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Neuroblastoma is the most common extra-cranial solid tumor in children. Despite advances in the treatment of childhood cancer, outcomes for children with advanced-stage neuroblastoma remain poor. Here we reported that 2-methoxyestradiol (2-ME) inhibited the proliferation and induced apoptosis in human neuroblastoma SK-N-SH and SH-SY5Y cells. 2-ME treatment also resulted in the generation of ROS and the loss of mitochondrial membrane potential in SK-N-SH and SH-SY5Y, indicating that 2-ME-induced apoptosis is mediated by ROS. This is supported by the results that have shown that co-treatment with antioxidants, VC, L-GSH and MitoQ(10), decreased 2-ME-induced generation of ROS and the loss of the mitochondrial membrane potential, increased the Bcl-2/Bax ratio, decreased 2-ME-induced activation of caspase-9 and caspase-3 and the up-regulation of apoptosis-inducing factor (AIF), and prevented 2-ME-induced apoptosis in SK-N-SH and SH-SY5Y cells. These results suggested that oxidative stress plays an important role in 2-ME-induced apoptotic death of human neuroblastoma cells., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: This study aims to investigate the effect of aerobic exercise training on BKCa channel in diabetic vascular smooth muscle and explore the underlying mechanism. Methods: Control m/m mice and diabetic db/db mice were randomly assigned to sedentary groups (W and D) and exercise training groups (WE and DE). Mice in exercise groups underwent training sessions lasting for 12 weeks, with a speed of 12 m/min for 60 min, five times per week. The thoracic aorta was extracted isolated and examined for measurement of vascular structure, global levels of reactive oxygen species (ROS), vasodilation, and protein expression. Rat thoracic aorta vascular smooth muscle cells (USMCs) were cultured, and siRNA transfection was conducted to detect whether AMPK contributed to the regulation. ROS level and protein expression were measured. Results: Compared with control mice, diabetic mice had a larger vascular medium thickness, impaired BKCa-mediated vasodilation, a higher level of ROS, and a lower expression of BKCa α, BKCa β1, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. Exercise training increased the expression of BKCa α, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. AMPK deletion led to lower ROS levels and expression of BKCa α, β1, Nrf2, and HO-1 in USMCs cultured in high glucose conditions. Conclusions: BKCa channel protein expression reduction in VSMCs contributes to vasodilation and vascular remodeling dysfunction in diabetes mellitus. Aerobic exercise can promote the expression of BKCa channel and improve BKCa-mediated vascular dysfunction in diabetic VSMCs through AMPK/Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Here an excellent trimodality imaging‐guided synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) is proposed. To this end, a mixed‐metal Cu/Zn‐metal‐organic framework (MOF) is first assembled at room temperature on a nano‐scale. Interestingly, heating the MOF results in a Cu+/2+‐coexisting hollow porous structure. Subsequent heating treatment is used to integrate Mn2+ and MnO2 in the presence of manganese(II) acetylacetonate. The hollow composite achieves efficient loading of a photosensitizer, indocyanine green (ICG). Under laser irradiation, the aggregated ICG achieves photothermal imaging and PTT. Once released in the tumor site, ICG exhibits fluorescence imaging and PDT capacity. Cu+/Mn2+ ions perform Fenton‐like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Cu2+/MnO2 scavenge glutathione to improve the reactive oxygen species‐based therapy, while the formed Mn2+ ions enable "turn on" magnetic resonance imaging. Significantly, O2 is produced from the catalytic decomposition of endogenous H2O2 to improve ICG‐mediated PDT. Moreover, photothermal‐induced local hyperthermia accelerates •OH generation to enhance CDT. This synergistic drug‐free antitumor strategy realizes high treatment efficacy and low side effects on normal tissues. Thus, this mixed‐metal MOF is an efficient strategy to realize hollow structures for multi‐function integration to improve therapeutic capacity. [ABSTRACT FROM AUTHOR]

• Radicals could be rapidly generated in HSO 3 −/Fe2+/PDS system (O 2 atmosphere). • Iron as single-electron shuttle enables interdependent activation of two oxidation processes. • The SO 4 •− production could be maximized by tuning electron transfer inside the system. • The system could inactivate chlorine-resistant pathogens in the distribution system. The generation of reactive oxygen species generally requires initiators in various environmental remediation processes, which necessitates high dosage of activators and downstream treatment for eliminating the accumulation of deactivated catalysts. Herein, a coupled process was constructed using trace iron for simultaneously activating HSO 3 −/O 2 system and peroxydisulfate (PDS) oxidation system, where the iron ions (2 mg/L) transferred single-electron from the former system to the latter due to the moderate redox potential (Fe3+/Fe2+, +0.77 V) between the potentials of SO 3 ·−/HSO 3 − (+0.63 V) and PDS/SO 4 ·− (+2.01 V). Hence, the phenol degradation quickly occurred at a first-order kinetic constant of k 1 =0.223 min−1 due to the accelerated generation of sulfate radical (SO 4 ·−) and hydroxyl radical (·OH) in the process. The k 1 value was almost 6-fold of that in the deoxygenated condition (0.040 min−1). Density function theory reveals that the single electron shuttle spatially separates the electron-donating activation of HSO 3 − and electron-accepting activation of PDS, while avoiding the "mutual-annihilation" of HSO 3 − and S 2 O 8 2− via direct two-electron transfer. Finally, utilizing the in-situ generated electron-shuttle (dissolved iron from cast iron pipe), the HSO 3 −/PDS reagent could efficiently inactivate the chlorine-resistant pathogens and inhibits biofilm regrowth inside the distribution systems at regular intervals or infectious disease outbreak in a neighborhood. [ABSTRACT FROM AUTHOR]

Cuminaldehyde (CA) has a strong antimicrobial activity against an array of pathogens. In this study, its growth inhibitory effect on a wild type strain (Pds01) and an imazalil-resistant strain (Pdw03) of Penicillium digitatum , the causative agent of postharvest green mold in citrus fruit was examined. CA strongly inhibited mycelial growth of both strains with minimum inhibitory concentration (MIC) of 0.3 mL L-1 and minimum fungicidal concentration (MFC) of 0.6 mL L-1. In vivo assays revealed that wax + CA (WCA, 10 × MFC) treatment could significantly reduce green mold incidence in Ponkan fruit incubated with P. digitatum. After 5 d of incubation, the disease incidence of 10 × MFC WCA treated fruit was 65.0 ± 3.4 % for Pds01 and 50.0 ± 2.1 % for Pdw03 which were much lower than the corresponding values in the control samples. The antifungal activity was attributed to activation of massive oxidative stress, as evidenced by the accumulation of reactive oxygen species, increased lipid peroxidation, damage to plasma membrane permeability of hyphal cells, leakage of intracellular components and eventual cell death. The imazalil-resistant strain was more susceptible to the damaging effect of CA than the wild type strain. Collectively, our present results suggest that CA may potentially be a new antifungal drug molecule for the control of postharvest green mold in citrus fruit. [Display omitted] • Cuminaldehyde inhibited mycelial growth of P. digitatum in vitro. • Cuminaldehyde diminished green mold growth progression in citrus fruit. • Cuminaldehyde damaged cell membrane integrity and hyphal surface morphology. • Cuminaldehyde triggered oxidative stress and lipid peroxidation in P. digitatum. [ABSTRACT FROM AUTHOR]

• •OH could be rapidly generated from Fe2+/EDTA system (O 2 atmosphere). • Fe2+-EDTA activate O 2 to induce H 2 O 2 in-situ via direct 2-electron transformation. • EDTA tune the production pathways of radical or intermediate in Fenton system. • The dual effect of •OH and O 2 •− was revealed in Fe3+/EDTA/H 2 O 2 system. The Fenton system was a generation system of reactive oxygen species via the chain reactions, which employed H 2 O 2 and O 2 as radical precursors and Fe2+/Fe3+ as electron-donor/acceptor for triggering or terminating the generation of radicals. Recent work mainly emphasized the Fe2+- activated H 2 O 2 and the application of in-situ generated •OH, while neglecting other side-reactions. In this work, EDTA (Ethylene diamine tetraacetic acid) was employed as a chelating agent of iron ions, which simultaneously changed the redox property of coordinated iron. The Fe2+-EDTA complexes in the presence of dissolved oxygen enabled the two-electron transfer from Fe2+ to O 2 and the in-situ production of H 2 O 2 , which further activate H 2 O 2 for yielding •OH. Meanwhile, coordinated Fe3+ exhibited non-negligible reactivity toward H 2 O 2 , which was higher than that of free Fe3+ in the traditional Fenton system. The complexation of EDTA with Fe3+ could enhance the Fe2+ generation reaction by the H 2 O 2 , accompanied by the O 2 •− formation. The enhancement of O 2 •− formation and Fe2+-EDTA regeneration induced the subsequent H 2 O 2 activation by Fe2+-EDTA, thus accelerating the Fe3+-EDTA/Fe2+-EDTA cycle for simultaneously producing O 2 •− and •OH. To sum up, the EDTA-chelated Fenton system extended the applicable pH range to circumneutral/alkaline level and tuned the redox property of coordinated iron for diversifying the •OH production routes. The research reinterpreted the chain reactions in the Fenton system, revealing another way to enhance the radical production or other property of the Fenton/Fenton-like system. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: Although herbs have long been alternatively applied for cancer treatment in China, its treatment effects and their potential mechanisms have not been sufficiently investigated. The chinese herb Spatholobus suberectus (SS) is commonly prescribed to cancer patients. In this study, the anti-cancer effect of SS and its molecular mechanisms have been investigated. Materials and methods: The effect of SS on cell proliferation was studied by cell growth assay and flow cytometry on breast cancer cell lines MCF-7 and colon cancer cell line HT-29. The role of SS in apoptosis was studied by flow cytometry, DNA fragmentation assay and mitochondrial membrane potential assay. Expression of proteins associated with cell cycle and apoptosis was determined by Western blot analysis. The in vivo effect of SS was tested in nude mouse cancer xenografts. Results: Cell growth assay showed that SS effectively inhibits tumor cell growth in a dose-dependent manner. Flow cytometry analysis showed that SS could arrest the cell cycle at G2/M checkpoint, which is associated with DNA damage and activation of phosphor-Chk1/Chk2. The pro-apoptotic effect of SS was demonstrated by Annexin V-PI staining and mitochondrial membrane potential assay. In vivo experiments show that the efficiency of SS alone group was superior to docetaxel or to docetaxel and SS combined. No obvious body weight loss or blood toxicity was observed in SS tested animals. Conclusions: Our data demonstrates that SS is a potential herb for cancer treatment by inhibiting tumor growth via induction of apoptosis and arrest of the cell cycle at G2/M phase. [Copyright &y& Elsevier]