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1.
Plant Biol (Stuttg) ; 26(2): 282-291, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38194355

RESUMO

The control of Huanglongbing (HLB), one of the most destructive pests of citrus, relies heavily on the reduction of Asian citrus psyllid (ACP), Diaphorina citri Kuwayama. An in-depth understanding of ACP feeding behaviours among citrus plants is urgent for comprehensive management of orchards. An investigation was conducted in 37 citrus orchards in HLB epidemic areas, sampling shoots in the area with aggregation feeding of ACP (ACPf) and shoots in a neighbouring area without ACP feeding (CK), to study the interaction between leaf chemical composition and ACP psyllid feeding behaviours. Results of FTIR showed a strong absorption peak intensity, mainly representing functional groups originating from cell wall components in the leaf with ACP feeding. As compared with the control, cell wall components, such as alkali-soluble pectin, water-soluble pectin, total soluble pectin, cellulose, and hemicellulose, of the cell wall of ACPf increased by 134.0%, 14.0%, 18.0%, 12.5%, and 20.35%, respectively. These results suggest that cell wall mechanical properties significantly decreased in the term of decreases in pectin performance and cellulose mechanical properties. In addition, there was a remarkably lower boron (B) content in leaves and cell wall components with ACP feeding. Further analysis indicated that leaf B content significantly affected leaf cell wall components. Taken together, we provide evidence to demonstrate that the regional distribution of nutrient imbalance in orchards could affect psyllid feeding behaviour by weakening the cell wall structure, resulting in epidemic variation in ACP. This could help us to understand the management of psyllid infections in orchards with unbalanced nutrition.


Assuntos
Citrus , Hemípteros , Animais , Hemípteros/fisiologia , Boro , Comportamento Alimentar , Nutrientes , Parede Celular , Celulose , Pectinas , Doenças das Plantas
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(2): 227-233, 2022 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-35184489

RESUMO

Objective: To understand the current status of taking nutrient supplements for residents aged 18 to 79 years old in Beijing and its related factors. Methods: Data were gathered from the 2017 Beijing Non-communicable and Chronic Disease Surveillance Program. Multiple classified cluster sampling method was used, and participants aged 18-79 were sampled from 16 districts. The questionnaire included chronic diseases and related risk factors, health knowledge, and oral nutritional supplements within 12 months. Multivariate logistic regression models were established to analyze associated factors that affect the intake of nutrient supplements. Results: The weighted prevalence of supplements use was 13.1% among 12 696 subjects within the past 12 months. The proportions of multivitamins (4.7%), B vitamins (4.5%), and folic acid (3.2%) were higher. The prevalence of supplement use of young people (18-39 years old) and the elderly (60-79 years old) was higher than middle-aged people (40-59 years old) (χ2=54.09, P<0.001). Except for the age group of 70-79 years old, the consumption rate of women was significantly higher than that of men (P<0.05). After adjusting age and sex, among patients with hypertension, diabetes, or dyslipidemia, the control rates of blood pressure, glucose and lipids of patients who take nutrient supplements were higher than those who do not (P<0.05). And participants who took nutrient supplements had a more heightened awareness rate of health knowledge, such as the hazards of smoking and second-hand smoke, and recommended amount of salt per day (P<0.001). The multi-factor logistic analysis found that nutrient supplement-related factors include women, old age, higher education level, living in urban, insufficient physical activity, sleeping problems, active physical examination, blood pressure control among patients, and health knowledge (P<0.05). Conclusions: The factors of nutrient supplements use were related to sex, age, education level, health status, and health literacy. We should pay attention to key populations and guide them to establish the correct concept of taking nutrient supplements.


Assuntos
Suplementos Nutricionais , Complexo Vitamínico B , Adolescente , Adulto , Idoso , Pequim/epidemiologia , Feminino , Ácido Fólico , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/efeitos adversos , Adulto Jovem
3.
Biomaterials ; 228: 119568, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677393

RESUMO

A general therapeutic strategy to treat breast cancer is attractive as different subtypes of breast cancers often exhibit distinct response to existing cancer therapeutics. To this end, we prepare a catalyst couple of glucose oxidase (GOx) and gallic acid-ferrous (GA-Fe) nanocomplexes, a type of near-infrared (NIR) absorbing Fenton catalyst, to enable NIR-trigger in-situ gelation and enhanced chemodynamic/starvation therapy that appears to be effective for different types of breast cancer cells. In this system, GOx is mixed with GA-Fe in a solution of N,N-dimethylacrylamide (DMAA) and poly (ethylene glycol) double acrylate (PEGDA). Upon intratumoral injection and NIR laser exposure, such GA-Fe show rapid temperature increase, which would simultaneously increase the catalytic efficiencies of GA-Fe and GOx. The cascade production of hydroxyl radicals (•OH) from glucose is then initiated to enable polymerization of DMAA and PEGDA to form a hydrogel at the injection site within the tumor. The continuous production of cytotoxic •OH together with glucose depletion by the intratumorally fixed catalyst couple would further confer effective destruction of breast cancer tumors by such chemodynamic/starvation therapy. Our work presents a hydrogel-based therapeutic strategy for local treatment of solid tumors with high tumor destruction efficacy and low systemic toxicity.


Assuntos
Neoplasias da Mama , Hipertermia Induzida , Neoplasias da Mama/tratamento farmacológico , Glucose , Glucose Oxidase , Humanos , Radical Hidroxila
4.
Zhonghua Yi Shi Za Zhi ; 49(1): 25-28, 2019 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-30970421

RESUMO

The earliest appearance of "Lacha" was in the Tang Dynasty. At first, it was only served as a type of tribute tea to the emperor and the royal families.Since the Song Dynasty, "Lacha" was viewed as a kind of medicine or drug.Sheng Ji Zonglu(, Comprehensive Record of Sagely Beneficence) is the most abundant literature of the medicinal formulas of "Lacha" since the Song Dynasty. The book presented 72 prescriptions, which involved 62 diseases.Its application forms were diverse, including decoction, pill, powder and so on.The main functions included resuscitating, clearing up the heads, aiding digestion, dissipating phlegm, detoxifying and treating sores, eliminating miasma, and reducing the toxicity of other drugs.


Assuntos
História da Medicina , Medicina Tradicional Chinesa , Beneficência , Livros , China , Prescrições
5.
J Anim Sci ; 94(8): 3271-3277, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27695776

RESUMO

This experiment was conducted to investigate the effects of microencapsulted (MEF) and the extract of seed (ECOS) on growth performance, immune functions, and serum biochemical parameters in broiler chickens. A total of 240 1-d-old male broilers were randomly allotted into 6 treatments with 8 replicates/treatment and 5 broilers in each cage. The dietary treatments included 1) a basal diet without antibiotic (group A), 2) the basal diet + 1 g MEF/kg diet (1 × 10 cfu/g MEF; group B), 3) the basal diet + 300 mg ECOS/kg diet (group C), 4) the basal diet + 300 mg ECOS/kg diet + 1 g MEF/kg diet (group D), 5) the basal diet + 500 mg ECOS/kg diet (group E), and 6) the basal diet + 500 mg ECOS/kg diet + 1 g MEF/kg diet (group F). The feeding experiment included 2 phases: the starter phase from Day 1 through 21 and the grower phase from Day 22 through 42. The results showed that a diet supplemented with MEF and ECOS had no significant effect on ADG, ADFI, feed conversion ratio, and average BW during the whole experimental period ( > 0.05), but group F showed an improving trend in growth performance. Serum IL-2, IgA, and IgG levels and spleen index were significantly affected by dietary treatment ( < 0.05). Serum IgA and IgG levels and spleen index in group F were significantly higher than in the group A ( < 0.05), and the IL-2 level was significantly decreased ( < 0.05) on Days 21 and 42. Compared with the group A, diets supplemented with MEF and ECOS can significantly decrease total cholesterol, low-density lipoprotein cholesterol, triglycerides, and blood urea nitrogen levels ( < 0.05) and increase the high-density lipoprotein cholesterol level on Days 21 and 42. Concentrations of serum biochemical parameters were significantly increased in group F ( < 0.05). In summary, the results indicated that dietary supplementation of MEF and/or ECOS had no significant effect on growth performance but significantly increased spleen index and the levels of serum IgA and IgG and improved serum lipid metabolism. The 1 g MEF/kg diet (1 × 10 cfu/g diet) plus 500 mg ECOS/kg diet was the optimum supplemental dose in this experiment.


Assuntos
Ração Animal/análise , Galinhas/crescimento & desenvolvimento , Suplementos Nutricionais , Composição de Medicamentos , Animais , Galinhas/fisiologia , Colesterol/sangue , Dieta/veterinária , Interleucina-2/sangue , Lipoproteínas HDL/sangue , Masculino , Distribuição Aleatória , Triglicerídeos/sangue
6.
Vet J ; 191(1): 115-20, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21900026

RESUMO

This study aimed to enhance the antibacterial activity of tilmicosin by solid lipid nanoparticles (SLN). Tilmicosin-loaded hydrogenated castor oil (HCO)-SLN was prepared using a hot homogenisation and ultrasonication method. The physicochemical characteristics of SLN were investigated by scanning electron microscopy (SEM) and photon correlation spectroscopy (PCS). The antibacterial activity of tilmicosin-SLN against Staphylococcus aureus was evaluated by growth inhibition and colony-counting method. A therapeutic study of tilmicosin-SLN was conducted by subcutaneous injection in a mouse mastitis model infected with S. aureus by teat canal infusion. Therapeutic efficacy was assessed by physical appearance of the mammary gland and measurement of colony-forming units (CFU) per gland. The results showed that the diameter, polydispersivity index, zeta potential, encapsulation efficiency and loading capacity of the nanoparticles were 343±26 nm, 0.33±0.08, -7.9±0.4 mV, 60.4±3.3% and 11.2±0.47%, respectively. Tilmicosin-SLN showed a sustained-release effect and sustained and enhanced antibacterial activity in vitro. SLN significantly enhanced the therapeutic efficacy of tilmicosin determined by lower CFU counts and a decreased degree of inflammation. These results demonstrated that the HCO-SLN is an effective carrier to enhance the antibacterial activity of tilmicosin.


Assuntos
Antibacterianos/uso terapêutico , Mastite Bovina/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/efeitos dos fármacos , Tilosina/análogos & derivados , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Óleo de Rícino/administração & dosagem , Bovinos , Química Farmacêutica , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Lipídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos , Nanopartículas , Infecções Estafilocócicas/tratamento farmacológico , Células-Tronco/efeitos dos fármacos , Tilosina/química , Tilosina/farmacologia , Tilosina/uso terapêutico
7.
IET Nanobiotechnol ; 5(3): 79-85, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21913789

RESUMO

Poly(lactic-co-glycolic acid) (PLGA) was used as a polymeric emulsifier to encapsulate plasmid DNA into hydrogenated castor oil (HCO)-solid lipid nanoparticles (SLN) by w/o/w double emulsion and solvent evaporation techniques. The effects of PLGA on the preparation, characteristics and transfection efficiency of DNA-loaded SLN were studied. The results showed that PLGA was essential to form the primary w/o emulsion and the stability of the emulsion was enhanced with the increase of PLGA content. DNA-loaded SLN were spherical with smooth surfaces. The SLN had a negative charge in weak acid and alkaline environment but acquired a positive charge in acidic pH and the cationisation capacity of the SLN increased with the increase of PLGA/HCO ratio. Agarose gel electrophoresis demonstrated that the majority of the DNA maintained its structural integrity after preparation and being extracted or released from DNA-loaded SLN. When PLGA/HCO ratio increased from 5 to 15%, the encapsulation efficiency, loading capacity and transfection efficiency of the nanoparticles increased significantly, whereas the changes of particle size and polydispersity index were insignificant. Cytotoxicity study in cell culture demonstrated that the SLN was not toxic.


Assuntos
Óleo de Rícino/química , DNA/química , Ácido Láctico/química , Nanopartículas/química , Plasmídeos/química , Ácido Poliglicólico/química , Análise de Variância , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Eletroforese em Gel de Ágar , Emulsões/química , Técnicas de Transferência de Genes , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
8.
J Microencapsul ; 24(7): 634-46, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17763057

RESUMO

The gelatin/gum arabic multinuclear microcapsules encapsulating peppermint oil were prepared by coacervation. The effect of various processing parameters, including the core/wall ratio, wall material concentration, pH value, as well as stirring speed on the morphology, particle size distribution, yield and loading was investigated. When the wall material concentration or the core/wall ratio increased, the morphology of multinuclear microcapsules changed from spherical to irregular and the average particle size increased, the optimal wall material concentration and the core/wall ratio were 1% and 2:1, respectively. The multinuclear spherical microcapsules with desired mean particle size can be manufactured by modulating the pH value and stirring speed. The ideal preparation conditions were pH 3.7 at 400 rpm of stirring speed. The yield of multinuclear microcapsules encapsulating peppermint oil by coacervation was approximately 90% and the processing parameters had very slight influence on the yield. When transglutaminase was used as the cross-linker instead of formaldehyde, morphology, mean particle size, yield and loading remained the same as that hardening with formaldehyde, but the particle size distribution became narrower.


Assuntos
Microesferas , Óleos de Plantas/química , Química/métodos , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/farmacologia , Composição de Medicamentos , Formaldeído/química , Goma Arábica/química , Concentração de Íons de Hidrogênio , Mentha piperita , Tamanho da Partícula , Tecnologia Farmacêutica , Transglutaminases/metabolismo , Água/química
9.
Org Lett ; 7(14): 2917-20, 2005 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-15987169

RESUMO

[reaction: see text] A novel approach for the stereocontrolled synthesis of eudesmanolides was developed based on a quasi-biomimetic strategy starting from a functionalized oxabicyclic template, as shown above, by which the first total syntheses of gallicadiol (6) and isogallicadiol (7) were achieved. The key elements of the synthesis include: (1) a facile and stereospecific synthesis of a functionalized epoxy aldehyde intermediate; (2) a mild Lewis acid-mediated stereoselective ene cyclization; and (3) a stereocontrolled gamma-lactonization.


Assuntos
Lactonas/química , Sesquiterpenos/síntese química , Artemisia/química , Cristalografia por Raios X , Conformação Molecular , Estrutura Molecular , Plantas Medicinais/química , Sesquiterpenos/química , Estereoisomerismo
10.
Biochem J ; 360(Pt 1): 49-56, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11695991

RESUMO

Caspase-9 is the apex caspase of the mitochondrial pathway of apoptosis, which plays a critical role in apoptotic initiation and progression. However, gene regulation of caspase-9 is largely unknown. This is in part due to the lack of information on the gene promoter. Here we have cloned the full-length cDNA of rat caspase-9 and have isolated promoter regions of this gene. The rat caspase-9 cDNA of 2058 bp predicts a protein of 454 amino acids, which contains a caspase-recruitment domain ('CARD') at the N-terminus and enzymic domains at the C-terminus. The enzyme's active site, with a characteristic motif of QACGG, was also identified. Overall, rat and human caspase-9 have 71% identity. With the cDNA sequence, we subsequently isolated the proximal 5'-flanking regions of rat caspase-9 by the procedure of genomic walking. The 2270 bp genomic segment is 'TATA-less', but contains several GC boxes. Elements binding known transcription factors such as Sp-1, Pit-1, CCAAT-enhancer-binding protein (C/EBP), glucocorticoid receptor and hypoxia-inducible factor 1 (HIF-1) were also identified. When cloned into reporter gene vectors, the genomic segment showed significant promoter activity, indicating that the 5'-flanking regions isolated by genomic walking contain the gene promoter of rat caspase-9. Of significance is that the cloned promoter segments were activated by severe hypoxia, conditions inducing caspase-9 transcription. Thus, the genomic sequences reported here contain not only the basal promoter of rat caspase-9 but also regulatory elements responsive to pathophysiological stimuli including hypoxia.


Assuntos
Caspases/genética , Regiões Promotoras Genéticas , Células 3T3 , Aminoácidos/química , Animais , Sequência de Bases , Sítios de Ligação , Northern Blotting , Caspase 9 , Linhagem Celular , Clonagem Molecular , DNA Complementar/metabolismo , Ativação Enzimática , Humanos , Hipóxia , Camundongos , Modelos Genéticos , Dados de Sequência Molecular , Células PC12 , Estrutura Terciária de Proteína , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
11.
J Biol Chem ; 276(49): 46624-31, 2001 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-11591714

RESUMO

In this study, we investigated the effect of tea polyphenols, (-)-epigallocatechin-3-gallate or theaflavins, on UVB-induced phosphatidylinositol 3-kinase (PI3K) activation in mouse epidermal JB6 Cl 41 cells. Pretreatment of cells with these polyphenols inhibited UVB-induced PI3K activation. Furthermore, UVB-induced activation of Akt and ribosomal p70 S6 kinase (p70 S6-K), PI3K downstream effectors, were also attenuated by the polyphenols. In addition to LY294002, a PI3K inhibitor, pretreatment with a specific mitogen-activated protein/extracellular signal-regulated protein kinases (Erks) kinase 1 inhibitor, U0126, or a specific p38 kinase inhibitor, SB202190, blocked UVB-induced activation of both Akt and p70 S6-K. Pretreatment with LY294002 restrained UVB-induced phosphorylation of Erks, suggesting that in UVB signaling, the Erk pathway is mediated by PI3K. Moreover, pretreatment with rapamycin, an inhibitor of p70 S6-K, inhibited UVB-induced activation of p70 S6-K, but UVB-induced activation of Akt did not change. Interestingly, UVB-induced p70 S6-K activation was directly blocked by the addition of (-)-epigallocatechin-3-gallate or theaflavins, whereas these polyphenols showed only a weak inhibition on UVB-induced Akt activation. Because PI3K is an important factor in carcinogenesis, the inhibitory effect of these polyphenols on activation of PI3K and its downstream effects may further explain the anti-tumor promotion action of these tea constituents.


Assuntos
Flavonoides , Fenóis/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Polímeros/farmacologia , Chá/química , Raios Ultravioleta , Animais , Linhagem Celular , Transformação Celular Neoplásica , Ativação Enzimática , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Polifenóis , Transdução de Sinais
12.
FASEB J ; 15(11): 2022-4, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11511526

RESUMO

Our previous study showed that tea polyphenols inhibited MAP kinase and AP-1 activities in mouse epidermal JB6 cells and the corresponding H-ras-transformed cell line 30.7b Ras 12. The present study investigated the mechanisms of this inhibition. The cells were incubated with (-)-epigallocatechin-3-gallate (EGCG) or theaflavin-3,3'-digallate (TFdiG) (20 mM) for different times, and the cell lysate was analyzed by immunoblotting. EGCG treatment decreased the levels of phospho-Erk1/2 and -MEK1/2 time-dependently (by 60% at 60 min). TFdiG lowered their levels by 38%-50% at 15 min. TFdiG effectively decreased total Raf-1 protein levels, most likely through lysosomal degradation. EGCG did not affect protein levels or the activity of Raf-1 significantly but decreased its association with MEK1 as determined by co-immunoprecipitation. In addition, EGCG and TFdiG (10 mM) inhibited the phosphorylation of Elk-1 by isolated phospho-Erk1/2 in vitro. This inhibition of Erk1/2 activity is Elk-1 concentration-dependent and ATP concentration-independent, which suggests that EGCG and TFdiG interfere with the binding of the protein substrate to the kinase. The presently demonstrated specific mechanisms of inhibition of MAP kinases by EGCG and TFdiG may help us to understand the effects of tea consumption on cancer, inflammatory diseases, and cardiovascular diseases.


Assuntos
Biflavonoides , Catequina/farmacologia , Proteínas de Ligação a DNA , Flavonoides , Ácido Gálico/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais , Fatores de Transcrição , Trifosfato de Adenosina/metabolismo , Catálise , Catequina/análogos & derivados , Linhagem Celular , Ácido Gálico/análogos & derivados , MAP Quinase Quinase 1 , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Fenóis/metabolismo , Fosforilação , Polímeros/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-raf/metabolismo , Transdução de Sinais/efeitos dos fármacos , Especificidade por Substrato , Chá , Proteínas Elk-1 do Domínio ets
14.
Cancer Res ; 61(15): 5749-56, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11479211

RESUMO

The fruit juice of Morinda citrifolia (noni), a plant originally grown in the Hawaiian and Tahitian islands, has long been used by islanders to treat diseases, including cancer. Two novel glycosides, 6-O-(beta-D-glucopyranosyl)-1-O-octanoyl-beta-D-glucopyranose and asperulosidic acid, extracted from the juice of noni fruits, were used to examine their effects on 12-O-tedtradecanoylphorbol-13-acetate (TPA)- and epidermal growth factor (EGF)-induced AP-1 transactivation and cell transformation in mouse epidermal JB6 cells. The results indicated that both compounds were effective in suppressing TPA- or EGF-induced cell transformation and associated AP-1 activity. TPA- or EGF-induced phosphorylation of c-Jun, but not extracellular signal-regulated kinases or p38 kinases, was also blocked by the compounds, indicating that c-Jun N-terminal kinases were critical in mediating TPA- or EGF-induced AP-1 activity and subsequent cell transformation in JB6 cells.


Assuntos
Anticarcinógenos/farmacologia , Transformação Celular Neoplásica/efeitos dos fármacos , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Rubiaceae/química , Pele/efeitos dos fármacos , Fator de Transcrição AP-1/antagonistas & inibidores , Ativação Transcricional/efeitos dos fármacos , Animais , Anticarcinógenos/isolamento & purificação , Adesão Celular/fisiologia , Linhagem Celular , Transformação Celular Neoplásica/genética , DNA/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Frutas/química , Glucosídeos/isolamento & purificação , Glicosídeos/isolamento & purificação , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Proteínas Proto-Oncogênicas c-jun/metabolismo , Pele/citologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/prevenção & controle , Acetato de Tetradecanoilforbol/farmacologia , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-1/fisiologia , Ativação Transcricional/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno
15.
Proc Natl Acad Sci U S A ; 98(13): 7510-5, 2001 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-11416221

RESUMO

Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 3 (omega3) fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 6 (omega6) fatty acids such as arachidonic acid (AA) reportedly promote risk. To investigate the effects of fatty acids on tumorigenesis, we performed experiments to examine the effects of the omega3 fatty acids EPA and DHA and of the omega6 fatty acid AA on phorbol 12-tetradecanoate 13-acetate (TPA)-induced or epidermal growth factor (EGF)-induced transcription activator protein 1 (AP-1) transactivation and on the subsequent cellular transformation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA- and EGF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation. AA treatment had no effect on either TPA- or EGF-induced AP-1 transactivation or transformation, but did abrogate the inhibitory effects of DHA on TPA- or EGF-induced AP-1 transactivation and cell transformation in a dose-dependent manner. The results of this study demonstrate that the inhibitory effects of omega3 fatty acids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA, the dietary ratio of omega6 to omega3 fatty acids may be a significant factor in mediating tumor development.


Assuntos
Transformação Celular Neoplásica/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Pele/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Ativação Transcricional/efeitos dos fármacos , Animais , Adesão Celular , Linhagem Celular , Fator de Crescimento Epidérmico/farmacologia , Ácidos Graxos Ômega-6 , Genes Reporter , Proteínas Quinases JNK Ativadas por Mitógeno , Cinética , Luciferases/genética , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oligodesoxirribonucleotídeos/metabolismo , Pele/citologia , Pele/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Fator de Transcrição AP-1/antagonistas & inibidores , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno
17.
Proc Natl Acad Sci U S A ; 98(10): 5786-91, 2001 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-11331771

RESUMO

Proteinase inhibitor I (Inh I) and proteinase inhibitor II (Inh II) from potato tubers are effective proteinase inhibitors of chymotrypsin and trypsin. Inh I and Inh II were shown to suppress irradiation-induced transformation in mouse embryo fibroblasts suggesting that they possess anticarcinogenic characteristics. We have previously demonstrated that Inh I and Inh II could effectively block UV irradiation-induced activation of transcription activator protein 1 (AP-1) in mouse JB6 epidermal cells, which mechanistically may explain their anticarcinogenic actions. In the present study, we investigated the effects of Inh I and Inh II on the expression and composition pattern of the AP-1 complex following stimulation by UV B (UVB) irradiation in the JB6 model. We found that Inh I and Inh II specifically inhibited UVB-induced AP-1, but not NFkappaB, activity in JB6 cells. Both Inh I and Inh II up-regulated AP-1 constituent proteins, JunD and Fra-2, and suppressed c-Jun and c-Fos expression and composition in bound AP-1 in response to UVB stimulation. This regulation of the AP-1 protein compositional pattern in response to Inh I or Inh II may be critical for the inhibition of UVB-induced AP-1 activity by these agents found in potatoes.


Assuntos
Proteínas Sanguíneas/farmacologia , Solanum tuberosum/metabolismo , Fator de Transcrição AP-1/antagonistas & inibidores , Sequência de Bases , Proteínas Sanguíneas/isolamento & purificação , Linhagem Celular , Primers do DNA , NF-kappa B/metabolismo , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-1/efeitos da radiação , Raios Ultravioleta
18.
Cancer Res ; 61(3): 850-3, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11221868

RESUMO

Many spices, including plants of the ginger family, possess anticarcinogenic activity. However, the molecular mechanisms by which they exert their antitumorigenic effects are unknown. Activator protein 1 (AP-1) has a critical role in tumor promotion, and blocking of tumor promoter-induced activation of AP-1 inhibits neoplastic transformation. Epidermal growth factor induces cell transformation and AP-1 activity. The purpose of this study was to investigate the effect of two structurally related compounds of the ginger family, [6]-gingerol and [6]-paradol, on EGF-induced cell transformation and AP-1 activation. Our results provide the first evidence that both block EGF-induced cell transformation but act by different mechanisms.


Assuntos
Anticarcinógenos/farmacologia , Transformação Celular Neoplásica/efeitos dos fármacos , Fator de Crescimento Epidérmico/antagonistas & inibidores , Álcoois Graxos/farmacologia , Fator de Transcrição AP-1/metabolismo , Animais , Catecóis , Morte Celular/efeitos dos fármacos , Linhagem Celular , Transformação Celular Neoplásica/induzido quimicamente , DNA/metabolismo , Indução Enzimática/efeitos dos fármacos , Células Epidérmicas , Epiderme/efeitos dos fármacos , Guaiacol/análogos & derivados , Guaiacol/farmacologia , Cetonas/farmacologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Plantas Medicinais , Proteínas Quinases p38 Ativadas por Mitógeno
19.
J Natl Cancer Inst ; 92(21): 1753-63, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11058618

RESUMO

BACKGROUND: From March 1986 through May 1991, we conducted a randomized nutritional intervention trial, the General Population Trial, in Linxian, China, a region with epidemic rates of squamous esophageal and adenomatous gastric cardia cancers. We found that participants who received selenium, beta-carotene, and vitamin E had significantly lower cancer mortality rates than those who did not. In the current study, we examined the relationship between selenium levels measured in pretrial (1985) sera from participants and the subsequent risk of developing squamous esophageal, gastric cardia, and gastric non-cardia cancers during the trial. METHODS: This study was designed and analyzed in accord with a stratified case-cohort sampling scheme, with the six strata defined by sex and three age categories. We measured serum selenium levels in 590 case subjects with esophageal cancer, 402 with gastric cardia cancers, and 87 with gastric non-cardia cancers as well as in 1062 control subjects. Relative risks (RRs), absolute risks, and population attributable risk for cancers were estimated on the basis of the Cox proportional hazards models. All statistical tests are two-sided. RESULTS: We found highly significant inverse associations of serum selenium levels with the incidence of esophageal (P: for trend <10(-4)) and gastric cardia (P: for trend <10(-6)) cancers. The RR and 95% confidence interval (CI) for comparison of highest to lowest quartile of serum selenium was 0.56 (95% CI = 0.44-0.71) for esophageal cancer and 0.47 (95% CI = 0.33-0.65) for gastric cardia cancer. The population proportion of these cancers that is attributable to low selenium levels was 26.4% (95% CI = 14.45-38.36). We found no evidence for a gradient of serum selenium associated with incidence of gastric non-cardia cancer (P: for trend =.96), with an RR of 1.07 (95% CI = 0.55-2.08) for the highest to lowest quartile of serum selenium. CONCLUSIONS: Our study supports findings from previous prospective studies and randomized trials that variations in selenium levels affect the incidence of certain cancers. In the United States, where intervention trials of selenium are in the planning stages, consideration should be given to including populations at high risk for squamous esophageal and gastric cardia cancers.


Assuntos
Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/epidemiologia , Selênio/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/epidemiologia , Adulto , Distribuição por Idade , Idoso , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Fatores de Risco , Selênio/administração & dosagem , Distribuição por Sexo , Neoplasias Gástricas/mortalidade
20.
Am J Physiol Renal Physiol ; 279(5): F927-43, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11053054

RESUMO

We have further examined the mechanisms for a severe mitochondrial energetic deficit, deenergization, and impaired respiration in complex I that develop in kidney proximal tubules during hypoxia-reoxygenation, and their prevention and reversal by supplementation with alpha-ketoglutarate (alpha-KG) + aspartate. The abnormalities preceded the mitochondrial permeability transition and cytochrome c loss. Anaerobic metabolism of alpha-KG + aspartate generated ATP and maintained mitochondrial membrane potential. Other citric-acid cycle intermediates that can promote anaerobic metabolism (malate and fumarate) were also effective singly or in combination with alpha-KG. Succinate, the end product of these anaerobic pathways that can bypass complex I, was not protective when provided only during hypoxia. However, during reoxygenation, succinate also rescued the tubules, and its benefit, like that of alpha-KG + malate, persisted after the extra substrate was withdrawn. Thus proximal tubules can be salvaged from hypoxia-reoxygenation mitochondrial injury by both anaerobic metabolism of citric-acid cycle intermediates and aerobic metabolism of succinate. These results bear on the understanding of a fundamental mode of mitochondrial dysfunction during tubule injury and on strategies to prevent and reverse it.


Assuntos
Metabolismo Energético/fisiologia , Túbulos Renais Proximais/metabolismo , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo , Aerobiose/fisiologia , Anaerobiose/fisiologia , Animais , Ácido Aspártico/metabolismo , Benzimidazóis/farmacocinética , Carbocianinas/farmacocinética , Hipóxia Celular/fisiologia , Ciclo do Ácido Cítrico/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Feminino , Corantes Fluorescentes/farmacocinética , Fumaratos/metabolismo , Ácidos Cetoglutáricos/metabolismo , Túbulos Renais Proximais/citologia , Malatos/metabolismo , Potenciais da Membrana , Mitocôndrias/efeitos dos fármacos , Oxigênio/metabolismo , Oxigênio/farmacologia , Coelhos , Rodaminas/farmacocinética , Especificidade por Substrato
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