RESUMO
BACKGROUND: This work aimed to investigate the inhibitory effect of regorafenib in combination with ginsenoside on the growth of HepG2 liver cancer cells. METHODS: HepG2 liver cancer cells were divided into blank control group, regorafenib single-drug group, ginsenoside single-drug group, and regorafenib/ginsenoside combination group. Cells in the regorafenib single-drug group were treated with regorafenib at 0.25 mg/L, 0.5 mg/L, and 1 mg/L, respectively, while cells in the ginsenoside single-drug group were treated with ginsenoside at 5.0 mg/L, 10.0 mg/L, and 20.0 mg/L, respectively. HepG2 cell proliferation, expression of survivin mRNA, and the apoptotic effector caspase-3 in HepG2 liver cancer cells were assessed. RESULTS: An inhibitory effect on the growth of HepG2 liver cancer cells was observed for both the single-drug therapies and the combination therapy. The synergistic inhibitory effect presented by the combination therapy was dependent on the gradient concentration and treatment time. RT-qPCR results showed that both regorafenib and ginsenoside significantly reduced the expression of survivin mRNA in HepG2 liver cancer cells and the expression level of survivin mRNA in the regorafenib/ginsenoside combination group was much lower than those in the regorafenib single-drug group and ginsenoside single-drug group. The two drugs demonstrated synergistic inhibitory effect when used in combination. CONCLUSIONS: The findings in this study offered a theoretical insight into clinical use of regorafenib and ginsenoside for treatment of liver cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Caspase 3/biossíntese , Ginsenosídeos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/farmacologia , Piridinas/farmacologia , Survivina/biossíntese , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Ginsenosídeos/administração & dosagem , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Piridinas/administração & dosagem , Survivina/genética , Survivina/metabolismoRESUMO
OBJECTIVES: This study was to evaluate the feasibility of simultaneous integrated boost on tumor hypoxia area by studying the dosimetric change of hypoxia imaging guidance on intensity-modulated radiation therapy for non-small cell lung cancer (NSCLC). METHODS: Five NSCLC patients with large hypoxic volume participated in this study. FDG PET/CT images were fused with CT localization images to delineate gross tumor volume. FMISO PET/CT images were fused with CT localization images to delineate hypoxic biological target volume (BTV) (tissue maximum ratio ≥ 1.3) by threshold. BTV was irradiated with 72, 78 and 84 Gy, respectively, 30 times. The dosimetry differences were compared in target volume and organ at risk between simultaneous integrated boost plans and conventional radiotherapy plans. RESULTS: Dosages on BTV of NSCLC hypoxic area were increased to 72, 78 and 84 Gy, respectively, by simultaneous integrated boost intensity-modulated radiation therapy. There was no obvious difference in dosage distributions on original target volume compared with those in conventional radiotherapy. Dosages on main organ at risk in chest met the dosimetric constraint, and there was no significant difference compared with those in conventional radiotherapy. CONCLUSION: It is feasible in dosiology that the dosages in NSCLC hypoxic area were added to 72, 78 and 84 Gy by simultaneous integrated boost with the guidance of 18F-FMISO PET/CT.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Hipóxia/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Imagem Multimodal/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Misonidazol/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Dosagem RadioterapêuticaRESUMO
PURPOSE: This study was conducted to investigate the efficacy and toxicity of combination treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy with paclitaxel plus different platinum agents in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study enrolled 242 patients treated with paclitaxel (135 mg/m2) plus platinum regimens. According to the different platinum agents used, patients were classified into: cisplatin 80 mg/m2 (CP), nidaplatinum 80 mg/m2 (NP), lobaplatin 35 mg/m2 (LP), and oxaliplatin 135 mg m2 (OP) groups, and survival and toxicity rates between the four groups were compared. The median overall survival (OS) was 31.1 months. RESULTS: No significant differences were observed among the CP, NP, LP, and OP groups with regard to 3-year survival rates (46.2, 56.4, 45.7, and 29.0%, respectively). A stratified analysis indicated that 3-year survival rates were significantly lower in the OP group. Renal toxicities and gastrointestinal reactions were more frequent in the CP group than in the other three groups. Three-year survival rates were similar among patients receiving 2, 3, or ≥4 cycles of chemotherapy (40.1, 49.5, and 50.8%, respectively). Multivariate analysis indicated that tumor volume and maximum diameter of metastatic lymph nodes might be independent prognostic factors. CONCLUSION: Paclitaxel plus nidaplatinum or lobaplatin is recommended in locally advanced ESCC due to their satisfying therapeutic effects and less toxicity. Tumor volume and maximum diameter of metastatic lymph nodes are independent prognostic factors in ESCC patients receiving IMRT and concurrent chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Compostos de Platina/administração & dosagem , Compostos de Platina/efeitos adversos , Modelos de Riscos Proporcionais , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos RetrospectivosRESUMO
Type 2 diabetes mellitus (T2-DM) is a chronic metabolic disorder characterized by high blood glucose levels. T2-DM patients suffer from many complications, such as diabetic fatty liver and diabetic nephropathy. The liver, the pivotal organ involved in both glucose and lipid metabolism, is primarily damaged in T2-DM patients, especially in those with high levels of blood lipid. In this study, the hepatoprotective activity of ginsenoside Rg1 was investigated in a T2-DM rat model. The results revealed a potent hepatoprotective effect of ginsenoside Rg1. This effect was primarily mediated by the antiapoptotic effect, inhibition of JNK activity, and suppression of inflammation after ginsenoside Rg1 treatment. Ginsenoside Rg1 also lowered the blood glucose level and insulin resistance index in T2-DM rats. Moreover, the blood lipid profile (total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels) and liver function (aspartate transaminase and alanine transaminase levels) improved after ginsenoside Rg1 treatment. The aforementioned hepatoprotective effects of ginsenoside Rg1 in the T2-DM rat model suggests its clinical potential as an adjuvant drug for T2-DM therapy, especially for T2-DM patients with fatty liver disease.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ginsenosídeos/farmacologia , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Fígado/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Insulina/sangue , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
The properties of metallic alloys can be significantly improved by developing non-equilibrium phases in the microstructures through rapid solidification techniques, thus the characterisation of these unusual structures is extremely important. In this research, the microstructures of three rapidly quenched alloys, namely Ni65.2 Nb33.8 Zr1.0 , Ni54.8 Nb31.1 Zr14.1 and Ni54.8 Nb21.6 Zr23.6 (at. %) were investigated in greater detail in order to determine the structures and compositions of their crystalline phases. These crystalline phases were characterised using a combination of scanning electron microscopy, energy dispersive x-ray spectroscopy, x-ray diffraction and transmission electron microscopy techniques. The phases were compared to the crystalline structures reported in the literature. Our results indicate some agreement with the Ni-Nb phase diagram and an isothermal section of the Ni-Nb-Zr phase diagram; however, it is detected zirconium solubility in the Ni3 Nb phase, as well as, the absence of expected crystalline phases.
RESUMO
Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1ß activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.
Assuntos
Anti-Inflamatórios/farmacologia , Artralgia/enzimologia , Condrócitos/enzimologia , Flavanonas/farmacologia , Articulação do Joelho/enzimologia , Metaloproteinase 3 da Matriz/biossíntese , Osteoartrite do Joelho/enzimologia , Animais , Artralgia/tratamento farmacológico , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Expressão Gênica , Interleucina-1beta/análise , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Articulação do Joelho/patologia , Masculino , Metaloproteinase 3 da Matriz/análise , Inibidor de NF-kappaB alfa/análise , Inibidor de NF-kappaB alfa/efeitos dos fármacos , NF-kappa B/análise , NF-kappa B/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Resultado do TratamentoRESUMO
This study aimed to evaluate the clinical significance of diffusion tensor imaging (DTI) in the early diagnosis of pyramidal tract Wallerian degeneration (WD) and assessment of neurological recovery following cerebral infarction. This study included 23 patients with acute cerebral infarction and 10 healthy adult controls. All participants underwent both magnetic resonance imaging (MRI) and DTI scans. DTI images were analyzed using the Functional MRI of the Brain Software Library to determine the regions of interest (ROI) and obtain the mean diffusivity (MD) and fractional anisotropy (FA) value for each ROI. The correlation between FA or MD and postinfarction functional recovery of the nervous system was further analyzed to assess the feasibility of using a DTI scan in the evaluation of functional recovery of the nervous system in patients with cerebral infarction. DTI may be useful in detecting signals of early postinfarction pyramidal tract WD and is useful for the evaluation of postinfarction neurological recovery. Cerebral lesions were detected using MRI in all patients. It was found that in some patients, the FA value of the ipsilateral pyramidal tract on DTI was decreased as early as day 3 after the onset of infarction and in all patients by day 7. Subsequent correlation studies showed that the FA value of the ipsilateral pyramidal tract on day 13 was negatively correlated with the National Institutes of Health Stroke Scale score, but positively correlated with the Barthel Index, motricity index, and modified Rankin Scale scores.
Assuntos
Infarto Cerebral/complicações , Imagem de Tensor de Difusão , Degeneração Walleriana/diagnóstico , Degeneração Walleriana/etiologia , Degeneração Walleriana/reabilitação , Estudos de Casos e Controles , HumanosRESUMO
Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis.
Assuntos
Animais , Masculino , Anti-Inflamatórios/farmacologia , Artralgia/enzimologia , Condrócitos/enzimologia , Flavanonas/farmacologia , Articulação do Joelho/enzimologia , Metaloproteinase 3 da Matriz/biossíntese , Osteoartrite do Joelho/enzimologia , Artralgia/tratamento farmacológico , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Expressão Gênica , Interleucina-1beta/análise , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Articulação do Joelho/patologia , Metaloproteinase 3 da Matriz/análise , NF-kappa B/análise , NF-kappa B/efeitos dos fármacos , Inibidor de NF-kappaB alfa/análise , Inibidor de NF-kappaB alfa/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Resultado do TratamentoRESUMO
Axillary branching is controlled by a very complex mechanism involving various endogenous and environmental factors. Previous studies have shown that Tb1/BRC1 is the point of integration in the network of molecular mechanisms regulating axillary branching in plants. In this study, we cloned the Tb1/BRC1 ortholog, NtBRC1, from Nicotiana tabacum and functionally analyzed its role in the control of axillary branching in tobacco. Overexpression of NtBRC1 resulted in significant retardation of axillary branching, and downregulation of this gene resulted in significant acceleration of axillary branching after decapitation. This indicates a negative role for this gene in the regulation of axillary branching. In-line with previous reports, NtBRC1 was found to be expressed predominantly in axillary buds. Additionally, as expected, expression was decreased 8 h following decapitation, which further confirms its role in the suppression of axillary branching. Furthermore, the expression of NtBRC1 was significantly downregulated by cytokinin, but was not affected by GR24, a synthetic strigolactone. Based on the data collected in the present study, we demonstrate that NtBRC1 negatively regulates axillary branching in tobacco after decapitation and functions downstream of the cytokinin signaling pathway inside axillary buds.
Assuntos
Nicotiana/fisiologia , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Clonagem Molecular , Citocininas/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Lactonas/farmacologia , Nicotiana/genéticaRESUMO
Glycine-rich protein (GRP) is involved in the response to abiotic and biotic stresses in plants. A novel GRP gene in Lablab purpureus has been identified. The cDNA of LpGRP was obtained from an SSH library constructed with root tissues of L. purpureus MEIDOU 2012 by waterholding for 10 days. The function of LpGRP was also evaluated in Arabidopsis. The cDNA of LpGRP has 555 bp and encodes a 184-amino acid protein. LpGRP was induced by drought and improved tolerance to abiotic stress. In LpGRP overexpressing Arabidopsis, the tolerance of transgenic seedlings to drought and salt was improved, and transgenic seeds showed insensitivity to both ABA and NaCl. The insensitivity to ABA indicated that there was crosstalk between LpGRP and ABA-responsive genes. These results indicated that LpGRP is a drought-responsive gene that can increase the drought and salt tolerance of Arabidopsis seedlings overexpressing LpGRP.
Assuntos
Proteínas de Arabidopsis/genética , Fabaceae/genética , Plantas Geneticamente Modificadas/genética , Estresse Fisiológico/genética , Arabidopsis/genética , Secas , Fabaceae/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Germinação/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Tolerância ao Sal/genética , Sementes/genética , Sementes/crescimento & desenvolvimentoRESUMO
In this study, a methylation-sensitive amplification polymorphism analysis system was used to analyze DNA methylation level in three cotton accessions. Two disease-sensitive near-isogenic lines, PD94042 and IL41, and one disease-resistant Gossypium mustelinum accession were exposed to Verticillium wilt, to investigate molecular disease resistance mechanisms in cotton. We observed multiple different DNA methylation types across the three accessions following Verticillium wilt exposure. These included hypomethylation, hypermethylation, and other patterns. In general, the global DNA methylation level was significantly increased in the disease-resistant accession G. mustelinum following disease exposure. In contrast, there was no significant difference in the disease-sensitive accession PD94042, and a significant decrease was observed in IL41. Our results suggest that disease-resistant cotton might employ a mechanism to increase methylation level in response to disease stress. The differing methylation patterns, together with the increase in global DNA methylation level, might play important roles in tolerance to Verticillium wilt in cotton. Through cloning and analysis of differently methylated DNA sequences, we were also able to identify several genes that may contribute to disease resistance in cotton. Our results revealed the effect of DNA methylation on cotton disease resistance, and also identified genes that played important roles, which may shed light on the future cotton disease-resistant molecular breeding.
Assuntos
Metilação de DNA , Gossypium/genética , Doenças das Plantas/genética , Resistência à Doença , Genes de Plantas , Melhoramento Vegetal , Polimorfismo Genético , Verticillium/genética , Verticillium/metabolismoRESUMO
Many studies exist for reconstructing gene regulatory networks (GRNs). In this paper, we propose a method based on an advanced neuro-fuzzy system, for gene regulatory network reconstruction from microarray time-series data. This approach uses a neural network with a weighted fuzzy function to model the relationships between genes. Fuzzy rules, which determine the regulators of genes, are very simplified through this method. Additionally, a regulator selection procedure is proposed, which extracts the exact dynamic relationship between genes, using the information obtained from the weighted fuzzy function. Time-series related features are extracted from the original data to employ the characteristics of temporal data that are useful for accurate GRN reconstruction. The microarray dataset of the yeast cell cycle was used for our study. We measured the mean squared prediction error for the efficiency of the proposed approach and evaluated the accuracy in terms of precision, sensitivity, and F-score. The proposed method outperformed the other existing approaches.
Assuntos
Redes Reguladoras de Genes , Saccharomyces cerevisiae/genética , Ciclo Celular , Biologia Computacional , Lógica Fuzzy , Regulação Fúngica da Expressão Gênica , Modelos Genéticos , Redes Neurais de ComputaçãoRESUMO
Biliary atresia (BA) is a destructive bile duct disease occurring in newborn children within a few weeks after birth. In this study, the effect of miR-29c and miR-129-5p on epithelial-mesenchymal transition (EMT) in experimental BA was explored by constructing BA mouse models via Rhesus rotavirus vaccine infection. miR-29c and miR-129-5p expression was analyzed by real-time quantitative polymerase chain reaction. EMT was established by induction with transforming growth factor (TGF)-ß1. miR-29c and miR-129-5p were overexpressed and inhibited, respectively, by Lipofectamine transfection. EMT-related protein (formin-like 2, FMNL2; E-cadherin; vimentin; and cytokeratin-19, CK-19) expression was analyzed by western blot and immunofluorescent assay. The results indicated that miR-29c and miR-129-5p were downregulated and upregulated in BA mice. TGF-ß1 induction caused a time-dependent decrease and increase in miR-29c and miR-129-5p, respectively. Additionally, TGF-ß1 induced an increase in FMNL2 and vimentin expression and a decrease in E-cadherin and CK-19 expression (P < 0.05). Overexpression or suppression of miRNA-29c or miR-129-5p, respectively, induced the inhibition of FMNL2 and vimentin, and promotion of E-cadherin and CK-19 expression, in the test groups compared to the non-intervention group (P < 0.05). However, the FMNL2, vimentin, E-cadherin, and CK- 19 expression did not differ between the control and non-intervention groups (P > 0.05). Thus, miR-29c upregulation or miR-129-5p downregulation effectively prevented EMT in BA by regulating the expression of EMT pathway-related proteins. Therefore, miR-29c and miR-129-5p could be utilized as therapeutic targets for BA in the future.
Assuntos
Atresia Biliar/genética , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , MicroRNAs/genética , Fator de Crescimento Transformador beta1/farmacologia , Animais , Animais Recém-Nascidos , Ductos Biliares/efeitos dos fármacos , Ductos Biliares/metabolismo , Ductos Biliares/patologia , Atresia Biliar/etiologia , Atresia Biliar/metabolismo , Atresia Biliar/patologia , Caderinas/genética , Caderinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Forminas , Regulação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Queratina-19/genética , Queratina-19/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , Cultura Primária de Células , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/efeitos adversos , Transdução de Sinais , Vimentina/genética , Vimentina/metabolismoRESUMO
Activity of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, is influenced by mutations in the corresponding gene, contributing to a decrease in 5,10-MTHF. Due to such polymorphisms, individuals differ in MTHFR enzyme activity and plasma folate levels. We investigated the relationship between two common MTHFR polymorphisms (C677T and A1298C) and breast cancer (BC) chemotherapy response. From February 2013 to January 2016, 148 advanced BC patients at the Center Hospital of Cangzhou were enrolled and treated with six different chemotherapy regimens. Subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Forty-one (27.7%), 70 (47.3%), and 37 (25.0%) patients carried the C/C, C/T, and T/T C677T genotypes, respectively; 101 (68.2%), 42 (28.4%), and 5 (3.4%) had the A/A, A/C, and C/C genotypes of A1298C, respectively. Total chemotherapy efficacy was 66.9% (99/148), with 7 (4.7%), 92 (62.2%), 36 (24.3%), and 13 (8.8%) cases showing complete response, partial response, no change, and progressive disease, respectively. Chemotherapy regimens did not differ in effectiveness (P > 0.05). Efficacy rates associated with C677T C/C, C/T, and T/T genotypes were 58.5, 58.6, and 91.9%, respectively, with T/T carriers exhibiting significantly better responses than the C/C (P < 0.05) and C/T groups (P < 0.05). Effectiveness among A1298C A/A, A/C, and C/C carriers was 70.6, 64.3, and 0.0%, respectively, but no difference was established between these genotypes in this regard (P > 0.05). The MTHFR C677T genotype may be associated with BC chemotherapy response, and could be of great value in guiding individualized treatment for this disease.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Adulto , Idoso , Neoplasias da Mama/enzimologia , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The aim of the current study was to investigate survivin expression in congenital choledochal cysts (CCCs), and its associations with clinical parameters of CCCs. In total, 121 children with CCCs were included in this study as the case group, and their cysts were staged according to the Todani classification system. Additionally, 49 normal gallbladder specimens from healthy children were included as the control group. Survivin detection was conducted using immunohistochemical staining. Associations between positive survivin expression and clinical parameters of CCCs were then analyzed. Positive survivin expression was observed in the cytoplasm, and was seen as granular with yellow or dark brown staining. In the case group, positive survivin expression was detected in most tissues. Specifically, compared to that of normal tissues, the cystic-shaped and fusiform-shaped CCC tissues had significantly higher positive survivin expression rates (all P < 0.05). Importantly, positive survivin expression was also shown to be significantly associated with gender and histological type (both P < 0.05). In conclusion, increased survivin expression was observed in CCC tissues, and was correlated with certain clinical parameters of CCCs, suggesting a possible prognostic value of survivin for CCC progression.
Assuntos
Cisto do Colédoco/genética , Proteínas Inibidoras de Apoptose/genética , Biomarcadores/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Cisto do Colédoco/metabolismo , Cisto do Colédoco/patologia , Feminino , Vesícula Biliar/metabolismo , Humanos , Lactente , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , SurvivinaRESUMO
In bioinformatics, sequence alignment is one of the most common problems. Multiple sequence alignment is an NP (nondeterministic polynomial time) problem, which requires further study and exploration. The chaos optimization algorithm is a type of chaos theory, and a procedure for combining the genetic algorithm (GA), which uses ergodicity, and inherent randomness of chaotic iteration. It is an efficient method to solve the basic premature phenomenon of the GA. Applying the Logistic map to the GA and using chaotic sequences to carry out the chaotic perturbation can improve the convergence of the basic GA. In addition, the random tournament selection and optimal preservation strategy are used in the GA. Experimental evidence indicates good results for this process.
Assuntos
Algoritmos , Alinhamento de Sequência/métodos , Análise de Sequência de DNA/métodos , Dinâmica não LinearRESUMO
El principal objetivo de este trabajo es brindar las bases para un esfuerzo coordinado con el fin de crear capacidad de análisis de riesgos para la inocuidad de los alimentos en la región de América Latina y el Caribe (ALC) reuniendo a organizaciones internacionales (Organización Panamericana de la Salud-OPS, Organización de las Naciones Unidas para la Alimentación y la Agricultura -FAO e Instituto Interamericano de Cooperación para la Agricultura-IICA) y universidades (Universidad de Nebraska-Lincoln, Universidad de Maryland, Universidad de Minnesota y Universidad Tecnológica de Texas) mediante la Alianza Estratégica para la Creación de Capacidades en Análisis de Riesgos para la Inocuidad de los Alimentos (AECAR). Esperamos que este trabajo, creado por la alianza, logre: a) generar confianza y fortalecer la comunicación entre todas las organizaciones que trabajan en la región; b) proporcionar las bases para enfoques coordinados, consistentes y efectivos para crear capacidad y desarrollar programas de estudio; y c) facilitar la implementación del marco para análisis de riesgos en la región. Este trabajo presenta los recursos actuales de los autores, considera algunos ejemplos exitosos de implementación de análisis de riesgos en la región (de los sectores académicos y gubernamentales), los desafíos experimentados al implementar el análisis de riesgos, y una hoja de ruta para la creación de capacidad propuesta por esta alianza para ampliar la adopción de análisis de riesgos en la región.
The main goal of this paper is to provide the foundation for a coordinated effort for food safety risk analysis capacity building in the Latin American and Caribbean (LAC) region by bringing together international organizations (Panamerican Health Organization-PAHO, Food and Agriculture Organization of the United Nations-FAO and the Interamerican Institute for Cooperation in Agriculture-IICA) and universities (University of Nebraska-Lincoln, University of Maryland, University of Minnesota and Texas Tech University) through the Strategic Alliance in Risk Analysis Capacity Building (SARAC). We expect that this paper, authored by the alliance, will: a) build trust and strengthen communication among all the organizations that work in the region; b) provide the foundation for coordinated, consistent, and effective approaches to capacity building and curriculum development; and c) facilitate the implementation of the risk analysis framework within the region. This paper provides the current resources by the authors, discusses some successful examples of risk analysis implementation in the region (from academia and government sectors), the challenges experienced on implementing risk analysis and a capacity building roadmap proposed by this alliance to enhance the adoption of risk analysis in the region.
Assuntos
Inocuidade dos Alimentos , Gestão de Riscos , Gestão de Riscos , Inocuidade dos Alimentos , AméricaRESUMO
This study aimed to evaluate the long-term survival and risk factors of traditional open surgical repair (OSR) vs thoracic endovascular aneurysm repair (TEVAR) for complicated type-B aortic dissection (TBAD). A total of 118 inpatients (45 OSR vs 73 TEVAR) with TBAD were enrolled from January 2004 to January 2015. Kaplan-Meier curves and Cox proportional hazards analysis were performed to identify the long-term survival rate and independent predictors of survival, respectively. Meta-analysis was used to further explore the long-term efficacy of OSR and TEVAR in the eight included studies using Review Manager 5.2 software. An overall 10-year survival rate of 41.9% was found, and it was similar in the two groups (56.7% OSR vs 26.1% TEVAR; log-rank P=0.953). The risk factors of long-term survival were refractory hypertension (OR=11.1; 95%CI=1.428-86.372; P=0.021] and preoperative aortic diameter >55 mm (OR=4.5; 95%CI=1.842-11.346; P=0.001). Long-term survival rate did not differ significantly between OSR and TEVAR (hazard ratio=0.87; 95%CI=0.52-1.47; P=0.61). Compared with OSR, TEVAR did not show long-term advantages for patients with TBAD. Refractory hypertension and total aortic diameter >55 mm can be used to predict the long-term survival of TBAD in the Chinese Han population.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/métodos , Doença Aguda , Adulto , Idoso , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/mortalidade , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Hipertensão/complicações , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
This study was designed to investigate and compare the HPV prevalence, genotypes distribution and associated risk factors in rural and urban women living in Xishuang Banna district, in the province of Yunnan. A total of 177 and 190 women from rural and urban areas were engaged, respectively. HPV DNA was amplified using the L1 consensus primers system (MY09/11 and GP5/6) and HPV GenoArray test was conducted for genotyping. Proportions were compared by chi-square test, and logistic regression was used to evaluate risk factors. A total of 54 women were positive for HPV DNA. Among rural women, 23 women were positive for HPV infection, of which 21 showed a single infection and 2 had a multiple infection. HPV-16 (10/23) was the most prevalent genotype followed by HPV-52 (5/23), and HPV-58 (5/23). Urban women had a higher infection rate for overall HPV (31/54) and for multiple genotype infection (8/31). HPV-52 (9/31) was the most prevalent genotype followed by HPV-39 (7/31) and HPV-68 (5/31). The age-specific HPV prevalence was also different between rural and urban women. In urban area, women with age <35 years had the highest HPV prevalence, which declined thereafter as age advanced. However, in rural women the highest HPV prevalence was observed in an older age group (>56 years). Ethnicity, smoking and parity were significantly associated with HPV infection among urban women. Our study demonstrates that HPV prevalence and genotype distribution varies among women from rural and urban areas in the south of Yunnan.
Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Fatores Etários , China/epidemiologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Papillomaviridae/patogenicidade , Reação em Cadeia da Polimerase , Prevalência , Medição de Risco , Fatores de Risco , Distribuição por SexoRESUMO
The aim of the current study was to explore the correlation between serum homocysteine (HCY) levels and the methylene tetrahydrofolate reductase (MTHFR) gene 677C/T polymorphism and coronary heart disease (CHD). We consecutively enrolled 208 patients with CHD confirmed by CTA or coronary angiography from our hospital. An additional 200 healthy volunteers were enrolled as the control group. Serum HCY levels, MTHFR C677T genotype, and other related indicators were evaluated for the two groups. Compared to those in the control group, the serum HCY levels in the CHD patients were significantly higher (P < 0.05). The proportion of individuals with the heterozygous MTHFR CT genotype and homozygous mutant TT genotype among CHD patients was significantly higher than that in the control group (P < 0.05). In the acute coronary syndrome (ACS) subgroup, the proportion of those with the CT and TT genotypes was significantly higher than that of the stable CHD subgroup (P < 0.05). In summary, serum HCY levels were elevated in CHD patients, and the frequency of the CT and TT genotypes were also significantly increased, especially among the ACS subgroup. Taken together, this suggests that serum HCY levels and MTHFR C677T genotypes are correlated with CHD.