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1.
J Clin Lab Anal ; 35(8): e23799, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34143515

RESUMO

BACKGROUND: The Insulin-like growth factor-1 (IGF-1) is primarily synthesized by hepatocytes in a growth hormone (GH)-dependent manner, it is also produced by bone and muscle. The effects of exercise on the associations between IGF-1 levels and bone turnover markers (BTM) were found in the previous studies. However, the associations between the levels of IGF-1 and BTM, liver function tests, and skeletal muscle markers in adults with general physical activity were not clear. METHODS: Ninety-four participants were recruited from healthy survey. Blood samples were collected to analyze the levels of IGF-1, total protein (TP), albumin (Alb), total bilirubin (T-Bil), direct bilirubin (D-Bil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine (CRTN), and glucose. Urine samples were collected to analyze the CRTN and deoxypyridinoline (Dpd) levels. RESULTS: The positively significant associations were found between the IGF-1 levels and the levels of ALP, BALP, and CK, respectively. No significant associations were found between the IGF-1 levels and the levels of TP, Alb, A/G, T-Bil, D-Bil, AST, ALT, LDH, glucose, urinary CRTN, urinary Dpd, and Dpd/CRTN ratios, respectively. CONCLUSION: The serum IGF-1 levels associated with the levels of skeletal muscle and bone formation markers (BFM), not the bone resorption markers under general physical activity in the healthy adults. The physician needs to consider the effects of bone formation and skeletal muscle markers on the IGF-1 levels in the management of IGF-1-related disorders.


Assuntos
Biomarcadores/sangue , Creatina Quinase/sangue , Exercício Físico/fisiologia , Fator de Crescimento Insulin-Like I/análise , Osteogênese/fisiologia , Adulto , Idoso , Fosfatase Alcalina/sangue , Bilirrubina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
Nitric Oxide ; 72: 1-6, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29102546

RESUMO

Breast cancer has a high incidence in Taiwanese women and worldwide. Previous studies have indicated that NO has multiple independent roles in carcinogenesis; genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene could modify its transcription and endogenous NO production. Previous studies have reported conflicting results for the relationship between polymorphisms in the eNOS gene and breast cancer risk. Estrogen levels are associated with eNOS expression; accordingly, variation in estrogen levels may contribute to the discordant results. Therefore, in this study, the effects of eNOS polymorphisms on breast cancer susceptibility were examined in terms of menopausal status in Taiwanese women. Three eNOS polymorphisms (-786T > C, VNTR, and 894G > T) were genotyped in 283 patients with breast cancer (139 premenopausal and 144 postmenopausal) and 200 cancer-free controls (100 premenopausal and 100 postmenopausal) by PCR-RFLP. There was a significantly higher breast cancer risk in premenopausal women carrying 894G > T T than in those with the 894G > T GG genotype; however, postmenopausal women carrying 894G > T T had a lower risk of developing breast cancer. In addition, based on a binary logistic regression analysis, interaction effects of these polymorphisms differed according to menopausal status. The relationship between eNOS polymorphisms and breast cancer hazard depended on menopause status, especially for the 894G > T polymorphism, which may provide an explanation for previous conflicting results.


Assuntos
Neoplasias da Mama/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Adulto , Povo Asiático/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Menopausa , Pessoa de Meia-Idade , Taiwan
3.
J Clin Lab Anal ; 30(1): 58-64, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25385317

RESUMO

BACKGROUND: In most research, there were positive associations between the insulin-like growth factor I (IGF-I) status, including IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3), and ratio of IGF-I/IGFBP-3, and risks of breast cancer (BC), which was influenced by many factors, including hormone statuses and ethnicity. Therefore, the alterations of the IGF-I status in Taiwanese women with BC by menopausal statuses and hormone receptors were investigated. METHODS: The levels of IGF-I and IGFBP-3 were determined by the enzyme-labeled chemiluminescent immunometric assay, and the protein expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) on paraffin-embedded sections of tissues with BC were analyzed by the immunohistochemical method. RESULTS: The ratios of IGF-I/IGFBP-3 were significantly higher in the women with BC than those in the controls, but not of the levels of IGF-I and IGFBP-3; furthermore, the significantly higher ratios were found only in the postmenopausal status. In addition, there was no significant difference between the IGF-I status and ER and PR statuses, and HER2 expression, respectively, in the women with BC. CONCLUSIONS: The ratios of IGF-I/IGFBP-3 were increased in postmenopausal Taiwanese women with BC, irrespective of their ages, ER and PR statuses, and HER2 expression.


Assuntos
Neoplasias da Mama/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Pós-Menopausa/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Inclusão em Parafina , Taiwan
4.
J Clin Lab Anal ; 29(5): 412-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25385143

RESUMO

BACKGROUND: VTCN1, a T-cell regulator, belongs to the immunoglobulin superfamily. It is more highly expressed in tumor tissues than in normal tissues, which suggests that it could serve as a tumor-related agent. We hypothesize the gene variants for this coinhibitory molecule may be associated with the risk of breast cancer, given such gene polymorphisms could affect its related gene expression. METHODS: Genotypes of the VTCN1 gene variants (rs10754339, rs10801935, and rs3738414) were analyzed in 566 patients with breast cancer and 400 age-frequency-matched controls. RESULTS: Compared with the major allele, the minor alleles of rs10754339, rs10801935, and rs3738414 did modulate the risk of breast cancer with ORs (95% CI) of 1.42 (1.07-1.89), 1.39 (1.10-1.77), and 0.81 (0.67-0.99), respectively. Those with the rs10754339 genotype AG and rs10801935 AC genotype had significantly increased risks when compared with their major genotypes. However, in rs3738414, the AA genotype had a marginally significant decreased risk compared with its wild genotype. In the haplotype-based analysis, the GCG allele was associated with significantly increased risk (OR: 1.56, 95% CI: 1.09-2.22) based on the AAG reference. Further analyses of the haplotype pairs showed GCG carriers had a significantly increased risk. CONCLUSIONS: In this study, the VTCN1 genetic variants (rs10754339, rs10801935, and rs3738414) indicate they could be connected with the risk of breast cancer, which in turn provides indirect evidence that T-cell immunity could be involved in the development of breast cancer.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Inibidor 1 da Ativação de Células T com Domínio V-Set/genética , Adulto , Feminino , Haplótipos , Humanos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética
5.
Clin Lab ; 60(11): 1895-901, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25648032

RESUMO

BACKGROUND: Because of the high cost of commercially available quantitative PCR kits, we developed a beacon- based real-time PCR (B-rt-PCR) for Cytomegalovirus (CMV) viral load determination. METHODS: A total of 197 samples from 60 immunocompromised patients, who were bone marrow transplantation recipients or had hematological malignancies, were tested using B-rt-PCR, COBAS Amplicor CMV Monitor test (Amplicor CMV test), and conventional CMV PCR. The correlation results among these 3 assays were calculated. RESULTS: In these 197 samples, the CMV viral load determined by B-rt-PCR for positive specimens ranged from 19.8 to 4148.7 copies/10(5) peripheral blood mononuclear cells (PBMCs). When any positive result of B-rt-PCR, the Amplicor CMV test, or conventional PCR was considered as "CMV positive" for the 56 specimens tested by all three methods, we found that the positive and negative predictive values, respectively, were 100% and 98.6% for B-rt-PCR, 100% and 46.2% for the Amplicor CMV test, and 100% and 89.4% for conventional PCR. These three methods had good specificity (all 100%). However, the sensitivity rate of B-rt-PCR (96.3%) was higher compared to the Amplicor CMV test (46.2%) and conventional PCR (89.4%). CONCLUSIONS: The B-rt-PCR is evaluated to be a sensitive method for CMV detection in immunocompromised patients.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/genética , DNA Viral/genética , Hospedeiro Imunocomprometido , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carga Viral
6.
J Clin Lab Anal ; 28(4): 261-8, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24577940

RESUMO

BACKGROUND: Iron overload is a major complication in patients with hemoglobin H (Hb H) disease and causes damage of tissues. METHODS: We investigated 26 Hb H patients and 75 controls to evaluate their oxidative stress and antioxidant statuses. RESULTS: There were significantly increased levels of superoxide anion in leucocytes, nitrite (NO2-), and malondialdehyde (MDA) in plasma, and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx) and oxidized glutathione (GSSG) in erythrocytes, decreased levels of nitrate (NO3-) and vitamin C in plasma, and reduced glutathione (GSH) in erythrocytes, in addition to the abnormal iron status in the patients when compared with those in the controls. Meanwhile, levels of serum ferritin were positively correlated with serum iron, plasma MDA, and erythrocyte SOD in the patients. In addition, the activities of SOD were positively correlated with those of GPx and GRx, and the levels of GSSG and MDA, but negatively correlated with those of GSH. Furthermore, the levels of MDA were negatively correlated those of vitamin C. CONCLUSIONS: These results demonstrate the presence of oxidative stress and decreased levels of antioxidants; moreover, the related metabolic antioxidant pathway is active in Hb H patients with iron overload.


Assuntos
Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Redes e Vias Metabólicas , Estresse Oxidativo , Talassemia alfa/metabolismo , Talassemia alfa/patologia , Adolescente , Alanina Transaminase/sangue , Antioxidantes/metabolismo , Estudos de Casos e Controles , Creatina Quinase/sangue , Eritrócitos/enzimologia , Feminino , Ferritinas/sangue , Humanos , Ferro/sangue , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/complicações , Masculino , Malondialdeído/sangue , Superóxido Dismutase/metabolismo , Adulto Jovem , Talassemia alfa/sangue , Talassemia alfa/complicações
7.
J Clin Lab Anal ; 27(6): 494-503, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24218133

RESUMO

BACKGROUND: Excessive alcohol intake can result in the oxidative stress in cells and the genetic variations of alcohol-metabolizing enzymes are responsible for the different degrees of toxicity of alcohol in several organs, such as the liver and immunological systems. We hypothesized that the alteration of oxidative stress due to some genetic variations of oxidative stress-related enzymes could result in changes of specific biomarkers, and heavy drinkers could be cautioned about the predictive likelihood to induce drinking-induced diseases. METHODS: A total of 108 heavy drinkers and 106 nonheavy drinkers were enrolled and the hematological, biochemical, and immunological tests were measured; the genotypes of oxidative stress-related enzymes, including manganese superoxide dismutase (MnSOD1183T>C), glutathione peroxidase 1 (GPX1Pro198Leu), catalase (CAT-262C>T), and myeloperoxidase (MPO-463G>A), were assayed by real-time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: For the males, the levels of carbohydrate-deficient transferrin (CDT), malondialdehyde (MDA), CD4(+), immunoglobulin G (IgG), immunoglobulin M (IgM), and IL-6 were significantly different between the two groups. Furthermore, there were higher proportions of CD19(+) cells and lower TNF-α levels in heavy drinkers with the MnSOD C carriers, and there were higher percentages of CD19(+) cells and IL-6 levels in heavy drinkers with the combined genotypes of MnSOD C carriers and MPO A carriers. CONCLUSIONS: Our findings indicate that heavy drinkers may be cautioned predictive likelihood for them to induce drinking-induced diseases by analyzing their MnSOD genotypes and immunological biomarkers.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/imunologia , Antígenos CD/sangue , Citocinas/sangue , Estresse Oxidativo/genética , Oxirredutases/genética , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Taiwan , Adulto Jovem
8.
Int J Mol Sci ; 14(7): 14439-59, 2013 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-23852020

RESUMO

Cholesteatoma is a destructive and expanding growth of keratinizing squamous epithelium in the middle ear or petrous apex. The molecular and cellular processes of the pathogenesis of acquired middle ear cholesteatoma have not been fully understood. In this study, comparative proteomic analysis was conducted to investigate the roles of specific proteins in the pathways regarding keratinocyte proliferation in cholesteatoma. The differential proteins were detected by comparing the two-dimension electrophoresis (2-DE) maps of the epithelial tissues of 12 attic cholesteatomas with those of retroauricular skins. There were 14 upregulated proteins in the epithelial tissues of cholesteatoma in comparison with retroauricular skin. The modulation of five crucial proteins, HSP27, PRDX2, GRP75, GRP78 and GRP94, was further determined by RT-PCR, Western blot and immunohistochemistry. Phosphorylation of HSP27 at Ser-82 was identified by mass spectroscopy. The results of this study suggested that phosphorylated HSP27 is the end expression of two potential signal-transduction pathways, and together with PRDX2, they are very likely involved in the proliferation of keratinocytes in cholesteatoma. Upregulations of GRP75, GRP78 and GRP94 in keratinocytes may be able to counter endoplasmic reticulum stress, to inhibit cell apoptosis, to prevent protein unfolding and to promote cholesteatoma growth.


Assuntos
Colesteatoma da Orelha Média/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Membrana/metabolismo , Peroxirredoxinas/metabolismo , Adolescente , Adulto , Colesteatoma da Orelha Média/patologia , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel Bidimensional , Chaperona BiP do Retículo Endoplasmático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Pele/metabolismo , Pele/patologia , Espectrometria de Massas em Tandem , Regulação para Cima , Adulto Jovem
9.
Ann Otol Rhinol Laryngol ; 132(6): 684-691, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35833235

RESUMO

BACKGROUND: Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from the same patients. METHODS: The present study is a retrospective study performed in an academic medical center. Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth. RESULTS: Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma. CONCLUSION: Our data suggests that CRT and AnxA2 downregulation are seen in cholesteatoma compared to retroauricular skin. We speculate that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma.


Assuntos
Anexina A2 , Colesteatoma da Orelha Média , Humanos , Regulação para Baixo , Estudos Retrospectivos , Anexina A2/metabolismo , Calreticulina/metabolismo , Cromatografia Líquida , Imuno-Histoquímica , Espectrometria de Massas em Tandem
10.
Int J Cancer ; 131(5): E733-43, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22174014

RESUMO

Little is known about any consequences of swallowing tobacco-free betel-quid (TF-BQ) juice/remnants following chewing and its carcinogenic impact on the upper aerodigestive tract (UADT) to gastrointestinal tract (GIT). We investigated the neoplastic impact of TF-BQ on different anatomical locations along UADT and GIT, and differences according to their histological categories. We conducted a multicenter case-control study examining patients with 2,163 pathology-proven UADT and GIT cancers, comparing them with 2,250 control subjects. Generalized additive models, piecewise regression and polytomous logistic models were applied to identify possible dose-dependent structures and cancer risks. Contrary to nonsignificant GIT-adenocarcinoma risk (aOR=0.9), TF-BQ users experienced a 1.7- to 16.2-fold higher risk of UADT-squamous cell carcinomas than nonusers, with the peak risk discovered in oral neoplasms. We separately observed a curvilinear and linear TF-BQ dose-risk relationship in oral/pharyngeal/esophageal and laryngeal cancers. Chewers of betel inflorescence were generally at a greater UADT cancer risk. A higher first-piecewise increased risk of esophageal cancer was recognized among areca-fluid swallowers than among nonswallowers (continuous aOR=1.12 vs. 1.03). TF-BQ use accounted for 66.1-78.7% and 17.8-33.2% of the cases of oral/pharyngeal and esophageal/laryngeal cancers, respectively. However, a reduction from heavy TF-BQ consumption to low-to-moderate consumption only reduced 11.3-34.6% of etiologic fraction of oral/pharyngeal cancers. Alcohol supra-additively modified the risk of TF-BQ in determining the development of oral, pharyngeal and esophageal cancers. In conclusion, the interplay of TF-BQ and alcohol/tobacco use, combined with how chewing habit is practiced, influences carcinogenic consequences on anatomically diverse sites of UADT and GIT cancers, and histologically different types.


Assuntos
Areca/efeitos adversos , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Neoplasias Gastrointestinais/patologia , Neoplasias Laríngeas/patologia , Neoplasias Faríngeas/patologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinógenos/farmacologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Feminino , Seguimentos , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/etiologia , Humanos , Incidência , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/epidemiologia , Neoplasias Faríngeas/etiologia , Prognóstico , Fatores de Risco , Fumar/efeitos adversos , Taiwan/epidemiologia
11.
Int J Legal Med ; 124(2): 155-60, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20094724

RESUMO

The objective of this study is to test the validity of sex determination in children and adolescents using lateral radiographic cephalometry and discriminant function analysis. Fifty male and 50 female cephalograms of Taiwanese children were used (males and females with mean age of 15.52 +/- 1.38 and 15.67 +/- 1.54 years, respectively). Twenty-two cephalometric measurements were performed using computerized cephalometry. Statistical analysis shows that all measurements were sexually dimorphic (p < 0.05). Nine measurements, statistically validated and clinically relevant, were used for discriminant function analysis. A stepwise discriminant procedure selected seven of the nine variables, producing 95% accuracy in sex determination. Resubstitution classification reveals the same discriminant rate. Cross-validation classification (the leave-one-out method) reveals that the correct sex determination rate is 91%. However, the combination of four variables using both the stepwise procedure and the resubstitution method achieves a 92% accuracy rate. A cross-validation classification procedure with the same four variables resulted in a 91% accuracy rate. Therefore, this study uses four cephalometric measurements as the minimum number of traits yielding the maximum discriminant effectiveness of sex determination in children and adolescents.


Assuntos
Cefalometria , Análise Discriminante , Determinação do Sexo pelo Esqueleto/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Antropologia Forense , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Masculino , Taiwan
12.
Biomed Pharmacother ; 129: 110386, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32563986

RESUMO

Toona sinensis (TS) is a medicinal herb possessing anti-apoptotic, anti-oxidant, and anti-inflammatory properties and is used to treat diabetes, cancer, and inflammatory diseases. In traditional Chinese medicine theory, TS clears dampness and heat, strengthens the stomach function, and regulates vital energy flow. TS is also used as an astringent and a pesticide. In this study, we aimed to evaluate how TS influences autophagy and cytokines during the inflammatory process in RAW 264.7 macrophages. The treatment groups were pre-supplemented with TS leaf extract; rapamycin was used to enhance autophagy and lipopolysaccharide (LPS) was used to induce inflammation. The expression of autophagy-related proteins was analyzed by western blotting. The survival rate of, and chemokine expression and oxidative stress in the cells were also assessed. TS leaf extract inhibited mammalian target of rapamycin (mTOR) phosphorylation at site S2448 in the macrophages. At relatively higher concentrations (50 and 75 µg/mL), TS elevated the expression of light chain 3 II (LC3-II), which further modulated autophagy. Pre-supplementation with TS leaf extract elevated the total glutathione (GSH) level and GSH/oxidized GSH (GSSG) ratio, but it decreased the GSSG, total nitric oxide, nitrate, nitrite, malondialdehyde, and superoxide anion levels. TS reversed the effects of LPS-induced cytokines, including interleukin (IL)-6 and IL-10. TS did not induce significant toxicity at the studied concentrations. In conclusion, TS leaf extract may modulate autophagy during inflammation. Furthermore, it may prevent cell damage via anti-inflammation and anti-oxidation. Thus, this study supports the ethnomedical use of TS in the prevention of inflammation-related diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Autofagia/efeitos dos fármacos , Citocinas/metabolismo , Inflamação/prevenção & controle , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Toona , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Proteínas Relacionadas à Autofagia/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Células RAW 264.7 , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Toona/química
13.
Clin Chim Acta ; 389(1-2): 14-8, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18078815

RESUMO

BACKGROUND: Alcohol abuse has been implicated as an important factor for accidents. We evaluated the roles of different genetic combinations of the ADH2 and ALDH2 genotypes on biomarkers in trauma patients with excessive alcohol intake at our emergency department. METHODS: Blood samples were obtained from 80 patients and 88 age-matched controls. The biomarkers, including AST, ALT, GGT, and MDA, were assayed. The polymerase chain reaction-restriction fragment length polymorphism method was used to determine the genetic polymorphisms of ADH2 and ALDH2. RESULTS: There were significant differences in the levels of AST, ALT, GGT, MDA, and AST/ALT ratios between the 2 groups. In addition, MDA values and AST/ALT ratios were significantly higher in the patients with normal activity of ADH2 than the patients with low activity of ADH2. Meanwhile, regarding ALDH2 genotypes, there were significantly higher ratios of AST/ALT in the patients with low activity of ALDH2. The highest AST/ALT ratios and MDA values were in the patients with ADH2 (*2/*2) and ALDH2 (*1/*2 and *2/*2). CONCLUSIONS: In conclusion, our results indicated that alcohol-induced liver damage or oxidative stress might be influenced by the genetic variation of ADH2 or ALDH2. Therefore, the combinations of different ADH2 and ALDH2 genotypes may be influential markers for susceptibility to alcohol-induced liver damage.


Assuntos
Álcool Desidrogenase/genética , Intoxicação Alcoólica/enzimologia , Aldeído Desidrogenase/genética , Serviço Hospitalar de Emergência , Variação Genética , Ferimentos e Lesões/enzimologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Clin Biochem ; 40(13-14): 1015-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17628517

RESUMO

OBJECTIVES: This study was undertaken to investigate if there is a disparity in the antioxidant status and the ability of superoxide anion (O(2)(-)) generation in the patients with acute myeloid leukemia (AML). DESIGN AND METHODS: The peripheral blood samples from thirty AML patients and thirty-six healthy subjects were collected and leukocytes, erythrocytes and plasma were separated for use in various parameter measurements. RESULTS: The generation of O(2)(-), as reflected by lucigenin-based CL (LBCL), by the leukocytes of patients with AML was found to be significantly elevated either in resting or stimuli-elicited condition as compared with that of healthy controls (p<0.05). Coincidentally, these data were matched up with the suppressed SOD activities, notably in Cu/Zn SOD isoform found in AML patients (p<0.05). Conversely, SOD and GPx activities in erythrocytes of patients with AML were shown to be significantly higher than their normal counterparts (p<0.05). CONCLUSIONS: These data suggest that altered expression of antioxidant enzymes and higher capability of O(2)(-) generation by leukocytes seem to be a distinct feature of AML.


Assuntos
Antioxidantes/metabolismo , Leucemia Mieloide/metabolismo , Superóxidos/metabolismo , Doença Aguda , Adulto , Estudos de Casos e Controles , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Humanos , Leucemia Mieloide/sangue , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Plasma/efeitos dos fármacos , Plasma/metabolismo , Superóxido Dismutase/metabolismo , Zimosan/farmacologia
15.
Clin Biochem ; 40(15): 1157-62, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17706189

RESUMO

OBJECTIVES: Glutathione status can be regarded as the redox status for many diseases. This study was performed to investigate the glutathione status in virus-originated hepatocellular carcinoma (HCC). DESIGN AND METHODS: The blood and tissue samples were obtained from 24 patients. Blood samples were also obtained from 137 controls for comparison. RESULTS: The GSH level and the ratios of GSH/GSSG and GSH/total glutathione of the blood samples from the patients were significantly lower than those of the controls, while the GSSG values were significantly higher. Meanwhile, levels of GSH and total glutathione, as well as the ratios of GSH/GSSH and GSH/total glutathione, were significantly decreased, whereas GSSG levels were significantly higher, in the HCC tissues than those of the adjacent cancer-free tissues. CONCLUSIONS: Glutathione status in the HCC suggested that the antioxidant system is severely impaired, supporting a consistent role of the free radical cytotoxicity in the pathophysiology of the disease.


Assuntos
Carcinoma Hepatocelular/sangue , Glutationa/sangue , Glutationa/metabolismo , Hepatite Viral Humana/complicações , Neoplasias Hepáticas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Dissulfeto de Glutationa/análise , Dissulfeto de Glutationa/sangue , Vírus de Hepatite , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade
16.
Clin Biochem ; 40(5-6): 370-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17292341

RESUMO

OBJECTIVES: The objective of this study was to investigate the distribution of genetic polymorphisms of alcohol-metabolizing enzymes in trauma patients with excessive alcohol consumption in the emergency department (ED). DESIGN AND METHODS: A total of 100 trauma patients and age-matched control subjects composed of 98 participants were enrolled in this study. The activities of liver enzymes and genotypes of alcohol-metabolizing enzymes, including ADH2, ALDH2, and CYP2E1, were analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: There was a significant difference in the allele frequencies of ALDH2 between the two groups. For the genotypes, there were significant differences in the genotype frequencies of ADH2 and ALDH2. There was also a significantly lower frequency in patients with the ALDH2*2 phenotype than those of the controls. For the activities of liver enzymes, there were significant differences between the two groups. For ADH2 and ALDH2, there were significantly higher ORs (odds ratios) in trauma patients with normal activity than those with weak or intermediate activity but there were no significant difference in CYP2E1 genotype between two groups. To investigate the interaction of alcohol-metabolizing enzyme genotypes, we have estimated the odds ratios in two alcohol-metabolizing pathways. The ORs of the combined genotypes of ADH2 (*1/*1+*1/*2) and ALDH2 (*1/*1) and the combined genotypes of either CYP2E1 (*c1/*c1) or CYP2E1 (*c1/*c2+*c2/*c2) and ALDH2 (*1/*1) were significantly higher than that of the reference group in the major and the minor pathway, respectively. CONCLUSIONS: Genetic variation of alcohol-metabolizing enzymes, especially ALDH2, may play an important role on the occasions of alcohol problems in the emergency department.


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/genética , Aldeído Desidrogenase/genética , Citocromo P-450 CYP2E1/genética , Adulto , Serviço Hospitalar de Emergência , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição
17.
J Int Adv Otol ; 13(1): 9-13, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28274897

RESUMO

OBJECTIVE: To describe the clinical manifestations of external auditory canal (EAC) cholesteatoma and evaluate the surgical outcomes of reconstruction using an inferior pedicled soft-tissue periosteum flap. MATERIALS AND METHODS: A total of 28 patients were enrolled in this retrospective study conducted at Kaohsiung Medical University Hospital in Taiwan between January 2004 and December 2013. EAC cholesteatoma was classified according to the disease extent. The surgery was performed to reconstruct a smooth contour of EAC. RESULTS: The average age of the 28 patients (9 males and 19 females: 30 surgical ears) was 53.7 years. The most common clinical manifestations were unilateral otalgia (63.3%) and otorrhea (46.7%), and the most frequent locations of EAC cholesteatoma with bony invasion were the posterior-inferior (40%), inferior (30%), posterior (20%), and posterior-inferior-anterior (10%) aspects. Based on Naim's staging systems of EAC cholesteatoma, 26 ears (86.7%) were classified as stage III and 4 ears (13.3%) as stage IV. All patients received surgical management via a postauricular approach, and the average length of postoperative follow-up was 61.5 months (range 8-131 months). One patient had recurrence after surgery for 1 year 3 months. CONCLUSION: Bony canaloplasty and obliteration with an inferior pedicled soft-tissue periosteum flap is a reliable procedure for EAC cholesteatoma.


Assuntos
Colesteatoma da Orelha Média/diagnóstico , Colesteatoma da Orelha Média/cirurgia , Meato Acústico Externo/cirurgia , Retalhos Cirúrgicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Colesteatoma da Orelha Média/complicações , Dor de Orelha/etiologia , Feminino , Seguimentos , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otológicos/métodos , Procedimentos de Cirurgia Plástica , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
18.
Sci Rep ; 7(1): 15976, 2017 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-29162840

RESUMO

Whey protein concentrate (WPC) is an amino acid-rich supplement that has been shown to increase cellular antioxidant capacity. Mammalian target of rapamycin (mTOR) is a crucial regulator of signaling in mammalian cells, and serves as a therapeutic target for triple-negative breast cancer (TNBC). This study was designed to investigate the effect of combining WPC with rapamycin on MDA-MB-231 human breast cancer cells. These cells were found to be insensitive to rapamycin and exhibited higher glutathione (GSH) and reactive oxygen species levels than non-tumorigenic MCF-10A cells. However, for MDA-MB-231 cells, the half maximal inhibitory concentration of rapamycin was lower when this drug was administered in combination with WPC than when used alone. Furthermore, combining WPC with rapamycin depleted GSH levels and reduced Nrf2 nuclear accumulation. In addition, WPC activated GSK3ß/mTOR signaling, and GSK3ß appeared to be involved in the WPC-mediated Nrf2 reduction and mTOR activation. In conclusion, WPC induced rapamycin sensitivity in MDA-MB-231 cells by altering their redox state and activating GSK3ß/mTOR signaling. These results not only suggest a novel therapeutic approach for breast cancer treatment, but also provide insight into the critical pathways affecting the resistance to mTOR inhibition observed in a subgroup of TNBC patients.


Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas do Soro do Leite/farmacologia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Humanos , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Oxirredução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco
19.
Food Chem Toxicol ; 107(Pt A): 440-448, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28709970

RESUMO

Glutathione (GSH) plays an important role in antioxidant defense and regulation of apoptosis. GSH deficiency is related to many diseases, including cancer, and increased GSH levels in cancer cells are associated with chemotherapy resistance because of resistance to apoptosis. In this study, we investigated the effects of whey protein concentrate (WPC), a precursor of GSH, in rats with mammary tumors induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA). DMBA treatment results in cellular changes that mimic the initiation and promotion of carcinogenesis of breast tissue. We aimed to examine the possible preventive effects of diets containing whey protein on DMBA-induced mammary tumors in rats. The results indicate that WPC (0.334 g/kg) supplementation significantly increased the liver GSH levels by 92%, and were accompanied by low Bax/Bcl-2 ratio (from 5 to 3) and cleaved caspase-3/procaspase-3 ratio (from 2.4 to 1.2) in DMBA-treated rats. Furthermore, tumor GSH levels were decreased by 47% in WPC-supplemented rats, which resulted in increased Bax/Bcl-2 ratio (from 0.9 to 2) and cleaved caspase-3/procaspase-3 ratio (from 1.1 to 2.7). In conclusion, supplementation with WPC could selectively deplete tumor GSH levels and, therefore, WPC supplementation might be a promising strategy to overcome treatment resistance in cancer therapy.


Assuntos
Apoptose , Neoplasias da Mama/dietoterapia , Glutationa/metabolismo , Proteínas do Soro do Leite/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/fisiopatologia , Caspase 3/genética , Caspase 3/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Fígado/citologia , Fígado/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Proteínas do Soro do Leite/química , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
20.
Clin Chim Acta ; 361(1-2): 104-11, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16009358

RESUMO

BACKGROUND: Reactive oxygen species (ROS), including superoxide anion radical (O2(-)), plays an important role in carcinogenesis. The human body has developed different antioxidant systems to defend against free radical attacks. We investigated the changes of the antioxidant status in the blood of patients with breast cancer. METHODS: The O2(-) generation and the levels of malondialdehyde (MDA) were measured as an index of lipid peroxidation along with the examination of the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), the levels of reduced glutathione (GSH), oxidized glutathione (GSSG), and vitamins A, C, and E. RESULTS: The results showed that the levels of O2(-) and MDA, and the activities of antioxidant enzymes in the blood of the patients with breast cancer were significantly higher than the controls. However, the levels of vitamin C, GSH, GSSG and ratio of GSH/GSSG in the blood of the patients with breast cancer were significantly decreased compared to control subjects. CONCLUSIONS: Oxidative stress may be involved in breast cancer. The increased activities of erythrocyte antioxidant enzymes may be a compensatory upregulation in response to the increased oxidative stress.


Assuntos
Antioxidantes/análise , Neoplasias da Mama/sangue , Peróxidos Lipídicos/sangue , Superóxidos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Humanos , Peróxidos Lipídicos/metabolismo , Malondialdeído/sangue , Pessoa de Meia-Idade
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