Objective To investigate whether intracellular amyloid β （iAβ） induces toxicity in wild type （WT） and APP/PS1 mice, a mouse model of Alzheimer＇s disease. Methods Different forms of Aβ aggregates were microinje...Objective To investigate whether intracellular amyloid β （iAβ） induces toxicity in wild type （WT） and APP/PS1 mice, a mouse model of Alzheimer＇s disease. Methods Different forms of Aβ aggregates were microinjected into cultured WT or APP/PS1 mouse hippocampal neurons. TUNEL staining was performed to examine neuronal cell death. Reactive oxidative species （ROS） were measured by MitoSOXTM Red mitochondrial superoxide indicator. Results Crude, monomer and protofibrilAβ induced more toxicity inAPP/PS1 neurons than in WT neurons. ROS are involved in mediating the vulnerability of APP/PS1 neurons to iAβ toxicity. Conclusion Oxidative stress may mediate cell death induced by iAβ in neurons.展开更多
Amyloid beta（Aβ）-induced oxidative stress is a major pathologic hallmark of Alzheimer＇s disease. Cyanidin, a natural flavonoid compound, is neuroprotective against oxidative damage-mediated degeneration. However, ...Amyloid beta（Aβ）-induced oxidative stress is a major pathologic hallmark of Alzheimer＇s disease. Cyanidin, a natural flavonoid compound, is neuroprotective against oxidative damage-mediated degeneration. However, its molecular mechanism remains unclear. Here, we investigated the effects of cyanidin pretreatment against Aβ-induced neurotoxicity in PC12 cells, and explored the underlying mechanisms. Cyanidin pretreatment significantly attenuated Aβ-induced cell mortality and morphological changes in PC12 cells. Mechanistically, cyanidin effectively blocked apoptosis induced by Aβ, by restoring the mitochondrial membrane potential via upregulation of Bcl-2 protein expression. Moreover, cyanidin markedly protected PC12 cells from Aβ-induced DNA damage by blocking reactive oxide species and superoxide accumulation. These results provide evidence that cyanidin suppresses Aβ-induced cytotoxicity, by preventing oxidative damage mediated by reactive oxide species, which in turn inhibits mitochondrial apoptosis. Our study demonstrates the therapeutic potential of cyanidin in the prevention of oxidative stress-mediated Aβ neurotoxicity.展开更多
Programmed cell death occurs in browning explants of Fraxinus mandshurica during somatic embryogenesis, but the underlying mechanism is unclear. In this study, single cotyledons of zygotic embryos of F. mandshurica we...Programmed cell death occurs in browning explants of Fraxinus mandshurica during somatic embryogenesis, but the underlying mechanism is unclear. In this study, single cotyledons of zygotic embryos of F. mandshurica were used as explants. Mitochondrial structure and function, caspase-3-like protease activity, hydrogen peroxide metabolism, and nitric oxide accumulation induced by high concentrations of sucrose and plant growth regulators were studied. The results show that plant growth regulators induced somatic embryogenesis and also promoted explant browning. High sucrose concentrations had similar effects. High concentrations of sucrose and plant growth regulators led to the accumulation of hydrogen peroxide and nitric oxide which induced changes in mitochondrial structure and function such as modifications in mitochondrial morphology, increased membrane permeability, decreased membrane potential, and the release of cytochrome c into the cytoplasm. An increase in caspase-3-like protease activity triggered programmed cell death in some browning explant cells. During somatic embryogenesis there were increased activities of superoxide dismutase, peroxidase, and catalase, which are associated with hydrogen peroxide metabolism and jointly maintain reactive oxygen species levels. Intracellular nitric oxide synthase and nitrate reductase activities were not significantly correlated with nitric oxide content. Instead, intracellular nitric oxide may be derived from non-enzymatic reactions. Our results indicate that hydrogen peroxide and nitric oxide may function as signals, playing key roles in somatic embryogenesis and programmed cell death of explant cells of F. mandshurica. The interaction between nitric oxide and reactive oxygen species determines the occurrence of programmed cell death in explant cells;somatic embryogenesis and programmed cell death are positively regulated by hydrogen peroxide. However, the regulation of nitric oxide is complex.展开更多
With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn pu...With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.展开更多
AIM: To investigate the mechanism of endoplasmic reticulum(ER) stress induction by an occult infection related hepatitis B virus S surface antigen(HBsAg)variant.METHODS: We used an HBsAg variant with lower secretion c...AIM: To investigate the mechanism of endoplasmic reticulum(ER) stress induction by an occult infection related hepatitis B virus S surface antigen(HBsAg)variant.METHODS: We used an HBsAg variant with lower secretion capacity, which was a KD variant from a Korean subject who was occultly infected with the genotype C. We compared the expression profiles of ER stress-related proteins between HuH-7 cells transfected with HBsAg plasmids of a wild-type and a KD variant using Western blot.RESULTS: Confocal microscopy indicated that the KD variant had higher levels of co-localization with ER than the wild-type HBsAg. The KD variant upregulated ER stress-related proteins and induced reactive oxygen species(ROS) compared to the wildtype via an increase in calcium. The KD variant also down-regulated anti-oxidant proteins(HO-1, catalase and SOD) compared to the wild-type, which indicates positive amplification loops of the ER-ROS axis. The KD variant also induced apoptotic cell death via the upregulation of caspase proteins(caspase 6, 9 and 12).Furthermore, the KD variant induced a higher level of nitric oxide than wild-type HBsAg via the up-regulation of the iNOS protein.CONCLUSION: Our data indicate that occult infection related HBsAg variants can lead to ER-derived oxidative stress and liver cell death in HuH-7 cells.展开更多
The pathogenesis of metabolic-associated fatty liver disease(MAFLD)is complex and thought to be dependent on multiple parallel hits on a background of genetic susceptibility.The evidence suggests that MAFLD progressio...The pathogenesis of metabolic-associated fatty liver disease(MAFLD)is complex and thought to be dependent on multiple parallel hits on a background of genetic susceptibility.The evidence suggests that MAFLD progression is a dynamic two-way process relating to repetitive bouts of metabolic stress and inflammation interspersed with endogenous anti-inflammatory reparative responses.In MAFLD,excessive hepatic lipid accumulation causes the production of lipotoxins that induce mitochondrial dysfunction,endoplasmic reticular stress,and over production of reactive oxygen species(ROS).Models of MAFLD show marked disruption of mitochondrial function and reduced oxidative capacitance with impact on cellular processes including mitophagy,oxidative phosphorylation,and mitochondrial biogenesis.In excess,ROS modify insulin and innate immune signaling and alter the expression and activity of essential enzymes involved in lipid homeostasis.ROS can also cause direct damage to intracellular structures causing hepatocyte injury and death.In select cases,the use of anti-oxidants and ROS scavengers have been shown to diminish the proapoptopic effects of fatty acids.Given this link,endogenous anti-oxidant pathways have been a target of interest,with Nrf2 activation showing a reduction in oxidative stress and inflammation in models of MAFLD.Thyroid hormone receptorβ(THRβ)agonists and nuclear peroxisome proliferationactivated receptor(PPAR)family have also gained interest in reducing hepatic lipotoxicity and restoring hepatic function in models of MAFLD.Unfortunately,the true interplay between the clinical and molecular components of MAFLD progression remain only partly understood.Most recently,multiomics-based strategies are being adopted for hypothesis-free analysis of the molecular changes in MAFLD.Transcriptome profiling maps the unique genotype-phenotype associations in MAFLD and with various single-cell tran scriptome-based projects underway,there is hope of novel physiological insights to MAFLD progression and uncover therapeutic targets.展开更多
Heavy metal pollution has become a worldwide problem in aquaculture. We studied copper （Cu^2＋） accumulation and physiological responses of two red algae Gracilaria lemaneiformis and Gracilaria lichenoides from Chin...Heavy metal pollution has become a worldwide problem in aquaculture. We studied copper （Cu^2＋） accumulation and physiological responses of two red algae Gracilaria lemaneiformis and Gracilaria lichenoides from China under Cu^2＋ exposure of 0-500 μg/L in concentration. Compared with G. lemaneiformis, G. lichenoides was more capable in accumulating Cu^2＋, specifically, more Cu〉 on extracellular side （cell wall） than on intracellular side （cytoplasm） and in cell organelles （especially chloroplast, cell nucleus, mitochondria, and ribosome）. In addition, G. lichenoides contained more insoluble polysaccharide in cell wall, which might promote the extracellular Cu^2＋-binding as an efficient barrier against metal toxicity. Conversely, G. lemaneiformis was more vulnerable than G. lichenoides to Cu^2＋ toxin for decreases in growth, pigment （chlorophyll a, chlorophyll b, phycobiliprotein, and B-carotene） content, and photosynthetic activity. Moreover, more serious oxidative damages in G. lemaneiformis than in G. lichenoides, in accumulation of reactive oxidative species and malondialdehyde, and in electrolyte leakage, because of lower antioxidant enzyme （superoxide dismutase and glutathione reductase） activities. Therefore, G. lichenoides was less susceptible to Cu〉 stress than G. lemaneiformis.展开更多
Background The vascular endothelial growth factor （VEGF） is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 （ICAM-1） is the key mediator o...Background The vascular endothelial growth factor （VEGF） is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 （ICAM-1） is the key mediator of the effect of VEGFs on retinal leukostasis. Although the VEGF is expressed in an early-stage diabetic retina, whether it directly up-regulates ICAM-1 in retinal endothelial cells （ECs） is unknown. In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs. Methods Bovine retinal ECs （BRECs） were isolated and cultured. Immunohistochemical staining was performed to identify BRECs. The cultured cells were divided into corresponding groups. Then, VEGF （100 ng/ml） and other inhibitors were used to treat the cells. Cell lysate and the cultured supernatant were collected, and then, the protein level of ICAM-1 and phosphorylation of the endothelial nitric oxide synthase （eNOS） were detected using Western blotting. Griess reaction was used to detect nitric oxide （NO）. Results Western blotting showed that the VEGF up-regulated the expression of ICAM-1 protein and increased phosphorylation of the eNOS in retinal ECs. Neither the block of NO nor protein kinase C （PKC） altered the expression of ICAM-1 or the phosphorylation of eNOS. The result of the Western blotting also showed that inhibition of phosphatidylinositol 3-kinase （PI3K） or reactive oxygen species （ROS） significantly reduced the expression of ICAM-1. Inhibition of PI3K also reduced phosphorylation of eNOS. Griess reaction showed that VEGF significantly increased during NO production. When eNOS was blocked by L-NAME or PI3K was blocked by LY294002, the basal level of NO production and the increment of NO caused by VEGF could be significantly decreased. Conclusion ROS-NO coupling in the retinal endothelium may be a new mechanism that could help to explain why VEGF induces ICAM-1 expression and the resulting leukostasis in diabetic retinopathy.展开更多
Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric o...Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.展开更多
The extensive use of tetracycline hydrochloride(TCH)poses a threat to human health and the aquatic environment.Here,magnetic p-n Bi2WO6/CuFe2O4 catalyst was fabricated to efficiently remove TCH.The obtained Bi2WO6/CuF...The extensive use of tetracycline hydrochloride(TCH)poses a threat to human health and the aquatic environment.Here,magnetic p-n Bi2WO6/CuFe2O4 catalyst was fabricated to efficiently remove TCH.The obtained Bi2WO6/CuFe2O4 exhibited 92.1%TCH degradation efficiency and 50.7%and 35.1%mineralization performance for TCH and raw secondary effluent from a wastewater treatment plant in a photo-Fenton-like system,respectively.The remarkable performance was attributed to the fact that photogenerated electrons accelerated the Fe(III)/Fe(II)and Cu(II)/Cu(I)conversion for the Fenton-like reaction between Fe(II)/Cu(I)and H2O2,thereby generating abundant·OH for pollutant oxidation.Various environmental factors including H2O2 concentration,initial pH,catalyst dosage,TCH concentration and inorganic ions were explored.The reactive oxidation species(ROS)quenching results and electron spin resonance(ESR)spectra confirmed that·O2-and·OH were responsible for the dark and photo-Fenton-like systems,respectively.The degradation mechanisms and pathways of TCH were proposed,and the toxicity of products was evaluated.This work contributes a highly efficient and environmentally friendly catalyst and provides a clear mechanistic explanation for the removal of antibiotic pollutants in environmental remediation.展开更多
Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to inve...Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.展开更多
This study was aimed at evaluating the anti-diabetic potential of passion fruit Passiflora edulis(EPE) extracts in diabetic rats, following Streptozotocin(STZ) induced oxidative stress. Thirty adult Wistar rats were d...This study was aimed at evaluating the anti-diabetic potential of passion fruit Passiflora edulis(EPE) extracts in diabetic rats, following Streptozotocin(STZ) induced oxidative stress. Thirty adult Wistar rats were divided into five groups, with six rats in each group. The control rats were injected intraperitoneally with citrate buffer(pH 4.5). The remaining groups of rats were administered single dose of 45 mg·kg-1 of STZ by intraperitoneal route to induce diabetes. The diabetic animals were treated with 250 and 500 mg·kg-1 of EPE and glibenclamide 0.6 mg·kg-1 for fifteen days by oral route. Blood glucose, end organ oxidative stress marker, and anti-oxidants were assayed. Further, histopathological investigation of pancreas was studied at the end of the experimentation. The results revealed that subacute administration of EPE significantly(P < 0.001) controlled the blood glucose level in the diabetic rats. In addition, EPE extract protected the end organs by restoring the anti-oxidants enzyme, significantly increasing super oxide dismutase level(SOD) and decreasing catalase(CAT) and TBARS level in visceral organs. In conclusion, that EPE extracts showed anti-diabetic and anti-oxidant potential against streptozotocin-induced diabetes.展开更多
Objective To investigate whether salidroside（SAL） has protective and anti-oxidative effects on astrocytes. Methods Firstly, SAL was extracted from the roots of Rhodiola rosea with 70% ethanol and butanol to obtain c...Objective To investigate whether salidroside（SAL） has protective and anti-oxidative effects on astrocytes. Methods Firstly, SAL was extracted from the roots of Rhodiola rosea with 70% ethanol and butanol to obtain crude phenylethyl alcohol glycosides which have been known as bioactive part of R. rosea; Secondly, WST-1 assay was carried out to assess the cell viability of astrocytes and cortical neurons under the treatment of the purified（〉 95%） SAL. Moreover, WST-1 assay was also used to evaluate the cytoprotective effects of SAL preventing astrocytes from staurosporine-induced cell death; Thirdly, we examined the spontaneous reactive oxygen species（ROS） and staurosporine-induced ROS generation in astrocytes in the absence or presence of SAL.Results SAL was observed to improve the astrocytes viability but not cortical neurons. In addition, SAL was able to ameliorate staurosporine-induced cell death. Moreover, SAL was able to attenuate the spontaneous ROS and staurosporine-induced ROS generation. Conclusion We here confirm that the anti-oxidative effect of SAL on primary astrocytes might be an important mechanism accounting for the cytoprotective effects from SAL.展开更多
Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional therapeutics.The existing metabolic intervention...Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional therapeutics.The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity,resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment.To address these limitations,here we developed a robust pyroelectric BaTiO_(3)@Au core–shell nanostructure(BTO@Au)to selectively and persistently block energy generation of tumor cells.Stimulated by near-infrared(NIR)laser,the Au shell could generate heat to activate the BaTiO_(3)core to produce reactive oxygen species(ROS)regardless of the constrained microenvironment,thus prominently inhibits mitochondrial oxidative phosphorylation(OXPHOS)and reduces ATP production to induce TNBC cell apoptosis.The therapeutic effects have been well demonstrated in vitro and in vivo,paving a new way for the development of metabolic interventions.展开更多
Recent studies have proposed that the high-valent iron species(such as Fe^(Ⅳ)O^(2+))rather than sulfate radical(SO_(4)^(·-))and hydroxyl radical(·OH)are the main reactive oxidant species(ROS)in Fe(Ⅱ)/perox...Recent studies have proposed that the high-valent iron species(such as Fe^(Ⅳ)O^(2+))rather than sulfate radical(SO_(4)^(·-))and hydroxyl radical(·OH)are the main reactive oxidant species(ROS)in Fe(Ⅱ)/peroxydisulfate(PDS)system with the methyl phenyl sulfoxide(PMSO)as the Fe^(Ⅳ)O^(2+)probe.However,many operational factors may interfere with the accuracy of this method,so the contribution of Fe^(Ⅳ)O^(2+)calculated by this method is controversial.In this study,the possible effect of Fe(Ⅱ)concentration,pollutant type,reducing agent,or coexisted anions on Fe^(Ⅳ)O^(2+)production and its corresponding contribution to the removal of target pollutants in the Fe(Ⅱ)/PDS system were investigated in detail,and the intrinsic mechanisms involved were also explored.This study shows that ROS generation is a complex process in the Fe(Ⅱ)/PDS system,and multiple combinatorial approaches are urgently required to deeply explore the contribution of ROS to the elimination of target contaminants.展开更多
Single-atom catalysts(SACs)have been widely recognized as state-of-the-art catalysts in environment remediation because of their exceptional performance,100%metal atomic utilization,almost no secondary pollution,and r...Single-atom catalysts(SACs)have been widely recognized as state-of-the-art catalysts in environment remediation because of their exceptional performance,100%metal atomic utilization,almost no secondary pollution,and robust structures.Most recently,the activation of persulfate with carbon-based SACs in advanced oxidation processes(AOPs)raises tremendous interest in the degradation of emerging contaminants in wastewater,owning to its efficient and versatile reactive oxidant species(ROS)generation.However,the comprehensive and critical review unraveling the underlying relationship between structures of carbon-based SACs and the corresponding generated ROS is still rare.Herein,we systematically summarize the fundamental understandings and intrinsic mechanisms between single metal atom active sites and produced ROS during AOPs.The types of emerging contaminants are firstly elaborated,presenting the prior pollutants that need to be degraded.Then,the preparation and characterization methods of carbon-based SACs are overviewed.The underlying material structure–ROS type relationship in persulfate-based AOPs is discussed in depth to expound the catalytic mechanisms.Finally,we briefly conclude the current development of carbon-based SACs in AOPs and propose the prospects for rational design and synthesis of carbon-based SACs with on-demand catalytic performances in AOPs in future research.展开更多
Per-and polyfluoroalkyl substances(PFAS)are found to have multiple adverse outcomes on human health.Recently,epidemiological and toxicological studies showed that exposure to PFAS had adverse impacts on pancreas and s...Per-and polyfluoroalkyl substances(PFAS)are found to have multiple adverse outcomes on human health.Recently,epidemiological and toxicological studies showed that exposure to PFAS had adverse impacts on pancreas and showed association with insulin abnormalities.To explore how PFAS may contribute to diabetes,we studied impacts of perfluorooctane sul-fonate(PFOS)on cell viability and insulin release capacity of pancreatic β cells by using in vivo and in vitro methods.We found that 28-day administration with PFOS(10 mg/(kg body weight·day))caused reductions of pancreas weight and islet size in male mice.PFOS admin-istration also led to lower serum insulin level both in fasting state and after glucose infusion among male mice.For cell-based in vitro bioassay,we used mouse β-TC-6 cancer cells and found 48-hr exposure to PFOS decreased the cell viability at 50 μmol/L.By measuring insulin content in supernatant,48-hr pretreatment of PFOS(100 μmol/L)decreased the insulin re-lease capacity of β-TC-6 cells after glucose stimulation.Although these concentrations were higher than the environmental concentration of PFOS,it might be reasonable for high con-centration of PFOS to exert observable toxic effects in mice considering mice had a faster removal efficiency of PFOS than human.PFOS exposure(50 μmol/L)to β-TC-6 cells induced intracellular accumulation of reactive oxidative specie(ROS).Excessive ROS induced the re-active toxicity of cells,which eventually invoke apoptosis and necrosis.Results in this study provide evidence for the possible causal link of exposure to PFOS and diabetes risk.展开更多
Halobenzoquinones（HBQs） are an emerging class of halogenated disinfection byproducts（DBPs） in drinking water, which raised public concerns due to potential carcinogenic effects to human bladder. Our previous work ...Halobenzoquinones（HBQs） are an emerging class of halogenated disinfection byproducts（DBPs） in drinking water, which raised public concerns due to potential carcinogenic effects to human bladder. Our previous work demonstrated that HBQs and hydrogen peroxide（H_2O_2）together generated oxidative DNA damage via a metal-independent and intercalationenhanced oxidation mechanism in vitro. This study further investigated the efficiency of various HBQs to induce oxidative DNA damage in T24 bladder cancer cells. Compared with T24 cells without treatment（3.1 lesions per 10~6 d G）, the level of 8-oxo-7,8-dihydro-2′-deoxyguanosine（8-oxod G） significantly increased by 1.4, 3.2, 8.8, and 9.2 times after treatment with tetrabromo-1,4-benzoquinone（TBBQ）, terachloro-1,4-benzoquinone（TCBQ）,2,6-dichloro-1,4-benzoquinone（2,6-DCBQ） and 2,5-dichloro-1,4-benzoquinone（2,5-DCBQ） for24 hr, respectively. Interestingly, we found that the oxidative potency of HBQs in T24 cells（2,5-DCBQ ≈ 2,6-DCBQ 〉 TCBQ 〉 TBBQ） is inconsistent with that of in vitro ds DNA oxidation（TCBQ 〉 TBBQ 〉 2,5-DCBQ 〉 2,6-DCBQ）, suggesting HBQs induce oxidative lesions in cellular genomic DNA probably involved with a complex mechanism.展开更多
Zinc oxide nanoparticles（ZnO NPs） are among the most commonly utilized nanomaterials. They are used in a wide range of applications, including medicine, sunscreens, cosmetics, paints, catalysis, electronics, as well...Zinc oxide nanoparticles（ZnO NPs） are among the most commonly utilized nanomaterials. They are used in a wide range of applications, including medicine, sunscreens, cosmetics, paints, catalysis, electronics, as well as biosensors, and hence, it is crucial to illustrate their biological effects and risks. In the present study, the effects and mechanism of ZnO NPs（≤5 nm） were investigated in rat glioma C6 cells in vitro. The results of transmission electron microscopy（TEM） and X-ray difffaction（XRD） show that ZnO NPs are pure with a uniform diameter of ca. 5 nm 3-（4,5-Dimethylthiazol-2yl）-2,5-diphenyltetrazolium bromide（MTT） assays on C6 cells show that ZnO NPs, at different concentrations（0-5 I^g/mL）, can induce significant cytotoxicity in C6 cells in a dose-dependent manner. An increased level of reactive oxygen species（ROS）, a decreased level of glutathione（GSH）, and an elevated level of glutathione disulfide（GSSG） and the toxicity mechanism are primarily attributed to the induced cellular oxidative stress. 4＇,6-Diamidino-2-phenylindole（DAPI） staining was used to observe the apoptosis. The results show that C6 cells treated with the ZnO NPs at various concentrations（0, 1.25, 2.5 and 5 μg/mL） can induce apoptosis in a dose-dependent manner. These results suggest that ZnO NPs are the killers of the rat glioma C6 cells, and oxidative stress is the underlying mechanism of this process.展开更多
Aim:Emerging evidence favors the important role of antioxidants,matrix metalloproteinases(MMPs),and nitric oxide(NO)in the healing of diabetic wounds.There is a lack of substantial evidence regarding the effects of ne...Aim:Emerging evidence favors the important role of antioxidants,matrix metalloproteinases(MMPs),and nitric oxide(NO)in the healing of diabetic wounds.There is a lack of substantial evidence regarding the effects of negative pressure on antioxidants,MMPs and NO in chronic wounds associated with diabetes.Methods:A total of 55 type 2 diabetic patients with leg ulcers were divided into 2 groups:a limited access dressing(LAD)group(n=27)and a conventional dressing group(n=28).Levels of hydroxyproline,total protein,MMP-2 and MMP-9,NO and antioxidants including reduced glutathione(GSH)and the oxidative biomarker malondialdehyde(MDA)were measured in the granulation tissue at days 0 and 10.Changes in levels between the LAD and conventional groups were determined by the Student’s t-test.Results:After 10 days of treatment,the LAD vs.conventional dressing group showed increase in the levels of hydroxyproline(mean±standard deviation=55.2±25.1 vs.29.2±1,P<0.05),total protein(12.8±6.5 vs.8.34±3.2,P<0.05),NO(1.13±0.52 vs.0.66±0.43,P<0.05),GSH(7.0±2.4 vs.6.6±2.2,P<0.05)and decrease in MMP-2(0.47±0.33 vs.0.62±0.30,P<0.05),MMP-9(0.32±0.20 vs.0.53±0.39,P<0.05)and MDA(6.8±2.3 vs.10.4±3.4,P<0.05).Conclusion:When compared to conventional dressings,LAD induces biochemical changes by significantly increasing the levels of hydroxyproline,total protein,NO and antioxidants levels,and significantly reducing MMPs(MMP-2 and MMP-9)and an oxidative biomarker in diabetic wounds.These biochemical changes are thought to favor diabetic wound healing.展开更多
基金supported by grants from the National Basic Research Development Program of the Ministry of Science and Technology of China (2009CB941301)Roche Research Grant, Peking University President Research Grant and the Recruiting Research Grant, Ministry of Education of China
文摘Objective To investigate whether intracellular amyloid β （iAβ） induces toxicity in wild type （WT） and APP/PS1 mice, a mouse model of Alzheimer＇s disease. Methods Different forms of Aβ aggregates were microinjected into cultured WT or APP/PS1 mouse hippocampal neurons. TUNEL staining was performed to examine neuronal cell death. Reactive oxidative species （ROS） were measured by MitoSOXTM Red mitochondrial superoxide indicator. Results Crude, monomer and protofibrilAβ induced more toxicity inAPP/PS1 neurons than in WT neurons. ROS are involved in mediating the vulnerability of APP/PS1 neurons to iAβ toxicity. Conclusion Oxidative stress may mediate cell death induced by iAβ in neurons.
基金supported by the Natural Science Foundation of Shandong Province of China,No.ZR2014HM046(to ZCZ)
文摘Amyloid beta（Aβ）-induced oxidative stress is a major pathologic hallmark of Alzheimer＇s disease. Cyanidin, a natural flavonoid compound, is neuroprotective against oxidative damage-mediated degeneration. However, its molecular mechanism remains unclear. Here, we investigated the effects of cyanidin pretreatment against Aβ-induced neurotoxicity in PC12 cells, and explored the underlying mechanisms. Cyanidin pretreatment significantly attenuated Aβ-induced cell mortality and morphological changes in PC12 cells. Mechanistically, cyanidin effectively blocked apoptosis induced by Aβ, by restoring the mitochondrial membrane potential via upregulation of Bcl-2 protein expression. Moreover, cyanidin markedly protected PC12 cells from Aβ-induced DNA damage by blocking reactive oxide species and superoxide accumulation. These results provide evidence that cyanidin suppresses Aβ-induced cytotoxicity, by preventing oxidative damage mediated by reactive oxide species, which in turn inhibits mitochondrial apoptosis. Our study demonstrates the therapeutic potential of cyanidin in the prevention of oxidative stress-mediated Aβ neurotoxicity.
基金This work was supported by the Fundamental Research Funds for the Central Universities(2572018BW02)the Innovation Project of State Key Laboratory of Tree Genetics and Breeding(2016C01)+1 种基金the National Key R&D Program of China(2017YFD0600600)the National Natural Science Foundation of China(31400535 and 31570596).
文摘Programmed cell death occurs in browning explants of Fraxinus mandshurica during somatic embryogenesis, but the underlying mechanism is unclear. In this study, single cotyledons of zygotic embryos of F. mandshurica were used as explants. Mitochondrial structure and function, caspase-3-like protease activity, hydrogen peroxide metabolism, and nitric oxide accumulation induced by high concentrations of sucrose and plant growth regulators were studied. The results show that plant growth regulators induced somatic embryogenesis and also promoted explant browning. High sucrose concentrations had similar effects. High concentrations of sucrose and plant growth regulators led to the accumulation of hydrogen peroxide and nitric oxide which induced changes in mitochondrial structure and function such as modifications in mitochondrial morphology, increased membrane permeability, decreased membrane potential, and the release of cytochrome c into the cytoplasm. An increase in caspase-3-like protease activity triggered programmed cell death in some browning explant cells. During somatic embryogenesis there were increased activities of superoxide dismutase, peroxidase, and catalase, which are associated with hydrogen peroxide metabolism and jointly maintain reactive oxygen species levels. Intracellular nitric oxide synthase and nitrate reductase activities were not significantly correlated with nitric oxide content. Instead, intracellular nitric oxide may be derived from non-enzymatic reactions. Our results indicate that hydrogen peroxide and nitric oxide may function as signals, playing key roles in somatic embryogenesis and programmed cell death of explant cells of F. mandshurica. The interaction between nitric oxide and reactive oxygen species determines the occurrence of programmed cell death in explant cells;somatic embryogenesis and programmed cell death are positively regulated by hydrogen peroxide. However, the regulation of nitric oxide is complex.
文摘With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.
基金Supported by National Research Foundation of Korea grant funded by the Korea government(MEST),No.2013-005810
文摘AIM: To investigate the mechanism of endoplasmic reticulum(ER) stress induction by an occult infection related hepatitis B virus S surface antigen(HBsAg)variant.METHODS: We used an HBsAg variant with lower secretion capacity, which was a KD variant from a Korean subject who was occultly infected with the genotype C. We compared the expression profiles of ER stress-related proteins between HuH-7 cells transfected with HBsAg plasmids of a wild-type and a KD variant using Western blot.RESULTS: Confocal microscopy indicated that the KD variant had higher levels of co-localization with ER than the wild-type HBsAg. The KD variant upregulated ER stress-related proteins and induced reactive oxygen species(ROS) compared to the wildtype via an increase in calcium. The KD variant also down-regulated anti-oxidant proteins(HO-1, catalase and SOD) compared to the wild-type, which indicates positive amplification loops of the ER-ROS axis. The KD variant also induced apoptotic cell death via the upregulation of caspase proteins(caspase 6, 9 and 12).Furthermore, the KD variant induced a higher level of nitric oxide than wild-type HBsAg via the up-regulation of the iNOS protein.CONCLUSION: Our data indicate that occult infection related HBsAg variants can lead to ER-derived oxidative stress and liver cell death in HuH-7 cells.
文摘The pathogenesis of metabolic-associated fatty liver disease(MAFLD)is complex and thought to be dependent on multiple parallel hits on a background of genetic susceptibility.The evidence suggests that MAFLD progression is a dynamic two-way process relating to repetitive bouts of metabolic stress and inflammation interspersed with endogenous anti-inflammatory reparative responses.In MAFLD,excessive hepatic lipid accumulation causes the production of lipotoxins that induce mitochondrial dysfunction,endoplasmic reticular stress,and over production of reactive oxygen species(ROS).Models of MAFLD show marked disruption of mitochondrial function and reduced oxidative capacitance with impact on cellular processes including mitophagy,oxidative phosphorylation,and mitochondrial biogenesis.In excess,ROS modify insulin and innate immune signaling and alter the expression and activity of essential enzymes involved in lipid homeostasis.ROS can also cause direct damage to intracellular structures causing hepatocyte injury and death.In select cases,the use of anti-oxidants and ROS scavengers have been shown to diminish the proapoptopic effects of fatty acids.Given this link,endogenous anti-oxidant pathways have been a target of interest,with Nrf2 activation showing a reduction in oxidative stress and inflammation in models of MAFLD.Thyroid hormone receptorβ(THRβ)agonists and nuclear peroxisome proliferationactivated receptor(PPAR)family have also gained interest in reducing hepatic lipotoxicity and restoring hepatic function in models of MAFLD.Unfortunately,the true interplay between the clinical and molecular components of MAFLD progression remain only partly understood.Most recently,multiomics-based strategies are being adopted for hypothesis-free analysis of the molecular changes in MAFLD.Transcriptome profiling maps the unique genotype-phenotype associations in MAFLD and with various single-cell tran scriptome-based projects underway,there is hope of novel physiological insights to MAFLD progression and uncover therapeutic targets.
基金Supported by the Society Development Program of the Natural Science Foundation of Jiangsu Province in China (No.BS2002016)
文摘Heavy metal pollution has become a worldwide problem in aquaculture. We studied copper （Cu^2＋） accumulation and physiological responses of two red algae Gracilaria lemaneiformis and Gracilaria lichenoides from China under Cu^2＋ exposure of 0-500 μg/L in concentration. Compared with G. lemaneiformis, G. lichenoides was more capable in accumulating Cu^2＋, specifically, more Cu〉 on extracellular side （cell wall） than on intracellular side （cytoplasm） and in cell organelles （especially chloroplast, cell nucleus, mitochondria, and ribosome）. In addition, G. lichenoides contained more insoluble polysaccharide in cell wall, which might promote the extracellular Cu^2＋-binding as an efficient barrier against metal toxicity. Conversely, G. lemaneiformis was more vulnerable than G. lichenoides to Cu^2＋ toxin for decreases in growth, pigment （chlorophyll a, chlorophyll b, phycobiliprotein, and B-carotene） content, and photosynthetic activity. Moreover, more serious oxidative damages in G. lemaneiformis than in G. lichenoides, in accumulation of reactive oxidative species and malondialdehyde, and in electrolyte leakage, because of lower antioxidant enzyme （superoxide dismutase and glutathione reductase） activities. Therefore, G. lichenoides was less susceptible to Cu〉 stress than G. lemaneiformis.
基金This study was supported in part by grants from the National Natural Science Foundation of China （No. 30571994, No. 30570713 and No. 30630032）.
文摘Background The vascular endothelial growth factor （VEGF） is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 （ICAM-1） is the key mediator of the effect of VEGFs on retinal leukostasis. Although the VEGF is expressed in an early-stage diabetic retina, whether it directly up-regulates ICAM-1 in retinal endothelial cells （ECs） is unknown. In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs. Methods Bovine retinal ECs （BRECs） were isolated and cultured. Immunohistochemical staining was performed to identify BRECs. The cultured cells were divided into corresponding groups. Then, VEGF （100 ng/ml） and other inhibitors were used to treat the cells. Cell lysate and the cultured supernatant were collected, and then, the protein level of ICAM-1 and phosphorylation of the endothelial nitric oxide synthase （eNOS） were detected using Western blotting. Griess reaction was used to detect nitric oxide （NO）. Results Western blotting showed that the VEGF up-regulated the expression of ICAM-1 protein and increased phosphorylation of the eNOS in retinal ECs. Neither the block of NO nor protein kinase C （PKC） altered the expression of ICAM-1 or the phosphorylation of eNOS. The result of the Western blotting also showed that inhibition of phosphatidylinositol 3-kinase （PI3K） or reactive oxygen species （ROS） significantly reduced the expression of ICAM-1. Inhibition of PI3K also reduced phosphorylation of eNOS. Griess reaction showed that VEGF significantly increased during NO production. When eNOS was blocked by L-NAME or PI3K was blocked by LY294002, the basal level of NO production and the increment of NO caused by VEGF could be significantly decreased. Conclusion ROS-NO coupling in the retinal endothelium may be a new mechanism that could help to explain why VEGF induces ICAM-1 expression and the resulting leukostasis in diabetic retinopathy.
基金supported by the Special Research Foundation of Doctoral Course in Colleges and Universities of China in 2013,No.20133420110009
文摘Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.
基金supported by the National Natural Science Foundation of China(Nos.51678270,21872063)111 Project of Jilin University,China(No.B16020)。
文摘The extensive use of tetracycline hydrochloride(TCH)poses a threat to human health and the aquatic environment.Here,magnetic p-n Bi2WO6/CuFe2O4 catalyst was fabricated to efficiently remove TCH.The obtained Bi2WO6/CuFe2O4 exhibited 92.1%TCH degradation efficiency and 50.7%and 35.1%mineralization performance for TCH and raw secondary effluent from a wastewater treatment plant in a photo-Fenton-like system,respectively.The remarkable performance was attributed to the fact that photogenerated electrons accelerated the Fe(III)/Fe(II)and Cu(II)/Cu(I)conversion for the Fenton-like reaction between Fe(II)/Cu(I)and H2O2,thereby generating abundant·OH for pollutant oxidation.Various environmental factors including H2O2 concentration,initial pH,catalyst dosage,TCH concentration and inorganic ions were explored.The reactive oxidation species(ROS)quenching results and electron spin resonance(ESR)spectra confirmed that·O2-and·OH were responsible for the dark and photo-Fenton-like systems,respectively.The degradation mechanisms and pathways of TCH were proposed,and the toxicity of products was evaluated.This work contributes a highly efficient and environmentally friendly catalyst and provides a clear mechanistic explanation for the removal of antibiotic pollutants in environmental remediation.
基金Project supported by the Major State Basic Research Development Program of China(Grant Nos.2013CB733802 and 2014CB744503)the National Natural Science Foundation of China(Grant Nos.81101101 and 51273165)+1 种基金the Key Project of Chinese Ministry of Education(Grant No.212149)the Fundamental Research Funds for the Central Universities,China(Grant Nos.2013121039 and ZK1002)
文摘Superparamagnetic iron oxide nanoparticles （SPIONs） are one of the most versatile and safe nanoparticles in a wide variety of biomedical applications. In the past decades, considerable efforts have been made to investigate the potential adverse biological effects and safety issues associated with SPIONs, which is essential for the development of next-generation SPIONs and for continued progress in translational research. In this mini review, we summarize recent developments in toxicity studies on SPIONs, focusing on the relationship between the physicochemical properties of SPIONs and their induced toxic biological responses for a better toxicological understanding of SPIONs.
文摘This study was aimed at evaluating the anti-diabetic potential of passion fruit Passiflora edulis(EPE) extracts in diabetic rats, following Streptozotocin(STZ) induced oxidative stress. Thirty adult Wistar rats were divided into five groups, with six rats in each group. The control rats were injected intraperitoneally with citrate buffer(pH 4.5). The remaining groups of rats were administered single dose of 45 mg·kg-1 of STZ by intraperitoneal route to induce diabetes. The diabetic animals were treated with 250 and 500 mg·kg-1 of EPE and glibenclamide 0.6 mg·kg-1 for fifteen days by oral route. Blood glucose, end organ oxidative stress marker, and anti-oxidants were assayed. Further, histopathological investigation of pancreas was studied at the end of the experimentation. The results revealed that subacute administration of EPE significantly(P < 0.001) controlled the blood glucose level in the diabetic rats. In addition, EPE extract protected the end organs by restoring the anti-oxidants enzyme, significantly increasing super oxide dismutase level(SOD) and decreasing catalase(CAT) and TBARS level in visceral organs. In conclusion, that EPE extracts showed anti-diabetic and anti-oxidant potential against streptozotocin-induced diabetes.
基金NCET-12-0578111 Project B08044Minzu University of China-YLDX01013
文摘Objective To investigate whether salidroside（SAL） has protective and anti-oxidative effects on astrocytes. Methods Firstly, SAL was extracted from the roots of Rhodiola rosea with 70% ethanol and butanol to obtain crude phenylethyl alcohol glycosides which have been known as bioactive part of R. rosea; Secondly, WST-1 assay was carried out to assess the cell viability of astrocytes and cortical neurons under the treatment of the purified（〉 95%） SAL. Moreover, WST-1 assay was also used to evaluate the cytoprotective effects of SAL preventing astrocytes from staurosporine-induced cell death; Thirdly, we examined the spontaneous reactive oxygen species（ROS） and staurosporine-induced ROS generation in astrocytes in the absence or presence of SAL.Results SAL was observed to improve the astrocytes viability but not cortical neurons. In addition, SAL was able to ameliorate staurosporine-induced cell death. Moreover, SAL was able to attenuate the spontaneous ROS and staurosporine-induced ROS generation. Conclusion We here confirm that the anti-oxidative effect of SAL on primary astrocytes might be an important mechanism accounting for the cytoprotective effects from SAL.
基金supported by the National Natural Science Foundation of China(Nos.22007063 and 82002063)Shanxi Medical Key Science and Technology Project Plan of China(No.2020XM01)+4 种基金the National University of Singapore Start-up Grant(No.NUHSRO/2020/133/Startup/08)NUS School of Medicine Nanomedicine Translational Research Program(No.NUHSRO/2021/034/TRP/09/Nanomedicine)the Science Research Start-up Fund for Doctor of Shanxi Province(No.XD1809 and XD2011)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0414)Shanxi Province Science Foundation for Youths(No.201901D211316).
文摘Abnormal metabolism has become a potential target for highly malignant and invasive triple-negative breast cancer(TNBC)due to its relatively low response to traditional therapeutics.The existing metabolic interventions demonstrated unsatisfactory therapeutic outcomes and potential systemic toxicity,resulting from the metabolic instability and limited targeting ability of inhibitors as well as complex tumor microenvironment.To address these limitations,here we developed a robust pyroelectric BaTiO_(3)@Au core–shell nanostructure(BTO@Au)to selectively and persistently block energy generation of tumor cells.Stimulated by near-infrared(NIR)laser,the Au shell could generate heat to activate the BaTiO_(3)core to produce reactive oxygen species(ROS)regardless of the constrained microenvironment,thus prominently inhibits mitochondrial oxidative phosphorylation(OXPHOS)and reduces ATP production to induce TNBC cell apoptosis.The therapeutic effects have been well demonstrated in vitro and in vivo,paving a new way for the development of metabolic interventions.
基金financially supported by the National Natural Science Foundation of China(Nos.51779088,51908528)the Fundamental Research Funds for the Central Universities(No.2021CDJQY-014)the Natural Science Foundation of Hunan Province,China(No.2021JJ30126)。
文摘Recent studies have proposed that the high-valent iron species(such as Fe^(Ⅳ)O^(2+))rather than sulfate radical(SO_(4)^(·-))and hydroxyl radical(·OH)are the main reactive oxidant species(ROS)in Fe(Ⅱ)/peroxydisulfate(PDS)system with the methyl phenyl sulfoxide(PMSO)as the Fe^(Ⅳ)O^(2+)probe.However,many operational factors may interfere with the accuracy of this method,so the contribution of Fe^(Ⅳ)O^(2+)calculated by this method is controversial.In this study,the possible effect of Fe(Ⅱ)concentration,pollutant type,reducing agent,or coexisted anions on Fe^(Ⅳ)O^(2+)production and its corresponding contribution to the removal of target pollutants in the Fe(Ⅱ)/PDS system were investigated in detail,and the intrinsic mechanisms involved were also explored.This study shows that ROS generation is a complex process in the Fe(Ⅱ)/PDS system,and multiple combinatorial approaches are urgently required to deeply explore the contribution of ROS to the elimination of target contaminants.
基金The authors would like to acknowledge the financial support of the China Postdoctoral Science Foundation(2022M711687 and 2022M721691)Key Laboratory for Organic Electronics&Information Displays(GZR2022010010)+3 种基金Nanjing University of Posts and Telecommunications(Start-up Grant:NY221005)the Special Professor Fund of Jiangsu Province(RK030STP21007 and RK030STP22001)Natural Science Foundation of Jiangsu Province(SBK2022044384)National Natural Science Foundation of China(22276100).
文摘Single-atom catalysts(SACs)have been widely recognized as state-of-the-art catalysts in environment remediation because of their exceptional performance,100%metal atomic utilization,almost no secondary pollution,and robust structures.Most recently,the activation of persulfate with carbon-based SACs in advanced oxidation processes(AOPs)raises tremendous interest in the degradation of emerging contaminants in wastewater,owning to its efficient and versatile reactive oxidant species(ROS)generation.However,the comprehensive and critical review unraveling the underlying relationship between structures of carbon-based SACs and the corresponding generated ROS is still rare.Herein,we systematically summarize the fundamental understandings and intrinsic mechanisms between single metal atom active sites and produced ROS during AOPs.The types of emerging contaminants are firstly elaborated,presenting the prior pollutants that need to be degraded.Then,the preparation and characterization methods of carbon-based SACs are overviewed.The underlying material structure–ROS type relationship in persulfate-based AOPs is discussed in depth to expound the catalytic mechanisms.Finally,we briefly conclude the current development of carbon-based SACs in AOPs and propose the prospects for rational design and synthesis of carbon-based SACs with on-demand catalytic performances in AOPs in future research.
基金This work was supported by the National Natural Science Foundation of China(Nos.U20A20133,21777187)the Royal Society International Collaboration Award for Research Professors(No.IC160121).
文摘Per-and polyfluoroalkyl substances(PFAS)are found to have multiple adverse outcomes on human health.Recently,epidemiological and toxicological studies showed that exposure to PFAS had adverse impacts on pancreas and showed association with insulin abnormalities.To explore how PFAS may contribute to diabetes,we studied impacts of perfluorooctane sul-fonate(PFOS)on cell viability and insulin release capacity of pancreatic β cells by using in vivo and in vitro methods.We found that 28-day administration with PFOS(10 mg/(kg body weight·day))caused reductions of pancreas weight and islet size in male mice.PFOS admin-istration also led to lower serum insulin level both in fasting state and after glucose infusion among male mice.For cell-based in vitro bioassay,we used mouse β-TC-6 cancer cells and found 48-hr exposure to PFOS decreased the cell viability at 50 μmol/L.By measuring insulin content in supernatant,48-hr pretreatment of PFOS(100 μmol/L)decreased the insulin re-lease capacity of β-TC-6 cells after glucose stimulation.Although these concentrations were higher than the environmental concentration of PFOS,it might be reasonable for high con-centration of PFOS to exert observable toxic effects in mice considering mice had a faster removal efficiency of PFOS than human.PFOS exposure(50 μmol/L)to β-TC-6 cells induced intracellular accumulation of reactive oxidative specie(ROS).Excessive ROS induced the re-active toxicity of cells,which eventually invoke apoptosis and necrosis.Results in this study provide evidence for the possible causal link of exposure to PFOS and diabetes risk.
基金supported by the Ministry of Science and Technology of China(Nos.2016YFA0203102,2016YFC0900301 and 2014CB932003)the National Natural Science Foundation of China(Nos.21375142,21321004,and 21435008)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB14030000)
文摘Halobenzoquinones（HBQs） are an emerging class of halogenated disinfection byproducts（DBPs） in drinking water, which raised public concerns due to potential carcinogenic effects to human bladder. Our previous work demonstrated that HBQs and hydrogen peroxide（H_2O_2）together generated oxidative DNA damage via a metal-independent and intercalationenhanced oxidation mechanism in vitro. This study further investigated the efficiency of various HBQs to induce oxidative DNA damage in T24 bladder cancer cells. Compared with T24 cells without treatment（3.1 lesions per 10~6 d G）, the level of 8-oxo-7,8-dihydro-2′-deoxyguanosine（8-oxod G） significantly increased by 1.4, 3.2, 8.8, and 9.2 times after treatment with tetrabromo-1,4-benzoquinone（TBBQ）, terachloro-1,4-benzoquinone（TCBQ）,2,6-dichloro-1,4-benzoquinone（2,6-DCBQ） and 2,5-dichloro-1,4-benzoquinone（2,5-DCBQ） for24 hr, respectively. Interestingly, we found that the oxidative potency of HBQs in T24 cells（2,5-DCBQ ≈ 2,6-DCBQ 〉 TCBQ 〉 TBBQ） is inconsistent with that of in vitro ds DNA oxidation（TCBQ 〉 TBBQ 〉 2,5-DCBQ 〉 2,6-DCBQ）, suggesting HBQs induce oxidative lesions in cellular genomic DNA probably involved with a complex mechanism.
文摘Zinc oxide nanoparticles（ZnO NPs） are among the most commonly utilized nanomaterials. They are used in a wide range of applications, including medicine, sunscreens, cosmetics, paints, catalysis, electronics, as well as biosensors, and hence, it is crucial to illustrate their biological effects and risks. In the present study, the effects and mechanism of ZnO NPs（≤5 nm） were investigated in rat glioma C6 cells in vitro. The results of transmission electron microscopy（TEM） and X-ray difffaction（XRD） show that ZnO NPs are pure with a uniform diameter of ca. 5 nm 3-（4,5-Dimethylthiazol-2yl）-2,5-diphenyltetrazolium bromide（MTT） assays on C6 cells show that ZnO NPs, at different concentrations（0-5 I^g/mL）, can induce significant cytotoxicity in C6 cells in a dose-dependent manner. An increased level of reactive oxygen species（ROS）, a decreased level of glutathione（GSH）, and an elevated level of glutathione disulfide（GSSG） and the toxicity mechanism are primarily attributed to the induced cellular oxidative stress. 4＇,6-Diamidino-2-phenylindole（DAPI） staining was used to observe the apoptosis. The results show that C6 cells treated with the ZnO NPs at various concentrations（0, 1.25, 2.5 and 5 μg/mL） can induce apoptosis in a dose-dependent manner. These results suggest that ZnO NPs are the killers of the rat glioma C6 cells, and oxidative stress is the underlying mechanism of this process.
文摘Aim:Emerging evidence favors the important role of antioxidants,matrix metalloproteinases(MMPs),and nitric oxide(NO)in the healing of diabetic wounds.There is a lack of substantial evidence regarding the effects of negative pressure on antioxidants,MMPs and NO in chronic wounds associated with diabetes.Methods:A total of 55 type 2 diabetic patients with leg ulcers were divided into 2 groups:a limited access dressing(LAD)group(n=27)and a conventional dressing group(n=28).Levels of hydroxyproline,total protein,MMP-2 and MMP-9,NO and antioxidants including reduced glutathione(GSH)and the oxidative biomarker malondialdehyde(MDA)were measured in the granulation tissue at days 0 and 10.Changes in levels between the LAD and conventional groups were determined by the Student’s t-test.Results:After 10 days of treatment,the LAD vs.conventional dressing group showed increase in the levels of hydroxyproline(mean±standard deviation=55.2±25.1 vs.29.2±1,P<0.05),total protein(12.8±6.5 vs.8.34±3.2,P<0.05),NO(1.13±0.52 vs.0.66±0.43,P<0.05),GSH(7.0±2.4 vs.6.6±2.2,P<0.05)and decrease in MMP-2(0.47±0.33 vs.0.62±0.30,P<0.05),MMP-9(0.32±0.20 vs.0.53±0.39,P<0.05)and MDA(6.8±2.3 vs.10.4±3.4,P<0.05).Conclusion:When compared to conventional dressings,LAD induces biochemical changes by significantly increasing the levels of hydroxyproline,total protein,NO and antioxidants levels,and significantly reducing MMPs(MMP-2 and MMP-9)and an oxidative biomarker in diabetic wounds.These biochemical changes are thought to favor diabetic wound healing.
