RESUMEN

Supporting materials for electrocatalysts must exhibit relative chemical inertness to facilitate unimpeded movement of gas, and demonstrate electrical conductivity to promote efficient electron transfer to the catalyst. Conventional catalyst electrodes, such as glassy carbon, carbon cloths, or Ni foam, are commonly employed. However, the challenge lies in the limited stability observed during testing due to the relatively weak adhesion between the catalyst and the electrode. Addressing this limitation is crucial for advancing the stability and performance of catalyst-electrode systems in various applications. Here, we suggest a novel fabrication method for a freestanding conducting film, accomplished through gelation, incorporating 1T-MoS2 and graphene oxide. 1T-MoS2 nanosheets play a crucial role in promoting the reduction of graphene oxide (GO) on the Zn foil. This contribution leads to accelerated film formation and enhanced electrical conductivity in the film. The synergistic effect also enhances the film's stability as catalyst supports. This study provides insights into the effective utilization of MoS2 and graphene oxide in the creating of advanced catalyst support systems with potential applications in diverse catalytic reaction.

RESUMEN

Fibrosarcoma is a skin tumor that is frequently observed in humans, dogs, and cats. Despite unsightly appearance, studies on fibrosarcoma have not significantly progressed, due to a relatively mild tumor severity and a lower incidence than that of other epithelial tumors. Here, we focused on the role of a recently-found dermis zinc transporter, ZIP13, in fibrosarcoma progression. We generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fibroblasts by stably expressing the Simian Virus (SV) 40-T antigen. The ZIP13-/- cell line exhibited an impairment in autophagy, followed by hypersensitivity to nutrient deficiency. The autophagy impairment in the ZIP13-/- cell line was due to the low expression of LC3 gene and protein, and was restored by the DNA demethylating agent, 5-aza-2'-deoxycytidine (5-aza) treatment. Moreover, the DNA methyltransferase activity was significantly increased in the ZIP13-/- cell line, indicating the disturbance of epigenetic regulations. Autophagy inhibitors effectively inhibited the growth of fibrosarcoma with relatively minor damages to normal cells in xenograft assay. Our data show that proper control over autophagy and zinc homeostasis could allow for the development of a new therapeutic strategy to treat fibrosarcoma.

Asunto(s)

Autofagia , Proteínas de Transporte de Catión/deficiencia , Dermis/metabolismo , Fibrosarcoma/patología , Animales , Autofagia/efectos de los fármacos , Azacitidina/farmacología , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Etilenodiaminas/farmacología , Fibrosarcoma/genética , Humanos , Ratones Noqueados , Proteínas Asociadas a Microtúbulos/metabolismo , Zinc/metabolismo

RESUMEN

Calorie restriction or a low-carbohydrate diet (LCD) can increase life span in normal cells while inhibiting carcinogenesis. Various phytochemicals also have calorie restriction-mimetic anticancer properties. We investigated whether an isocaloric carbohydrate-restriction diet and AMP-activated protein kinase (AMPK)-activating phytochemicals induce synergic tumor suppression. We used a mixture of AMPK-activating phytochemical extracts including curcumin, quercetin, catechins, and resveratrol. Survival analysis was carried out in a B16F10 melanoma model fed a control diet (62.14% kcal carbohydrate, 24.65% kcal protein and 13.2% kcal fat), a control diet with multiple phytochemicals (MP), LCD (16.5, 55.2, and 28.3% kcal, respectively), LCD with multiple phytochemicals (LCDmp), a moderate-carbohydrate diet (MCD, 31.9, 62.4, and 5.7% kcal, respectively), or MCD with phytochemicals (MCDmp). Compared with the control group, MP, LCD, or MCD intervention did not produce survival benefit, but LCDmp (22.80±1.58 vs. 28.00±1.64 days, P=0.040) and MCDmp (23.80±1.08 vs. 30.13±2.29 days, P=0.008) increased the median survival time significantly. Suppression of the IGF-1R/PI3K/Akt/mTOR signaling, activation of the AMPK/SIRT1/LKB1pathway, and NF-κB suppression were the critical tumor-suppression mechanisms. In addition, SIRT1 suppressed proliferation of the B16F10 and A375SM cells under a low-glucose condition. Alterations in histone methylation within Pten and FoxO3a were observed after the MCDmp intervention. In the transgenic liver cancer model developed by hydrodynamic transfection of the HrasG12V and shp53, MCDmp and LCDmp interventions induced significant cancer-prevention effects. Microarray analysis showed that PPARα increased with decreased IL-6 and NF-κB within the hepatocytes after an MCDmp intervention. In conclusion, an isocaloric carbohydrate-restriction diet and natural AMPK-activating agents induce synergistic anticancer effects. SIRT1 acts as a tumor suppressor under a low-glucose condition.

Asunto(s)

Proteínas Quinasas Activadas por AMP/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Suplementos Dietéticos , Neoplasias Hepáticas Experimentales/prevención & control , Melanoma Experimental/prevención & control , Fitoquímicos/administración & dosificación , Sirtuina 1/metabolismo , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular/efectos de los fármacos , Inmunoprecipitación de Cromatina , Carbohidratos de la Dieta/farmacología , Sinergismo Farmacológico , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/mortalidad , Neoplasias Hepáticas Experimentales/patología , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/mortalidad , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación , Fitoquímicos/farmacocinética , Transducción de Señal , Sirtuina 1/genética , Tasa de Supervivencia , Células Tumorales Cultivadas

RESUMEN

3-D profiles of discontinuous surfaces patterned with high step structures are measured using four wavelengths generated by phase-locking to the frequency comb of an Er-doped fiber femtosecond laser stabilized to the Rb atomic clock. This frequency-comb-referenced method of multi-wavelength interferometry permits extending the phase non-ambiguity range by a factor of 64,500 while maintaining the sub-wavelength measurement precision of single-wavelength interferometry. Experimental results show a repeatability of 3.13 nm (one-sigma) in measuring step heights of 1800, 500, and 70 µm. The proposed method is accurate enough for the standard calibration of gauge blocks and also fast to be suited for the industrial inspection of microelectronics products.

Asunto(s)

Interferometría/instrumentación , Ensayo de Materiales/instrumentación , Propiedades de Superficie , Diseño de Equipo , Análisis de Falla de Equipo

RESUMEN

Multiple lines of evidence support an inverse association between consumption of garlic and the risk of cancer. Chemopreventive effects of garlic have been attributed to its oil-soluble sulfur ingredients, such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), but their underlying molecular mechanisms remain largely unresolved. In the present study, we found that DATS showed the most potent anti-proliferative effects in human breast cancer MCF-7 cells. MCF-7 cells treated with DATS underwent apoptotic death as revealed by a progressive increase in the proportion of the sub-G0/G1 cell population and a typical pattern of annexin V/propidium iodide staining. DATS induced phosphorylation of the antiapoptotic Bcl-2 and proteolytic cleavage of poly(ADP-ribose)polymerase (PARP) in MCF-7 cells. DATS treatment activated c-Jun N-terminal kinase (JNK). DATS-induced apoptosis was blunted in MCF-7 cells treated with a specific JNK inhibitor SP600125 or transiently transfected with dominant negative JNK. DATS treatment resulted in accumulation of reactive oxygen species (ROS). DATS-induced apoptosis as well as activation of JNK was abrogated by N-acetyl-l-cysteine (NAC). Furthermore, DATS induced phosphorylation and expression of c-Jun, which were attenuated by NAC. MCF-7 cells treated with DATS also exhibited increased DNA binding activity of AP-1, which was blocked by NAC and the JNK inhibitor. Proteolytic cleavage of PARP induced by DATS was abrogated in the cells transfected with c-jun siRNA. Oral administration of 5µmol/kg DATS to female Balb/c mice inhibited the growth of human MCF-7 cell tumor xenografts. These results suggest that DATS-induced apoptosis is mediated through ROS generation and subsequent activation of JNK and AP-1.

Asunto(s)

Compuestos Alílicos/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sulfuros/farmacología , Factor de Transcripción AP-1/metabolismo , Animales , Neoplasias de la Mama , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Fosforilación , Trasplante Heterólogo

RESUMEN

AIMS: We have investigated the effects of magnesium lithospermate B (MLB), the active compound of the Oriental herbal remedy, Salvia miltiorrhizae, on endothelial dysfunction associated with diabetes mellitus using cultured endothelial cells and an animal model of type 2 diabetes mellitus. METHODS AND RESULTS: The effect of MLB on vasodilatory function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was assessed. MLB treatment for 20 weeks starting at 12 weeks attenuated the decrease in endothelium-dependent vasodilation in OLETF rats. MLB treatment also increased serum nitrite level and reduced serum advanced glycation end products concentration. The effect of MLB was greater than an equivalent dose of alpha-lipoic acid (alphaLA), a popular antioxidant treatment. MLB rescued the inhibition of endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation in endothelial cells cultured in hyperglycaemia. This effect was dependent on Akt phosphorylation and associated with decreased O-linked N-acetylglucosamine protein modification of eNOS. MLB also increased nuclear factor erythroid 2-related factor-2 (Nrf-2) activation in a phosphoinositide 3-kinase/Akt pathway dependent manner. MLB treatment induced the expression of the Nrf-2-regulated antioxidant enzyme, heme oxygenase-1. The antioxidant alphaLA could not produce this effect. Moreover, MLB decreased oxidative stress and endothelial cell apoptosis caused by hyperglycaemia. CONCLUSION: MLB is a naturally occurring, new generation antioxidant that activates eNOS and ameliorates endothelial dysfunction in diabetes by enhancing vasodilation in addition to reducing oxidative stress. The relative strong performance of MLB makes it an ideal candidate for further, expanded trials as a new generation of antioxidant to treat diabetes-related complications.

Asunto(s)

Antioxidantes/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Endotelio Vascular/efectos de los fármacos , Glucosa/metabolismo , Vasodilatación/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Células Cultivadas , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Productos Finales de Glicación Avanzada/sangre , Glicosilación , Hemo-Oxigenasa 1/metabolismo , Humanos , Leucocitos/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Nitritos/sangre , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Procesamiento Proteico-Postraduccional , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Endogámicas OLETF , Ratas Long-Evans , Especies Reactivas de Oxígeno/metabolismo , Factores de Tiempo

RESUMEN

Hyperglycemia-induced oxidative stress is known to play an important role in the development of several diabetic complications, including atherosclerosis. Although a number of antioxidants are available, none have been found to be suitable for regulating the oxidative stress response and enhancing antioxidative defense mechanisms. In this study, we evaluated the effects of magnesium lithospermate B (LAB) against oxidative stress. We also endeavored to identify the target molecule of LAB in vascular smooth muscle cells (VSMCs) and the underlying biochemical pathways related to diabetic atherosclerosis. Modified MTT and transwell assays showed that the increased proliferation and migration of rat aortic VSMCs in culture with high glucose was significantly inhibited by LAB. LAB also attenuated neointimal hyperplasia after balloon catheter injury in diabetic rat carotid arteries. To determine molecular targets of LAB, we studied the effects of LAB on aldose reductase (AR) activity, O-GlcNAcylation, and protein kinase C (PKC) activity in VSMCs under normoglycemic or hyperglycemic conditions and showed the improvement of major biochemical pathways by LAB. Potential involvement of the nuclear factor erythroid 2-related factor-2 (Nrf2)--antioxidant responsive element (ARE)-NAD(P)H: quinone oxidoreductase-1 (NQO1) pathway was assessed using siRNA methods. We found that LAB activates the NQO1 via the Nrf2-ARE pathway, which plays an important role in inhibition of the major molecular mechanisms that lead to vascular damage and the proliferation and migration of VSMCs. Together, these findings demonstrate that the induction of the Nrf2-ARE-NQO1 pathway by LAB could be a new therapeutic strategy to prevent diabetic atherosclerosis.

Asunto(s)

Aterosclerosis/prevención & control , Medicamentos Herbarios Chinos/uso terapéutico , NAD(P)H Deshidrogenasa (Quinona)/fisiología , Factor 2 Relacionado con NF-E2/fisiología , Elementos de Respuesta/fisiología , Aldehído Reductasa/metabolismo , Animales , Antioxidantes/farmacología , Aterosclerosis/metabolismo , Diabetes Mellitus Experimental/complicaciones , Masculino , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteína Quinasa C/metabolismo , Ratas , Ratas Sprague-Dawley

RESUMEN

PURPOSE: Oral cancer is the fifth most common form of cancer in the world and comprises 6.5% of all cancer deaths. Since one of the major risk factors for oral cancer is tobacco use, we hypothesized that polymorphic genes coding for tobacco carcinogen-metabolizing enzymes may play a role in oral cancer susceptibility. MATERIALS AND METHODS: To investigate the association between polymorphisms of the CYP1A1 and GSTM1 genes and risks for oral squamous cell carcinoma (OSCC) in the Korean population, the prevalence of the CYP1A1 Mspl and GSTM1 null polymorphisms were examined in 72 patients with histologically confirmed primary OSCC, as well as in 221 healthy control subjects. RESULTS: A significant risk increase for oral cancer was observed among subjects with the homozygous CYP1A1 (m2/m2) genotype (OR=3.8, 95% CI=1.9-7.7), but not the GSTM1 null genotype (OR=0.7, 95% CI=0.4-1.3). Risk for oral cancer was significantly increased in subjects with the homozygous CYP1A1 (m2/m2)genotype, regardless of smoking history (smokers; OR=4.4; 95% CI=1.2-16.3; non- smokers OR=4.9; 95% CI=1.9-12.5). Using the potentially most protective genotype GSTM1 (+)/CYP1A1 [(m1/m1)+ (m1/m2)] as the reference group, an increased risk for oral cancer was observed among subjects with the GSTM1 (+)/ CYP1A1 (m2/m2) (OR= 2.0, 95% CI=0.8-5.2), and GSTM1 (-)/ CYP1A1 (m2/m2) (OR=4.9, 95% CI=1.5-15.5) genotypes (p < 0.009, (chi2 trend test). CONCLUSION: Our results suggest that individuals with a genotype of CYP1A1 (m2/m2) and GSTM1 (-) are highly susceptible for OSCC and that the CYP1A1 (m2/m2) genotype is closely associated with increased risk of OSCC in Koreans.

Asunto(s)

Citocromo P-450 CYP1A1/genética , Predisposición Genética a la Enfermedad , Glutatión Transferasa/genética , Neoplasias de la Boca/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Eliminación de Gen , Genotipo , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/epidemiología , Factores de Riesgo , Fumar/epidemiología

RESUMEN

Xanthorrhizol is a sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhiza. In this study, the anti-metastatic activity of xanthorrhizol was evaluated by using an in vivo mouse lung metastasis model and a tumor mass formation assay. Interestingly, xanthorrhizol dramatically inhibited the formation of tumor nodules in the lung tissue and the intra-abdominal tumor mass formation. Next, to examine the mechanism of the anti-metastatic action of xanthorrhizol in the mouse lung metastasis, expression patterns of the several intracellular signaling molecules were evaluated using the lung tissues with tumor nodules. Higher expression levels of cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), and phosphorylated extracellular signal-regulated kinase (ERK) were observed in the metastatic group compared with control, but these were attenuated by the treatment of xanthorrhizol. In conclusion, xanthorrhizol exerts anti-metastatic activity in vivo and this effect could be highly linked to the metastasis-related multiplex signal pathway including ERK, COX-2, and MMP-9.

Asunto(s)

Antineoplásicos/administración & dosificación , Biomarcadores de Tumor/metabolismo , Curcuma/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Fenoles/administración & dosificación , Fitoterapia/métodos , Animales , Relación Dosis-Respuesta a Droga , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Neoplasias Experimentales/secundario , Extractos Vegetales/administración & dosificación , Resultado del Tratamiento

RESUMEN

OBJECTIVES: Although the direct cause for periodontitis is oral bacterial infection, its progression depends upon genetic and environmental factors. Smoking, one of the environmental factors, is a risk factor for the development and severity of periodontitis. Therefore, individual susceptibility to periodontitis may be influenced by the polymorphisms of genes coding for enzymes metabolizing tobacco-derived substances. The object of this study is to investigate roles of genetic polymorphisms of these metabolizing enzymes in the risk for periodontitis. MATERIAL AND METHODS: We investigated three important enzymes: cytochrome P450 (CYP) 1A1, CYP2E1 and glutathione S-transferase (GST) M1, involved in the metabolic activation and detoxification of tobacco-derived substances. The prevalence of the polymorphisms of these genes was examined in 115 patients with periodontitis as well as in 126 control subjects. RESULTS: Significantly increased risk for periodontitis was observed for subjects with the polymorphic CYP1A1 m2 allele (odds ratio (OR)=2.3, 95% confidence interval (CI)=1.2-4.4). A significant risk increase for periodontitis associated with the GSTM1 allele was observed (OR=2.1, 95% CI=1.3-3.6). However, no association was observed between the CYP2E1 Pst1 polymorphism and risk for periodontitis (OR=1.3, 95% CI=0.6-2.5). CONCLUSION: These results suggest that the GSTM1 and CYP1A1 polymorphisms may play an important role in risk for periodontitis.

Asunto(s)

Citocromo P-450 CYP1A1/genética , Glutatión Transferasa/genética , Periodontitis/enzimología , Periodontitis/genética , Fumar/genética , Fumar/metabolismo , Biotransformación/genética , Estudios de Casos y Controles , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Glutatión Transferasa/metabolismo , Humanos , Modelos Logísticos , Oportunidad Relativa , Polimorfismo de Longitud del Fragmento de Restricción , Medición de Riesgo