Urinary 8-hydroxy-2 -deoxyguanosine(8-OHdG) is an excellent marker of oxidative DNA damage.In this study,employing guanosine as dummy template a novel molecularly imprinted(MIP) monolithic capillary column had been sy...Urinary 8-hydroxy-2 -deoxyguanosine(8-OHdG) is an excellent marker of oxidative DNA damage.In this study,employing guanosine as dummy template a novel molecularly imprinted(MIP) monolithic capillary column had been synthesized,and that was used as medium of in-tube solid phase microextraction(SPME).Coupled with capillary electrophoresis-electrochemical detection(CE-ECD),the system of extraction and detection of 8-OHdG in urinary sample had been developed.Because of its greater phase ratio combined with conv...展开更多
Spontaneous preterm birth (SPTB) is characterized by the delivery of a baby before 37 completed weeks of gestation, and this condition is associated with significant health challenges for the newborn. Emerging evidenc...Spontaneous preterm birth (SPTB) is characterized by the delivery of a baby before 37 completed weeks of gestation, and this condition is associated with significant health challenges for the newborn. Emerging evidence highlights the importance of biomarkers for understanding the mechanisms underlying SPTB. One such biomarker, 8-OH-2dG, plays a critical role in evaluating oxidative stress and its impact on pregnancy outcomes. It has been demonstrated that 8-OH-2dG is a product of oxidative DNA damage and is widely recognized as a key indicator of cellular oxidative stress. Elevated reactive oxygen species in SPTB result in higher levels of the DNA degradation product 8-OH-2dG in amniotic fluid, causing damage to maternal and fetal tissues that could lead to premature rupture of fetal membranes. Therefore, evaluating the role of 8-OH-2dG in SPTB is of great interest. This review provides an overview of the current knowledge on 8-OH-2dG as a biomarker for SPTB and aims to elucidate its mechanism in this condition.展开更多
Reactive oxygen species may be involved in the progression of gastric carcinomas. To clarify whether the pathology of gastric carcinoma are related to oxidative DNA damage, the expression of 8-hydroxy-2＇-deoxyguanosi...Reactive oxygen species may be involved in the progression of gastric carcinomas. To clarify whether the pathology of gastric carcinoma are related to oxidative DNA damage, the expression of 8-hydroxy-2＇-deoxyguanosine （8-OHdG） was examined in 30 patients with gastric carcinomas. Methods： The expression of 8-OHdG and apoptosis in the gastric carcinoma were measured using the methods of immunocytochemistry and deoxynucleartididyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）, respectively. Results： Of the 30 cases, 25（83%） showed stronger immunoreactivity than normal control. The patients with poorly differentiated gastric carcinoma had a larger tumor size and higher labeling indices of TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated gastric carcinoma. Conclusion： Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic gastric injuries and determination of 8-OHdG is useful in assessing high-grade malignancy in gastric carcinomas.展开更多
8-hydroxy-2’-deoxyguanosine (8-OHdG), a typical form ofDNA adducts, is a key molecular biomarker for DNA oxidativedamage. The aim of the present study was to evaluote the correla-tion between the sperm DNA 8-OHdG lev...8-hydroxy-2’-deoxyguanosine (8-OHdG), a typical form ofDNA adducts, is a key molecular biomarker for DNA oxidativedamage. The aim of the present study was to evaluote the correla-tion between the sperm DNA 8-OHdG level and the semen quality.In 52 male infertile patients, the sperm DNA 8-OHdG level wasdetermined by a high performance liquid chromatograph with elec-trochemical detector and the semen quality was examined according展开更多
8-Oxoguanine （8-oxoG）, a critical mutagenic DNA lesion induced by reactive oxy- gen species, gives rise to a G·C→T·A transversion during replication and thereby must be repaired. The effects of explicit a...8-Oxoguanine （8-oxoG）, a critical mutagenic DNA lesion induced by reactive oxy- gen species, gives rise to a G·C→T·A transversion during replication and thereby must be repaired. The effects of explicit and implicit solvent molecules on the hydrolysis cleavage of N-Glycosidic bond in 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxo-dG） have been systematically clarified in the present work based upon two types of computational models. Detailed potential energy surface （PES） scans and full unconstraint optimizations for all the representative points on PESs were carried out at the B3LYP/6-31＋G（d） level of theory. The effect of implicit solvent was tested by single-point calculation at the SCRF/IEF-PCM model. The results illustrate that the direct hydrolysis model involving one explicit water molecule can’t provide a complete depiction of the hydrolysis process of 8-oxo-dG, attributed to the insufficiency of nucleophile activation and leaving group stabilization. The expansion hydrolysis model involving four explicit water molecules, however, facilitates discrete proton transfer and therefore produces smooth reaction surfaces for both the dissociative （SN1） and concerted （SN2） pathways. The presence of the implicit solvent substantially lowers all activation energies and the SN1 process is more favorable than the SN2 process. The data and insights present here agree well with the experimental results and have given out a baseline for the enzymatic deglycosylation reaction of 8-oxo-dG.展开更多
2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) 4l-s produced from reaction between dimedone with various aldehydes in acetonitrile using ZnO as a catalyst;whereas in the presence of ZnO-acetyl ...2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) 4l-s produced from reaction between dimedone with various aldehydes in acetonitrile using ZnO as a catalyst;whereas in the presence of ZnO-acetyl chloride catalysts the reaction is limited to give only 1,8-dioxo-octahydroxanthenes 3a-k in very good yields.展开更多
Previous studies have reported a neuroprotective effect of 8-hydroxy-2-（di-n-propylamino）tetralin （8-OH-DPAT） against traumatic brain injury. In accordance with the Marmarou method, rat models of diffuse axonal in...Previous studies have reported a neuroprotective effect of 8-hydroxy-2-（di-n-propylamino）tetralin （8-OH-DPAT） against traumatic brain injury. In accordance with the Marmarou method, rat models of diffuse axonal injury were established. 8-OH-DPAT was intraperitoneally injected into model rats. 8-OH-DPAT treated rats maintained at constant temperature served as normal temperature controls TUNEL results revealed that neural cell swelling, brain tissue necrosis and cell apoptosis occurred around the injured tissue. Moreover, the number of Bax-, Bcl-2- and caspase-3-positive cells increased at 6 hours after diffuse axonal injury, and peaked at 24 hours. However, brain injury was attenuated, the number of apoptotic cells reduced, Bax and caspase-3 expression decreased, and Bcl-2 expression increased at 6, 12, 24, 72 and 168 hours after diffuse axonal injury in normal temperature control and in 8-OH-DPAT-intervention rats. The difference was most significant at 24 hours. All indices in 8-OH-DPAT-intervention rats were better than those in the constant temperature group. These results suggest that 8-OH-DPAT inhibits Bax and caspase-3 expression, increases Bcl-2 expression, and reduces neural cell apoptosis, resulting in neuroprotection against diffuse axonal injury. This effect is associated with a decrease in brain temperature.展开更多
A composite film of DNA/poly(3-methylthiophene)(P3MT) modified glassy carbon electrode(GCE) has been fabricated by electro-deposition method.P3MT film was first electropolymerized at the GCE and the DNA layer was then...A composite film of DNA/poly(3-methylthiophene)(P3MT) modified glassy carbon electrode(GCE) has been fabricated by electro-deposition method.P3MT film was first electropolymerized at the GCE and the DNA layer was then immobilized on the P3MT layer by electrochemical method.The voltammetric behavior of 8-hydroxy-2'-deoxyguanosine(8-OH-dG) at the composite film modified electrode was studied.The effects of scan rates,pH and the interference of uric acid(UA) on the voltammetric behavior and detection of 8-OH-dG were also discussed.The experimental results suggest that the electrochemical behavior of 8-OH-dG at the composite film modified electrode was greatly improved due to the combination of the advantages of P3MT and DNA.In 0.1 M pH 7.0 phosphate buffer solution(PBS),the anodic peak currents of 8-OH-dG were linear with the 8-OH-dG concentration in two intervals,viz.0.28―4.2 μM and 4.2―19.6 μM.The detection limit of 56 nM 8-OH-dG could be estimated(S/N=3).This proposed composite film modified electrode shows excellent reproducibility and stability.It may have the potential application for the detection of 8-OH-dG in human urine.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
Oxidative stress may be the unifying factor for the injury caused by hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major isoflavonoid derived from Radix puerariae and has been shown to be effective ...Oxidative stress may be the unifying factor for the injury caused by hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major isoflavonoid derived from Radix puerariae and has been shown to be effective in increasing superoxide dismutase activity. This study sought to investigate the neuroprotective effect of puerarin on high glucose-induced oxidative stress and Schwann cell apoptosis in vitro. Intracellular reactive oxygen radicals and mitochondrial transmembrane potential were detected by flow cytometry analysis. Apoptosis was confirmed by TUNEL and oxidative stress was monitored using an enzyme-linked immunosorbent assay for the DNA marker 8-hydroxy-2-deoxyguanosine. The expression levels of bax and bcl-2 were analyzed by quantitative real-time reverse transcriptase-PCR, while protein expression of cleaved caspase-3 and -9 were analyzed by means of western blotting. Results suggested that puerarin treatment inhibited high glucose-induced oxidative stress, mitochondrial depolarization and apoptosis in a dose-dependent manner. Furthermore, puerarin treatment downregulated Bax expression, upregulated bcl-2 expression and attenuated the activation of caspase-3 and -9. Overall, our results indicated that puerarin antagonized high glucose-induced oxidative stress and apoptosis in Schwann cells.展开更多
AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesi...AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.展开更多
The major clinical disturbances in Parkinson’s disease (PD) are consequence of dopamine depletion in the neostriatum, due to degeneration of dopaminergic neurons. The aim of the present study was to determine whether...The major clinical disturbances in Parkinson’s disease (PD) are consequence of dopamine depletion in the neostriatum, due to degeneration of dopaminergic neurons. The aim of the present study was to determine whether oxidative stress (OS) occurs during the clinical course of Parkinson’s disease and to evaluate the influence of therapy on the levels of some important final products of oxidation of lipids, proteins and nucleic acids in PD patients with drug therapy. For this purpose, we investigated the levels of malondialdehid (MDA), protein carbonyl content (PCC) and 8-hydroxy-2’-deoxyguanosine quantity (8-OHdG) in PD patients with and without drug therapy. The observed changes in MDA levels, PCC and 8-OHdG quantity in blood of untreated PD patients, suggested impaired antioxidant status and presence of oxidative stress in Parkinson disease. After treatment with Madopar, the elevation in by-products significantly progresses. Our results demonstrate that administration of Madopar causes in greater degree oxidative stress than that induced by Parkinson disease, by itself.展开更多
Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy （2-oxopropyl）-methyl ester 2, were isola...Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy （2-oxopropyl）-methyl ester 2, were isolated from Ervatamia hainanensis. Their structures were elucidated on the basis of spectroscopic methods.展开更多
A new halogenated biindole and a new apo-carotenone have been isolated from the ethanolic extract of the green alga Chaetomorpha basiretorsa Sethcell. On the basis of chemical and spectroscopic methods including 2D NM...A new halogenated biindole and a new apo-carotenone have been isolated from the ethanolic extract of the green alga Chaetomorpha basiretorsa Sethcell. On the basis of chemical and spectroscopic methods including 2D NMR technique, their structures have been elucidated as 4,4′-dichloro-5,5′-dibromo-7,7′-dimethoxy-2,2′-bi-1H-indole and 1′S*,4′R*-8-(4′-hydroxy-2′,6′,6′- trimethylcyclohex-2-enyl)-6-methyloct-3E,5E,7E-trien-2-one, respectively.展开更多
A new chromone derivative, 3-[1- (2, 4, 6-trihydroxyphenyl) 3-di-(4-hydroxyphenyl) 1-propanone-2-yl] 5,7-dihydroxy-8-di(4-hydroxyphenyl)methyl-4H-1-benzopyran-4-one, named as isomohsenone was isolated from the roots o...A new chromone derivative, 3-[1- (2, 4, 6-trihydroxyphenyl) 3-di-(4-hydroxyphenyl) 1-propanone-2-yl] 5,7-dihydroxy-8-di(4-hydroxyphenyl)methyl-4H-1-benzopyran-4-one, named as isomohsenone was isolated from the roots of Stellera chamaejasme L. together with known chamaechromone. Its structure was determined by the analysis of MS and NMR data, especially 2D NMR spectra.展开更多
A novel method for the determination of cationic surfactant by laser thermal lens spectrometry was developed. It was based on the reaction between 1-hydroxy-2-(5-nitro-2-Pyri- dylazo)-8-aminonaphthalene-3,6-disulfoni...A novel method for the determination of cationic surfactant by laser thermal lens spectrometry was developed. It was based on the reaction between 1-hydroxy-2-(5-nitro-2-Pyri- dylazo)-8-aminonaphthalene-3,6-disulfonic acid (5-NO2-PAH) and cationic surfactant to form 1:2 ionic association complex in a weakly basic medium (pH 9.44). The determination conditions and the mechanism were discussed. The method has been applied to the analysis of wastewater and moat water samples.展开更多
Objective To establish a fast and sensitive method for the detection of 8-hydroxy-2’-deoxyguanosine （8-OHdG） in precision-cut rat liver slices by HPLC-MS/MS and to investigate isoniazid （INH） -induced oxidative D...Objective To establish a fast and sensitive method for the detection of 8-hydroxy-2’-deoxyguanosine （8-OHdG） in precision-cut rat liver slices by HPLC-MS/MS and to investigate isoniazid （INH） -induced oxidative DNA damage. Methods Precision-cut liver slices （300 μm） were prepared from male rats, and incubated with INH （0.018 mol/L） for 2 h after 1 h preincubation. DNA in the slices was extracted and digested into free nucleosides at 37℃ . The samples were injected into HPLC-MS/MS after the proteins were removed. The level of oxidative DNA damage was estimated using the ratio of 8-OHdG to deoxyguanosine （dG）. Results The limit of detection of 8-OHdG was 1 ng/mL （S/N=3） and the intra-assay relative standard variation was 3.38% when one transition 284.3/168.4 was used as a quantifier and another two transitions 284.3/140.2, 306.1/190.2 as qualifiers. 8-OHdG and dG were well separated, as indicated by elution at 10.02 and 7.37 min, respectively. INH significantly increased the ratio of 8-OHdG to dG in rat liver slices （P〈0.05）. Conclusion 8-OHdG in precision-cut liver slices could be sensitively determined by HPLC-MS/MS. HPLC-MS/MS coupled with precision-cut tissue slices is a fast and reliable analytical technique to evaluate oxidative DNA damage of target tissues caused by procarcinogens and cytotoxins.展开更多
Methylene blue sensitized singlet oxygen oxidation of dl-α-tocopherol in dodecylsulfate (SDS) or cetyl trimethyl ammonium brondde (CTAB) ndcelles led to the formation, besidesα-tocopherol quinone and its epoxide, of...Methylene blue sensitized singlet oxygen oxidation of dl-α-tocopherol in dodecylsulfate (SDS) or cetyl trimethyl ammonium brondde (CTAB) ndcelles led to the formation, besidesα-tocopherol quinone and its epoxide, of a hitherto unknown spiro compound 6-hydroxy-2,6,8,9-tetramethyl-2-phytyl- 1-oxaspiro [4, 5] dec -8 - en - 7, 10-dione.展开更多
This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential h...This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential hypothermic and behavioral responses to the anticholinesterase, diisopropylfluorophosphate (DFP). FSL rats are more sensitive to the hypothermic effects of cholinergic, serotonergic, and dopaminergic agonists but less sensitive to the locomotor or stereotypic effects of dopamine agonists. FSL rats exhibit greater immobility in the forced swim test and reduced social interaction compared with FRL rats, but do not differ in saccharin intake, behavior in the elevated plus maze, or responses for rewarding brain self-stimulation. The exaggerated immobility and reduced social interaction are counteracted by chronic treatment with antidepressants. Because FSL rats were more sensitive to 5-HT1A receptor agonists, high (HDS) and low (LDS) 8-OH-DPATsensitive lines were selectively bred for differential hypothermic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). HDS rats were also more sensitive to the hypothermic effects of oxotremorine, a cholinergic agonist, but selection for this response did not diverge with later selection. HDS rats exhibited greater immobility in the forced swim test than LDS rats and this correlated response could be seen early in selection (generation 3). HDS rats also showed reduced social interaction compared to LDS rats, but did not differ in behavior in the elevated plus maze. These findings confirm that selection for hypothermic responses to pharmacological agents do have behavioral consequences, notably the production of depressive-like phenotypes, which can be counteracted by chronic antidepressant treatment. Because increased 5-HT1A receptor sensitivity was common to both selected lines (FSL and HDS), neurobiological processes dependent on this receptor could contribute to the abnormal behaviors that manifest in these rat lines and thus suggesting a mechanism underlying depressive behaviors in humans. However, available human data are inconsistent with this hypothesis and suggest that other mechanisms underlie these behavioral abnormalities in HDS and FSL rats. These mechanisms as well as additional behavioral testing in these rat lines will be discussed.展开更多
Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. Clinical trials focused on prevention of cardiovascular and neoplasti...Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. Clinical trials focused on prevention of cardiovascular and neoplastic diseases involving antioxidant supplementation have however provided predominantly negative obserations in large-scale studies. Screening of patient cohorts to assess baseline oxidative stress on the basis of a biomarker profile is decisive but lacking. For the first time, we evaluated the level of oxidative stress, testing more than 10 established biomarkers, in a comprehensive initial survey of 617 patients displaying chronic human pathologies. Multiple diseasespecific abnormalities were identified in plasma, whole blood and/or urine. This is the case for vitamins and oligo elements, vitamin C, vitamin E, β-carotene, selenium, zinc and copper;endogenous antioxidants such as reduced and oxidised glutathione, thiols, urate, and glutathione peroxidase activity, and a biomarker of oxidative DNA damage (8-hydroxy-2’-deoxy guanosine). The distinct biomarker profiles suggest the involvment of multiple forms of oxidative insults which arein some way partially specific to each pathological condition. This finding is in favor of the determination of an integrated score to combine contributions of distinct biomarkers, in order to screen patients presenting elevated levels of oxidative stress.展开更多
基金the support of the National Natural Science Foundation of China(No.20575051).
文摘Urinary 8-hydroxy-2 -deoxyguanosine(8-OHdG) is an excellent marker of oxidative DNA damage.In this study,employing guanosine as dummy template a novel molecularly imprinted(MIP) monolithic capillary column had been synthesized,and that was used as medium of in-tube solid phase microextraction(SPME).Coupled with capillary electrophoresis-electrochemical detection(CE-ECD),the system of extraction and detection of 8-OHdG in urinary sample had been developed.Because of its greater phase ratio combined with conv...
文摘Spontaneous preterm birth (SPTB) is characterized by the delivery of a baby before 37 completed weeks of gestation, and this condition is associated with significant health challenges for the newborn. Emerging evidence highlights the importance of biomarkers for understanding the mechanisms underlying SPTB. One such biomarker, 8-OH-2dG, plays a critical role in evaluating oxidative stress and its impact on pregnancy outcomes. It has been demonstrated that 8-OH-2dG is a product of oxidative DNA damage and is widely recognized as a key indicator of cellular oxidative stress. Elevated reactive oxygen species in SPTB result in higher levels of the DNA degradation product 8-OH-2dG in amniotic fluid, causing damage to maternal and fetal tissues that could lead to premature rupture of fetal membranes. Therefore, evaluating the role of 8-OH-2dG in SPTB is of great interest. This review provides an overview of the current knowledge on 8-OH-2dG as a biomarker for SPTB and aims to elucidate its mechanism in this condition.
基金Nature Science Fundation of Jiangsu Province (BK2004146)Science Fund of Department of Education of Jiangsu Province (03KJB310085)
文摘Reactive oxygen species may be involved in the progression of gastric carcinomas. To clarify whether the pathology of gastric carcinoma are related to oxidative DNA damage, the expression of 8-hydroxy-2＇-deoxyguanosine （8-OHdG） was examined in 30 patients with gastric carcinomas. Methods： The expression of 8-OHdG and apoptosis in the gastric carcinoma were measured using the methods of immunocytochemistry and deoxynucleartididyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）, respectively. Results： Of the 30 cases, 25（83%） showed stronger immunoreactivity than normal control. The patients with poorly differentiated gastric carcinoma had a larger tumor size and higher labeling indices of TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated gastric carcinoma. Conclusion： Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic gastric injuries and determination of 8-OHdG is useful in assessing high-grade malignancy in gastric carcinomas.
文摘8-hydroxy-2’-deoxyguanosine (8-OHdG), a typical form ofDNA adducts, is a key molecular biomarker for DNA oxidativedamage. The aim of the present study was to evaluote the correla-tion between the sperm DNA 8-OHdG level and the semen quality.In 52 male infertile patients, the sperm DNA 8-OHdG level wasdetermined by a high performance liquid chromatograph with elec-trochemical detector and the semen quality was examined according
基金supported by the National Natural Science Foundation of China(21203153 and 21173151)Science&Technology Department(2011JY0136)+1 种基金Department of Education(12ZA174)of Sichuan ProvinceChina West Normal University(11B002)
文摘8-Oxoguanine （8-oxoG）, a critical mutagenic DNA lesion induced by reactive oxy- gen species, gives rise to a G·C→T·A transversion during replication and thereby must be repaired. The effects of explicit and implicit solvent molecules on the hydrolysis cleavage of N-Glycosidic bond in 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxo-dG） have been systematically clarified in the present work based upon two types of computational models. Detailed potential energy surface （PES） scans and full unconstraint optimizations for all the representative points on PESs were carried out at the B3LYP/6-31＋G（d） level of theory. The effect of implicit solvent was tested by single-point calculation at the SCRF/IEF-PCM model. The results illustrate that the direct hydrolysis model involving one explicit water molecule can’t provide a complete depiction of the hydrolysis process of 8-oxo-dG, attributed to the insufficiency of nucleophile activation and leaving group stabilization. The expansion hydrolysis model involving four explicit water molecules, however, facilitates discrete proton transfer and therefore produces smooth reaction surfaces for both the dissociative （SN1） and concerted （SN2） pathways. The presence of the implicit solvent substantially lowers all activation energies and the SN1 process is more favorable than the SN2 process. The data and insights present here agree well with the experimental results and have given out a baseline for the enzymatic deglycosylation reaction of 8-oxo-dG.
基金support from the Research Council of University of Sistan and Baluchestan, Iran
文摘2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) 4l-s produced from reaction between dimedone with various aldehydes in acetonitrile using ZnO as a catalyst;whereas in the presence of ZnO-acetyl chloride catalysts the reaction is limited to give only 1,8-dioxo-octahydroxanthenes 3a-k in very good yields.
基金funded by the Natural Science Foundation of Technology Department of Liaoning Province, No.20032047
文摘Previous studies have reported a neuroprotective effect of 8-hydroxy-2-（di-n-propylamino）tetralin （8-OH-DPAT） against traumatic brain injury. In accordance with the Marmarou method, rat models of diffuse axonal injury were established. 8-OH-DPAT was intraperitoneally injected into model rats. 8-OH-DPAT treated rats maintained at constant temperature served as normal temperature controls TUNEL results revealed that neural cell swelling, brain tissue necrosis and cell apoptosis occurred around the injured tissue. Moreover, the number of Bax-, Bcl-2- and caspase-3-positive cells increased at 6 hours after diffuse axonal injury, and peaked at 24 hours. However, brain injury was attenuated, the number of apoptotic cells reduced, Bax and caspase-3 expression decreased, and Bcl-2 expression increased at 6, 12, 24, 72 and 168 hours after diffuse axonal injury in normal temperature control and in 8-OH-DPAT-intervention rats. The difference was most significant at 24 hours. All indices in 8-OH-DPAT-intervention rats were better than those in the constant temperature group. These results suggest that 8-OH-DPAT inhibits Bax and caspase-3 expression, increases Bcl-2 expression, and reduces neural cell apoptosis, resulting in neuroprotection against diffuse axonal injury. This effect is associated with a decrease in brain temperature.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 20475024 & 20775031)the Shandong Tai-Shan Scholar Research Fund
文摘A composite film of DNA/poly(3-methylthiophene)(P3MT) modified glassy carbon electrode(GCE) has been fabricated by electro-deposition method.P3MT film was first electropolymerized at the GCE and the DNA layer was then immobilized on the P3MT layer by electrochemical method.The voltammetric behavior of 8-hydroxy-2'-deoxyguanosine(8-OH-dG) at the composite film modified electrode was studied.The effects of scan rates,pH and the interference of uric acid(UA) on the voltammetric behavior and detection of 8-OH-dG were also discussed.The experimental results suggest that the electrochemical behavior of 8-OH-dG at the composite film modified electrode was greatly improved due to the combination of the advantages of P3MT and DNA.In 0.1 M pH 7.0 phosphate buffer solution(PBS),the anodic peak currents of 8-OH-dG were linear with the 8-OH-dG concentration in two intervals,viz.0.28―4.2 μM and 4.2―19.6 μM.The detection limit of 56 nM 8-OH-dG could be estimated(S/N=3).This proposed composite film modified electrode shows excellent reproducibility and stability.It may have the potential application for the detection of 8-OH-dG in human urine.
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.
基金supported by the National Natural Science Foundation of China, No. 30973354
文摘Oxidative stress may be the unifying factor for the injury caused by hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major isoflavonoid derived from Radix puerariae and has been shown to be effective in increasing superoxide dismutase activity. This study sought to investigate the neuroprotective effect of puerarin on high glucose-induced oxidative stress and Schwann cell apoptosis in vitro. Intracellular reactive oxygen radicals and mitochondrial transmembrane potential were detected by flow cytometry analysis. Apoptosis was confirmed by TUNEL and oxidative stress was monitored using an enzyme-linked immunosorbent assay for the DNA marker 8-hydroxy-2-deoxyguanosine. The expression levels of bax and bcl-2 were analyzed by quantitative real-time reverse transcriptase-PCR, while protein expression of cleaved caspase-3 and -9 were analyzed by means of western blotting. Results suggested that puerarin treatment inhibited high glucose-induced oxidative stress, mitochondrial depolarization and apoptosis in a dose-dependent manner. Furthermore, puerarin treatment downregulated Bax expression, upregulated bcl-2 expression and attenuated the activation of caspase-3 and -9. Overall, our results indicated that puerarin antagonized high glucose-induced oxidative stress and apoptosis in Schwann cells.
基金Supported by the Khon Kaen University Research Fund in Thailand Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan
文摘AIM： Nitrative and oxidative DNA damage such as 8-nitroguanine and 8-oxo-7,8-dihydro-2＇-deoxyguanosine （8-oxodG） formation has been implicated in initiation and/ or promotion of inflammation-mediated carcinogenesis. The aim of this study is to clarify whether these DNA lesions participate in the progression of intrahepatic cholangiocarcinoma. METHODS： We investigated the relation of the formation of 8-nitroguanine and 8-oxodG and the expression of hypoxia-inducible factor-1α （HIF-1α） with tumor invasion in 37 patients with intra-hepatic cholangiocarcinoma. RESULTS： Immunohistochemical analyses revealed that 8-nitroguanine and 8-oxodG formation occurred to a much greater extent in cancerous tissues than in non-cancerous tissues. HIF-1α could be detected in cancerous tissues in all patients, suggesting low oxygen tension in the tumors. HIF-1α expression was correlated with inducible niltric oxide synthase （iNOS） expression （r = 0.369 and P = 0.025） and 8-oxodG formation （r = 0.398 and P = 0.015）. Double immunofluorescence study revealed that iNOS and HIF-1α co-localized in cancerous tissues. Notably, the formation of 8-oxodG was correlated significantly with lymphatic invasion （r = 0.386 and P = 0.018）. Moreover, 8- nitroguanine and 8-oxodG in non-cancerous tissues were associated significantly with neural invasion （P = 0.042 and P = 0.026, respectively）. These results suggest that reciprocal activation between HIF-1α and iNOS mediates persistent DNA damage, which induces tumor invasiveness via mutations, resulting in poor prognosis. CONCLUSION： The formation of 8-nitroguanine and 8-oxodG plays an important role in multiple steps of genetic changes leading to tumor progression, including invasiveness.
文摘The major clinical disturbances in Parkinson’s disease (PD) are consequence of dopamine depletion in the neostriatum, due to degeneration of dopaminergic neurons. The aim of the present study was to determine whether oxidative stress (OS) occurs during the clinical course of Parkinson’s disease and to evaluate the influence of therapy on the levels of some important final products of oxidation of lipids, proteins and nucleic acids in PD patients with drug therapy. For this purpose, we investigated the levels of malondialdehid (MDA), protein carbonyl content (PCC) and 8-hydroxy-2’-deoxyguanosine quantity (8-OHdG) in PD patients with and without drug therapy. The observed changes in MDA levels, PCC and 8-OHdG quantity in blood of untreated PD patients, suggested impaired antioxidant status and presence of oxidative stress in Parkinson disease. After treatment with Madopar, the elevation in by-products significantly progresses. Our results demonstrate that administration of Madopar causes in greater degree oxidative stress than that induced by Parkinson disease, by itself.
文摘Two new indole alkaloids, named ibogamine-18-carboxylic acid, 3, 4-didehydro-7, 8-dioxo-methyl ester 1, ibogamine-18-carboxylic acid, 16, 17-didehydro-9, 17-dihydro-9-hydroxy （2-oxopropyl）-methyl ester 2, were isolated from Ervatamia hainanensis. Their structures were elucidated on the basis of spectroscopic methods.
基金supported by national 863 project(Grant No.2004AA625030,2001AA620503)NNSFC(Grant No.20432030)Key Innovative Project of the Academy(Grant No.KZCX3-SW-215).
文摘A new halogenated biindole and a new apo-carotenone have been isolated from the ethanolic extract of the green alga Chaetomorpha basiretorsa Sethcell. On the basis of chemical and spectroscopic methods including 2D NMR technique, their structures have been elucidated as 4,4′-dichloro-5,5′-dibromo-7,7′-dimethoxy-2,2′-bi-1H-indole and 1′S*,4′R*-8-(4′-hydroxy-2′,6′,6′- trimethylcyclohex-2-enyl)-6-methyloct-3E,5E,7E-trien-2-one, respectively.
文摘A new chromone derivative, 3-[1- (2, 4, 6-trihydroxyphenyl) 3-di-(4-hydroxyphenyl) 1-propanone-2-yl] 5,7-dihydroxy-8-di(4-hydroxyphenyl)methyl-4H-1-benzopyran-4-one, named as isomohsenone was isolated from the roots of Stellera chamaejasme L. together with known chamaechromone. Its structure was determined by the analysis of MS and NMR data, especially 2D NMR spectra.
文摘A novel method for the determination of cationic surfactant by laser thermal lens spectrometry was developed. It was based on the reaction between 1-hydroxy-2-(5-nitro-2-Pyri- dylazo)-8-aminonaphthalene-3,6-disulfonic acid (5-NO2-PAH) and cationic surfactant to form 1:2 ionic association complex in a weakly basic medium (pH 9.44). The determination conditions and the mechanism were discussed. The method has been applied to the analysis of wastewater and moat water samples.
基金This research was supported by the National Natural Science Foundation of China (No. 30600773).
文摘Objective To establish a fast and sensitive method for the detection of 8-hydroxy-2’-deoxyguanosine （8-OHdG） in precision-cut rat liver slices by HPLC-MS/MS and to investigate isoniazid （INH） -induced oxidative DNA damage. Methods Precision-cut liver slices （300 μm） were prepared from male rats, and incubated with INH （0.018 mol/L） for 2 h after 1 h preincubation. DNA in the slices was extracted and digested into free nucleosides at 37℃ . The samples were injected into HPLC-MS/MS after the proteins were removed. The level of oxidative DNA damage was estimated using the ratio of 8-OHdG to deoxyguanosine （dG）. Results The limit of detection of 8-OHdG was 1 ng/mL （S/N=3） and the intra-assay relative standard variation was 3.38% when one transition 284.3/168.4 was used as a quantifier and another two transitions 284.3/140.2, 306.1/190.2 as qualifiers. 8-OHdG and dG were well separated, as indicated by elution at 10.02 and 7.37 min, respectively. INH significantly increased the ratio of 8-OHdG to dG in rat liver slices （P〈0.05）. Conclusion 8-OHdG in precision-cut liver slices could be sensitively determined by HPLC-MS/MS. HPLC-MS/MS coupled with precision-cut tissue slices is a fast and reliable analytical technique to evaluate oxidative DNA damage of target tissues caused by procarcinogens and cytotoxins.
文摘Methylene blue sensitized singlet oxygen oxidation of dl-α-tocopherol in dodecylsulfate (SDS) or cetyl trimethyl ammonium brondde (CTAB) ndcelles led to the formation, besidesα-tocopherol quinone and its epoxide, of a hitherto unknown spiro compound 6-hydroxy-2,6,8,9-tetramethyl-2-phytyl- 1-oxaspiro [4, 5] dec -8 - en - 7, 10-dione.
文摘This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential hypothermic and behavioral responses to the anticholinesterase, diisopropylfluorophosphate (DFP). FSL rats are more sensitive to the hypothermic effects of cholinergic, serotonergic, and dopaminergic agonists but less sensitive to the locomotor or stereotypic effects of dopamine agonists. FSL rats exhibit greater immobility in the forced swim test and reduced social interaction compared with FRL rats, but do not differ in saccharin intake, behavior in the elevated plus maze, or responses for rewarding brain self-stimulation. The exaggerated immobility and reduced social interaction are counteracted by chronic treatment with antidepressants. Because FSL rats were more sensitive to 5-HT1A receptor agonists, high (HDS) and low (LDS) 8-OH-DPATsensitive lines were selectively bred for differential hypothermic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). HDS rats were also more sensitive to the hypothermic effects of oxotremorine, a cholinergic agonist, but selection for this response did not diverge with later selection. HDS rats exhibited greater immobility in the forced swim test than LDS rats and this correlated response could be seen early in selection (generation 3). HDS rats also showed reduced social interaction compared to LDS rats, but did not differ in behavior in the elevated plus maze. These findings confirm that selection for hypothermic responses to pharmacological agents do have behavioral consequences, notably the production of depressive-like phenotypes, which can be counteracted by chronic antidepressant treatment. Because increased 5-HT1A receptor sensitivity was common to both selected lines (FSL and HDS), neurobiological processes dependent on this receptor could contribute to the abnormal behaviors that manifest in these rat lines and thus suggesting a mechanism underlying depressive behaviors in humans. However, available human data are inconsistent with this hypothesis and suggest that other mechanisms underlie these behavioral abnormalities in HDS and FSL rats. These mechanisms as well as additional behavioral testing in these rat lines will be discussed.
文摘Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. Clinical trials focused on prevention of cardiovascular and neoplastic diseases involving antioxidant supplementation have however provided predominantly negative obserations in large-scale studies. Screening of patient cohorts to assess baseline oxidative stress on the basis of a biomarker profile is decisive but lacking. For the first time, we evaluated the level of oxidative stress, testing more than 10 established biomarkers, in a comprehensive initial survey of 617 patients displaying chronic human pathologies. Multiple diseasespecific abnormalities were identified in plasma, whole blood and/or urine. This is the case for vitamins and oligo elements, vitamin C, vitamin E, β-carotene, selenium, zinc and copper;endogenous antioxidants such as reduced and oxidised glutathione, thiols, urate, and glutathione peroxidase activity, and a biomarker of oxidative DNA damage (8-hydroxy-2’-deoxy guanosine). The distinct biomarker profiles suggest the involvment of multiple forms of oxidative insults which arein some way partially specific to each pathological condition. This finding is in favor of the determination of an integrated score to combine contributions of distinct biomarkers, in order to screen patients presenting elevated levels of oxidative stress.
