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1.
Foods ; 13(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38928841

RESUMO

Given the link between excessive salt consumption and hypertension, reducing salt levels in bread, an important staple food in Japan, is essential. γ-Aminobutyric acid (GABA) has a salty taste-enhancing effect in vivo, and its production is influenced by the type of spice extract in vitro. However, the effects of spices on GABA levels, total free amino acid composition, and taste quality in whole-wheat bread remain unclear. Therefore, this study aimed to investigate whether the addition of spice extracts, which do not affect bread flavor and taste, can increase the GABA level in low-salt whole-wheat bread and whether free amino acid content affects the taste quality of bread using an automatic home bread maker. Through free amino acid composition analysis and sensory testing, we evaluated the influence of six spice extracts on the composition of free amino acids, including GABA, in whole-wheat bread. We found that cumin and anise extracts were effective in increasing the GABA level to approximately twice that in whole-wheat bread. Moreover, both the preference and saltiness of the bread were favorable, indicating that these extracts are useful for reducing the salt content of whole-wheat bread. This study provides a theoretical basis for guiding industrial production.

2.
J Cosmet Dermatol ; 21(7): 3095-3101, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34743412

RESUMO

BACKGROUND: Clinical studies have clarified the usefulness of moisturizers for dry skin diseases. However, few reports exist on the appropriate application of moisturizers with respect to the skin physiological functions. AIMS: To clarify the optimal moisturizer application method on the basis of skin physiological functions. METHODS: This study investigated the appropriate time, dose, and frequency of moisturizer application from the perspective of skin physiology. In healthy subjects, the stratum corneum water content (SCW) was compared between different moisturizer application times (immediately [≤5 min] and 90 min after bathing), doses (0.5, 1.0, and 2.0 mg/cm2 ), and frequencies (once and twice daily). Thereafter, patients with dry skin were treated with the moisturizer once or twice daily for 8 weeks at the time, and application dose was determined to be optimal for the healthy subjects; the moisturizing effect was evaluated based on the SCW, trypsin activity, and desmoglein 1 localization score in the stratum corneum. RESULTS: In healthy subjects, compared to at control sites, the SCW was significantly higher at sites treated with the moisturizer immediately after bathing, with 1.0 and 2.0 mg/cm2 of the moisturizer, and with once- and twice-daily applications. In patients with dry skin, the SCW was significantly higher compared to control sites and the desmoglein 1 localization score was significantly lower after 8 weeks only when the moisturizer was applied twice daily. CONCLUSIONS: Moisturizer application of ≥1.0 mg/cm2 twice daily (immediately after bathing at night and in the morning) had a moisturizing effect, as verified from the skin physiological functions.


Assuntos
Desmogleína 1 , Emolientes , Desmogleína 1/metabolismo , Epiderme , Humanos , Pele , Fenômenos Fisiológicos da Pele , Água/metabolismo , Perda Insensível de Água
3.
J Hand Surg Eur Vol ; 43(5): 513-517, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29105590

RESUMO

We present seven cases of a relatively rare swan neck deformity resulting from chronic radial collateral ligament (RCL) injury of the proximal interphalangeal (PIP) joint in the little finger. All patients were middle-aged women (mean 51 years old, range 42-55), and the duration between the initial injury and surgery was 20 years (range 5-40). The chief complaint was painful snapping of the PIP joint. All patients had hyperextension and ulnar deviation of the PIP joint with mobile swan neck deformities that had not improved with conservative treatment. Radiographs revealed osteoarthritis and ulnar deviation of the PIP joints in all cases. We describe a method for reconstruction of both the palmar plate and the RCL of the affected PIP joint using a distally-based ulnar slip of flexor superficialis tendon. The prevention of PIP joint hyperextension was critical for successful resolution of symptoms; the aim of RCL augmentation was to prevent the recurrence of the deformity. LEVEL OF EVIDENCE: IV.


Assuntos
Ligamentos Colaterais/lesões , Traumatismos dos Dedos/cirurgia , Articulações dos Dedos/cirurgia , Deformidades Adquiridas da Mão/cirurgia , Tenodese/métodos , Adulto , Ligamentos Colaterais/diagnóstico por imagem , Feminino , Traumatismos dos Dedos/complicações , Traumatismos dos Dedos/diagnóstico por imagem , Articulações dos Dedos/diagnóstico por imagem , Deformidades Adquiridas da Mão/diagnóstico por imagem , Deformidades Adquiridas da Mão/etiologia , Humanos , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Osteoartrite/etiologia , Placa Palmar/diagnóstico por imagem , Placa Palmar/lesões , Estudos Retrospectivos
5.
Psychiatry Clin Neurosci ; 70(9): 413-20, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27278784

RESUMO

AIM: The Great East Japan Earthquake and in particular, the Fukushima Daiichi Nuclear Power Plant accident, have had a serious psychological impact on not only residents, but also relief workers in Fukushima. Although public employees work in highly stressful situations and play a very important role in long-term relief, their psychiatric features have yet to be clarified. The two aims of this study were to identify the current prevalence rate of depression and post-traumatic stress disorder among public employees working in the disaster area using diagnostic interviews, and to speculate on the psychosocial factors affecting their mental condition. METHODS: We conducted diagnostic interviews and self-administered questionnaires with 168 public employees working in two coastal towns in Fukushima. RESULTS: Results showed that the current prevalence of depression among public employees is as high as 17.9%, in contrast to the relatively low prevalence of post-traumatic stress disorder (4.8%). Based on the results of self-administered questionnaires and interview contents, frequent exposure to strong complaints or anger from residents and role conflicts were considered the cause of the high prevalence of depression. CONCLUSION: The present study reveals the serious mental status of public employees working in Fukushima and sheds light on the urgent need to establish an efficient care network to provide adequate psychiatric intervention.


Assuntos
Depressão/epidemiologia , Emprego/estatística & dados numéricos , Acidente Nuclear de Fukushima , Setor Público/estatística & dados numéricos , Socorro em Desastres , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Terremotos , Feminino , Humanos , Entrevista Psicológica , Japão , Masculino , Pessoa de Meia-Idade , Prevalência
7.
Eur J Drug Metab Pharmacokinet ; 41(4): 457-63, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25716431

RESUMO

Niemann-Pick C1-like 1 (NPC1L1), ATP-binding cassette (ABC)G5, and ABCG8 are all involved in intestinal cholesterol absorption. It is unclear whether a high-cholesterol (HC) diet affects the expression of these transporters in rats and mice as well as humans. We examined the effects of an HC diet on their expression in small intestine and the differences between rats and mice in the responsive of this expression to an HC diet. In addition to these transporters, alterations in six representative drug and nutrient transporters (multidrug resistance-associated protein, breast cancer resistance protein, peptide transporter, sodium-glucose linked transporter, glucose transporter, and L-type amino acid transporter) and transcriptional factors such as hepatocyte nuclear factor (HNF)4α, sterol regulatory element-binding protein (SREBP)2, and liver X receptor (LXR)α were determined. In rats and mice fed an HC diet for 7 days, the mRNA and protein levels of NPC1L1 in the small intestine were determined by real-time reverse transcription polymerase chain reaction and western blotting, respectively. The mRNA levels of ABCG5 and ABCG8, six representative transporters, and transcriptional factors such as HNF4α, SREBP2, and LXR were examined. Significant decreases in the expression levels of NPC1L1 were observed in mice, but not rats, fed the HC diet. The mRNA levels of ABCG5 and ABCG8 were significantly increased in HC rats but not in mice. Only minor changes in the mRNA levels of the other transporters were seen in HC rats and mice. Decreased mRNA levels of HNF4α and SREBP2 in mice could be involved in the reduction in NPC1L1 expression observed upon the introduction of an HC diet. These results indicate that the effects of an HC diet on the expression levels of NPC1L1, ABCG5, and ABCG8 differ between mice and rats.


Assuntos
Transporte Biológico/efeitos dos fármacos , Colesterol/efeitos adversos , Dieta/efeitos adversos , Proteínas de Membrana Transportadoras/metabolismo , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
8.
Int J Med Sci ; 12(10): 759-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26516303

RESUMO

The expression of Notch in 30 cases of pleomorphic adenoma was examined by immunohistochemistry. Comparing the results of our study with previous literatures, from the partial CK7 expression and substantial Notch expression in ductal epithelial cells as well as the Notch expression in solid tumor nests, it can be inferred that Notch is involved in cell differentiation. CK13 expression was observed in cells undergoing squamous metaplasia and Notch expression was seen in the nucleus of basal and squamous cells. The intense Notch expression in basal cells and weak expression in squamous cells suggests that Notch is involved in the differentiation from basal to squamous cell. Moreover, the loss of nuclear expression on the inner layer would signify that differentiation is about to end or has been terminated. Notch was expressed in the cytoplasm of cartilage cells and in the cell membrane of mucous cells but not in the nucleus indicating that differentiation has been concluded. Notch involvement is suspected in cell differentiation in areas showing ductal structures and squamous metaplasia. In summary, Notch is involved in cell differentiation of ductal cells in PA. Nuclear expression was shown in tumor cells in solid nests and surrounding structures. Moreover, Notch is expressed by basal cells undergoing squamous metaplasia suggesting the participation of Notch in cell differentiation in PA.


Assuntos
Adenoma Pleomorfo/patologia , Diferenciação Celular , Receptores Notch/fisiologia , Neoplasias das Glândulas Salivares/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratina-13/análise , Masculino , Pessoa de Meia-Idade
11.
Exp Dermatol ; 22(8): 556-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23802610

RESUMO

It is widely recognized that tobacco smoke causes skin pigmentation. No studies, however, have directly evaluated the mechanisms of the changes in smoker's skin pigmentation. In this study, when cultured with water-soluble tobacco smoke extract, the human epidermal melanocytes grew to a large size and produced more melanins. We evaluated melanocyte activation by quantifying microphthalmia-associated transcription factor (MITF) expression by real-time polymerase chain reaction. MITF expression was significantly and dose-dependently increased by exposure to tobacco smoke extract. The Wnt/ß-catenin signalling pathway seemed to mediate the tobacco smoke extract-induced melanocyte activation. Immunocytochemical studies revealed that the activated melanocytes actively expressed aryl hydrocarbon receptors (AhR) around the nuclear membrane. The tobacco smoke extract-induced MITF activation was inhibited by RNA silencing of the AhR. This study provides the evidence that tobacco smoke enhances pigmentation in vitro and that the increase in pigmentation may involve ß-catenin- and AhR-mediated mechanisms inside human melanocytes.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação da Expressão Gênica , Fator de Transcrição Associado à Microftalmia/metabolismo , Nicotiana/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Pigmentação da Pele/efeitos dos fármacos , Fumaça , Núcleo Celular/metabolismo , Inativação Gênica , Humanos , Imuno-Histoquímica , Melanócitos/citologia , Melanócitos/efeitos dos fármacos , RNA/metabolismo , RNA Interferente Pequeno/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
12.
Phytomedicine ; 20(3-4): 196-201, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23207252

RESUMO

Endothelial progenitor cells (EPCs) are known to repair vascular injuries. Recent studies suggest that Saiko-ka-ryukotsu-borei-To (SKRBT), a traditional herbal medicine that has been used to treat stress-related neuropsychiatric disorders, has protective effects on cardiovascular diseases such as hypertension and arteriosclerosis. Spontaneously hypertensive rats (SHRs) were fed diets containing lyophilized SKRBT extract for 6 weeks. Peripheral blood mononuclear cells (MNCs) were isolated and cultured to assay EPC colony formation. Oxidative stress in MNCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay and flowcytometric analyses. Treatment with SKRBT increased EPC colony numbers significantly (p<0.05) with decrease in oxidative stress and without affecting blood pressure in SHRs. Treatment with SKRBT did not reduce the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in cardiovascular organs. Serum IL-6 level was significantly reduced. SKRBT is a feasible herbal medicine that protects against cardiovascular diseases through an increase in EPC function along with anti-oxidative effects, and may affect the link between chronic inflammation and cardiovascular disease.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Hipertensão/prevenção & controle , Fitoterapia , Animais , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Leucócitos Mononucleares/metabolismo , Masculino , NADPH Oxidases/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
13.
Auris Nasus Larynx ; 39(3): 294-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21862265

RESUMO

OBJECTIVE: The aim of the present study was to evaluate the effects of dietary zinc deprivation on zinc concentration, the activity of angiotensin converting enzyme (ACE) and ratio of apo/holo-activities of ACE (ACE ratio) in the serum of mice. METHODS: Twenty-two male mice were deprived of dietary zinc for up to 9 days. Zinc concentration in the serum was measured by means of atomic absorption spectrometry. Also, the activity of ACE in the serum was measured by HPLC as the activity of holo-ACE. After addition of zinc to the serum in vitro, the increase of ACE activity over the initial value was determined as that of apo-ACE. Finally, the ratio of apo/holo-ACE activities was calculated. RESULTS: There was a significant decrease of zinc concentration, but a slight decrease of the activity of ACE in the serum of mice by intake of zinc-deficient diet for 9 days. ACE ratio tended to increase on day 5 and was significantly increased on day 9 in mice deprived of dietary zinc. CONCLUSION: These findings suggest that ACE ratio is as sensitive as serum zinc concentration for the evaluation of zinc deficiency and can be used for the biochemical diagnosis of zinc nutritional status in patients with zinc deficiency-induced taste impairment.


Assuntos
Peptidil Dipeptidase A/metabolismo , Zinco/deficiência , Zinco/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Camundongos , Estado Nutricional , Espectrofotometria Atômica , Distúrbios do Paladar/diagnóstico , Distúrbios do Paladar/metabolismo , Zinco/sangue
14.
J Nutr Sci Vitaminol (Tokyo) ; 57(1): 36-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21512289

RESUMO

The senescence-accelerated mouse (SAMP8) is an animal model used in studies of aging. The purpose of this study was to investigate the effect of different types of dietary lipids on longevity and age-related deterioration in memory in SAMP8 mice. Eight-month-old mice were fed diets with 5% lard (Lard group), 5% soybean oil (Soy group), 2% lecithin +3% soybean oil (Lecithin+Soy group) or 2% fish oil+3% soybean oil (Fish+Soy group), and learning and memory were examined by passive avoidance test at 8 and 10 mo of age. At the end of the experiment, the mice were killed, and the brain fatty acid composition was analyzed. The results indicated that the survival rates at 12 mo decreased in the order: Fish+Soy>Soy>Lecithin+Soy>Lard and were 50, 40, 30 and 20%, respectively. The rate of the lard group was lower than that of the Fish+Soy group, but this difference was not statistically significant. At 10 mo of age, the passive avoidance times of the Fish+Soy, Lecithin+Soy, Soy and Lard groups were 166, 170, 149 and 127 s, respectively. The passive avoidance times of the Fish+Soy and Lecithin+Soy groups were longer than that of the Lard group (p<0.01) at 10 mo. The brain DHA concentration was the highest in the Fish+Soy group SAMP8 mice, the linoleic acid levels was highest in the Soy group and the palmitic acid level was lowest in the Lard group (p<0.05). In conclusion, compared with SAMP8 mice fed a high saturated fatty acid diet, SAMP8 mice given a high poly-unsaturated fatty acid diet had higher brain concentrations of poly-unsaturated acid, better memory and greater longevity.


Assuntos
Envelhecimento/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Ácidos Docosa-Hexaenoicos/análise , Longevidade/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dieta , Óleos de Peixe/administração & dosagem , Aprendizagem/efeitos dos fármacos , Ácido Linoleico/análise , Masculino , Camundongos , Modelos Animais , Óleos de Plantas/administração & dosagem , Óleo de Soja/administração & dosagem
15.
Obesity (Silver Spring) ; 19(8): 1663-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21475145

RESUMO

Obesity is associated with increased markers of oxidative stress. We examined whether oxidative stress is reduced within the first week after Roux-en-Y gastric bypass (RYGB) surgery and could be related to changes in adipose tissue depots. The reactive oxygen species (ROS) marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and activity of antioxidant glutathione peroxidases (GPX) in plasma were compared before and ~1 week after RYGB. The effects of RYGB on subcutaneous adipose tissue and interstitial fluid 8-iso-PGF2α levels and subcutaneous adipose tissue expression of GPX-3 were also assessed. Levels of 8-iso-PGF2α in subcutaneous and visceral adipose tissue were determined. Plasma 8-iso-PGF2α levels decreased (122 ± 75 to 56 ± 15 pg/ml, P = 0.001) and GPX activity increased (84 ± 18 to 108 ± 25 nmol/min/ml, P = 0.003) in the first week post-RYGB. RYGB also resulted in reductions of 8-iso-PGF2α in subcutaneous adipose tissue (1,742 ± 931 to 1,132 ± 420 pg/g fat, P = 0.046) and interstitial fluid (348 ± 118 to 221 ± 83 pg/ml, P = 0.046) that were comparable to plasma (26-33%, P = 0.74). Adipose GPX-3 expression was increased (6.7 ± 4.7-fold, P = 0.004) in the first postoperative week. The improvements in oxidative stress occurred with minimal weight loss (2.4 ± 3.4%, P = 0.031) and elevations in plasma interleukin-6 (18.0 ± 46.8 to 28.0 ± 58.9 pg/ml, P = 0.004). Subcutaneous and visceral adipose tissues express comparable 8-iso-PGF2α levels (1,204 ± 470 and 1,331 ± 264 pg/g fat, respectively; P = 0.34). These data suggest that RYGB affects adipose tissue leading to the restoration of adipose redox balance within the first postoperative week and that plasma 8-iso-PGF2α is primarily derived from subcutaneous adipose tissue.


Assuntos
Dinoprosta/metabolismo , Líquido Extracelular/metabolismo , Derivação Gástrica , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Estresse Oxidativo , Gordura Subcutânea/metabolismo , Dinoprosta/sangue , Glutationa Peroxidase/metabolismo , Humanos , Interleucina-6/sangue , Obesidade/cirurgia , Período Pós-Operatório , Redução de Peso
16.
Nutr Res ; 28(4): 239-44, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19083414

RESUMO

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD), is a disorder characterized by diffuse inflammation of the gastrointestinal tract. The immune response and inflammation are mediated by polyunsaturated fatty acids and influenced by dietary fats and lipid metabolism. This study examined the qualitative and quantitative fat intake of IBD patients and healthy controls on plasma phospholipid and erythrocyte membrane phospholipid (EMP) fatty acid content. Measurement of the fatty acid composition of plasma phospholipid and EMP were performed in 29 UC patients, 20 CD patients, and 31 healthy controls. Anthropometric characteristics and data on dietary intake were also collected. We observed significantly lower lipid intake in UC and CD patients vs controls. The UC and CD patients had significantly higher levels of linoleic acid in their EMP than did controls. There were no significant differences in the levels of n-3 polyunsaturated fatty acids, but there were significantly higher levels of the n-6 in the EMP of UC and CD patients compared with controls. The significant differences persisted after the data were adjusted for potential confounders and lipid intake. Higher levels of linoleic acids and n-6 fatty acids, which are involved in production of proinflammatory mediators, were found in IBD patients compared with controls, thereby implicating n-6 fatty acids in the pathophysiology of the disease.


Assuntos
Membrana Eritrocítica/química , Doenças Inflamatórias Intestinais/metabolismo , Ácido Linoleico/análise , Fosfolipídeos/química , Adulto , Antropometria , Estudos de Casos e Controles , Colite Ulcerativa/sangue , Colite Ulcerativa/metabolismo , Doença de Crohn/sangue , Doença de Crohn/metabolismo , Ácidos Graxos Ômega-6/análise , Feminino , Humanos , Doenças Inflamatórias Intestinais/sangue , Masculino , Inquéritos e Questionários
17.
J Nutr Sci Vitaminol (Tokyo) ; 53(2): 153-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17616003

RESUMO

Nutrition may play an important role in the pathogenesis and treatment of ulcerative colitis. Several studies suggest an association between dietary factors and the onset of ulcerative colitis; however, only few studies have examined the relationship between dietary intake and relapse of ulcerative colitis. The aim of this study was to assess the dietary intake and antioxidative capacity of ulcerative colitis patients and to elucidate the efficacy of dietary therapy for ulcerative colitis. Dietary intake, fatty acid composition of phospholipids in plasma and neutrophils, serum fat-soluble vitamin levels, and oxygen radical absorbance capacity were analyzed in 29 ulcerative colitis patients (7 males and 22 females), who were treated at the Department of Gastroenterology, Okayama University Hospital. Total fat intake, fat energy ratio and linoleic acid intake were significantly lower, while protein and carbohydrate intakes were significantly higher, in the patients than age- and sex-matched controls. In the neutrophil phospholipids of ulcerative colitis patients, significantly higher levels of linoleic aicd and arachidonic acid and a lower level of eicosapentaenoic acid were observed. The concentrations of serum retinol and beta-carotene but not alpha-tocopherol were significantly lower and serum oxygen radical absorbance capacity was also lower than in the controls. Significant correlations between serum oxygen radical absorbance capacity and retinol (r = 0.567, p = 0.0031), alpha-tocopherol (r = 0.560, p = 0.0036) and beta-carotene (r = 0.440, p = 0.0279) concentrations were observed in the ulcerative colitis patients. A diet restricting the intake of linoleic acid and supplemented with eicosapentaenoic acid and antioxidative vitamins may be recommendable for the nutritional management of ulcerative colitis patients.


Assuntos
Antioxidantes/metabolismo , Colite Ulcerativa/metabolismo , Dieta/métodos , Ácidos Graxos/metabolismo , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vitaminas/sangue , Adulto , Albuminas/metabolismo , Antioxidantes/análise , Registros de Dieta , Feminino , Humanos , Masculino , Fosfolipídeos/metabolismo , Proteínas/metabolismo , Vitamina A/sangue , alfa-Tocoferol/sangue , beta Caroteno/sangue
18.
Melanoma Res ; 17(2): 91-103, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17496784

RESUMO

Members of the nuclear factor-kappa beta (NF-kappaB) family maintain cellular homeostasis by enhancing the transcription of genes involved in inflammation, immune response, cell proliferation, and apoptosis. Melanoma tumor cells often express inflammatory mediators through enhanced activation of NF-kappaB. The NF-kappaB activation appears to result from the enhancer formation including NF-kappaB and lysine acetyl transferases such as p300, CREB (cyclic AMP-responsive element binding protein)-binding protein (CBP), and/or p300/CBP associating factor (PCAF). We observed that proteins expressed by Hs294T metastatic melanoma cells are highly acetylated compared with normal melanocytes, and dominant-negative PCAF reduced the basal and tumor necrosis factor-alpha-stimulated transcriptional activity of NF-kappaB. The promoter activity of NF-kappaB-regulated chemokines was also reduced by the expression of dominant-negative PCAF. The promoters of these chemokines contain a CCAAT displacement protein (CDP)-binding site near the NF-kappaB element. compared with vector-transduced cells, in CDP-transduced Hs294T cells: (i) over-expressed CDP bound efficiently to PCAF, (ii) tumor necrosis factor-alpha-stimulated chemokine expression and NF-kappaB-mediated transcription were reduced, and (iii) the binding of CBP to Rel A was reduced. These data suggest that CDP inhibits cytokine-induced NF-kappaB-regulated chemokine transcription. This study contributes to our understanding of the role of CDP in an enhanceosome of NF-kappaB-mediated chemokine transcription in human melanoma cells.


Assuntos
Quimiocinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/fisiologia , Melanoma/metabolismo , NF-kappa B/metabolismo , Proteínas Nucleares/fisiologia , Proteínas Repressoras/fisiologia , Transcrição Gênica , Apoptose , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Histona Acetiltransferases/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Metástase Neoplásica , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8B/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição de p300-CBP
19.
Cancer Res ; 66(11): 5665-75, 2006 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-16740704

RESUMO

The CXC chemokine receptor 4 (CXCR4) contributes to the metastasis of human breast cancer cells. The CXCR4 COOH-terminal domain (CTD) seems to play a major role in regulating receptor desensitization and down-regulation. We expressed either wild-type CXCR4 (CXCR4-WT) or CTD-truncated CXCR4 (CXCR4-DeltaCTD) in MCF-7 human mammary carcinoma cells to determine whether the CTD is involved in CXCR4-modulated proliferation of mammary carcinoma cells. CXCR4-WT-transduced MCF-7 cells (MCF-7/CXCR4-WT cells) do not differ from vector-transduced MCF-7 control cells in morphology or growth rate. However, CXCR4-DeltaCTD-transduced MCF-7 cells (MCF-7/CXCR4-DeltaCTD cells) exhibit a higher growth rate and altered morphology, potentially indicating an epithelial-to-mesenchymal transition. Furthermore, extracellular signal-regulated kinase (ERK) activation and cell motility are increased in these cells. Ligand induces receptor association with beta-arrestin for both CXCR4-WT and CXCR4-DeltaCTD in these MCF-7 cells. Overexpressed CXCR4-WT localizes predominantly to the cell surface in unstimulated cells, whereas a significant portion of overexpressed CXCR4-DeltaCTD resides intracellularly in recycling endosomes. Analysis with human oligomicroarray, Western blot, and immunohistochemistry showed that E-cadherin and Zonula occludens are down-regulated in MCF-7/CXCR4-DeltaCTD cells. The array analysis also indicates that mesenchymal marker proteins and certain growth factor receptors are up-regulated in MCF-7/CXCR4-DeltaCTD cells. These observations suggest that (a) the overexpression of CXCR4-DeltaCTD leads to a gain-of-function of CXCR4-mediated signaling and (b) the CTD of CXCR4-WT may perform a feedback repressor function in this signaling pathway. These data will contribute to our understanding of how CXCR4-DeltaCTD may promote progression of breast tumors to metastatic lesions.


Assuntos
Neoplasias da Mama/patologia , Comunicação Celular/fisiologia , Movimento Celular/fisiologia , Receptores CXCR4/fisiologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Regulação para Baixo , Ativação Enzimática , Células Epiteliais/fisiologia , Vetores Genéticos/genética , Humanos , Mesoderma/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Estrutura Terciária de Proteína , Receptores CXCR4/biossíntese , Receptores CXCR4/genética , Retroviridae/genética , Relação Estrutura-Atividade , Transdução Genética
20.
Pigment Cell Res ; 19(2): 112-24, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16524427

RESUMO

Metastatic melanoma is an aggressive skin cancer that is notoriously resistant to current cancer therapies. In human melanoma, nuclear factor-kappa B (NF-kappaB) is upregulated, leading to the deregulation of gene transcription. In this review, we discuss (i) the relationship between gene alteration in melanoma and upregulation of NF-kappaB, (ii) mechanisms by which activated NF-kappaB switch from pro-apoptotic to anti-apoptotic functions in melanoma and (iii) autocrine mechanisms that promote constitutive activation of NF-kappaB in metastatic melanoma.


Assuntos
Comunicação Autócrina , Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , NF-kappa B/biossíntese , Neoplasias Cutâneas/metabolismo , Regulação para Cima , Animais , Humanos , Melanoma/patologia , Metástase Neoplásica/patologia , Neoplasias Cutâneas/patologia , Transcrição Gênica
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