RESUMEN
Chronic inflammation-induced oxidative stress is an important driving force for developing colitis-associated cancer (CAC). 4-hydroxynonenal (4-HNE) is a highly reactive aldehyde derived from lipid peroxidation of ω-6 polyunsaturated fatty acids that contributes to colorectal carcinogenesis. Glutathione S-transferase alpha 4 (Gsta4) specifically conjugates glutathione to 4-HNE and thereby detoxifies 4-HNE. The correlation of these oxidative biomarkers with the pathological changes in CAC is, however, unclear. In this study, we investigated the expression of Gsta4 and 4-HNE adducts in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced murine CAC, and analyzed the correlations of 4-HNE and Gsta4 with inflammatory cytokines and the pathological scores in the colon biopsies. Real-time quantitative PCR showed that expression of IL6, TNFα, and Gsta4 sequentially increased in colon tissues for mice treated with DSS for 1, 2, and 3 cycles, respectively. Moreover, immunohistochemical staining showed remarkably increased expression of 4-HNE adducts, Gsta4, TNFα, and IL6 in the colon biopsies after 3 cycles of DSS treatment. Correlation analysis demonstrated that 4-HNE adducts in the colon biopsies were positively correlated with Gsta4 expression. Additionally, the expression of Gsta4 and 4-HNE adducts were strongly correlated with the pathological changes of colon, as well as the expression of TNFα and IL6 in colon tissues. These results provide evidence for the association of oxidative biomarkers Gsta4 and 4-HNE with the pathological changes of CAC and may help developing novel histopathological biomarkers and prevention targets for CAC.
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Allyl-isothiocyanate (AITC) is a common Isothiocyanates (ITC) and its chemo-preventive and anti-tumor effects are believed to be related to the activation of NF-E2 p45-related Factor 2 (Nrf2). However, its anti-tumor effects on colorectal cancer (CRC) are not well elucidated. Here, we investigated the therapeutic in vitro and/or in vivo effects and mechanisms of action (MOA) for AITC on CRC cell line HCT116 (human) and MC38 (mouse). AITC treatment in a low concentration range (1 mg/kg in vivo) significantly inhibited the tumor cell growth and increased the expression of p21 and Nrf2. The AITC-mediated induction of p21 was dependent on Nrf2 but independent on p53 in vitro and in vivo at low dose. In contrast, the high dose of AITC (5 mg/kg in vivo) failed to increase substantial levels of p21/MdmX, and impaired the total antioxidant capacity of tumors and subsequent anti-tumor effect in vivo. These results suggest that an optimal dose of AITC is important and required for the proper Nrf2 activation and its anti-CRC effects and thus, providing insights into the potential applications of AITC for the prevention and treatment of CRC.
Asunto(s)
Neoplasias Colorrectales , Factor 2 Relacionado con NF-E2 , Humanos , Animales , Ratones , Isotiocianatos/farmacología , Isotiocianatos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológicoRESUMEN
Ultrafine explosives show high safety and reliable initiation and have been widely used in aerospace, military, and industrial systems. The outstanding performance of ultrafine explosives is largely given by the unique void defects according to the simulation results. However, the structures and effects of internal nano-voids in ultrafine explosive particles have been rarely investigated experimentally. In this work, contrast-variation small angle X-ray scattering was verified to reliably measure the structures of internal nano-voids in ultrafine explosive 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) and 2,2',4,4',6,6'-hexanitro diphenylethylene (HNS). The size of nano-voids is around 10 nm, and the estimated number of nano-voids in a single particle is considerable. Moreover, the thermal stability of ultrafine LLM-105 was improved via changing the structures of nano-voids. This work provides a methodology for the study of nano-void defects in ultrafine organic particles and may pave the path to enhance the performance of ultrafine explosives via defect engineering.
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Major challenges encountered when developing manganese-based materials for ozone decomposition are related to the low stability and water inactivation. To solve these problems, a hierarchical structure consisted of graphene encapsulating α-MnO2 nanofiber was developed. The optimized catalyst exhibited a stable ozone conversion efficiency of 80% and excellent stability over 100 h under a relative humidity (RH) of 20%. Even though the RH increased to 50%, the ozone conversion also reached 70%, well beyond the performance of α-MnO2 nanofiber. Here, surface graphite carbon was activated by capturing the electron from inner unsaturated Mn atoms. The excellent stability originated from the moderate local work function, which compromised the reaction barriers in the adsorption of ozone molecule and the desorption of the intermediate oxygen species. The hydrophobic graphene shells hindered the chemisorption of water vapour, consequently enhanced its water resistance. This work offered insights for catalyst design and would promote the practical application of manganese-based catalysts in ozone decomposition.
RESUMEN
α-MnO2 is a promising material for ozone catalytic decomposition and the oxygen vacancy is often regarded as the active site for ozone adsorption and decomposition. Here, α-MnO2 nanowire with tunable K+ concentration was prepared through a hydrothermal process in KOH solution. High concentration K+ in the tunnel can expand crystal cell and break the charge balance, leading to a lower average oxidation state (AOS) of Mn, which means abundant oxygen vacancy. DFT calculation has also proven that the samples with higher K+ concentration exhibit lower formation energy for oxygen vacancy. Due to the enormous active oxygen vacancies existing in the α-MnO2 nanowire, the lifetime of the catalyst (corresponding to 100% ozone removal rate, 25 °C) is increased from 3 to 15 h. The FT-IR results confirmed that the accumulation of intermediate oxygen species on the catalyst surface is the main reason why it is deactivated after long time reaction. In this work, the performance of the catalyst has been improved because the abundant active oxygen vacancies are fabricated by the electrostatic interaction between oxygen atoms inside the tunnels and the introduced K+, which offers us a new perspective to design a high efficiency catalyst and may promote manganese oxide for practical ozone elimination.
Asunto(s)
Ozono , Catálisis , Oxidación-Reducción , Oxígeno , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Iron-based (oxy)hydroxides are especially attractive electrocatalysts for the oxygen evolution reaction (OER) owing to their earth abundance, low cost, and nontoxicity. However, poor OER kinetics on the surface restricts the performance of the FeOOH electrocatalyst. Herein, a highly efficient and stable Ni(OH)2 /ß-like FeOOH electrocatalyst is obtained by facile electroactivation treatment. The activated Ni(OH)2 /ß-like FeOOH sample indicates an overpotential of 300â mV at 10â mA cm-2 for the OER, and no clear current decay after 50â h of testing; this is comparable to the most efficient nickel- and cobalt-based electrocatalysts on planar substrates. Furthermore, studies suggest that ß-like FeOOH plays a key role in remarkably enhancing the performance during the electroactivation process owing to its metastable tunnel structure with a lower barrier for interface diffusion of Ni2+ ions between the bilayer electrocatalyst. This study develops a new strategy to explore efficient and low-cost electrocatalysts and deepens understanding of bilayer electrocatalysts for the OER.
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SAM- and SH3-domain containing 1 (SASH1) is a recently identified tumor suppressor gene that is required in the tumorigenesis of breast and other solid carcinomas. The SASH1 protein contains SH3 and SAM domains, indicating that it may serve an important role in intracellular signal transduction. The purpose of the present study was to investigate the expression of SASH1 in ovarian carcinoma and the correlation between its expression with clinical pathological features and clinical significance, and the effect of SASH1 on cell proliferation, apoptosis and migration of ovarian SKOV3 cells. The human ovarian carcinoma tissues and adjacent normal tissues were collected following surgery. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression levels of SASH1 mRNA and protein, respectively. The expression levels of SASH1 mRNA and protein in ovarian carcinoma tissues were significantly lower than that observed in adjacent normal tissues (P<0.05). The expression levels of SASH1 in samples from patients without lymph nodes metastasis and patients with early FIGO stage was lower than those with lymph nodes metastasis and patients with advanced FIGO stage (P<0.05). Flow cytometry analysis and Transwell invasion chamber experiments were used to investigate the effect of SASH1 on the cell proliferation, apoptosis and migration of SKOV3 cells. The recombinant plasmid pcDNA3.1-SASH1 was constructed and transfected into SKOV3 cells. In addition, the SKOV3 cells in the pcDNA3.1-SASH1 group exhibited significantly reduced cell growth, proliferation, and migration ability compared to the empty vector group and normal group (P<0.01). There were a greater number of apoptotic cells in the pcDNA3.1-SASH1 group compared to the empty vector group and normal group (P<0.01). Taken together, these results indicated that SASH1 may be a tumor suppressor gene in ovarian carcinoma, and SASH1 expression inhibited growth, proliferation and migration, and enhanced apoptosis of SKOV3 cells.
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OBJECTIVE: To compare therapeutic effects of elongated needle therapy and routine acupuncture therapy on dysuria induced by benign prostatic hyperplasia (BPH). METHODS: Randomized, controlled, multi-central method was adopted and 150 cases confirmed to the enrolled criteria were divided into two groups by odd or even number, an elongated needle group (n = 72) and a routine acupuncture group (n = 78). Acupuncture was given at bilateral Zhibian (BL 54) and Zhongji (CV 3) in the two groups, once daily, 5 sessions constituting one course, with a 2-day interval between two courses. The treatment was given for 2 courses. Changes of I-PSS symptom cumulative score, urine flowing rate, residual urine in bladder before and after the treatment were observed. RESULTS: The effective rate was 83.3% in the elongated needle group and 44.9% in the routine acupuncture group. There were significant differences between the two groups in improvemet of I-PSS score, increase of urine flowing rate and reduction of residual urine in bladder (all P < 0.05). CONCLUSION: The elongated needle therapy has a definite therapeutic effect on dysuria induced by benign prostatic hyperplasia.