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The relationship between coffee consumption and thyroid cancer (TC) occurrence has been evaluated in several observational studies with controversial results. The study aims to examine the associations between coffee consumption and TC occurrence. Systematic searches up to February 2019 were conducted. We estimated summary adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). The dose-response analysis was conducted by using generalised least square trend estimation. A total of ten studies involving 379,825 participants and 1,254 TC cases were included. The total summary RR showed that high coffee consumption was a protection factor of TC (RR = 0.75; 95% CI, 0.62-0.91). With the linear cubic spline model, the occurrence of TC was reduced by 5% with each one cup/day increment of coffee consumption (RR = 0.95; 95% CI, 0.91-0.99).This meta-analysis provides quantitative evidence that coffee consumption was inversely associated with the TC occurrence in a linear dose-response manner.
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Café , Neoplasias da Glândula Tireoide/epidemiologia , Relação Dose-Resposta a Droga , Humanos , Fatores de RiscoRESUMO
Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being (p = 0.003), functional well-being (p = 0.006), breast cancer subscale (p = 0.038), and FACT-B Total scores (p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer.
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Neoplasias da Mama , Qualidade de Vida , Idoso , China , Feminino , Hábitos , Humanos , Estilo de Vida , Qualidade de Vida/psicologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To identify atypical hyperplasia (AH) of the breast by shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), and to explore the molecular fingerprinting characteristics of breast AH. METHODS: Breast hyperplasia was studied in 11 hospitals across China from January 2015 to December 2016. All patients completed questionnaires on women's health. The differences between patients with and without breast AH were compared. AH breast lesions were detected by Raman spectroscopy followed by the SHINERS technique. RESULTS: There were no significant differences in clinical features and risk-related factors between patients with breast AH (n = 37) and the control group (n = 2576). Fifteen cases of breast AH lesions were detected by Raman spectroscopy. The main different Raman peaks in patients with AH appeared at 880, 1001, 1086, 1156, 1260, and 1610 cm-1, attributed to the different vibrational modes of nucleic acids, ß-carotene, and proteins. Shell-isolated nanoparticles had different enhancement effects on the nucleic acid, protein, and lipid components in AH. CONCLUSION: Raman spectroscopy can detect characteristic molecular changes in breast AH lesions, and may thus be useful for the non-invasive early diagnosis and for investigating the mechanism of tumorigenesis in patients with breast AH.
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Neoplasias da Mama , Lesões Pré-Cancerosas , Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , China , Feminino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologiaRESUMO
Nitric oxide (NO)-release in blood serum initiated by gold nanoparticles has been prove to be a reaction between RSNO and the gold nanoparitcles. In this reaction the NO production was catalyzed on the surface of the nanoparticles, and a new bond of Au-thiolate was simultaneously formed.
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Ouro/farmacologia , Nanopartículas Metálicas/química , Óxido Nítrico/sangue , Estresse Oxidativo , Técnicas Biossensoriais , Cisteína/análogos & derivados , Cisteína/sangue , Humanos , Compostos Nitrosos/sangue , Espécies Reativas de Oxigênio/sangue , S-Nitrosoglutationa/sangue , S-Nitrosotióis/sangue , Soroalbumina BovinaRESUMO
This study was designed to investigate the changes of urinary microvesicle-bound uromodulin and total urinary uromodulin levels in human urine and the correlations with the severity of diabetic kidney disease (DKD). 31 healthy subjects without diabetes and 100 patients with type 2 diabetes mellitus (T2DM) were included in this study. The patients with T2DM were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n = 46); microalbuminuria group (DN1, n = 32); and macroalbuminuria group (DN2, n = 22). We use a specific monoclonal antibody AD-1 to capture the urinary microvesicles. Urinary microvesicle-bound uromodulin and total urinary uromodulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the levels of urinary microvesicle-bound uromodulin in DN1 and DN2 groups were significantly higher than those in control group and DM group (P < 0.01). Multiple stepwise linear regression analysis showed that UACR was independent determinant for urinary microvesicle-bound uromodulin (P < 0.05) but not for total urinary uromodulin. These findings suggest that the levels of urinary microvesicle-bound uromodulin are associated with the severity of DKD. The uromodulin in urinary microvesicles may be a specific marker of DKD and potentially may be used to predict the onset and/or monitor the progression of DKD.
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Albuminúria/diagnóstico , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/diagnóstico , Uromodulina/urina , Adulto , Idoso , Albuminúria/urina , Biomarcadores/urina , Nefropatias Diabéticas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The present study investigated the inhibitory effect of curcumin on human breast cancer MCF-7 cells and investigated the potential underlying molecular mechanisms. MCF-7 cells were cultured with curcumin at different concentrations and time points. The effects of curcumin treatment on breast cancer cell proliferation were studied using a MTT assay. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to assess the mRNA and protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax), nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κB) and inhibitor of NF-κB-α (IκBα). The proliferation of MCF-7 cells in the group treated with curcumin was markedly decreased compared with the control, with the greatest inhibitory effect at a concentration of 20 µM. The expression of Bax mRNA was increased and Bcl-2 mRNA expression was decreased compared with the control. Additionally, protein expression of NF-κB and IκB was increased. The data indicate that curcumin is able to inhibit breast cancer cell proliferation, possibly by regulating the NF-κB signaling pathway.
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OBJECTIVE: To investigate the relationships among the expression of thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) and the prognosis of breast cancer. METHODS: Immunochemistry (ABC method) was used to detect the expression of TS, TP, and DPD in the samples of breast cancer resected during operation from 28 female patients. The microvessel density (MVD) in the cancer tissue was measured by immunochemistry (LSAB method). RESULTS: The TS positive rate was 30.26% and the TP positive rate was 21%, and the DPD positive rate was 30.03%. The expression levels of TS and TP were both correlated with the tumor size, lymph node status, histological grading of tumor, and microvessel count (MVC) (all P < 0.01), and was not correlated with age, status of estrogen receptors, status of prasterone receptors (all P > 0.05). The DPD expression was not correlated with the age, tumor size, lymph node status, histological grading of tumor, status of estrogen receptors, status of prasterone receptors, and MVC. The ten-year disease-free survival rate of the TS-positive patients was 0, significantly lower than that of the TS-negative patients (25%, P < 0.01). The ten-year overall survival rate of the TS-positive patients was 3.9%, significantly lower than that of the TS-negative patients (58.8%, P < 0.01). The ten-year disease-free survival rate of the TP-positive patients was 0, significantly lower than the TP-negative patients (25.4%, P < 0.01). The ten-year overall survival rate of the TP-positive patients was 0.9%, significantly lower than that of the TP-negative patients (61.8%, P < 0.01). The ten-year disease-free survival rate and ten-year overall survival rate of the DPD positive patients were not significantly different from those of the DPD negative patients (both P > 0.05). MCV and TS expression were strong protective factors of disease-free survival rate and overall survival rate. CONCLUSION: The levels of TS and TP are both prognostic indicis of breast cancer.
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Neoplasias da Mama/enzimologia , Carcinoma Ductal de Mama/enzimologia , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Quimioterapia Adjuvante , Di-Hidrouracila Desidrogenase (NADP)/biossíntese , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Timidina Fosforilase/biossíntese , Timidilato Sintase/biossínteseRESUMO
OBJECTIVE: Our aim was to investigation the roles of MHC class I chain-related gene A(MICA) and natural killer cell group 2D(NKG2D) in human renal cancer cells. MATERIALS AND METHODS: The expression of membrane MICA (mMICA) on renal cells and NKG2D on NK cells were detected by flow cytometry (FCM); the content of sMICA were detected by enzyme linked immunosorbent assay (ELISA) and the distribution of mMICA on renal tumor tissues by immunohistochemistry; the interaction between MICA and NKG2D was observed by antibody closed method. RESULTS: Our results showed that the expression of mMICA in renal cancer tissues was significantly higher than in controls, where the soluble MICA was not expressed. Cytotoxic activity of NK cells was significantly reduced after exposure to NKG2D and MICA antibodies (P<0.05), and serum containing sMICA can obviously lower the function of NKG2D (P<0.05). CONCLUSIONS: The interaction of mMICA and NKG2D play important roles in mediation of cytotoxicity of NK cells in RCC. On the other hand, sMICA may mediate tumor immune escape through down- regulated NKG2D expression.
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Carcinoma de Células Renais/metabolismo , Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/metabolismo , Neoplasias Renais/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Apoptose , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Estudos de Casos e Controles , Proliferação de Células , Citotoxicidade Imunológica/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Células Tumorais CultivadasRESUMO
OBJECTIVE: To study the relationship between the expression of thymidylate synthase (TS) gene and the prognosis of colorectal carcinoma and between the TS expression and the effect of 5-fluorouracil (5-Fu) on advanced colorectal carcinoma. METHODS: 134 formalin-fixed and paraffin-embedded specimens of colorectal carcinoma obtained during operation from 134 patients, 65 males and 69 females, aged 34 approximately 76 with an average age of 51 +/- 11, 16 with differentiated carcinoma and 118 with undifferentiated carcinoma, 4 with infiltration into mucous layer, 21 into submucous layer, 100 into muscular layer, and 5 into serous layer, 25 without lymphatic metastasis and 109 with lymphatic metastasis, 4 in stage IB, 15 in stage II, 90 in stage IIIA, and 27 in stage IIIB by Dukes staging, underwent immunohistochemistry (ABC methods) to determine the expression of TS. After operation all patients received chemotherapy with leucovorin and 5-Fu for 4 approximately 6 periods and were followed up for 9 approximately 72 months. RESULTS: Eighty-two specimens showed high TS expression and 52 showed low TS expression. The grade of TS expression was significantly correlated with four clinicopathologic variables: histological type, depth of invasion, lymphatic metastasis, and Dukes' stage (all P < 0.001). The 5-year survival rate for the low TS group was 57.69%, significantly lower than that of the high TS group (21.95%, P < 0.001). Multivariate analysis revealed that three variables (histological type, depth of infiltration, and TS grade) independently contributed to the survival rate (all P < 0.05), especially the TS grade (all P < 0.0001). The relative hazard ratio of TS grade was 1.241. CONCLUSION: The expression of TS is one of the important prognosis indicators of colorectal carcinoma. It is also a relatively reliable indicator of whether 5-Fu should be used in the treatment of patients with colorectal carcinoma.
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Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Colo/enzimologia , Fluoruracila/uso terapêutico , Neoplasias Retais/enzimologia , Timidilato Sintase/biossíntese , Adulto , Idoso , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Timidilato Sintase/genéticaRESUMO
OBJECTIVE: To systematically assess imaging diagnostic tests for fatty liver and provide a decision-making basis for clinical diagnosis and screening. METHODS: Electronic searches were conducted on the Chinese Biomedical Database, PubMed, and EMBASE, combining with manually searching of Chinese literature. All searches were completed until November 2002. All studies which evaluated imaging diagnostic test of human fatty liver were included. Data of diagnostic accuracy in the included studies were extracted, and methodological quality of the studies was assessed independently by two reviewers according to the established quality standard. Quantitative analysis or qualitative description were performed based on available data. RESULTS: Of 13 studies that met the eligibility criteria, 10 studies evaluated the diagnostic accuracy of B-mode ultrasound, 3 studies evaluated contrast-enhanced (helical) CT. To assess 7 diagnostic test studies for fatty liver that used liver biopsy as reference test: the pooled sensitivity of B-mode ultrasound was 0.89 (95% confidence interval 0.87-0.92), specificity was 0.94 (95% confidence interval 0.92-0.96) and the Q value was 0.90 by adjusted SROC method. To assess 2 diagnostic test studies for fatty liver that used CT as reference test: the pooled sensitivity, specificity, and Q value were 0.92 (95% confidence interval 0.89-0.96), 0.88 (95% confidence interval 0.84-0.92), and 0.90 respectively by adjusted SROC method. CONCLUSIONS: B-mode ultrasound method can be regarded as an effective method for fatty liver diagnosis and screening. The methodologic quality of diagnostic test needs to be improved.
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Fígado Gorduroso/diagnóstico , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada Espiral , UltrassonografiaRESUMO
The aim of the present study was to determine the protection of allogeneic bone marrow mesenchymal stem cells (BMSCs) on an ischaemia/reperfusion (I/R)induced acute kidney injury (AKI) rat model and to investigate the underlying mechanisms. The BMSCs were isolated and cultured from adult SpragueDawley (SD) rats and the I/Rinduced AKI model was established by bilateral clamping of renal pedicles for 60 min. Following successfully establishing the AKI model, 1x106 BMSCs were administered by intrarenal injection. All animals were randomly divided into four groups (n=10 in each): 1 (sham control), 2 (I/R), 3 (I/R+culture medium) and 4 (I/R+BMSCs). Serum levels of creatinine (Cr) and blood urea nitrogen (BUN) were measured in all four groups at 24 and 72 h. Three days postsurgery, the level of inflammatory factors, including interleukin6 (IL6), tumour necrosis factorα (TNFα) and vascular endothelial growth factor (VEGF) in the kidney was analysed by quantitative polymerase chain reaction. Three days following surgery, mRNA expression levels of IL6 and TNFα were significantly lower, however, the expression level of VEGF was significantly higher in group 4 compared with groups 2 and 3 (P<0.05). By contrast, the immunofluorescence results showed that the injected BMSCs differentiated into vascular endothelial cells. In conclusion, the present study identified that intrarenal administration of BMSCs improved I/Rinduced AKI through the antiinflammatory effect and a paracrine mechanism and therefore, may be hypothesised for the use in clinical trials.
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Injúria Renal Aguda/cirurgia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Células da Medula Óssea/citologia , Células Cultivadas , Creatinina/sangue , Modelos Animais de Doenças , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Transplante Homólogo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: The relationship between obesity and hypertension varies with geographical area, race and definitions of obesity. Our study aimed to investigate the prevalence of obesity using standard Chinese criteria based on the body mass index (BMI) and the waist circumference (WC) and to examine the association between obesity and hypertension among middle-aged and elderly people in Jinan city. METHODS: This cross-sectional study examined 1,870 subjects from the blocks randomly selected from among the 6 communities of Jinan, China in 2011-2012. The Student's t-test was used to compare numerical data, and the χ2 test was used to compare categorical data. Multivariate logistic regression analyses were performed to assess the effects of general and central obesity on hypertension after adjusting for age or for education level, smoking, alcohol consumption, and continuous age. RESULTS: The prevalence of general obesity among people age 50 years and older was 21.1% (17.0% for males and 23.1% for females), and the prevalence of central obesity was 77.8% for men and 78.7% for women. For men, compared with a normal BMI, the ORs and 95% CIs for overweight and general obesity were 1.853 (1.252, 2.744) and 3.422 (1.894, 6.182), respectively, after adjusting for age, smoking, alcohol consumption and educational level. Compared with a normal WC, the ORs and 95% CIs for central obesity were 2.334 (1.573, 3.465) and 2.318 (1.544, 3.479), respectively, for men. For women, compared with a normal BMI, the ORs and 95% CIs were 1.942 (1.473, 2.599) and 4.011 (2.817, 5.712), respectively, after adjusting for age, smoking, alcohol consumption and educational level. Compared with a normal WC, the ORs and 95% CIs for central obesity were 2.488 (1.865, 3.319) and 2.379 (1.773, 3.192), respectively, for women. CONCLUSIONS: The relationship between hypertension and general obesity was stronger than the relationship between hypertension and either overweight or central obesity in both genders.
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Hipertensão/complicações , Obesidade/complicações , Obesidade/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Circunferência da CinturaRESUMO
The overall incidence and mortality of renal cell carcinoma (RCC), the most common kidney cancer, are steadily increasing for reasons that are not fully explained. Our aim was to explore the expression of membrane MHC class I chain-related gene A (mMICA) in human RCC cell lines and tissue specimens, and to determine expression of soluble MICA (sMICA) in serum of patients with renal cell carcinoma, we used flow cytometry (FCM) and immunohistochemistry as well as an enzyme linked immunosorbent assay (ELISA) . The results showed that percentage of mMICA expression was significantly increased in human kidney cancer tissues and RCC cell lines (786-O and Ketr-3) than that in healthy adults and human embryonic kidney 293 (HEK293) cell line individuality (P<0.05). sMICA content in healthy adults was negative, but in renal cancer patients was significantly elevated (P<0.05). Our research showed that high expression of MICA in human kidney cancer, this results show that MICA might serve as potential tumor-associated antigen (TAA) in RCC.
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Carcinoma de Células Renais/sangue , Antígenos de Histocompatibilidade Classe I/biossíntese , Antígenos de Histocompatibilidade Classe I/sangue , Neoplasias Renais/sangue , Proteínas de Membrana/sangue , Antígenos de Neoplasias , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/mortalidade , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Células HEK293 , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/mortalidade , Proteínas de Membrana/biossíntese , RNA Mensageiro/biossínteseRESUMO
The aim of the present study was to investigate the association of human leukocyte antigen (HLA) gene polymorphism and clinical phenotypes of patients with mesangial proliferative glomerulonephritis (MsPGN). The genotyping of HLA-A, HLA-B and HLA-DRB1 alleles was detected in 1,536 consecutive MsPGN patients during the previous five years and 2,027 age- and gender-matched healthy individuals by using the polymerase chain reaction-sequence-specific primers method. The clinical and pathological data of the patients were collected and the genotype frequencies (GF) and odds ratio (OR) were analyzed. The allele frequencies of HLA-A*23, A*25, B*15, B*40, B*53 and DRB1*18 were significantly higher in MsPGN patients than in the controls (P<0.05). These alleles were considered as the suspected susceptibility genes (SSG) for MsPGN. Of note, results of the follow-up survey study demonstrated poorer prognosis of patients with SSG than those without SSG. On the other hand, the frequencies of A*32, A*33, B*50, B*58, B*60, B*71, DRB1*16 were lower in MsPGN patients than in the controls (P<0.05). However, the alleles A*20, A*22, A*35, A*36, A*38, B*21, B*73 and B*78 were not expressed in MsPGN patients. HLA gene polymorphism is associated with hereditary susceptibility to MsPGN. Therefore, there might be corresponding susceptibility and protective genes associated with MsPGN.
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Encapsulating anticancer drugs to synthetic polymer is a promising approach to improve the efficiency and reduce the side effects of anticancer drugs. In this study, novel chitosan derivatives with polyamidoamine moieties (CS-PAMAM) were synthesized and characterized by morphology, particle size, and zeta potential. Then the anticancer drug-methotrexate-encapsulated CS-PAMAM was prepared by hydrophobic-hydrophilic interactions. The drug release assay showed that the amount of the methotrexate release from CS-PAMAM was pH depended. Meanwhile, the cell viability assay illustrated that CS-PAMAM was suitable for the drug delivery because of its low cytotoxicity on cells. Moreover, our results showed that the CS-PAMAM could significantly improve the cytotoxicity of free methotrexate on A549 cells. These results demonstrate that CS-PAMAM may provide a suitable platform for the water-insoluble drug delivery.
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Antineoplásicos/química , Quitosana/química , Dendrímeros/química , Portadores de Fármacos/química , Metotrexato/química , Nanopartículas/química , Animais , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/síntese química , Dendrímeros/metabolismo , Dendrímeros/toxicidade , Portadores de Fármacos/síntese química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Fluoresceína-5-Isotiocianato/química , Espaço Intracelular/metabolismo , Camundongos , Agregação Plaquetária/efeitos dos fármacosRESUMO
A nanocarrier, namely, hydroxylethyl-chitosan nanoparticles was developed in this research for delivering antioxidants with 6-hydroxy-2, 5, 7, 8-tetra-methylchromane-2-carboxylic acid (trolox) as a model antioxidant. The trolox-encapsulated chitosan nanoparticles (trolox-CS NPs) were prepared by modifying chitosan with epoxyethane, which self-assembled into NPs and entrapped trolox, and then characterized by their size, size distribution, morphology and in vitro trolox release profile. Intracellular trafficking of CS NPs was observed. The anti-oxidant effect and potential mechanism of trolox-CS NPs were subsequently investigated in RAW264.7 cells. The effects of trolox-CS NPs on RAW264.7 cells damaged by tert-butylhydroperoxide (t-BHP) were determined by MTT assay for cell viability, MDA assay for membrane lipid peroxidation, JC-1 probe and Annexin V-FITC/PI double staining for mitochondria membrane potential (MMP) and RAW264.7 apoptosis, respectively. The trolox-CS NPs significantly improved cell viability and reduced MDA content compared with those of cells treated with free trolox. The trolox-CS NPs treatment inhibited MMP collapse and RAW264.7 apoptosis more obviously than free trolox. Molecular basis of apoptosis studied by western blotting revealed that trolox-CS NPs may block mitochondria-mediated apoptosis pathway through up-regulation of Bcl-2 and down-regulation of Bax and inhibiting the activation of pro-caspase 3, PARP and Bid.
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Quitosana/química , Cromanos/química , Nanopartículas/química , terc-Butil Hidroperóxido/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
In the present study, five cyclic nitrone superoxide spin adducts, i.e. DMPO-OOH, M(3)PO-OOH, EMPO-OOH, DEPMPO-OOH and DEPDMPO-OOH, were chosen as model compounds to investigate the effect of 2,5-subsitituents on their stability, through structural analysis and decay thermodynamics using density functional theory (DFT) calculations. Analysis of the optimized geometries reveals that none of the previously proposed stabilizing factors, including intramolecular H-bonds, intramolecular non-bonding interactions, bulky steric protection nor the C(2)-N(1) bond distance can be used to clearly explain the effect of 2,5-substituents on the stability of the spin adducts. Subsequent study found that spin densities on the nitroxyl nitrogen and oxygen are well correlated with the half-lives of the spin adducts and consequently are the proper parameters to characterize the effect of 2,5-substituents on their stability. Examination of the decomposition thermodynamics further supports the effect of the substituents on the persistence of cyclic nitrone superoxide spin adducts.
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Óxidos N-Cíclicos/química , Óxidos de Nitrogênio/química , Marcadores de Spin , Superóxidos/química , Espectroscopia de Ressonância de Spin Eletrônica , Modelos Químicos , Estrutura Molecular , Pirróis/química , Detecção de SpinRESUMO
To study the FLT3 gene expression and its internal tandem duplication in hematologic malignancies and its clinical significance, polymerase chain reaction (PCR) and DNA sequencing were used to detect the FLT3/ITD mutation in blast cells of bone marrow from 86 patients with hematologic malignancies, including 32 cases of acute myeoloid leukemia (AML), 18 cases of acute lymphoblastic leukemia (ALL), 2 cases of acute hybrid leukemia (AHL), 12 cases of myelodysplastic syndromes (MDS), 10 cases of chronic myelogenous leukemia (CML), 3 cases of non-Hodgkin's lymphoma (NHL) and 9 cases of multiple myeloma (MM). The resultes showed that the expression of FLT3/ITD gene could be detected in 5 of 32 (15.6%) AML patients, including 1/7 of M(3), 1/10 of M(4) and 3/10 of M(5). More FLT3 aberrations were found in AML-M(5). No FLT3/ITD was found in 18 cases of ALL, in 2 cases of AHL, in 12 cases of MDS and in 10 cases of CML. No FLT3 was found in 3 cases of NHL and in 9 cases of MM. Sequence analysis in 2 case with abnormal PCR electrophoretic patterns revealed that the ITDs were located within exon 14 from 27 to 63 bp, which was a simple tandem duplication, and did not altered the reading frame. FLT3/ITD was associated with a higher peripheral blood white cell count (p < 0.01), higher percentage of bone marrow blast cells (p < 0.01) and lower complete mission rate. It is concluded that more FLT3/ITD mutation occurs in AML-M(5) patients. Sequence of the mutants is in frame mutation. FLT3/ITD mutation is associated with higher peripheral blood white cell count, higher percentage of bone marrow blast cells and lower complete remission rate, FIT3/IID gene mutation may be used to predict prognosis of patients with AML.
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Duplicação Gênica , Neoplasias Hematológicas/genética , Mutação , Sequências de Repetição em Tandem , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Sequência de Bases , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Prognóstico , Adulto JovemRESUMO
OBJECTIVE: To investigate the factors affecting the survival and to predict the survival time of glioma. METHODS: Graph method was applied to fit the type of probability distribution of patients' postoperative survival time. As one suitable model, Weibull regression model tested by residual analysis was used to identify prognostic factors for postoperative survival and to predict patients' post-operative survival time. RESULTS: In multivariate analysis of Weibull regression model, following characteristics showed significant influence on postoperative survival time including: sex, age, epilepsy, type of glioma, density of glioma, type of surgery, times of surgery and mode of postoperative therapy. According to predictive value, patients were clustered into three groups. The survival probability of one year for the first group was less than 50% and that of five years for the second group about 50%, for the third group around 80%. CONCLUSION: Sex, age, epilepsy, type of glioma, density of glioma, type of surgery, times of surgery and mode of postoperative therapy were important risk factors and Weibull regression model might help to predict patients' postoperative survival time.