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Conventional imaging examinations are not sensitive enough for the early detection of recurrent or metastatic lesions in renal cell carcinoma (RCC) patients. We aimed to explore the role of

Background: Glioma is characterized by a high recurrence rate, while the results of the traditional imaging methods (including magnetic resonance imaging, MRI) to distinguish recurrence from treatment-related changes (TRCs) are poor. Prostate-specific membrane antigen (PSMA) (US10815200B2, Deutsches Krebsforschungszentrum, German Cancer Research Center) is a type II transmembrane glycoprotein overexpressed in glioma vascular endothelium, and it is a promising target for imaging and therapy. Objective: The study aimed to assess the performance of PSMA positron emission tomography/magnetic resonance (PET/MR) for diagnosing recurrence and predicting prognosis in glioma patients. Materials and Methods: Patients suspected of glioma recurrence who underwent 18F-PSMA-1007 PET/MR were prospectively enrolled. Eight metabolic parameters and fifteen texture features of the lesion were extracted from PSMA PET/MR. The ability of PSMA PET/MR to diagnose glioma recurrence was investigated and compared with conventional MRI. The diagnostic agreement was assessed using Cohen κ scores and the predictive parameters of PSMA PET/MR were obtained. Kaplan-Meier method and Cox proportional hazard model were used to analyze recurrence-free survival (RFS) and overall survival (OS). Finally, the expression of PSMA was analyzed by immunohistochemistry (IHC Results: Nineteen patients with a mean age of 48.11±15.72 were assessed. The maximum tumor-to-parotid ratio (TPRmax) and texture features extracted from PET and T1-weighted contrast enhancement (T1-CE) MR showed differences between recurrence and TRCs (all P Conclusion: This primitive study shows multiparameter PSMA PET/MR to be useful in identifying glioma (especially GBM) recurrence by providing excellent tumor background comparison, tumor heterogeneity, recurrence prediction and prognosis information, although it did not improve the diagnostic performance compared to conventional MRI. Further and larger studies are required to define its potential clinical application in this setting.

Polyethylene (PE) cable has become an important carrier of the modern power grid due to its excellent electrical insulation performance. However, small damages can inevitably occur during the preparation and operation of the materials, which can distort electric field and trigger discharge, seriously threatening power supply safety. The self-healing of insulation materials by doping microcapsules is a new research innovation. In this paper, the self-healing PE/microcapsules insulation composite material was prepared, and the self-healing behavior of mechanical damage was emphatically analyzed by scratch damage test and crack propagation simulation. The results show that the composite material with 1 wt% microcapsule has better insulation strength. Moreover, the composite material can fill the defective structures, restore local electrical properties, and reverse the deterioration process of the material. The properties of PE/microcapsules composite material are mainly related to the characteristics of the microcapsule itself and the interface introduced by the microcapsules. The properties of the repaired product can directly affect the recovery degree of the damaged area. The stress action during damage can smoothly trigger its self-healing behavior. In conclusion, the PE composite material doped with 1 wt% microcapsules can achieve a good self-healing effect on mechanical damage.

Purpose Prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance (PET/MR) is a novel imaging technology in neuro-oncology. This study aimed to investigate whether PET/MR-derived parameters could provide clinical characteristics and tumor heterogeneity in post-treatment glioma. The ability of PSMA PET/MR to distinguishing recurrence from treatment-related changes (TRCs) was evaluated. Methods Twenty-four glioma patients (fourteen males and ten females) suspected of recurrence who underwent PSMA PET/MR were included in this study. The results of PET/MR were evaluated qualitatively and quantitatively, including the visual intensity, classical metabolic and metric parameters, and primary tumor texture features. Results Classical metabolic parameters of PET including tumor-to-brain ratio (TBR max and mean), standardized uptake value (SUVmax and SUVpeak) showed differences in Karnofsky score (KPS) and metric parameters (area of lesion derived from MR) in 1p19q deletion status (P < 0.05). For the texture features, the shape-based, first-order and high-order primary tumor texture features of MR suggested the power to differentiate tumor grade and gene status (All P < 0.05). The sensitivity, specificity, and positive and negative predictive values of PSMA PET/MR in identifying recurrence were 64.29% (9/14), 80% (8/10), 81.82% (9/11), and 61.54% (8/13), respectively. Conclusion This work highlights the role of postoperative PSMA PET/MR in tumor-targeted imaging and differentiating recurrence in glioma, especially glioblastoma. PSMA PET/MR-derived parameters especially textural features provide additional value for characterizing glioma patient status and tumor heterogeneity. Our results indicate the significance of the hybrid PSMA PET/MR system in providing non-invasive glioma biological features, guiding precise surgical resection, and stratifying patients with PSMA targeted therapy.

In this paper, a method for calculating the dielectric constant of non-polar/polar block copolymers is proposed, which combines the group contribution (GC) method, correlativity index (CI) method, and dipole moment fluctuation (DMF) method. The CI method and the DMF method are used to calculate the non-polar and polar repeating units' dielectric constants, respectively. The Vogel model and GC method are used to convert the dielectric constant of the repeating unit to that of the block copolymer. The Vogel model is a formula describing the relationship between the molar polarizability, which participates in the calculation in the GC method, and dielectric constant. We also designed two other methods, CI-GC and DMF-GC, as a comparison. We selected seven typical polymers for the validation of this calculation method and found that CI/DMF-GC has the best accuracy by comparing it with the experimental values. This new method can calculate the dielectric constant of a new block copolymer without the help of experiments. It is of great significance for improving the development efficiency of new block copolymers.

Recently, flexible pressure sensors have attracted considerable interest in electronic skins, wearable devices, intelligent robots and biomedical diagnostics. However, the design of high sensitivity flexible pressure sensors often relies on expensive materials and complex process technology, which greatly limit their popularity and applications. Even worse, chemical-based sensors are poorly biocompatible and harmful to the environment. Here, we developed a flexible capacitive pressure sensor based on reduced graphene oxide cotton fiber by a simple and low-cost preparation process. The environmentally friendly sensor exhibited a comprehensive performance with not only ultra-high sensitivity (up to 15.84 kPa−1) and a broad sensing range (0–500 kPa), but also excellent repeatability (over 400 cycles), low hysteresis (⩽11.6%), low detection limit (−1, frequency from 100 Hz to 10 kHz). Based on its superior performance, the proposed sensor can detect various external stimuli (vertical stress, bending and airflow) and has been successfully applied for facial expression recognition, breathing detection, joint movement and walking detection, showing great potential for application in artificial electronic skin and wearable healthcare devices.

// Chen Lin 1, * , Shanshan Wang 1, * , Weiwei Xie 1 , Rongliang Zheng 2 , Yu Gan 3 , Jianhua Chang 1 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China 2 Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510000, P.R. China 3 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, P.R. China * These authors contributed equally to this work Correspondence to: Jianhua Chang, email: changjianhua@163.com Yu Gan, email: ganyu@shSCI.org Keywords: apatinib, KIF5B-RET, invasion and migration, Src signaling pathway, targeted therapy Received: April 23, 2016 Accepted: July 10, 2016 Published: August 01, 2016 ABSTRACT The Rearranged during transfection (RET) fusion gene is a newly identified oncogenic mutation in non-small cell lung cancer (NSCLC). The aim of this study is to explore the biological functions of the gene in tumorigenesis and metastasis in RET gene fusion-driven preclinical models. We also investigate the anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms underlying. Our results suggested that KIF5B-RET fusion gene promoted cell invasion and migration, which were probably mediated through Src signaling pathway. Apatinib exerted its anti-cancer effect not only via cytotoxicity, but also via inhibition of migration and invasion by suppressing RET/Src signaling pathway, supporting a potential role for Apatinib in the treatment of KIF5B-RET driven tumors.

Verbascoside, pedicularioside A, cistanoside C, salidroside, 6-O-(E)-feruloyl-glucose and 6-O-(E)-p-hydroxycinnamoyl-glucose were isolated from Pedicularis species and other plants. The scavenging activities of these phytophenols towards hydrated electron, the strongest reducing radical, were investigated by pulse radiolysis. With the exception of salidroside, the other phytophenols react with hydrated electrons (e(aq)(-)) at rate constants close to the diffusion-controlled rate (4.9-7.5 x 10(9)M(-1) s(-1)), indicating that these phytophenols are effective e(aq)(-) scavengers. This property is consistent with the phytophenols' ability to quickly repair DNA radical anions. The comparison of the reaction rate constants indicates that the conjugated carbonyl group is essential to the e;(1 scavenging activities, whereas the phenolic hydroxyl groups, which determine the antioxidant capacity, have no significant effect on the e(aq)(-) scavenging activities. We propose that the reducing radical-scavenging activity of the phytophenols is a novel pharmacological mechanism for prevention and treatment of diseases in which reducing radicals play a key role. Our finding provides a criterion for screening the scavengers of reducing radicals. (C) 2010 Elsevier Ltd. All rights reserved.

Many studies have shown that in a chemical system natural polyphenols can rapidly repair DNA oxidative damage. In this paper we report that in a cellular system the non-enzymatic fast repair activities of two natural polyphenols might also exist. The viability of a Chinese hamster ovary cell line (AA8) highly expressing the XRCC1 gene (a DNA repairing protein) treated with H2O2 is significantly higher than that of a normal Chinese hamster ovary cell line (CHO). Following inhibition of the enzymatic repair system by different inhibitors--methoxyamine (MX), 3-aminobenzamide (3AB) or nicotinamide (NIC)--DNA oxidative damage by H2O2 increased 2-5-fold in both cell lines. However, when natural polyphenols--rosmarinic acid (RA) or verbascoside (VER)--were added, DNA oxidative damage was significantly reduced. This decrease of DNA oxidative damage by RA or VER is not due to their scavenging activity for reactive oxygen species (ROS) because cells suffered from heavy ROS throughout the whole experimental process. Therefore, the decrease of DNA damage might be due to their non-enzymatic fast repair mechanisms. Further investigation showed that H2O2 induced a drop in the mitochondrial membrane potential (MMP), and that RA and VER were able to attenuate the drop. Previous studies have shown that H2O2 initiates a chain of events in cells, involving mtDNA damage, a drop in MMP and loss of repair activity. These results, taken together with our present results, suggest that the non-enzymatic fast repair mechanism exists not only in chemical systems but also might exist in cells.

The repair activities and reaction mechanisms of phenylpropanoid glycosides (PPGs) and their analogues, isolated from Chinese folk medicinal herbs, towards oxidative DNA damage were studied with pulse radiolytic technique. On pulse irradiation of nitrogen-saturated 4 mM poly C aqueous solution containing one of the tested polyphenols, 40 mM K2S2O8 and 200 mM t-BuOH, the transient absorption spectrum of the oxidative radical of poly C decays with the concurrent formation of the phenoxyl radical of the tested polyphenols within several tens of microseconds after the electron pulse irradiation. The result indicated that there was a repair reaction between oxidative radical of poly C and the tested polyphenols. The repair activities also were observed for the tested polyphenols towards the radical cations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The rate constants were determined to be 3.7-6.4 x 10(9), 4.8-5.5 x 10(8) and 8.8-10.3 x 10(8) M(-1).sec(-1) for the repair reactions of oxidative radical of poly C and radical cations of ssDNA and dsDNA, respectively. The result of this study together with those of our previous studies demonstrates that PPGs and their analogues can fast repair not only the damage of deoxynucleoside and deoxynucleotide but also the damage of integral DNA, with the latter being closer to a cellular condition.

Using the MTT assay and the telomeric repeat amplification protocol (TRAP)-based PCR-ELISA assay, the cytotoxicity and telomerase inhibiting ability of 17 sesquiterpenes (extracted from Chinese herbs) were tested in the human ovarian cancer cell line HO-8910. The results indicated that seven sesquiterpenes inhibited cell proliferation without having an effect on telomerase activity; two sesquiterpenes inhibited neither cell proliferation nor telomerase activity; and the other eight sesquiterpenes inhibited both cell proliferation and telomerase activity to a certain extent. Without exception, none of these 17 sesquiterpenes could only inhibit telomerase activity without inhibiting cell proliferation. This indicated that the telomerase inhibiting activity is not a universal mechanism for all anticancer drugs but is only one of several possible mechanisms. The structure-activity relationships of 5 groups of sesquiterpenes are also discussed. This study may help to develop anticancer drugs.

Ginsenoside Rh 2 , a panoxadiol saponins, possesses various antitumour properties. Cyclophosphamide, an alkylating agent, has been shown to possess various genotoxic and carcinogenic effects, however, it is still used extensively as an antitumour agent and immunosuppressant in the clinic. Previous reports reveal that cyclophosphamide is involved in some secondary neoplasmas. In this study, the antitumour activity and genotoxic effect of oral intake of ginsenoside Rh 2 combined with intraperitoneal injection of cyclophosphamide was investigated. Meanwhile, C57BL/6 mice bearing B16 melanoma and Lewis lung carcinoma cells were respectively used to estimate the antitumour activity in vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronucleus. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis as well. The results indicated that oral administration of Rh 2 (5, 10 and 20 mg/kg body weight) alone has no obvious antitumour activity and genotoxic effect in mice, while Rh 2 synergistically enhanced the antitumour activity of cyclophosphamide (40 mg/kg body weight) in a dose-dependent manner. Rh 2 decreased the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Our results suggest that ginsenoside Rh 2 is able to enhance the antitumour activity and decrease the genotoxic effect of cyclophosphamide.

The protection effect of verbascoside (Ver) against Fenton reaction on plasmid pBR322 DNA was studied using agarose gel electrophoresis and UV-visible spectroscopy. The pBR322 plasmid DNA is damaged by hydroxyl radical (OH*) generated from the Fenton reaction with H2O2 and Fe(II) or Fe(III). This DNA damage is characterized by the diminution of supercoiled DNA forms or by the increase of relaxed or linear DNA forms after oxidative attack. The UV spectrum study showed that verbascoside can form complexes with Fe(II) or Fe(III), and the complexation can be reversed by the addition of EDTA. The formation constants of verbascoside-Fe complexes were estimated as 10(21.03) and 10(31.94) M(-2) for Fe(II) and Fe(III) respectively. The inhibition of Fenton reaction by verbascoside could be partially explained by the sequestration of Fe ions.

Our previous study demonstrates that copper induces histone hypoacetylation by inhibiting histone acetyltransferase (HAT) activity. However, it lacks direct evidences whether copper-inhibited histone acetylation right contributes to the toxicity of copper. Exposure of human leukemia cells (HL-60) to Cu2+ resulted in cell proliferation arrest and a concentration- and time-dependent decrease of histone acetylation. At the same time, Cu2+-induced significant increase of H2O2 and O2.- generation via a concentration- and time-dependent manner too. The histone acetylation was efficiently suppressed by exogenous H2O2, and enhanced by superoxide dismutase (the scavenger of O2.-), catalase (the scavenger of H2O2) or the combination of both, indicating that Cu2+ at least partially inhibited histone acetylation through triggering oxidative stress. Further studies found that sodium butyrate, the inhibitor of histone deacetylase (HDAC), which had no obvious effect on oxidative stress but increased histone acetylation at the concentration of 50 microM, attenuated Cu2+-inhibited cell proliferation, indicating that histone acetylation inhibition is simultaneously involved in the cytotoxicity of Cu2+. Considering the important role of histone acetylation in gene transcription and regulation of cell fate, the present study may open a new door to further understand the mechanism of Cu2+-induced toxicity.

The effects of synthesized 7-OH-4-CH(3)-coumarin on proliferation and differentiation of human hepatoma carcinoma cell line, SMMC-7721, were examined. Results showed that 7-OH-4-CH(3)-coumarin suppressed the proliferation of the SMMC-7721 cells in a dose-dependent manner, with an IC(50) value of 356 +/- 1.8 .M, while concentrations< or =200 mM could trigger differentiation. After treatment with this compound at 100 mM, the growth curve of human hepatoma cells decreased markedly. When treated with 50 and 100 mM, the cells' electrophoresis rate decreased from 2.2 mm/s/V/cm in the control group to 1.5 and 1.8 mm/s/V/cm, respectively, and the alpha-fetoprotein content decreased from 123 ng/mg in the control group to 68 and 45 ng/mg, respectively. The microvilli on the surface of treated cells were also reduced. All the above indexes related to cell malignancy were alleviated significantly. Results showed that 7-OH-4-CH(3)-coumarin could reverse human hepatoma cells' malignant phenotypic characteristics and induce redifferentiation.

Sylvatesmin (SYL) and lantbeside (LAN) are two lignans, isolated from a Chinese folk medicinal herb, Lancea tibetica . Their abilities of scavenging oxidizing free radical models, OH, SO 4 − and N 3 , were investigated in aqueous solution by pulse radiolysis techniques. The OH-adduct radicals with small amount of oxidized products were formed by the reaction of SYL or LAN with OH radical. SYL undergoes one-electron oxidation either by SO 4 − or N 3 radicals, LAN can only be detected to react with stronger oxidant SO 4 − radical anion. No reaction between LAN and N 3 radical was detectable. The relationship of structure with the abilities of scavenging free radicals was discussed. The reaction rate constants were determined by analysis of the build-up trace of the radical products.

Cope’s rat snakes (Elaphe taeniura) favor to expose under sunlight in order to increase their body temperature simultaneously increasing the risk of skin damage by ultraviolet B (UVB) irradiation. We have investigated the effects of UVB irradiation on their skin. Results show that the UVB transmission of the keratinous layer was only 5.1 ± 0.36%. The peak of epidermal damage and malondialdehyde (MDA) content, a product of lipid peroxidation, simultaneously occurred 72–96, 48 or 24 h after exposure to 300, 500 and 800 mJ/cm2 of UVB radiation, respectively. Superoxide dismutase (SOD) activity was inhibited by UVB and the lowest activity occurred 24, 48, 12 and 12 h after exposure to 110, 300, 500 and 800 mJ/cm2 of UVB, respectively. SOD activity recovered later to some extent but mostly remained below control level. After exposure to different doses of UVB radiation, catalase (CAT) activity was inhibited immediately, and then gradually recovered and even increased to peak levels above control level. The highest CAT levels accompanied the most serious damage of skin morphology. Later on, CAT activity decreased and recovered again close to or below control level, which was accompanied by shedding off the damaged epidermal complex. This indicated that the epidermal damage induced by UVB is closely related to lipid peroxidation, where CAT acts as a primary antioxidant enzyme. Moreover, the keratinous layer protects the viable cell layer against UVB damage as well.

Verbascoside and rutin possess anti-cancer properties and are capable of repairing DNA damaged by oxygen radicals, acting as powerful antioxidants. Based on kinetic measurements and experiments on tumor cells, docking studies of the two ligand molecules with the receptor telomeric DNA fragments have been carried out. The docking calculations performed using JUMNA software showed that the both molecules can be docked into the minor groove of telomeric DNA and form complexes with suitable geometry for electron transfer between guanine radical and ligands. The reaction mechanism via the electron transfer process is further confirmed through energy calculations for transition states using MOPAC 93 program. Complexes can be formed without major distortion of DNA structure and are further stabilized by the interaction of DNA with the saccharide side-groups. By comparing their energies, the difference of activities of the two compounds can be explained.

Screening of natural products with anti-tumor activity as telomerase inhibitor is a new subject in the field of tumor therapy. Using telomerase PCR ELISA, telomere DNA hybridization and flow cytometry analysis, the effects of verbascoside, a phenylpropanoid glucoside extracted from Pedicularis striata Pall, on telomerase activity, telomere length and cell cycle of human gastric carcinoma cells MKN45 was examined in vitro. After being treated with a 50 % inhibition concentration of verbascoside (17.8 microg/ml), telomerase activity in the cells was significantly inhibited but not in the cellular supernatant, the average telomere length became remarkably short, and the sub-G0 /G1 peak and G2/M arrest were also displayed when compared to the control cells. These results suggest that verbascoside mediated-cell differentiation and apoptosis may be affected by telomere-telomerase-cell cycle dependent modulation. Thus, the antitumor mechanism of verbascoside is demonstrated once more by its inhibiting effect on telomerase activity in tumor cells, and the telomerase assay may provide a valuable screening method for antitumor activity of natural products.

The uptake and distribution of eight metallic elements were examined in wheat seedlings for a period of 12 d with a radioactive multitracer technique. The radioactive nuclides of the seedlings were simultaneously determined by gamma-ray spectrometry. All of the elements studied were taken up by the wheat seedlings and mainly accumulated in the roots. Only some elements were transported to shoots and leaves of the seedlings or bound to leaf proteins, and two elements were transported into the chloroplast. Uptake of most elements reached a maximum on the fifth or the eighth day and then gradually decreased afterward. In the cases of 95mTc and 72Se, the uptake increased continuously within 12 d without the peak uptake. The change of elemental concentrations was dependent on uptake and excretion rates. The dynamics of metal elements taken up by the wheat seedlings and their distribution in roots, shoots, and leaves were different for each element, suggesting that it may depend on the characteristics of the elements.

Experiments show that the natural substances phenylpropanoid glycosides (PPGs) extracted from pelicularis spicata are capable of repairing DNA damaged by oxygen radicals. Based on kinetic measurements and experiments on tumor cells, a theoretical study of the interaction between PPG molecules and isolated DNA bases, as well as a DNA fragment has been performed. An interaction mechanism reported early has been refined. The docking calculations performed using junction minimization of nucleic acids (JUMNA) software showed that the PPG molecules can be docked into the minor groove of DNA and form complexes with the geometry suitable for an electron transfer between guanine radical and the ligand. Such complexes can be formed without major distortions of DNA structure and are further stabilized by the interaction with the rhamnosyl side-groups.

The effects of quercetin and rutin on the repair of the radical cations of dCMP and poly C were studied using the technique of pulse radiolysis. The radical cations of dCMP and poly C were formed by the reaction of dCMP and poly C with SO( 4)(-). After pulse irradiation of nitrogen-saturated aqueous solutions containing dCMP, 20 mM K(2)S(2)O(8), 200 mM t-BuOH and either rutin or quercetin, the initially formed radical cation of dCMP, detected spectrophotometrically, rapidly decayed with the concurrent formation of the phenoxyl radical of rutin or quercetin within 8-40 micros. The repair efficiencies of the tested compounds towards the poly C radical cation were also determined using the same procedure. The results indicate that dCMP and poly C radical cations can be rapidly repaired by quercetin and rutin. The rate constants of the repair reactions were determined to be 4.3-8.8x10(8) M/s and 1.5-3.6x10(8) M/s for dCMP and poly C radical cations, respectively. Together with findings from our previous studies, the present results demonstrate that non-enzymatic fast repair may be a universal form of repair involving phenolic antioxidants.

In aqueous solution, the deprotonated radical cations of dCMP, TMP and Poly C created by SO 4 − can react with dAMP at a close to diffusion control rate constants which indicates a rapid electron transfer from dAMP to deprotonated radical cations of deoxynucleotides. Analogous reaction was found to occur between the deprotonated radical cation of dAMP, dCMP, TMP or Poly C and dGMP. The rate constants were determined to be 0.64–1.3×10 8 M −1 s −1 for electron transfer from dAMP toward deprotonated radical cations and 1.2–3.3×10 8 M −1 s −1 for the case of dGMP. Thus, the electron loss center caused by one electron oxidant or by ionizing radiation will end up at guanine in DNA.

Repair effect on TMP radical anions by phenylpropanoid glycosides (PPGs) and their analogs, isolated from Chinese folk medicinal herbs, were studied using a pulse radiolysis technique. The radical anion of TMP was formed by the reaction of hydrated electron with TMP. On pulse irradiation of a nitrogen saturated TMP aqueous solution containing 0.2 mol/l t -BuOH and one of the PPGs or their analogs, the transient absorption spectrum of the radical anion of TMP decayed with the formation of that of the radical anion of PPGs or their analogs within several decades of microseconds after electron pulse irradiation. The results indicated that TMP radical anions can be repaired by PPGs or their analogs. The rate constants of the repair reactions were deduced to be 1.64–2.75×10 9 M −1 s −1 . A deeper understanding of this new repair mechanism will undoubtedly help researchers design strategies to prevent and/or intervene more effectively in free radical related diseases.

DNA damaged by oxygen radicals has been implicated as a causative event in a number of degenerative diseases, including cancer and aging. So it is very significant to look for ways in which either oxygen radicals are scavenged prior to DNA damage or damaged DNA is repaired to supplement the cells’ inadequate repair capacity. The repair activities and reaction mechanism of phenylpropanoid glycosides (PPGs) and their derivatives, isolated from Chinese folk medicinal herbs, towards both dGMP-OH adducts and dAMP-OH adducts were studied with the pulse radiolytic technique. On pulse irradiation of nitrous oxide saturated 2 mM dGMP or dAMP aqueous solution containing one of the PPGs or their derivatives, the transient absorption spectra of the hydroxyl adduct of dGMP or dAMP decayed with the formation of that of phenoxyl radicals of PPGs or their derivatives within several decades of microseconds after electron pulse irradiation. The result indicated that dGMP or dAMP hydroxyl adducts can be repaired by PPGs or their derivatives. The rate constants of the repair reactions were deduced to be 0.641–1.28×10 9 M −1 s −1 for dGMP-OH and 0.2–0.491×10 9 M −1 s −1 for dAMP-OH , which positively correlated to the number of phenolic hydroxyl groups in the glycoside structure. A deeper understanding of this new repair mechanism may help researchers to design strategies to prevent and/or intervene more effectively in free radical related diseases.

The reaction of hydroxyl radical with 1 phenylpropanoid glycoside (PPG), cistanoside C, and its 3 derivatives: 1-0-beta-D-2-(p-hydroxyphenyl)-ethanyl-glucose, 6-O-(E)-femloyl-glucose and 6-O-(E)-p-hydroxy-cinnarnoylglucose isolated from folk medicinal herbs was investigated by pulse radiolysis technique respectively. The reaction rate constants were determined by analysis of built-up trace of absorption at lambda(max) of specific transient absorption spectra of PPG and its derivatives upon attacking . OH. All four compounds react with . OH at close to diffusion controlled rate (1. 03 x 10(9)-19.139 x 10(9) L . mol(-1) . s(-1)), suggesting that they are effective . OH scavengers. The results demonstrated that the numbers of phenolic hydroxyl groups of PPG and its derivatives are directly related to their scavenging activities. By comparing the reaction rates of . OH with 1-O-beta-D-2-(p-hydroxyphenyl)-ethanyl-glucose, 6-O-(E)-feruloyl-glucose or 6-O-(E)-p-hydroxy-cinnomoyl-glucose, it is evident that the phenylethyl group is more impofiant than phenylacryloyl group for scavenging . OH.

Verbascoside is a natural antioxidant extracted from Pedicularis striata Pall (Jueyehesen). After being treated with 20 mumol/l verbascoside, the growth curve and mitotic index of human gastric adenocarcinoma MGc80-3 cells decreased remarkably, cell doubling time was delayed, the cellular growth inhibitory rate amounted to 53.2%, cell surface charge assayed by cell electrophoresis obviously changed, the electrophoresis rate dropped from 3.51 microns/s/v/cm to 2.74, i.e., the percent of retardation reached 28.4%. There was a 75% decrease of the tumorigenicity for the treated cells compared with the untreated cells inoculated subcutaneously in BALB/C nude mice. Scanning electron microscopy revealed that the microvilli on the surface of treated cells had been reduced obviously. It confirmed that verbascoside, similar to DMSO, could reverse MGc80-3 cells' malignant phenotypic characteristics and induced redifferentiation of MGc80-3 cells.

The scavenging activities of six phenylpropanoid glycosides, i.e. leucosceptoside A and martynoside, isolated from Pedicularis alashanica Maxim, verbascoside, and pediculariosides A, M and N isolated from Pedicularis striata Pall ssp. arachnoidea Franch Tsoong, on superoxide anion and hydroxyl radicals have been studied by the spin trapping method. The results demonstrated that the number of phenolic hydroxyl groups in the structures of the phenylpropanoid glycosides is related to their scavenging activities. The scavenging effects of the phenylpropanoid glycosides possessing two o-dihydroxyl groups were stronger than the effects of the compounds possessing two o-hydroxy-methoxy groups.

Genomic instability is a characteristic of most cancers and could be directly caused by DNA damage. DNA repair maintains genomic integrity, reducing the onset of cancer. A distinct DNA fast repair process, synonymous fast repair, is initiated and finished in a microsecond time scale, enormously faster by approximately 9 orders than enzymatic repair, and thus eradicates the headstream of DNA damage, DNA radicals exclusively, in the earliest stage of carcinogenesis. The known enzymatic repair cannot repair DNA radicals and mutation, but fast repair can. Therefore, the fast repair mechanism is a defence in the front line in fighting carcinogenesis. If there was no fast repair, certainly much more DNA steady damage would accumulate and would lead to mutation and cancer with high risk. Almost all the tested phytophenols with fast repair activity, except one, are able to suppress the hallmarks of cancer, such as morphological normalization, redifferentiation, decrease of cancer growth and transplanting rate, inhibition of telomerase, metastasis and angiogenesisin vitro and in vivo, reducing cancer incidence and mortality rate in animals.

The activities of six phenylpropanoid glycosides as chain-breaking antioxidants have been studied for the autoxidation of linoleic acid in cetyl trimethylammonium bromide (CTAB) micelles at 37 degrees C. Verbascoside, isoverbascoside, echinacoside and pedicularioside A, which possess four phenolic hydroxyl groups, exhibited antioxidant activities, while cistanoside D possessing only two phenolic hydroxyl groups and permethyl verbascoside without phenolic hydroxyl group did not suppress the oxidation appreciably. The ratio of rate constants for inhibition and propagation kinh/kp and stoichiometric factor n were determined.

This tutorial review highlights the mechanism of a novel non-enzymatic fast repair of DNA damage, which refers exclusively to repair DNA radicals including DNA-OH* adducts, DNA radical cations and anions by various endogenous, natural and synthetic compounds. The repair rate constants are as high as 10(9) M(-1) s(-1). In cells, when the enzymatic repair system was inhibited or before the enzymatic repair mechanism was initiated, DNA oxidative damage was significantly reduced by natural polyphenols. This decrease of DNA damage is assigned to the fast repair. Fast repair takes place through an electron transfer process, and docking of polyphenol into the DNA minor groove could be the essential step.

ROS (reactive oxygen species) take an important signalling role in angiogenesis. Although there are several ways to produce ROS in cells, multicomponent non-phagocytic NADPH oxidase is an important source of ROS that contribute to angiogenesis. In the present work, we examined the effects of H2O2 on angiogenesis including proliferation and migration in HUVECs (human umbilical vein endothelial cells), new vessel formation in chicken embryo CAM (chorioallantoic membrane) and endothelial cell apoptosis, which is closely related to anti-angiogenesis. Our results showed that H2O2 dose-dependently increased the generation of O-2(-) (superoxide anion) in HUVECs, which was suppressed by DPI (diphenylene iodonium) and APO (apocynin), two inhibitors of NADPH oxidase. H2O2 at low concentrations (10 mu M) stimulated cell proliferation and migration, but at higher concentrations, inhibited both. Similarly, H2O2 at 4 nmol/cm(2) strongly induced new vessel formation in CAM, while it suppressed at high concentrations (higher than 4 nmol/cm(2)). Also, H2O2 (200 similar to 500 mu M) could stimulate apoptosis in HUVECs. All the effects of H2O2 on angiogenesis could be suppressed by NADPH oxidase inhibitors, which suggests that NADPH oxidase acts downstream of H2O2 to produce O-2(-) and then to regulate angiogenesis. In summary, our results suggest that H2O2 as well as O-2(-) mediated by NADPH oxidase have biphasic effects on angiogenesis in vitro and in vivo.

Two new sesquiterpenes petrovin A (1) and petrovin B (2) have been isolated from Chinese herb Saussurea petro-vii and their structures established by spectroscopic methods. Compounds 1 and 2 showed...

This tutorial review highlights the mechanism of a novel non-enzymatic fast repair of DNA damage, which refers exclusively to repair DNA radicals including DNA-OH* adducts, DNA radical cations and anions by various endogenous, natural and synthetic compounds. The repair rate constants are as high as 10(9) M(-1) s(-1). In cells, when the enzymatic repair system was inhibited or before the enzymatic repair mechanism was initiated, DNA oxidative damage was significantly reduced by natural polyphenols. This decrease of DNA damage is assigned to the fast repair. Fast repair takes place through an electron transfer process, and docking of polyphenol into the DNA minor groove could be the essential step.

The effects of the phenylpropanoid glycosides verbascoside and martynoside from Pedicularis plicata were investigated on muscle contractility in Bufo gastrocnemius muscle electrically stimulated in vitro. The maximum amplitude and maintained time of contraction were mechanically recorded and used as indices of muscle contractility. After 30 min pretreatment of the muscle, verbascoside at 20.0 µM resisted muscle fatigue significantly while martynoside at 80.0 µM improved muscle contractility only slightly. These two glycosides resisted muscle fatigue depending on their antioxidative activities, which is in agreement with the role of reactive oxygen species (ROS) in promoting fatigue in skeletal muscle. Copyright © 1999 John Wiley & Sons, Ltd.

The non-enzymatic repair of DNA oxidative damage can occur in a purely chemical system, but data show that it might also occur in cells. Human hepatoma cells (SMMC-7721) and human hepatocyte cells (LO2) were treated with 200microM H(2)O(2) for 30min to induce oxidative DNA damage quantified by amount of 8-OHdG and degree of DNA strand breaks, without inducing enzymatic repair. The dynamics of enzymatic repair activity quantified by unscheduled DNA synthesis, within 30min after removal of H(2)O(2) enzymatic repair mechanism has not been initiated. However, pre-incubation with low micromolar level polyphenols, quercetin or rutin can significantly attenuate DNA damage in both cell lines, indicating that the polyphenols did not work through an enzymatic mechanism. Unscheduled DNA synthesis after removal of H(2)O(2) was also markedly decreased by quercetin and rutin. Combined with our previous studies of fast reaction chemistry, the inhibitory effect of polyphenols have to be assigned to non-enzymatic repair mechanism rather than to enzymatic repair mechanism or antioxidant mechanism.

Heroin has been shown to elevate dopamine (DA) level. It is well known that an increase in DA oxidative metabolism leads to increased reactive oxygen species (ROS) formation, and thus, ROS have been frequently associated with neuronal cell death due to damage to carbohydrates, amino acids, phospholipids, and nucleic acids. This study investigated whether there are oxidative stress and effects of exogenous antioxidants in heroin-administered mice. The heroin-dependent mice model was made via intraperitoneal injection. Oxidative damage of DNA, protein, and lipid was measured by analysis of single cell electrophoresis, the 2,4-dinitrophenylhydrazine method, and thiobarbituric acid method respectively. The activities of antioxidative enzymes and total antioxidant capacity were assayed by spectrophotometry. After administration with heroin, the mice not only showed decrease of total antioxidant capacity in serum and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione (GSH) peroxidase in brain, but also exhibited the oxidative damages of DNA, protein and lipid. On the other hand, exogenous antioxidants could restrain the oxidative stress, even alleviate withdrawal syndrome in heroin-administered mice. Our results also imply a possibility that ROS may participate in the whole process of dependence and withdrawal of heroin. Therefore, strategies of blocking oxidative stress may be useful in the development of therapy for opiate abuse.

Vitamin K3 (VK3) is a well-known anticancer agent, but its mechanism remains elusive. In the present study, VK3 was found to simultaneously induce cell death, reactive oxygen species (ROS) generation, including superoxide anion (O2*-) and hydrogen peroxide (H2O2) generation, and histone hyperacetylation in human leukemia HL-60 cells in a concentration- and time-dependent manner. Catalase (CAT), an antioxidant enzyme that specifically scavenges H2O2, could significantly diminish both histone acetylation increase and cell death caused by VK3, whereas superoxide dismutase (SOD), an enzyme that specifically eliminates O2*-, showed no effect on both of these, leading to the conclusion that H2O2 generation, but not O2*- generation, contributes to VK3-induced histone hyperacetylation and cell death. This conclusion was confirmed by the finding that enhancement of VK3-induced H2O2 generation by vitamin C (VC) could significantly promote both the histone hyperacetylation and cell death. Further studies suggested that histone hyperacetylation played an important role in VK3-induced cell death, since sodium butyrate, a histone deacetylase (HDAC) inhibitor, showed no effect on ROS generation, but obviously potentiated VK3-induced histone hyperacetylation and cell death. Collectively, these results demonstrate a novel mechanism for the anticancer activity of VK3, i.e., VK3 induced tumor cell death through H2O2 generation, which then further induced histone hyperacetylation.

This study investigates the oxidative damage of biomolecules in livers of mice treated with morphine intraperitoneally. The oxidative damage of DNA as measured by single cell electrophoresis and high-performance liquid chromatography equipped with electrochemical and UV detection, the protein carbonyl content was measured by 2,4-dinitrophenylhydrazine method, and the malondialdehyde content was measured by the HPLC method. The activities of antioxidative enzymes, superoxide dismutase, catalase and glutathione peroxidase, and the activity of alanine aminotransferase were assayed by spectrophotometer method. Glutathione and oxidized glutathione were detected by fluorescence spectrophotometer method. All the indexes of oxidative damage, such as 8-OHdG, protein carbonyl group and malondialdehyde content, and the activity of alanine aminotransferase (n=27) increased significantly compared to those of control (n=27) (P0.01) in livers of morphine-administered alone mice, while the indexes related with the in vivo antioxidative capacity, such as the ratio of glutathione and oxidized glutathione, activities of superoxide dismutase, catalase and glutathione peroxidase significantly decreased (P0.01). When mice were treated with morphine combined with exogenous antioxidants, glutathione and ascorbic acid, all the indexes of oxidative damage and the activity of alanine aminotransferase showed no changes as compared to those of control (P0.05), i.e., both glutathione and ascorbic acid completely abolished the damage of morphine on the hepatocyte. These results implied that morphine caused a seriously oxidative stress in mice livers and hence caused hepatotoxicity, while exogenous antioxidants were able to prevent the oxidative damage of biomolecules and hepatotoxicity caused by morphine. Thus, blocking oxidative damage may be a useful strategy for the development of a new therapy for opiate abuse.

The oxidative stress of heroin administered mice via intraperitoneal injection, and the therapeutic effects of exogenous antioxidants on the restrain of the oxidative damage of biomolecules and withdrawal syndrome were studied. After administered with heroin, mice showed decrease of total antioxidant capacity in blood, increase of reactive oxygen species production in white blood cells, and increase of oxidative damages of protein and lipid in brain and liver, but not in heart. On the other hand, exogenous antioxidants could restrain the oxidative stress, even alleviate withdrawal syndrome.

Dose-dependent regulation of cellular processes is one important characteristic of signaling molecules. Although recent studies suggest that reactive oxygen species (ROS) may act as in vivo signaling molecules, the dose-dependent regulation of ROS on cellular processes together in one system needs to be evaluated. After treating cells with gradually increased O(2)(-), generated by the hypoxanthine-xanthine oxidase system, it was found that: (i) the proliferation of hepatoma cells firstly increased at 1-2 microM O(2)(-), then decreased markedly as the concentration increased; (2) at 8 or 16 microM O(2)(-), re-differentiation of hepatoma cells was induced, as indicated by the indices relating to cell malignancy or differentiation, such as cell surface charge, alpha-fetoprotein, gamma-glutamyltranspeptidase, tyrosine-alpha-ketoglutarate transaminase, cAMP, and the tumor's clonogenic potential; (iii) at 16 microM O(2)(-), accompanied by the re-differentiation of cells, cell apoptosis was also simultaneously induced as indicated by the appearance of apoptotic bodies, detached cells, and other apoptotic morphological features, as well as specific DNA fragmentation; (iv) at the highest concentration of O(2)(-) (32 microM) in this study, cell necrosis was dramatically induced as shown by Trypan blue exclusion; (v), an increase of intracellular Ca(2+) ([Ca(2+)](i)) was observed at all concentrations of O(2)(-) treatment, and this [Ca(2+)](i) increase was found to be involved in the regulation of O(2)(-) on the cellular processes. In conclusion, these results indicate that O(2)(-) could dose-dependently regulate the processes of cells, where Ca(2+) is one of its molecular targets, and hence provide a direct support for the hypothesis that ROS themselves are important signaling molecules.

The pharmacological activities and mechanisms of action of natural phenylpropanoid glycosides extracted from a variety of plants are summarized in this review, such as antitumor, antivirus, anti-inflammation, antibacteria, antiartherosclerosis, anti-platelet-aggregation, antihypertension, antifatigue, analgesia, hepatoprotection, immunosuppression, protection of sex and learning behavior, protection of neurodegeneration, reverse transformation of tumor cells, inhibition of telomerase and shortening telomere length in tumor cells, effects on enzymes and cytokines, antioxidation, free radical scavenging and fast repair of oxidative damaged DNA. Molecular modeling is discussed as well as structure-activity relationships.