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1.
Chemistry ; 28(24): e202104490, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35236006

RESUMO

Ga2 O3 -decorated and -defective surface models based on anatase TiO2 have been established. The thermodynamic reaction pathways, including protonation, deoxygenation and hydroxylation steps, during CO2 conversion with H2 O to C1 products were calculated. The calculation results demonstrate that a Ga2 O3 cocatalyst enhances the selective adsorption of CO2 and slightly weakens the competitive adsorption of H2 O. The promotion effect of Ga2 O3 on the subsequent reaction depends on the availability of protons and electrons. Free-energy calculations revealed that the basic functional site generated by Ga2 O3 not only suppresses the back reaction of the OH group after H2 O directly provides protons but also maintains the surface defect oxygen vacancy (VO ), which promotes the reaction thermodynamics but tends to be consumed in the process. Additionally, Ga2 O3 decoration promotes VO formation, and the coexistence of Ga2 O3 and VO further decreases the reaction rate-determining step energy barrier, promoting C1 production.

2.
BMC Neurol ; 22(1): 429, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380279

RESUMO

BACKGROUND: C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke. METHODS: There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured. RESULTS: Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke and increased during stage III (11th day to one month) and stage IV (1 month after), compared to control. In the non-hyperlipidemia group, serum CTRP9, tAPN, and HMW were decreased in ischemic stroke patients compared to control (P < 0.05). Serum CTRP9 is closely related to serum tAPN and HMW (r = 0.992, 0.991). Serum CTRP9 are protective against ischemic stroke (OR = 0.400, 95% CI 0.197-0.810, P < 0.05). CONCLUSIONS: Lower serum CTRP9, tAPN, LMW, and HMW are significantly associated with increased ischemic stroke risk in non-hyperlipidemia subjects. CTRP9, tAPN, and HMW isoforms may be valuable clinical indicators for patients with ischemic stroke.


Assuntos
Adiponectina , AVC Isquêmico , Humanos , Adiponectina/metabolismo , Glicoproteínas/metabolismo , Peso Molecular
3.
MycoKeys ; 102: 301-315, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495535

RESUMO

Rich and diverse fungal species occur in different habitats on the earth. Many new taxa are being reported and described in increasing numbers with the advent of molecular phylogenetics. However, there are still a number of unknown fungi that have not yet been discovered and described. During a survey of fungal diversity in different habitats in China, we identified and proposed two new species, based on the morphology and multi-gene phylogenetic analyses. Herein, we report the descriptions, illustrations and molecular phylogeny of the two new species, Bisifusariumkeratinophilumsp. nov. and Ovatosporasinensissp. nov.

4.
Artigo em Zh | MEDLINE | ID: mdl-23905241

RESUMO

OBJECTIVE: To study the 3, 4- dinitro-furazan-based oxidation furazan (DNTF) of sub-acute toxicity and chronic toxicity, to determine the acute toxicity classification DNTF, the nature of toxic effects and major target organ for the development provide the basis for occupational exposure limits. METHODS: ( 1) Acute toxicity: The oral gavage method once infected, symptoms of poisoning of animals observed to calculate the LD50DNTF and 95% confidence limits. ( 2) sub-chronic experiment: selection of 96 healthy SD rats were randomly divided into four groups, doses of 25, 56.2, 125 mg/kg and the negative control group, Exposure for ninety days,five days a week, once a day, The rats were killed at end of Exposure, heart, liver, spleen, lung, kidney, brain,testis, uterus were taken to observe the pathological changes. RESULTS: ( 1) Acute oral toxicity test results indicate that DNTF rat oral LD50 greater than 5000 mg/kg, DNTF mice treated by oral LD50 4589 mg/kg, 95%confidence limit for the 4026-5230 mg/kg, Acute toxicity grade level is low toxicity compounds. (2) Sub-chronic toxicity experiment, the high-dose male rats, high, medium and low-dose group female rats weight gain than the negative control group, compared with the control group, the difference was statistically significant (P<0.05).125 mg/kg of serum alanine aminotransferase, aspartate aminotransferase was significantly higher. 125 mg/kg dose groups, liver, kidney, lung, testicular factor was significantly higher. Liver, kidney, lung histological examination showed obvious morphological changes. CONCLUSION: Acute toxicity grade DNTF low toxicity level compounds, target organ toxicity of liver, kidney and lung.


Assuntos
Nitrofurazona/análogos & derivados , Oxidiazóis/toxicidade , Animais , Feminino , Dose Letal Mediana , Masculino , Camundongos , Nitrofurazona/toxicidade , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade
5.
J Fungi (Basel) ; 9(6)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37367581

RESUMO

The genus Acrophialophora belongs to the family Chaetomiaceae. With the addition of new species and transferred species from other genera, the genus Acrophialophora has expanded. In this study, eight new species related to Acrophialophora were isolated from soil samples in China. Using muti-locus phylogenetic (ITS, LSU, tub2 and RPB2) analysis combined with morphological characteristics, eight new species (Acrophialophora curvata, A. fujianensis, A. guangdongensis, A. longicatenata, A. minuta, A. multiforma, A. rhombica, and A. yunnanensis) are described. Descriptions, illustrations, and notes of the new species are also provided.

6.
Hum Brain Mapp ; 32(11): 1847-55, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21170956

RESUMO

Neuropsychiatric systemic lupus erythematosus (NP-SLE) is a common complication of systemic lupus erythematosus (SLE), and clinical interventions are of only limited efficacy despite relatively high prevalence. Such complications have been studied extensively, but the pathoetiology of NP-SLE has not yet been elucidated. Diagnosis of NP-SLE focuses primarily on psychological manifestations, and the underlying mechanisms leading to neuropsychiatric complications remain unknown. To address potential changes in brain function before NP-SLE development, we used resting-state functional magnetic resonance imaging (MRI) to compare regional brain activity in SLE patients versus matched controls. We report that regional activity in cerebellum and in areas of the default mode network are attenuated in patients with SLE, and moreover individual alterations in cerebellar activity correlated positively with the disease activity index. These findings provide direct evidence that significant alteration of brain function, resembling that observed in patients with NP-SLE, is already present in SLE patients without neuropsychiatric complications, highlighting the need for early evaluation and intervention in SLE patients. Furthermore, the disease activity rating correlated with regional functional alterations in the cerebellum, suggesting that the cerebellum could play a role in the pathogenesis of NP-SLE.


Assuntos
Encéfalo/fisiopatologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Cerebelo/fisiopatologia , Interpretação Estatística de Dados , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/etiologia , Transtornos Mentais/fisiopatologia , Oxigênio/sangue
7.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 7): m1009, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21836834

RESUMO

The title compound, (C(2)H(8)N)(C(5)H(12)NO)[ZnCl(4)], was synthesized by hydro-thermal reaction of ZnCl(2) with 4-methyl-morpholine in a dimethyl-formamide solution. The asymmetric unit is composed of half a [ZnCl(4)](2-) anion, half a 4-methyl-morpholin-4-ium cation and half a dimethyl-ammonium cation, all located on mirror planes parallel to ac. All the amine H atoms are involved in inter-molecular N-H⋯Cl hydrogen bonds, building up an infinite chain parallel to the c axis.

8.
Artigo em Zh | MEDLINE | ID: mdl-21941788

RESUMO

OBJECTIVE: Through a detection of dust in the coal mines workplace, to understand the status of occupational hazards, and the evaluation of occupational hazards, provide subject to control occupational hazards. METHOD: According to production process and "hazardous substances in workplace air monitoring, sampling norms" and other standards to determine the sampling points and sampling of coal dust. RESULT: Underground mining operations in 21 subjects with time-weighted average concentration of dust types pass rate of 28.6%, of which five types of dust hazard grade II, six types of dust hazard rating of 0, and the remaining types of grade I dust hazard levels. Coal dust test six types of time-weighted average concentration of 83.3% pass rate, only one types of dust hazard grade I, all the rest is 0. Calculated by the detection of dust overrun 18 times operating sites, the pass rate of 72.2% results. CONCLUSION: Purified water spray and air flow curtain of dust control has played a certain role, but the work of underground working conditions and environmental constraints, most of the dust concentration in workplace occupational exposure limits do not meet the requirements, recommended the strengthening of dust or Dust the daily management and maintenance of equipment, strengthen the ventilation, personal protection officers to strengthen operations.


Assuntos
Poluentes Ocupacionais do Ar/análise , Minas de Carvão , Poeira/análise , Exposição Ocupacional/análise , Monitoramento Ambiental , Humanos , Local de Trabalho
9.
Artigo em Zh | MEDLINE | ID: mdl-22468297

RESUMO

OBJECTIVE: To study the acute, subacute and subchronic toxicity induced by ammonium dinitramide (ADN), and to ascertain the gradation and target organs of acute toxicity induced by AND. METHODS: According to technical specifications for toxicity determination of chemicals, the oral tests for acute, subacute and subchronic toxicity induced by AND were performed for 90 days. RESULTS: The oral LDx for mouse and rat was 568.9 mg/kg and 616.6 mg/kg ADN respectively. The gradation of acute toxicity induced by AND was low level. The results of oral subacute and subchronic toxicity tests (for 28 and 90 days) showed that a gain in weight in group exposed to 123 mg/kg AND was significantly lower than that in control group (P<0.05), the TBIL and ALT in group exposed to 61.6 and 123 mg/kg AND significantly increased and the ratio of liver weight to body weight obviously decreased, as compared with control group, the number of animals with hepatic pathological changes in group exposed to 61.6 and 123 mg/kg AND was significantly higher than that in control group (P<0.05). CONCLUSION: The gradation of acute toxicity induced by ADN was low level. When the exposure dose of AND was 30.8 mg/kg, the adverse effect was not observed, and the target organ was liver.


Assuntos
Nitritos/toxicidade , Compostos de Amônio Quaternário/toxicidade , Animais , Peso Corporal , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
10.
Artigo em Zh | MEDLINE | ID: mdl-22468299

RESUMO

OBJECTIVE: To study the mutagenicity and teratogenicity induced by ammonium dinitramide(ADN). METHODS: According to technical specifications for toxicity determination of chemicals, Salmonella typhimurium reverse mutation assay (Ames assay), in vivo mammalian erythrocyte micronucleus test, sperm malformation test and teratogenesis test were used to detect the mutagenicity and teratogenicity induced by AND. RESULTS: When the exposure doses of AND were 8-5000 pg/plate, the result of Ames assay was negative. As compared with control group, the micronucleus rate of mice exposed to 113.8 mg/kg AND significantly increased(P<0.05), the sperm malformation rates of mice exposed to 54.4-272.0 mg/kg AND did not increased significantly. The survival rate of fetuses decreased, the rate of assimilated fetuses increased, the rate of fetus sternum agenesis enhanced in mice exposed to 319 mg/kg AND, as compared with controls. The rates of in the 4th-6th fetus sternum agenesis in groups exposed to 21.3, 79.7 and 319 mg/kg AND were higher than that in control group. The malformation rate of fetus bowels in groups exposed to 319 mg/kg AND was higher than that in control group. The teratogenic index of ADN was 30. CONCLUSION: AND may be a mutagen and induce the teratogenic effect.


Assuntos
Nitritos/toxicidade , Compostos de Amônio Quaternário/toxicidade , Animais , Embrião de Mamíferos/efeitos dos fármacos , Embrião de Mamíferos/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Testes para Micronúcleos , Testes de Mutagenicidade , Gravidez , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Esterno/efeitos dos fármacos , Esterno/patologia
11.
Minerva Anestesiol ; 87(6): 655-662, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33325216

RESUMO

BACKGROUND: There is a controversy about whether the use of a lung-protective ventilation strategy(LPVS) can reduce the incidence of postoperative pulmonary complications (PPCs) and improve the clinical outcomes in moderate-risk patients were assessed by the Assess Respiratory Risk in Surgical Patients in Catalonia(ARISCAT). METHODS: One hundred moderate-risk patients predicted by the ARISCAT, scheduled to undergo abdominal surgery were randomized into two groups: conventional ventilation strategy group (G0) and lung-protective ventilation strategy group (G1). Lung ultrasonography (LUS) and the LUS score were performed before induction of anesthesia (T0), 30min after extubation (T1), and 24h (T2), 72h (T3) after surgery. The incidence and severity of PPCs within the postoperative 7 days, the duration of postoperative oxygen supplementation, and postoperative hospital stay (PHS) were recorded. RESULTS: The LUS score of both groups at T1-3 was higher than those at T0 (P<0.05), moreover, the LUS score of G1 was lower than that of G0 at T1-3. The incidence of PPCs of G1 (10.9%) was lower than that of G0 (29.8%) (relative risk, 0.37; 95% confidence interval [CI], 0.14 to 0.93; P=0.02) and the severity of PPCs of G1 were lower than those of G0 (P<0.05). The PHS of G1 was less than that of G0 (8[7-10] vs. 9[8-11], P<0.05). CONCLUSIONS: The LPVS can decrease lung aeration loss assessed by LUS and reduce the incidence of PPCs in moderate-risk patients.


Assuntos
Pneumopatias , Respiração Artificial , Humanos , Tempo de Internação , Pulmão/diagnóstico por imagem , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Pneumopatias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle
12.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 12): o3296, 2010 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-21589575

RESUMO

In the crystal of the title molecular salt, C(6)H(9)N(2) (+)·C(7)H(5)O(2) (-), the cations and anions are linked by N-H⋯O hydrogen bonds, buiding an R(2) (2)(9) ring. Futher N-H⋯O hydrogen bonds generate chains, which develop parallel to the a axis through the formation of R(4) (3)(10) rings..

13.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 12): o3297, 2010 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-21589576

RESUMO

In the cation of the title compound, C(6)H(6)N(5) (+)·Cl(-), the tetra-zole and pyridine rings are nearly coplanar, making a dihedral angle of 5.58 (11)°. The organic cations are linked to the chloride anions via N-H⋯Cl hydrogen bonds, forming chains along [110].

14.
Biomed Res Int ; 2020: 5219367, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33426054

RESUMO

OBJECTIVE: The present study investigated whether optic nerve sheath diameter (ONSD) could be used to predict neurological outcomes in post-cardiac arrest (CA) patients. METHODS: We performed a comprehensive literature search in the Cochrane Library, ScienceDirect, PubMed, and Web of Science from inception to June 2020 for eligible articles. Stata 14.0 software was used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs), sensitivity, specificity, summary receiver operating characteristic (SROC) curve, subgroup analysis, sensitivity analysis, and publication bias. RESULTS: Eight studies involving 473 patients were considered eligible for this meta-analysis. The pooled result using a random-effects model showed that broadened ONSD is associated with poor neurological outcomes in post-CA patients (OR = 15.62, 95% CI: 5.50-44.34, P < 0.001; I 2 = 58.4%, P = 0.018), with a sensibility of 0.60 (95% CI: 0.45-0.73) and specificity of 0.94 (95% CI: 0.83-0.98). The area under the curve of the SROC curve for ONSD was 0.87 (95% CI: 0.84-0.90). Subgroup analysis revealed that sample size and time of ONSD measurement may be the source of heterogeneity. Sensitivity analysis demonstrated the stability of the results of this meta-analysis. No publication bias using Deeks' funnel plot was noted across the studies (P = 0.23). CONCLUSION: This meta-analysis confirmed that ONSD can be used to predict neurological outcomes in post-CA patients.


Assuntos
Parada Cardíaca , Nervo Óptico/patologia , Parada Cardíaca/diagnóstico , Parada Cardíaca/epidemiologia , Parada Cardíaca/patologia , Parada Cardíaca/fisiopatologia , Humanos , Doenças do Sistema Nervoso , Prognóstico , Curva ROC , Ressuscitação , Sensibilidade e Especificidade
15.
Int J Cancer ; 125(1): 139-45, 2009 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-19350634

RESUMO

Environmental dietary carcinogens and genetic polymorphisms in metabolic enzymes have been reported to be the risk factors for gastric cancer. This study was undertaken to investigate the effects of the diet, the N-acetyltransferase (NAT) 2 acetylation status and their interaction on gastric cancer risk. The study population consisted of 471 gastric cancer patients and 471 age- and sex-matched control subjects. NAT2 genotypes were identified using single-nucleotide primer extension reaction methods. Thirty-one alleles related to 12 polymorphism sites were assayed in this study. Significantly increased odds ratios were observed in former smokers (OR = 2.39, 95% CI = 1.57-3.62), heavy drinkers (OR = 1.28, 95% CI = 1.06-1.55) and individuals who eat well-done meat (OR = 1.24, 95% CI = 1.09-1.41). The odds ratios (95% CI) for high intake of kimchi, stews and soybean paste were 3.27 (2.44-4.37), 1.96 (1.50-2.58) and 1.63 (1.24-2.14), respectively. The NAT2 genotype alone was not associated with gastric cancer risk. A significant gene-environment interaction was observed between environmental carcinogens and NAT2 genotypes. The odds ratios for kimchi, stews and soybean paste were higher in slow/intermediate acetylators than in rapid acetylators. The odds ratios for slow/intermediate acetylators were 2.28 (95% CI: 1.29-4.04) for light smokers and 3.42 (95% CI: 2.06-5.68) for well-done meat intake. The NAT2 acetylator genotype may be an important modifier of the effects of environmental factors on gastric cancer risk.


Assuntos
Arilamina N-Acetiltransferase/genética , Dieta , Comportamento Alimentar , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/genética , Acetilação , Carcinógenos , Estudos de Casos e Controles , Exposição Ambiental , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Neoplasias Gástricas/epidemiologia
16.
Cancer Causes Control ; 20(2): 137-45, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18798003

RESUMO

OBJECTIVES: We investigated the association of genetic polymorphisms of NQO1, ALDH2, CYP2E1, and the combined genotype of these genes on lung cancer risk, and also evaluated the association after stratification by cumulative smoking amounts and alcohol drinking levels. METHODS: The case-control study was performed in 387 lung cancer patients and 387 age- and sex-matched cancer-free controls. Direct interview was conducted and the genotypes of NQO1, ALDH2, and CYP2E1 were investigated using PCR-RFLP or 5'-nuclease activity assay. RESULTS: The proportion of individuals with occupational history of mining was significantly higher in cases than in controls. The risk of lung cancer was significantly lower in light-drinkers (<108 g/week) than non-drinkers. The NQO1 Pro/Ser + Ser/Ser genotype showed an increased risk for lung cancer with a marginal significance (OR = 1.35, 95% CI = 0.99-1.86) compared with NQO1 Pro/Pro genotype. In heavy-smokers, the combination of NQO1 Pro/Ser + Ser/Ser and CYP2E1 c1/c1 genotype was associated with a significantly increased risk for lung cancer (OR = 2.25, 95% CI = 1.14-4.43) compared with those of NQO1 Pro/Pro and CYP2E1 c1/c2 + c2/c2 genotype. We found a significant interaction between alcohol drinking level and the CYP2E1 genotype (P = 0.0227). CONCLUSIONS: Our result suggests that the risk of lung cancer is affected by smoking, alcohol drinking, and the genetic polymorphism of NQO1. In particular, genetic polymorphisms for NQO1, CYP2E1, and ALDH2 synergistically with cumulative smoking amounts and alcohol drinking levels interact in the carcinogenesis of lung cancer in Koreans.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Aldeído Desidrogenase/genética , Citocromo P-450 CYP2E1/genética , Neoplasias Pulmonares/genética , NAD(P)H Desidrogenase (Quinona)/genética , Fumar/efeitos adversos , Aldeído-Desidrogenase Mitocondrial , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco
17.
Fa Yi Xue Za Zhi ; 24(3): 165-7, 171, 2008 Jun.
Artigo em Zh | MEDLINE | ID: mdl-18709847

RESUMO

OBJECTIVE: To observe the degradation of actin in cardiac muscle, brain and skeletal muscle of rats after death and to find an objective parameter interval (PMI) estimation. METHODS: Twenty eight clear Sprague Dawley rats put into an artificial climate incubator (set at 20 degrees C) for 0, 24, 48, 72, The actin contents in the above tissues were quantitated by Western-blot Pro Plus 5.0 image analysis system, and were then statistically analyzed RESULTS: Actin content in all these tissues decreased gradually with prolonged differences between the groups was statistically significant (P < 0.05), with fastest, then the lung, the spleen, the liver, the kidney, the cardiac muscle order. There was a strong correlation between actin degradation and determination (R2) exceeded 0.75 in all these tissues. CONCLUSION: degradation, the actin contents in cardiac muscle, liver, spleen, lung, kindey, rats decreased gradually with prolonged PMI, which may potentially be PMI estimation.


Assuntos
Actinas/metabolismo , Encéfalo/metabolismo , Patologia Legal/métodos , Miocárdio/metabolismo , Mudanças Depois da Morte , Animais , Morte , Feminino , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
18.
J Occup Health ; 49(5): 363-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17951967

RESUMO

Excessive alcohol consumption is associated with increased risks of many diseases including cancer. We evaluated oxidative DNA damage in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Olive tail moment, which was measured using a comet assay, was not increased by ethanol treatment in both Aldh2 +/+ and Aldh2 -/- mice. However, after controlling for the effect of ethanol exposure, the Aldh2 genotype was a significant determinant for Olive tail moments. Although the ethanol treatment significantly increased the hepatic 8-OHdG generation in only Aldh2 +/+ mice, the level of 8-OHdG was the highest in Aldh2 -/- ethanol treated mice. The increase in the level of 8-OHdG was associated with hepatic expression of cytochrome P450 2E1 (CYP2E1). The levels of Olive tail moment and the hepatic 8-OHdG in the Aldh2 -/- control group were significantly higher than those of the Aldh2 +/+ control group. The level of CYP2E1 in liver tissue showed a similar pattern to those of the oxidative DNA damage markers. This study shows that acute ethanol consumption increases oxidative DNA damage and that expression of CYP2E1 protein may play a pivotal role in the induction of oxidative DNA damage. The finding that oxidative DNA damage was more intense in Aldh2 -/- mice than in Aldh2 +/+ mice suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.


Assuntos
Aldeído Desidrogenase/genética , Citocromo P-450 CYP2E1/genética , Dano ao DNA/genética , Etanol/toxicidade , Hepatopatias/genética , Fígado/efeitos dos fármacos , Estresse Oxidativo/genética , Polimorfismo Genético , 8-Hidroxi-2'-Desoxiguanosina , Aldeído Desidrogenase/deficiência , Aldeído-Desidrogenase Mitocondrial , Análise de Variância , Animais , Western Blotting , Doença Hepática Induzida por Substâncias e Drogas , Ensaio Cometa , Citocromo P-450 CYP2E1/análise , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Desoxiguanosina/genética , Modelos Animais de Doenças , Predisposição Genética para Doença , Fígado/enzimologia , Masculino , Camundongos , Camundongos Knockout/genética , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Estresse Oxidativo/efeitos dos fármacos
19.
Am J Cancer Res ; 6(11): 2690-2699, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27904781

RESUMO

Cervical cancer is one of the most lethal malignancies amongst women, partially because it is unresponsive to many chemotherapeutic drugs. The mechanism underlying cisplatin (DDP) resistance in cervical cancer remains largely elusive. In this study, by detecting the 12 most reported down-regulated miRNAs in chemotherapy-sensitive and -resistant cervical cancer cells, we found that miR-497 was significantly reduced in chemotherapy-resistant HeLa/DDP cells and contributed to DDP chemosensitivity. Transketolase (TKT), a thiamine-dependent enzyme that plays a role in the channeling of excess glucose phosphates to glycolysis in the pentose phosphate pathway, was identified as a direct target of miR-497. TKT expression in clinical specimens was characterized by immunohistochemistry and the result showed that TKT was highly expressed in 81.1% (60/74) of samples examined. Data from Oncomine databases revealed that TKT was significantly up-regulated in cervical cancer tissues compared to normal controls. Gain-of-function and loss-of-function studies showed that the miR-497/TKT axis was a critical modulator in DDP chemosensitivity as demonstrated by cell viability and apoptosis assays. Mechanistically, DDP chemosensitivity induced by the miR-497/TKT axis was associated with glutathione (GSH) depletion and reactive oxygen species (ROS) generation, and GSH treatment effectively abrogated miR-497/TKT-mediated chemosensitivity. In conclusion, these findings suggest that a deregulated miR-497/TKT axis has important implications in the cervical cancer cellular response to DDP, and thus targeting this axis may be a promising way to improve chemosensitivity in cervical cancer.

20.
Am J Cancer Res ; 6(2): 312-20, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27186405

RESUMO

MicroRNAs (miRNA) play crucial roles in regulating cell proliferation, differentiation and developmental timing. Aberrantly expressed miRNAs have recently emerged as key regulators of metabolism. However, little is known about its role in tumor metabolism of cervical cancer. In this study, we determined the oncogenic effects of miRNAs on Warburg effect, a metabolic phenotype that allows cancer cells to utilize glucose even under aerobic conditions. A gain-of-function study was performed in 12 down-regulated miRNAs that frequently reported in cervical cancer. We found that miR-34a plays a suppressive role in Warburg effect as evidenced by decreased lactate production and glucose consumption. Knockdown of oncoprotein E6 expression of human papillomavirus in SiHa and HeLa cells by siRNAs lead to an increased protein level of p53, decreased level of miR-34a, as well as reduced Warburg effect. Subsequently, lactate dehydrogenase A (LDHA), which catalyzes the last key step in glycolysis, was identified as a direct target of miR-34a. Silencing of LDHA or introduction of miR-34a significantly attenuated colony formation ability and invasive capacity of SiHa and HeLa cells, and these effects were fully compromised by reintroduction of LDHA. In conclusion, our findings demonstrated that deregulated miR-34a/LDHA axis induced by HPV E6/p53 signaling facilitates tumor growth and invasion through regulating Warburg effect in cervical cancer, and provided new insights into the mechanism by which miR-34a contributes to the development and progression of cervical cancer.

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