Age related defect of the osteogenic differentiation of mesenchymal stem cells(MSCs) plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation....Age related defect of the osteogenic differentiation of mesenchymal stem cells(MSCs) plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species(ROS) production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1(SOD1) was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.展开更多
Photo-catalytic oxidation of intracellular nicotinamide adenine dinucleotide(2'-phosphate)(NAD(P)H)has attracted much attention for cancer therapy.However,the general oxygen-dependent mechanism heavily depresses t...Photo-catalytic oxidation of intracellular nicotinamide adenine dinucleotide(2'-phosphate)(NAD(P)H)has attracted much attention for cancer therapy.However,the general oxygen-dependent mechanism heavily depresses the efficacy in hypoxic tumors.To solve this problem,herein platinum nanoparticles(Pt NPs)with catalase-like(CAT-like)and catalytic H_(2)evolution activities were introduced as a powerful assistant to enhance the photo-catalytic NAD(P)H oxidation of Ru1([Ru(phen)2(PIP-OCH_(3))]^(2+),phen=1,10-phenanthroline,PIP-OCH_(3)=2-(4-methoxy phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline)under hypoxic and even oxygen-free conditions.Firstly,Pt NPs can transform the original and in situ formed H_(2)O_(2)once again into O_(2)by the CAT-like activity,thus relieving tumor hypoxia and realizing cyclic utilization(at least in part)of the precious oxygen in hypoxia.Secondly,Pt NPs can also be served as H_(2)evolution catalysts while using Ru1 as the photosensitizer and NAD(P)H as the electron and proton donor.In this process,NAD(P)H is oxidized without the participation of oxygen,which can provide an effective way even under oxygen-free conditions.Via co-encapsulation of Rul and Pt NPs in bovine serum albumin(BSA)with tumor targeting ability,the resultant Ru/Pt@BSA could photo-catalyze intracellular NAD(P)H oxidation under hypoxic conditions(3%O_(2)),and exhibited an efficient and selective anticancer activity both in vitro and in vivo.Our results may provide new sights for efficient and targeted cancer treatment underhypoxic conditions.展开更多
基金financially supported by National Natural Science Foundation of China (81100240)‘985’ project of Sun Yat-Sen University grant+2 种基金Sun Yat-Sen university young teachers training project (13YKPY42)Natural Science Foundation of Guangdong Province,China(S2012010009495)Science and Technology Planning Project of Guangdong Province,China(2012B031800185)
文摘Age related defect of the osteogenic differentiation of mesenchymal stem cells(MSCs) plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species(ROS) production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1(SOD1) was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.
基金financially supported by Research Equipment Development Project of Chinese Academy of Sciences(No.YJKYYQ20210014).
文摘Photo-catalytic oxidation of intracellular nicotinamide adenine dinucleotide(2'-phosphate)(NAD(P)H)has attracted much attention for cancer therapy.However,the general oxygen-dependent mechanism heavily depresses the efficacy in hypoxic tumors.To solve this problem,herein platinum nanoparticles(Pt NPs)with catalase-like(CAT-like)and catalytic H_(2)evolution activities were introduced as a powerful assistant to enhance the photo-catalytic NAD(P)H oxidation of Ru1([Ru(phen)2(PIP-OCH_(3))]^(2+),phen=1,10-phenanthroline,PIP-OCH_(3)=2-(4-methoxy phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline)under hypoxic and even oxygen-free conditions.Firstly,Pt NPs can transform the original and in situ formed H_(2)O_(2)once again into O_(2)by the CAT-like activity,thus relieving tumor hypoxia and realizing cyclic utilization(at least in part)of the precious oxygen in hypoxia.Secondly,Pt NPs can also be served as H_(2)evolution catalysts while using Ru1 as the photosensitizer and NAD(P)H as the electron and proton donor.In this process,NAD(P)H is oxidized without the participation of oxygen,which can provide an effective way even under oxygen-free conditions.Via co-encapsulation of Rul and Pt NPs in bovine serum albumin(BSA)with tumor targeting ability,the resultant Ru/Pt@BSA could photo-catalyze intracellular NAD(P)H oxidation under hypoxic conditions(3%O_(2)),and exhibited an efficient and selective anticancer activity both in vitro and in vivo.Our results may provide new sights for efficient and targeted cancer treatment underhypoxic conditions.