomes from clinical trials involving GMGMs, typified by UA, emphasizes their promising prospects in the pursuit of improved health and longevity. Collectively, the multifaceted impacts of GMGMs present intriguing avenues for future research and therapeutic interventions. [BMB Reports 2024; 57(5): 207-215].

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into endothelial cells in an inflammatory microenvironment. However, the regulatory mechanisms underlying this process are not entirely understood. Here, we found that TIE2 in BM-MSCs was upregulated at the transcriptional level after stimulation with tumor necrosis factor-alpha (TNFα), a major pro-inflammatory cytokine. Additionally, the STAT-binding sequence within the proximal region of TIE2 was necessary for TNFα-induced TIE2 promoter activation. TIE2 and STAT3 knockdown reduced TNFα-induced endothelial tube formation in BMMSCs. Among the major TNFα-activated MAP kinases (ERK1/2, JNK1/2, and p38 MAPK) in BM-MSCs, only inhibition of the p38 kinase abrogated TNFα-induced TIE2 upregulation by inhibiting the JAK-STAT signaling pathway. These findings suggest that p38 MAP contributes to the endothelial differentiation of BM-MSCs by activating the JAK-STAT-TIE2 signaling axis in the inflammatory microenvironment. [BMB Reports 2024; 57(5): 238-243].