The mitochondria are essential organelles that generate large amounts of ATP via the electron transport chain (ECT). Mitochondrial dysfunction causes reactive oxygen species accumulation, energy stress, and cell death. Endothelial mitochondrial dysfunction is an important factor causing abnormal function of the endothelium, which plays a central role during atherosclerosis development. Atherosclerosis-related risk factors, including high glucose levels, hypertension, ischemia, hypoxia, and diabetes, promote mitochondrial dysfunction in endothelial cells. This review summarizes the physiological and pathophysiological roles of endothelial mitochondria in endothelial function and atherosclerosis.
Iron is indispensable in numerous biologic processes, but abnormal iron regulation and accumulation is related to pathological processes in cardiovascular diseases. However, the underlying mechanisms still need to be further explored. Iron plays a key role in metal-catalyzed oxidative reactions that generate reactive oxygen species (ROS), which can cause oxidative stress. As the center for oxygen and iron utilization, mitochondria are vulnerable to damage from iron-induced oxidative stress and participate in processes involved in iron-related damage in cardiovascular disease, although the mechanism remains unclear. In this review, the pathological roles of iron-related oxidative stress in cardiovascular diseases are summarized, and the potential effects and mechanisms of mitochondrial iron homeostasis and dysfunction in these diseases are especially highlighted.
The aim was to identify the risk factors of long-term vascular access complications. The study cohort consisted of 239 incident hemodialysis (HD) patients from 1998 to 2010 in a single center. Among these patients, 59.8% had initially been dialyzing with a temporary catheter. Within 3 months after starting dialysis, all catheters had been converted into permanent accesses. 45 patients incurred long-term access complications after the first 2 years of dialysis, and 34 (75.6%) had used a temporary catheter starting HD. Complication occurrence was associated with age, initiation dialysis with a catheter and heart failure by logistic regression (odds ratios were 1.04, 2.77 and 2.23, respectively; p < 0.05). The 2-year primary patency rates of arteriovenous fistulae were significantly higher than those of arteriovenous grafts (79.5 vs. 50%, p = 0.002). We concluded that age, using a catheter and heart failure in HD initiation had a strong impact on long-term access complications.
The health benefits of Dracocephalum heterophyllum are widely reported in traditional Tibetan medicines, but the reported chemical composition is limited, probably due to difficulties in separating and purifying compounds. In this study, antioxidative phenylethanoids were isolated from an extract of Dracocephalum heterophyllum using medium- and high-pressure liquid chromatography, coupled with on-line HPLC–1,1-diphenyl-2-picrylhydrazyl recognition. Firstly, crude samples (1.3 kg) of Dracocephalum heterophyllum were pretreated via silica gel medium-pressure liquid chromatography to yield 994.0 g of Fr2, of which 10.8 g was then pretreated via MCI GEL®CHP20P medium-pressure liquid chromatography. The resulting Fr23 and Fr25 were further separated and purified using high-pressure liquid chromatography, and yielded 8.08 mg of Fr2391, 9.76 mg of Fr2551, 16.09 mg of Fr2581, and 8.75 mg of Fr2582. Furthermore, analysis of the purity and structures of the phenylethanoids suggested that Fr2391, Fr2551, Fr2581, and Fr2582 corresponded to decaffeoylverbascoside, rosmarinic acid, acteoside, and 2′-O-acetylplantamajoside, respectively, with all being over 95% pure. Finally, the antioxidant potential of the compounds was explored based on their ability to scavenge 1,1-diphenyl-2-picrylhydrazine, as well as through molecular docking of proteins related to antioxidant pathways. Altogether, our findings revealed that the proposed method is promising for separating pure antioxidative phenylethanoids from other natural compounds.
In this study, a 100 g sample of Saxifraga atrata was processed to separate 1.3 g of 11-O-(4′-O-methylgalloyl)-bergenin (Fr1) after 1 cycle of MCI GEL® CHP20P medium pressure liquid chromatography using methanol/water. Subsequently, COX-2 affinity ultrafiltration coupled with reversed-phase liquid chromatography was successfully used to screen for potential COX-2 ligands in this target fraction (Fr1). After 20 reversed-phase liquid chromatography runs, 74.1 mg of >99% pure 11-O-(4′-O-methylgalloyl)-bergenin (Fr11) was obtained. In addition, the anti-inflammatory activity of 11-O-(4′-O-methylgalloyl)-bergenin was further validated through molecular docking analyses which suggested it was capable of binding strongly to ALOX15, iNOS, ERBB2, SELE, and NF-κB. As such, the AA metabolism, MAPK, and NF-κB signaling pathways were hypothesized to be the main pathways through which 11-O-(4′-O-methylgalloyl)-bergenin regulates inflammatory responses, potentially functioning by reducing pro-inflammatory cytokine production, blocking pro-inflammatory factor binding to cognate receptors and inhibiting the expression of key proteins. In summary, affinity ultrafiltration-HPLC coupling technology can rapidly screen for multi-target bioactive components and when combined with molecular docking analyses, this approach can further elucidate the pharmacological mechanisms of action for these compounds, providing valuable information to guide the further development of new multi-target drugs derived from natural products.
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