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
Different amounts of vitamin C were added to diets fed to juveniles （2.5＋0.15 g） of sea cucumber Apostichopus japonicus （Selenka） in an attempt to reduce the stress response of specimens exposed to nitrite stress...Different amounts of vitamin C were added to diets fed to juveniles （2.5＋0.15 g） of sea cucumber Apostichopus japonicus （Selenka） in an attempt to reduce the stress response of specimens exposed to nitrite stress. A commercial feed was used as the control diet and three experimental diets were made by supplementing 1 000, 1 500, or 2 000 mg vitamin C/kg diet to control diet separately in a 45-day experiment. Sea cucumbers were exposed to three different levels （0.5, 1.0, and 1.5 mg/L） of nitrite stress for 4, 8, and 12 h at four time intervals （0, 15, 30, and 45 d）. Growth of the animals was recorded during the experiment. Reactive oxygen species （ROS） （i.e. hydroxyl free radical （-OH）, malondialdehyde （MDA） and total antioxidant capacity （T-AOC）） and antioxidant enzyme activities （i.e., superoxide dismutase （SOD） and eatalase （CAT）） were measured. Response surface methodology （RSM） was used to analyze the effect of multiple factors on ROS indices and enzyme activities. Weight gain （WG） and special growth rate （SGR） of vitamin C supplementation groups were significantly higher than those of control group （P〈0.05）. The levels of-OH and MDA increased under exposure time extending and nitrite concentration increasing, whereas T-AOC level decreased. SOD and CAT activities increased at 4 h and 8 h and decreased at 12 h. During the days in which the animal consumed experimental diets, the levels of-OH and MDA decreased and that of T-AOC increased. This result suggests that diets containing vitamin C could reduce the nitrite stress response in the animals and increase their antioxidant capacity. The multifactor regression equation of growth performance, ROS indices, and duration of feeding results suggest that vitamin C supplementation of 1 400-2 000 mg/kg diet for 29-35 days could reduce effectively the effects of nitrite exposure.展开更多
Transcription factors(TFs)regulate diverse stress defensive-associated physiological processes and plant stress responses.We characterized TaNF-YB11,a gene of the NF-YB TF family in Triticum aestivum,in mediating plan...Transcription factors(TFs)regulate diverse stress defensive-associated physiological processes and plant stress responses.We characterized TaNF-YB11,a gene of the NF-YB TF family in Triticum aestivum,in mediating plant drought tolerance.TaNF-YB11 harbors the conserved domains specified by its NF-YB partners and targets the nucleus after the endoplasmic reticulum(ER)assortment.Yeast two-hybrid assay indicated the interactions of TaNF-YB11 with TaNF-YA2 and TaNF-YC3,two proteins encoded by genes in the NF-YA and NF-YC families,respectively.These results suggested that the heterotrimer established among them further regulated downstream genes at the transcriptional level.The transcripts of TaNF-YB11 were promoted in roots and leaves under a 27-h drought regime.Moreover,its upregulated expression levels under drought were gradually restored following a recovery treatment,suggesting its involvement in plant drought response.TaNF-YB11 conferred improved drought tolerance on plants;the lines overexpressing target gene displayed improved phenotype and biomass compared with wild type(WT)under drought treatments due to enhancement of stomata closing,osmolyte accumulation,and cellular reactive oxygen species(ROS)homeostasis.Knockdown expression of TaP5CS2,a P5CS family gene modulating proline biosynthesis that showed upregulated expression in drought-challenged TaNF-YB11 lines,alleviated proline accumulation of plants treated by drought.Likewise,TaSOD2 and TaCAT3,two genes encoding superoxide dismutase(SOD)and catalase(CAT)that were upregulated underlying TaNF-YB11 regulation,played critical roles in ROS homeostasis via regulating SOD and CAT activities.RNA-seq analysis revealed that numerous genes associated with processes of‘cellular processes',‘environmental information processing',‘genetic information processing',‘metabolism',and‘organismal systems'modified transcription under drought underlying control of TaNF-YB11.These results suggested that the TaNF-YB11-mediated drought response is possibly accomplished through the target gene in modifying gene transcription at the global level,which modulates complicated biological processes related to drought response.TaNF-YB11 is essential in plant drought adaptation and a valuable target for molecular breeding of drought-tolerant cultivars in T.aestivum.展开更多
Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species （ROS） and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of t...Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species （ROS） and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of these chemotherapeutics is due to induction of oxidative stress and ROS-mediated apoptosis in cancer. On the other hand, the harmful side effects of conventional anticancer chemotherapy are also due to increased production of ROS and disruption of redox-homeostasis of normal cells and tissues. This article describes the mechanisms for triggering and modulation of apoptosis through ROS-dependent and ROS^independent pathways. We try to answer the question： ＂Is it possible to induce highly specific apoptosis only in cancer cells, without overproduction of ROS, as well as without harmful effects on normal cells and tissues？＂ The review also suggests a new therapeutic strategy for selective killing of cancer cells, without significant impact on viability of normal cells and tissues, by combining anticancer drugs with redox-modulators, affecting specific signaling pathways and avoiding oxidative stress.展开更多
Cancer cells utilize cytosolic glycolysis for their energy production even in the presence of adequate levels of oxygen (Warbug effect) due to mitochondrial defects. Dichloroacetic acid (DCA) shifts cytosolic glucose ...Cancer cells utilize cytosolic glycolysis for their energy production even in the presence of adequate levels of oxygen (Warbug effect) due to mitochondrial defects. Dichloroacetic acid (DCA) shifts cytosolic glucose metabolism to aerobic oxidation by inhibiting mitochondrial pyruvate dehydrogenase kinase (PDK) and increasing pyruvate uptake. Therefore, DCA has potential in reversing the glycolytic metabolism defect in cancerous cells. DCA is also known to induce apoptosis in a number of cancer cell lines, the mechanism of which is not well understood. In this study, an attempt has been made to investigate the effects of DCA on aggressive human breast cancer (MCF-7) cells as compared with less aggressive mouse osteoblastic (MC3T3) cells. Cell cytotoxicity was determined by MTT, crystal violet and Trypan blue exclusion assays. Western blot was used to detect any changes in the expression of apoptotic markers. Flow cytometry was used to measure apoptotic and necrotic effects of DCA. Mitochondrial integrity was determined by change in mitochondrial membrane potential (Δψm), whereas oxidative damage was determined by production of reactive oxygen species (ROS). DCA caused a concentration-dependent cytotoxicity both in MCF-7 and MC3T3 cell lines. MCF-7 cells were most affected. Flow cytometry results showed a significantly higher apoptosis in MCF-7 even at lower concentrations of DCA. However, higher concentrations of DCA were necrotic. Western blotting showed an increased expression of Mn-SOD-1 upon DCA treatment. Further, DCA decreased Δψm and increased ROS production. The effects of DCA were more pronounced on MCF-7 cells as compared to MC3T3 cells. Our results suggest that DCA-induced cytotoxicity in cancerous cells is mediated via changes in Δψm and production of ROS.展开更多
Objective: To evaluate the anti-tumor effects of SeO2 and its mechanisms on three human lung cancer cell lines. Methods: Three lung cancer cells A549, GLC-82 and PG were treated with 3-30 μmol/L SeO2. Flow cytometry ...Objective: To evaluate the anti-tumor effects of SeO2 and its mechanisms on three human lung cancer cell lines. Methods: Three lung cancer cells A549, GLC-82 and PG were treated with 3-30 μmol/L SeO2. Flow cytometry was used to detect apoptosis, and analyze the changes of expression of p53 and Bcl-2, as well as ROS and Ca2+ level within cells. Results:SeO2 markedly inhibited cell proliferation and viability, and prompted apoptosis after 48 h treatment. SeO2 at 10 μmol/L induced 47.8% apoptosis in A549 cells, 40.8% in GLC-82 cells, 18.2% in PG cells. SeO2 at 30 μmol/L induced 37.8% apoposis in PG cells,but did not increase apoptotic raes in other two cells. SeO2 could down-regulate the mean fluorescent intensity of Bcl-2 from 65.8 to 9.6 in A549, but not in GLC-82 and in PG cells, up-regulate wild type p53 level in all three cells. SeO2 decreased the ROS and Ca2+ level markedly within three tested cells. Conclusion: SeO2 showed anti-tumor effect via apoptosis pathway in three lung cancer cell lines. The decrease of ROS and Ca2+ level within cells as well as regulation of Bcl-2 and p53 expression may play important roles in above apoptotic procedure.展开更多
The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs ...The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.展开更多
Double staining flow cytometry was performed using 7-amino actinomycin D and 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate,to detect the level fluctuation of reactive oxygen species (ROS) during the cel...Double staining flow cytometry was performed using 7-amino actinomycin D and 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate,to detect the level fluctuation of reactive oxygen species (ROS) during the cell cycle of normal NB4 cells. Our results showed that NB4 cells possessed higher level of ROS in G2/M phase than in G1 and S phases. Double staining flow cytometry,with TdT mediated dUTP nick end labeling (Tunel) and propidium iodide (PI),indicated that As2O3 (2 μM) could induce apoptosis in NB4 cells prevailingly from G2/M phase,and this efficacy was enhanced upon co-administration of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) (2.5 μM) which could produce the endogenous ROS. These results suggested that different ROS level in different cell cycle phases of NB4 cells might determin the selective induction of G2/M apoptosis and the cells' susceptibility to apoptosis by As2O3.展开更多
Titania (TiO2) induced photocatalysis has been widely investigated and applied as a disinfection strategy in many industrial and clinical applications. Reactive oxygen species (ROS), including hydroxyl radicals (&...Titania (TiO2) induced photocatalysis has been widely investigated and applied as a disinfection strategy in many industrial and clinical applications. Reactive oxygen species (ROS), including hydroxyl radicals (&8226OH), superoxide radicals () and hydrogen peroxide (H2O2), generated in the photocatalytic reaction process are considered to be the active components prompting the bactericidal effect. In the present work, the kinetics of photocatalytic inactivation of Staphylococcus epidermidis and specific contributions of •OH, and H2O2 to the bactericidal process were studied using two disinfection settings sutilizing photocatalytic resin-TiO2 nanocomposite surfaces and suspended TiO2 nanoparticles, respectively. In antibacterial tests against S. epidermidis with a layer of bacterial suspension on the resin-TiO2 surfaces, H2O2 was found to be the most efficient ROS component contributing to the antibacterial effect. Disinfection kinetics showed a two-step behavior with an initial region having a lower disinfection rate followed by a higher rate region after 10 min of UV irradiation. By contrast, in antibacterial tests with suspended bacteria and photocatalytic TiO2 nanoparticles, •OH and H2O2 showed equal significance in the bacterial inactivation having a typical Chick-Watson disinfection kinetics behavior with a steady disinfection rate. The results contribute to the understanding of the bactericidal mechanism and kinetics of photocatalytic disinfection that are essential for designing specific antibacterial applications of photocatalytic materials.展开更多
Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shel...Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.展开更多
Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,m...Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(Ros)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.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Supported by the Main Direction Program of Knowledge Innovation of Chinese Academy of Sciences(No.KZCX2-EWQ215)
文摘Different amounts of vitamin C were added to diets fed to juveniles （2.5＋0.15 g） of sea cucumber Apostichopus japonicus （Selenka） in an attempt to reduce the stress response of specimens exposed to nitrite stress. A commercial feed was used as the control diet and three experimental diets were made by supplementing 1 000, 1 500, or 2 000 mg vitamin C/kg diet to control diet separately in a 45-day experiment. Sea cucumbers were exposed to three different levels （0.5, 1.0, and 1.5 mg/L） of nitrite stress for 4, 8, and 12 h at four time intervals （0, 15, 30, and 45 d）. Growth of the animals was recorded during the experiment. Reactive oxygen species （ROS） （i.e. hydroxyl free radical （-OH）, malondialdehyde （MDA） and total antioxidant capacity （T-AOC）） and antioxidant enzyme activities （i.e., superoxide dismutase （SOD） and eatalase （CAT）） were measured. Response surface methodology （RSM） was used to analyze the effect of multiple factors on ROS indices and enzyme activities. Weight gain （WG） and special growth rate （SGR） of vitamin C supplementation groups were significantly higher than those of control group （P〈0.05）. The levels of-OH and MDA increased under exposure time extending and nitrite concentration increasing, whereas T-AOC level decreased. SOD and CAT activities increased at 4 h and 8 h and decreased at 12 h. During the days in which the animal consumed experimental diets, the levels of-OH and MDA decreased and that of T-AOC increased. This result suggests that diets containing vitamin C could reduce the nitrite stress response in the animals and increase their antioxidant capacity. The multifactor regression equation of growth performance, ROS indices, and duration of feeding results suggest that vitamin C supplementation of 1 400-2 000 mg/kg diet for 29-35 days could reduce effectively the effects of nitrite exposure.
基金supported by the National Natural Science Foundation of China(31872869)the State Key Laboratory of North China Crop Improvement and Regulation(NCCIR2022ZZ-7)+2 种基金the National Key R&DProgram of China(SQ2022YFD1200002)the Science and Technology Planning Project of Hebei Province,China(216Z6401G)the Postgraduate Innovation Funding Project of Hebei Province,China(CXZZSS2021071)。
文摘Transcription factors(TFs)regulate diverse stress defensive-associated physiological processes and plant stress responses.We characterized TaNF-YB11,a gene of the NF-YB TF family in Triticum aestivum,in mediating plant drought tolerance.TaNF-YB11 harbors the conserved domains specified by its NF-YB partners and targets the nucleus after the endoplasmic reticulum(ER)assortment.Yeast two-hybrid assay indicated the interactions of TaNF-YB11 with TaNF-YA2 and TaNF-YC3,two proteins encoded by genes in the NF-YA and NF-YC families,respectively.These results suggested that the heterotrimer established among them further regulated downstream genes at the transcriptional level.The transcripts of TaNF-YB11 were promoted in roots and leaves under a 27-h drought regime.Moreover,its upregulated expression levels under drought were gradually restored following a recovery treatment,suggesting its involvement in plant drought response.TaNF-YB11 conferred improved drought tolerance on plants;the lines overexpressing target gene displayed improved phenotype and biomass compared with wild type(WT)under drought treatments due to enhancement of stomata closing,osmolyte accumulation,and cellular reactive oxygen species(ROS)homeostasis.Knockdown expression of TaP5CS2,a P5CS family gene modulating proline biosynthesis that showed upregulated expression in drought-challenged TaNF-YB11 lines,alleviated proline accumulation of plants treated by drought.Likewise,TaSOD2 and TaCAT3,two genes encoding superoxide dismutase(SOD)and catalase(CAT)that were upregulated underlying TaNF-YB11 regulation,played critical roles in ROS homeostasis via regulating SOD and CAT activities.RNA-seq analysis revealed that numerous genes associated with processes of‘cellular processes',‘environmental information processing',‘genetic information processing',‘metabolism',and‘organismal systems'modified transcription under drought underlying control of TaNF-YB11.These results suggested that the TaNF-YB11-mediated drought response is possibly accomplished through the target gene in modifying gene transcription at the global level,which modulates complicated biological processes related to drought response.TaNF-YB11 is essential in plant drought adaptation and a valuable target for molecular breeding of drought-tolerant cultivars in T.aestivum.
文摘Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species （ROS） and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of these chemotherapeutics is due to induction of oxidative stress and ROS-mediated apoptosis in cancer. On the other hand, the harmful side effects of conventional anticancer chemotherapy are also due to increased production of ROS and disruption of redox-homeostasis of normal cells and tissues. This article describes the mechanisms for triggering and modulation of apoptosis through ROS-dependent and ROS^independent pathways. We try to answer the question： ＂Is it possible to induce highly specific apoptosis only in cancer cells, without overproduction of ROS, as well as without harmful effects on normal cells and tissues？＂ The review also suggests a new therapeutic strategy for selective killing of cancer cells, without significant impact on viability of normal cells and tissues, by combining anticancer drugs with redox-modulators, affecting specific signaling pathways and avoiding oxidative stress.
文摘Cancer cells utilize cytosolic glycolysis for their energy production even in the presence of adequate levels of oxygen (Warbug effect) due to mitochondrial defects. Dichloroacetic acid (DCA) shifts cytosolic glucose metabolism to aerobic oxidation by inhibiting mitochondrial pyruvate dehydrogenase kinase (PDK) and increasing pyruvate uptake. Therefore, DCA has potential in reversing the glycolytic metabolism defect in cancerous cells. DCA is also known to induce apoptosis in a number of cancer cell lines, the mechanism of which is not well understood. In this study, an attempt has been made to investigate the effects of DCA on aggressive human breast cancer (MCF-7) cells as compared with less aggressive mouse osteoblastic (MC3T3) cells. Cell cytotoxicity was determined by MTT, crystal violet and Trypan blue exclusion assays. Western blot was used to detect any changes in the expression of apoptotic markers. Flow cytometry was used to measure apoptotic and necrotic effects of DCA. Mitochondrial integrity was determined by change in mitochondrial membrane potential (Δψm), whereas oxidative damage was determined by production of reactive oxygen species (ROS). DCA caused a concentration-dependent cytotoxicity both in MCF-7 and MC3T3 cell lines. MCF-7 cells were most affected. Flow cytometry results showed a significantly higher apoptosis in MCF-7 even at lower concentrations of DCA. However, higher concentrations of DCA were necrotic. Western blotting showed an increased expression of Mn-SOD-1 upon DCA treatment. Further, DCA decreased Δψm and increased ROS production. The effects of DCA were more pronounced on MCF-7 cells as compared to MC3T3 cells. Our results suggest that DCA-induced cytotoxicity in cancerous cells is mediated via changes in Δψm and production of ROS.
基金This project was partially supported by Science Foundation of Lanzhou Command of PLA(No.YZ-0106).
文摘Objective: To evaluate the anti-tumor effects of SeO2 and its mechanisms on three human lung cancer cell lines. Methods: Three lung cancer cells A549, GLC-82 and PG were treated with 3-30 μmol/L SeO2. Flow cytometry was used to detect apoptosis, and analyze the changes of expression of p53 and Bcl-2, as well as ROS and Ca2+ level within cells. Results:SeO2 markedly inhibited cell proliferation and viability, and prompted apoptosis after 48 h treatment. SeO2 at 10 μmol/L induced 47.8% apoptosis in A549 cells, 40.8% in GLC-82 cells, 18.2% in PG cells. SeO2 at 30 μmol/L induced 37.8% apoposis in PG cells,but did not increase apoptotic raes in other two cells. SeO2 could down-regulate the mean fluorescent intensity of Bcl-2 from 65.8 to 9.6 in A549, but not in GLC-82 and in PG cells, up-regulate wild type p53 level in all three cells. SeO2 decreased the ROS and Ca2+ level markedly within three tested cells. Conclusion: SeO2 showed anti-tumor effect via apoptosis pathway in three lung cancer cell lines. The decrease of ROS and Ca2+ level within cells as well as regulation of Bcl-2 and p53 expression may play important roles in above apoptotic procedure.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3804500)the National Natural Science Foundation of China(Grant No.52202352,22335006)+4 种基金the Shanghai Municipal Health Commission(Grant No.20224Y0010)the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-5-012)the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000)the Fundamental Research Funds for the Central Universities(Grant No.22120230237,2023-3-YB-11,22120220618)the Basic Research Program of Shanghai Municipal Government(23DX1900200).
文摘The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.
基金supported by research grants from National Natural Science Foundation of China(No.30170475)
文摘Double staining flow cytometry was performed using 7-amino actinomycin D and 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate,to detect the level fluctuation of reactive oxygen species (ROS) during the cell cycle of normal NB4 cells. Our results showed that NB4 cells possessed higher level of ROS in G2/M phase than in G1 and S phases. Double staining flow cytometry,with TdT mediated dUTP nick end labeling (Tunel) and propidium iodide (PI),indicated that As2O3 (2 μM) could induce apoptosis in NB4 cells prevailingly from G2/M phase,and this efficacy was enhanced upon co-administration of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) (2.5 μM) which could produce the endogenous ROS. These results suggested that different ROS level in different cell cycle phases of NB4 cells might determin the selective induction of G2/M apoptosis and the cells' susceptibility to apoptosis by As2O3.
基金The Carl Trygger Foundation,The Goran Gustafsson Foundation,The Swedish Research Council,Vinnova and The Swedish Foundation for Strategic Research for financially supporting this work
文摘Titania (TiO2) induced photocatalysis has been widely investigated and applied as a disinfection strategy in many industrial and clinical applications. Reactive oxygen species (ROS), including hydroxyl radicals (&8226OH), superoxide radicals () and hydrogen peroxide (H2O2), generated in the photocatalytic reaction process are considered to be the active components prompting the bactericidal effect. In the present work, the kinetics of photocatalytic inactivation of Staphylococcus epidermidis and specific contributions of •OH, and H2O2 to the bactericidal process were studied using two disinfection settings sutilizing photocatalytic resin-TiO2 nanocomposite surfaces and suspended TiO2 nanoparticles, respectively. In antibacterial tests against S. epidermidis with a layer of bacterial suspension on the resin-TiO2 surfaces, H2O2 was found to be the most efficient ROS component contributing to the antibacterial effect. Disinfection kinetics showed a two-step behavior with an initial region having a lower disinfection rate followed by a higher rate region after 10 min of UV irradiation. By contrast, in antibacterial tests with suspended bacteria and photocatalytic TiO2 nanoparticles, •OH and H2O2 showed equal significance in the bacterial inactivation having a typical Chick-Watson disinfection kinetics behavior with a steady disinfection rate. The results contribute to the understanding of the bactericidal mechanism and kinetics of photocatalytic disinfection that are essential for designing specific antibacterial applications of photocatalytic materials.
基金supported by the Natural Science Foundation of Fujian Province of China(No.2022J01043)China Scholarship Council(201806315005 and 201703170071).
文摘Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.
基金This work was supported by funding from Natural Science Foundation of China(Grant Nos.:82372519 and 81902664)the PostdoctoralFellowshipProgramof CPSF(GrantNo.:GZB20240544)+3 种基金the China Postdoctoral Science Foundation(Grant No.:2024M752432)the Natural Science Foundation of Hebei Province(Grant Nos.:H2022206368 and H2022206446)Medical Science Research Program of the Hebei Provincial Health Commission(Grant No.:20241603)Pilot Program of Southwest University(Program No.:SWU-XDZD22006)。
文摘Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(Ros)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.
