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1.
Fish Physiol Biochem ; 50(2): 635-651, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38165563

RESUMO

Largemouth bass (Micropterus salmoides) were fed with three diets containing 6%, 12%, and 18% wheat starch for 70 days to examine their impacts on growth performance, glucose and lipid metabolisms, and liver and intestinal health. The results suggested that the 18% starch group inhibited the growth, and improved the hepatic glycogen content compared with the 6% and 12% starch groups (P < 0.05). High starch significantly improved the activities of glycolysis-related enzymes, hexokinase (HK), glucokinase (GK), phosphofructokinase (PFK), and pyruvate kinase (PK) (P < 0.05); promoted the mRNA expression of glycolysis-related phosphofructokinase (pfk); decreased the activities of gluconeogenesis-related enzymes, pyruvate carboxylase (PC), and phosphoenolpyruvate carboxykinase (PEPCK); and reduced the mRNA expression of gluconeogenesis-related fructose-1,6-bisphosphatase-1(fbp1) (P < 0.05). High starch reduced the hepatic mRNA expressions of bile acid metabolism-related cholesterol hydroxylase (cyp7a1) and small heterodimer partner (shp) (P < 0.05), increased the activity of hepatic fatty acid synthase (FAS) (P < 0.05), and reduced the hepatic mRNA expressions of lipid metabolism-related peroxisome proliferator-activated receptor α (ppar-α) and carnitine palmitoyltransferase 1α (cpt-1α) (P < 0.05). High starch promoted inflammation; significantly reduced the mRNA expressions of anti-inflammatory cytokines transforming growth factor-ß1 (tgf-ß1), interleukin-10 (il-10), and interleukin-11ß (il-11ß); and increased the mRNA expressions of pro-inflammatory cytokine tumor necrosis factor-α (tnf-α), interleukin-1ß (il-1ß), and interleukin-8 (il-8) in the liver and intestinal tract (P < 0.05). Additionally, high starch negatively influenced the intestinal microbiota, with the reduced relative abundance of Trichotes and Actinobacteria and the increased relative abundance of Firmicutes and Proteobacteria. In conclusion, low dietary wheat starch level (6%) was more profitable to the growth and health of M. salmoides, while high dietary starch level (12% and 18%) could regulate the glucose and lipid metabolisms, impair the liver and intestinal health, and thus decrease the growth performance of M. salmoides.


Assuntos
Bass , Glucose , Animais , Glucose/metabolismo , Amido/farmacologia , Bass/fisiologia , Triticum/metabolismo , Metabolismo dos Lipídeos , Dieta/veterinária , Fígado/metabolismo , Carboidratos da Dieta/metabolismo , Lipídeos , Fosfofrutoquinases/metabolismo , RNA Mensageiro/metabolismo
2.
Sci Rep ; 13(1): 2887, 2023 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-36807368

RESUMO

Many people eat polished rice, while rice bran, a by-product known to be rich in protein and expected to have potential functions for health benefits, has not been effectively utilized. In this study, we determined that orally administered Val-Tyr-Thr-Pro-Gly (VYTPG) derived from rice bran protein improved cognitive decline in mice fed a high-fat diet (HFD). It was demonstrated that VYTPG was released from model peptides corresponding to fragment sequences of original rice proteins (Os01g0941500, Os01g0872700, and allergenic protein) after treatment with thermolysin, a microorganism-derived enzyme often used in industrial scale processes. The thermolysin digest also improved cognitive decline after oral administration in mice. Because VYTPG (1.0 mg/kg) potently improved cognitive decline and is enzymatically produced from the rice bran, we named it rice-memolin. Next, we investigated the mechanisms underlying the cognitive decline improvement associated with rice-memolin. Methyllycaconitine, an antagonist for α7 nicotinic acetylcholine receptor, suppressed the rice-memolin-induced effect, suggesting that rice-memolin improved cognitive decline coupled to the acetylcholine system. Rice-memolin increased the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells and promoted the mRNA expression of EGF and FGF-2 in the hippocampus, implying that these neurotropic factors play a role in hippocampal neurogenesis after rice-memolin administration. Epidemiologic studies demonstrated that diabetes is a risk factor for dementia; therefore, we also examined the effect of rice-memolin on glucose metabolism. Rice-memolin improved glucose intolerance. In conclusion, we identified a novel rice-derived peptide that can improve cognitive decline. The mechanisms are associated with acetylcholine and hippocampal neurogenesis. Rice-memolin is the first rice-brain-derived peptide able to improve cognitive decline.


Assuntos
Oryza , Camundongos , Animais , Termolisina , Acetilcolina , Peptídeos/farmacologia , Cognição , Administração Oral
3.
J Clin Transl Hepatol ; 10(6): 1107-1116, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36381090

RESUMO

Background and Aims: Recognition of excessive activation of hepatic stellate cells (HSCs) in liver fibrosis prompted us to investigate the regulatory mechanisms of HSCs. We aimed to examine the role of O-GlcNAcylation modification of alanine, serine, cysteine transporter 2 (ASCT2) in HSCs and liver fibrosis. Methods: The expression of O-GlcNAcylation modification in fibrotic mice livers and activated HSCs was analyzed by western blotting. Immunoprecipitation was used to assess the interaction of ASCT2 and O-GlcNAc transferase (OGT). In addition, ASCT2 protein stability was assayed after cycloheximide (CHX) treatment. The O-GlcNAcylation site of ASCT2 was predicted and mutated by site-directed mutagenesis. Real-time PCR, immunofluorescence, kit determinations and Seahorse assays were used to clarify the effect of ASCT2 O-GlcNAcylation on HSC glutaminolysis and HSC activation. Western blotting, immunochemistry, and immunohistofluorescence were used to analyze the effect of ASCT2 O-GlcNAcylation in vivo. Results: We observed significantly increased O-GlcNAcylation modification of ASCT2. ASCT2 was found to interact with OGT to regulate ASCT2 stability. We predicted and confirmed that O-GlcNAcylation of ASCT2 at Thr122 site resulted in HSCs activation. We found Thr122 O-GlcNAcylation of ASCT2 mediated membrane trafficking of glutamine transport and attenuated HSC glutaminolysis. Finally, we validated the expression and function of ASCT2 O-GlcNAcylation after injection of AAV8-ASCT2 shRNA in CCl4-induced liver fibrosis mice in vivo. Conclusions: Thr122 O-GlcNAcylation regulation of ASCT2 resulted in stability and membrane trafficking-mediated glutaminolysis in HSCs and liver fibrosis. Further studies are required to assess its role as a putative therapeutic target.

4.
Fish Shellfish Immunol ; 128: 651-663, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36028056

RESUMO

A 56-day feeding trial was conducted to examine the preventive and reparative functions of host-associated probiotics against high soybean meal (SM)-induced negative effects in Japanese seabass (Lateolabrax japonicus). Fish continuously fed low SM (containing 16% SM) and high SM (containing 40% SM) diets were named as positive (PC) and negative (C) control, respectively. Preventive functions of probiotics were evaluated by continuously feeding diets LF3 (Lactococcus petauri LF3 supplemented in high SM diet, group PLF3) and LF4 (Bacillus siamensis LF4 supplemented in high SM diet, group PLF4), while reparative functions were estimated by feeding the high SM diet during 0-28 days, then feeding diets LF3 (group RLF3) and LF4 (group RLF4) until day 56. Compared with the group PC, suppressed growth and immunity, and damaged intestinal health were observed in the group C on days 28 and 56. Fish in groups PLF3 and PLF4, rather than in groups RLF3 and RLF4, showed higher growth compared with the group C and displayed similar immune status to the group PC, indicating that the initial and continued application of probiotic LF3 and LF4 can efficiently improve high SM induced growth and immune deficiency in Japanese seabass, but probiotics had limited reparative benefits when they were administrated at the middle of the feeding trial (28 d). Furthermore, probiotics showed good preventive functions and limited reparative functions on gut health via improving intestinal morphology and inflammation markers, for example, decreasing diamine oxidase activity and d-lactate content, while up-regulating anti-inflammatory TGF-ß1 expression and down-regulating pro-inflammatory TNF-α, IL-1ß, and IL-8 expressions. Moreover, dietary supplementation of probiotics (especially on day 56) could effectively shape the gut microbiota, such as significantly decreasing abundances of opportunistic pathogens (phylum Actinobacteria, genera Pseudomonas and Moheibacter on day 28, phylum Proteobacteria, genus Plesiomonas on day 56), significantly increasing gut microbial diversity and abundances of possible beneficial bacteria (phylum Bacteroidetes and genus Lactobacillus on day 28, phyla Firmicutes, Bacteroidetes and Cyanobacteria, genera Bacillus, Lactobacillus and Bacteroides on day 56). In conclusion, we evidenced for the first time that host-associated L. petauri LF3 and B. siamensis LF4 can provide effectively preventive and certain reparative functions against high SM-induced adverse effects in L. japonicus.


Assuntos
Amina Oxidase (contendo Cobre) , Probióticos , Ração Animal/análise , Animais , Dieta/veterinária , Interleucina-8 , Lactatos , Lactobacillus , Probióticos/farmacologia , Glycine max , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfa
5.
Phytomedicine ; 104: 154291, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35839735

RESUMO

BACKGROUND: Triple-negative breast carcinomas (TNBCs) are a breast carcinoma with the most aggressive form, which is demonstrated as enhanced invasion and recurrence. Britannin is extracted mainly from the traditional Chinese herb Inula japonica Thunb, and few studies have focused on its effect on TNBC. Moreover, there is still no report concerning the role of Britannin in degrading the transcripts of Zinc finger E-box-binding homeobox 1 (ZEB1) proteins. PURPOSE: To explore the potential effect of Britannin on invasion and stemness of TNBCs and its underlying mechanism. METHODS: Cellular activity was measured using MTT, and cell cycle was measured using flow cytometry (FCM). The effect of Britannin on the migrating and invading abilities of MDA-MB-231 and 4T1 cells were measured using the wound healing and transwell assays. The sizes and number of breast carcinoma cells were measured by tumor formation assay and in vitro limiting-dilution assay. CD44 expression in tumor spheroids was tested by immunofluorescence assay. Nextly, the expressions of epithelial-mesenchymal transition (EMT) markers and ZEB1 protein expressional level were detected by western blot . ZEB1 mRNA expressional level was analyzed using RT-qPCR. Drug affinity-responsive target stability (DARTS) method was used to detect the binding activity between Britannin and ZEB1. Co-immunoprecipitation (Co-IP) analysis was applied to test the ubiquitination of ZEB1. The mouse models for experimental lung metastasis of 4T1 cells were established to detect the anti-metastasis effect of Britannin in vivo, and the expressional levels of EMT markers in lung metastases were detected by immunohistochemistry. RESULTS: Britannin could inhibit cell growth and G2/M arrest in TNBC cells. Britannin could inhibit the migrating and invading ability without inducing severe apoptosis of MDA-MB-231 and 4T1 cells. Meanwhile, Britannin reduced the size and number of spheroids formed in these two cells, and decreased the expressional level of stem cells biomarker CD44 in tumor spheroids. Mechanism research showed that Britannin specifically bound to ZEB1 and induced its ubiquitination in MDA-MB-231 cells. Afterwards, Britannin disturbed protein stability and promoted ZEB1 protein degradation. Importantly, Britannin could not inhibit cell invasion and spheroid formation after ZEB1 expression was knocked down. Finally, Britannin inhibition of 4T1 cell metastasis was confirmed through establishing mouse models for the experimental lung metastasis. It was proved that both Britannin and paclitaxel could decrease the lung metastases, and Britannin could also down-regulate the protein expressional levels of ZEB1, MMP9 and CD44. CONCLUSION: This study reveals that Britannin suppresses the invasion and metastasis of TNBC cells through degrading ZEB1, which suggests that Britannin can be used to prevent tumor metastasis and recurrence via degrading ZEB1proteins.


Assuntos
Neoplasias Pulmonares , Neoplasias de Mama Triplo Negativas , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/genética , Pontos de Checagem da Fase G2 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Lactonas , Neoplasias Pulmonares/metabolismo , Camundongos , Sesquiterpenos , Neoplasias de Mama Triplo Negativas/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
6.
IUBMB Life ; 74(6): 508-518, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35294085

RESUMO

Hypertrophic scar (HS) is a condition characterized by excessive synthesis and deposition of collagen. There are many clinical methods to alleviate HS, but most of them are accompanied by many complications. To investigate the effects of ß-Elemene, extracted from the ginger family plant Wenyujin, on human hypertrophic scar fibroblast (hHSFs). Cultured hHSFs and human normal fibroblasts, observed the effect of ß-Elemene on apoptosis, extracellular matrix, and endoplasmic reticulum stress (ERS) by western blot, Real Time-Polymerase Chain Reaction (RT-PCR), and flow cytometry. Based on our findings, it is clear that ß-Elemene could inhibit the expression of α-smooth muscle actin (α-SMA), collagen I, and fibronectin, reduced collagen deposition. Further studies had found that ß-Elemene could increase the expression of ERS-related proteins CHOP and Calnexin in a dose-dependent manner, thereby promoting the aggregation of cleaved-caspase-3 and inducing hHSFs to undergo poptosis. This process may depend on the regulation of P53. The results of our study indicates that ß-Elemene induced hHSFs to undergo apoptosis though ERS pathway in a P53-dependent manner, which means that our research provided a new strategy for the development of drugs for the treatment of HS.


Assuntos
Cicatriz Hipertrófica , Apoptose , Células Cultivadas , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/metabolismo , Colágeno/metabolismo , Fibroblastos , Humanos , Sesquiterpenos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
7.
Oxid Med Cell Longev ; 2021: 3456725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925691

RESUMO

Relevant researches have recognized the vital role of inducing ferroptosis in the treatment of tumor. The latest findings indicate that PEBP1/15-LO can play an essential role in the process of cell death. However, its role in regulating ferroptosis in hepatocellular carcinoma (simplified by HCC) remains unclear. The previous research of our team has proved that DHA can induce ferroptosis of hepatic stellate cells. In this study, we found that DHA could also induce ferroptosis in HCC cells. Interestingly, DHA induced ferroptosis by promoting the formation of PEBP1/15-LO and promoting cell membrane lipid peroxidation. In addition, we also found that DHA had no obvious regulatory effect on 15-LO, but it could promote PEBP1 protein expression. Importantly, we discovered the upregulation of PEBP1 induced by DHA was related to the inhibition of its ubiquitination degradation. In vivo experiments have also obtained consistent results that DHA can inhibit tumor growth and affect the expression of ferroptosis markers in tumor tissues, which would be partially offset by interference with PEBP1.


Assuntos
Araquidonato 15-Lipoxigenase/metabolismo , Artemisininas/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Ferroptose , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Animais , Antimaláricos/farmacologia , Apoptose , Araquidonato 15-Lipoxigenase/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína de Ligação a Fosfatidiletanolamina/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Front Oncol ; 11: 639909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816284

RESUMO

BACKGROUND: To evaluate the value of pretreatment inflammatory-nutritional biomarkers in predicting responses to neoadjuvant chemoradiotherapy (nCRT) and survival in patients with locally advanced rectal cancer (LARC). METHODS: Patients with LARC who underwent nCRT and subsequent surgery between October 2012 and December 2019 were considered for inclusion. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and prognostic nutritional index (PNI) were calculated from according to routine laboratory data within 1 week prior to nCRT. The correlations between baseline inflammatory-nutritional biomarkers and responses were analyzed using Chi-square test or Fisher's exact test, and multivariate logistic regression analysis was performed to identify the independent predictors of pathological responses to nCRT. Univariate and multivariate Cox proportional hazard models were used to assess the correlations of predictors with disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 273 patients with LARC were enrolled in this study. Higher LMR and PNI were observed in the good-response group, meanwhile higher NLR and PLR were observed in the poor-response group. Multivariate logistic regression analysis results revealed that PLR and PNI independently predicted responses to nCRT. Multivariable Cox regression analysis determined that PNI was an independent predictor of DFS and OS in patients with LARC. The value of pretreatment PNI in predicting responses and survival was continuously superior to those of NLR, PLR, and LMR. The optimal cutoff value of the PNI was approximate 45. Subgroup analyses indicated that the pathological responses and survival in the high PNI group (≥ 45) were significantly better than those in the low PNI group (< 45), especially in patients with clinical stage III rectal cancer. CONCLUSION: The pretreatment PNI can serve as a promising predictor of response to nCRT and survival in patients with LACR, which is superior to NLR, PLR, and LMR, and the patients with clinical stage III rectal cancer who have a higher PNI are more likely to benefit from nCRT.

9.
Drug Des Devel Ther ; 14: 3815-3826, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061289

RESUMO

PURPOSE: To evaluate the effects of quercetin on proliferation, invasion and migration of endometrial stromal cells (ESCs) from adenomyosis patients. METHODS: Primary ectopic ESCs (EESCs) and eutopic ESCs (EuESCs) were obtained and purified from patients undergoing total hysterectomy for adenomyosis and identified by immunocytochemistry staining. The cytotoxicity and inhibition rate were determined by CCK-8 assay to obtain the IC50 value. Cell proliferative, migratory, and invasive abilities were detected by BrdU, wound scratch, transwell assays, respectively. Western blot analysis was employed to explore the effects of quercetin on the expression of MMP-2, MMP-9, Ezrin and Fascin proteins in cells. RESULTS: Both EESCs and EuESCs were characterized with strongly positive staining for vimentin and almost negative for cytokeratin. Quercetin inhibited the viability of EESCs and EuESCs in a dose- and time-dependent manner, with an IC50 = 33.00 µM for EuESCs and IC50 = 74.88 µM for EESCs at 72 h. Thus, the final concentrations and action time of quercetin in EuESCs (0, 20, 40, and 80 µM for 72 h) and EESCs (0, 40, 80, and 160 µM for 72 h) were selected. BrdU assay showed that quercetin dose-dependently suppressed the proliferation of EESCs and EuESCs, while the inhibition rate in EESCs was higher. Similarly, administration of quercetin in EESCs and EuESCs significantly decreased the motility and invasiveness in a dose-dependent fashion, with stronger inhibitory effects on EESCs. Finally, Western blot analysis demonstrated that invasion- and migration-related proteins (MMP-2, MMP-9, Erzin, and Fascin) were significantly downregulated with the quercetin concentration increasing. Moreover, the decreased level of these proteins in EESCs under quercetin exposure was greater than that in EuESCs. CONCLUSION: Quercetin can inhibit the proliferation of EESCs in adenomyosis and reduce their mobility and invasiveness. These inhibitory effects may be related to the downregulation of MMP-2, MMP-9, Fascin, and Erzin proteins.


Assuntos
Adenomiose/tratamento farmacológico , Endométrio/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Adenomiose/metabolismo , Adenomiose/patologia , Adulto , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Endométrio/metabolismo , Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Quercetina , Células Estromais/metabolismo , Células Estromais/patologia
10.
Acta Biochim Biophys Sin (Shanghai) ; 52(10): 1131-1139, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33085742

RESUMO

Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Southeast Asia. Nowadays, radiotherapy is the therapy of choice for NPC patients, and chemotherapy has been found as an alternative treatment for advanced NPC patients. However, finding novel drugs and pharmacologically therapeutic targets for NPC patients is still urgent and beneficial. Our study showed that BIX-01294 (BIX) can induce autophagic vacuoles formation and conversion of LC3B-I to LC3B-II in NPC cells in both dose- and time-dependent manners. Notably, the combination of BIX and chemotherapeutic drugs significantly decreased the cell viability and increased the lactate dehydrogenase release. Meanwhile, BIX plus cis-platinum (Cis) treatment induced pyroptosis in NPC cells as featured by cell swelling and bubble blowing from the plasma membrane, the increased frequency of annexin V and propidium iodide (PI) double-positive cells, as well as the cleavage of gasdermin E (GSDME) and caspase-3. Moreover, the deficiency of GSDME completely shifted pyroptosis to apoptosis. Furthermore, the inhibition of autophagy by chloroquine and the knockout of ATG5 gene significantly blocked the BIX-induced autophagy as well as pyroptosis in both in vitro and in vivo studies. Our data demonstrated that BIX-combined chemotherapeutic drugs could induce the Bax/caspase-3/GSDME-mediated pyroptosis through the activation of autophagy to enhance the chemosensitivity in NPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Autofagia/efeitos dos fármacos , Azepinas/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Piroptose/efeitos dos fármacos , Quinazolinas/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Proteína 5 Relacionada à Autofagia/genética , Azepinas/administração & dosagem , Sistemas CRISPR-Cas , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cloroquina/administração & dosagem , Cloroquina/farmacologia , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Técnicas de Inativação de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Associadas aos Microtúbulos/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Quinazolinas/administração & dosagem , Receptores de Estrogênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
11.
J Appl Clin Med Phys ; 20(10): 24-32, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31460704

RESUMO

The purpose of this study was to investigate the potential advantages of the fixed-jaw technique (FJT) over the conventional split-field technique (SFT) for cervical and upper thoracic esophageal cancer (EC) patients treated with intensity-modulated radiotherapy. The SFT and FJT plans were generated for 15 patients with cervical and upper thoracic EC. Dosimetric parameters and delivery efficiency were compared. An area ratio (AR) of the jaw opening to multileaf collimator (MLC) aperture weighted by the number of monitor units (MUs) was defined to evaluate the impact of the transmission through the MLC on the dose gradient outside the PTV50.4, and the correlation between the gradient index (GI) and AR was analyzed. The FJT plans achieved a better GI and AR (P < 0.001). There was a positive correlation between the GI and AR in the FJT (r = 0.883, P < 0.001) and SFT plans (r = 0.836, P < 0.001), respectively. Moreover, the mean dose (Dmean ), V5Gy -V40Gy for the lungs and the Dmean , V5Gy -V50Gy for the body-PTV50.4 in the FJT plans were lower than those in the SFT plans (P < 0.05). The FJT plans demonstrated a reduction trend in the doses to the spinal cord PRV and heart, but only the difference in the heart Dmean reached statistical significance (P < 0.05). The FJT plans reduced the number of MUs and subfields by 5.5% and 17.9% and slightly shortened the delivery time by 0.23 min (P < 0.05). The gamma-index passing rates were above 95% for both plans. The FJT combined with target splitting can provide superior organs at risk sparing and similar target coverage without compromising delivery efficiency and should be a preferred intensity-modulated radiotherapy planning method for cervical and upper thoracic EC patients.


Assuntos
Neoplasias Esofágicas/radioterapia , Arcada Osseodentária/fisiologia , Órgãos em Risco/efeitos da radiação , Melhoria de Qualidade , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/normas , Neoplasias Torácicas/radioterapia , Idoso , Algoritmos , Humanos , Arcada Osseodentária/efeitos da radiação , Registro da Relação Maxilomandibular , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
12.
J Transl Med ; 16(1): 46, 2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29490660

RESUMO

BACKGROUND: The role of transforming growth factorß (TGF-ß)-induced tumor progression in advanced malignancy is well established, but the involvement of long non-coding RNAs (lncRNAs) in TGF-ß signaling remains unclear. This study aimed to identify TGF-ß-associated lncRNAs in head and neck squamous cell carcinoma (HNSCC). METHODS: Expression profiling of lncRNAs was obtained using Gene Expression Omnibus and The Cancer Genome Atlas. Real-time quantitative PCR was used to analyze the expression of EPB41L4A-AS2 in HNSCC cell line. We used bioinformatics resources (DAvID) to conduct Gene Ontology biological processes and KEGG pathways at the significant level. Wound healing assay, cell migration and invasion assays, were used to examine the effects of EPB41L4A-AS2 on tumor cell metastasis in vivo. Protein levels of EPB41L4A-AS2 targets were determined by western blot. RESULTS: A novel TGF-ß-associated lncRNA, EPB41L4A-AS2, was found downregulated by TGF-ß and associated with invasion and metastasis. The relationship of EPB41L4A-AS2 with the clinicopathological features and prognosis of HNSCC patients was evaluated. Bioinformatic analyses revealed that EPB41L4A-AS2 may be involved in processes associated with the tumor-associated signaling pathway, especially the TGF-ß signaling pathway. Furthermore, a TGF-ß-induced epithelial-to-mesenchymal transition (EMT) model was established. Low EPB41L4A-AS2 expression was determined, and overexpression of this gene inhibited cell migration and invasion in the EMT model. Moreover, EPB41L4A-AS2 suppressed TGFBR1 expression. CONCLUSIONS: EPB41L4A-AS2 might serve as a negative regulator of TGF-ß signaling and as an effective prognostic biomarker and important target in anti-metastasis therapies of HNSCC patients.


Assuntos
Biologia Computacional/métodos , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Fator de Crescimento Transformador beta/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Genéticos , Invasividade Neoplásica , Metástase Neoplásica , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida , Regulação para Cima/genética
13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 40(4): 301-4, 2016.
Artigo em Chinês | MEDLINE | ID: mdl-29775532

RESUMO

Objective: To improve the efficiency and accuracy of extraction and analysis of dosimetry data in radiotherapy plans for a batch of patients. Methods: With the interface function provided in Matlab platform, a program was written to extract the dosimetry data exported from treatment planning system in DICOM RT format and exported the dose-volume data to an Excel file with the SPSS compatible format. This method was compared with manual operation for 14 gastric carcinoma patients to validate the efficiency and accuracy. Results: The output Excel data were compatible with SPSS in format, the dosimetry data error for PTV dose interval of 90%-98%, PTV dose interval of 99%-106% and all OARs were -3.48E-5 ± 3.01E-5, -1.11E-3 ± 7.68E-4, -7.85E-5 ± 9.91E-5 respectively. Compared with manual operation, the time required was reduced from 5.3 h to 0.19 h and input error was reduced from 0.002 to 0. Conclusion: The automatic extraction of dosimetry data in DICOM RT format for batch patients, the SPSS compatible data exportation, quick analysis were achieved in this paper. The efficiency of clinical researches based on dosimetry data analysis of large number of patients will be improved with this methods.


Assuntos
Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Radiometria , Radioterapia de Intensidade Modulada
14.
Clin Imaging ; 38(5): 611-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24993640

RESUMO

OBJECTIVES: To increase the awareness on intracranial papillary meningiomas (PMs) by presenting magnetic resonance imaging (MRI) findings on this disease. MATERIALS AND METHODS: The MRI findings and clinical presentations of nine discrete lesions in eight patients with pathologically documented PMs were retrospectively analyzed. RESULTS: Most tumors occurred in young adults. The tumors originated from the convexity meninges in five cases and from the parasagittal regions in four cases. The tumor shape was irregular in six cases, lobulated in two cases, and round in one case. By MRI, nine masses were primarily isointense (n=5) or mildly hypointense (n=4) to gray matter on T1-weighted images and inhomogeneous hyperintense (n=3) or isointense (n=6) to the cortex on T2-weighted and fluid-attenuated inversion recovery images. On diffusion-weighted imaging, the signal intensity of the tumor was increased in all lesions compared with the adjacent parenchyma. Tumor and brain interfaces were unclear in seven cases, cyst formation was observed in eight tumors, scattered hemorrhage was observed in three tumors, signal voids due to vessels were visible in four cases, and eight tumors had moderate or marked irregular peritumoral edema. Enhancement was homogeneous (n=2) or heterogeneous (n=7), an area of focal nodular enhancement was observed in three lesions, and the dural tail sign was visible in seven cases. CONCLUSION: Although PM is rare, it should be considered in the differential diagnosis when evaluating intracranial neoplasms. Younger patient age, as well as imaging features such as unclear tumor-brain interface, internal heterogeneity including cyst formation, irregular enhancement, signal voids of vessels, and marked peritumoral edema can help distinguish PM from typical benign meningiomas.


Assuntos
Neoplasias Encefálicas/diagnóstico , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Meningioma/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
15.
J Neuroradiol ; 41(3): 188-94, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24524869

RESUMO

PURPOSE: This study aimed to determine whether the use of apparent diffusion coefficient (ADC) values can improve the diagnostic efficacy of magnetic resonance imaging (MRI) to differentiate hemangiopericytoma (HPC) from angiomatous and anaplastic meningioma. MATERIALS AND METHODS: Preoperative diffusion-weighted imaging (DWI) studies of 38 patients with pathologically proven intracranial HPC (n = 12) and angiomatous (n = 13) or anaplastic meningioma (n = 13) were retrospectively reviewed. ADC values were measured in the tumor parenchyma and peritumoral edema, and used to obtain normalized ADC (NADC) ratios (ADC of tumor/ADC of normal white matter). RESULTS: Mean ADC values were significantly different between HPC and anaplastic meningioma (1.17 ± 0.30 × 10(-3) mm(2)/s and 0.75 ± 0.11 × 10(-3) mm(2)/s, respectively). Mean NADC ratios were also significantly lower in the malignant cases (0.95 ± 0.13) compared with the benign HPCs (1.53 ± 0.39; P < 0.05). Mean ADC values and NADC ratios did not differ significantly between angiomatous meningioma and HPC (P > 0.05), whereas mean ADC values and NADC ratios were lower for anaplastic meningioma than for either angiomatous meningioma or HPC (P < 0.05). Mean ADC value in peritumoral edema in HPC (1.48 ± 0.11 × 10(-3) mm(2)/s) was lower than in either angiomatous (1.73 ± 0.28 × 10(-3) mm(2)/s) or anaplastic (1.72 ± 0.25 × 10(-3) mm(2)/s) meningioma (P < 0.05), and there was no significant difference between ADC values in anaplastic versus angiomatous meningioma (P > 0.05). CONCLUSION: ADC values in tumor parenchyma and peritumoral edema can provide helpful information that is otherwise not available from conventional MRI to differentiate HPC from angiomatous and anaplastic meningioma.


Assuntos
Neoplasias Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Hemangioma Cavernoso/patologia , Hemangiopericitoma/patologia , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Meníngeas/patologia , Meningioma/patologia , Adulto , Idoso , Algoritmos , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
16.
J Comput Assist Tomogr ; 37(5): 658-65, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24045237

RESUMO

INTRODUCTION: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm originating in the central nervous system (CNS), with imaging features currently not well known. The purposes were to describe and characterize clinical features and imaging findings of CNS SFT. METHODS: We retrospectively reviewed computed tomographic (CT; n = 10) and magnetic resonance (MR) images (n = 18) of 22 patients with SFT (13 males and 9 females; mean, 47.6 years) with associated clinical records. RESULTS: Each lesion was found as a solitary, well-defined mass, ranging in size from 12 to 70 mm (mean, 38 mm). The tumor shape was roundlike in 16 cases (72.7%) and irregular in 6 cases (27.2%). The cerebellopontine angle zone was the most affected area (n = 6). On precontrast CT scans, 10 cases showed predominantly hyperattenuation (n = 9) and isoattenuation (n = 1). No lesion contained calcification, and 2 cases showed bone invasions. All 18 tumors examined by MR imaging showed homogeneous hypointensive (n = 5) or isointensive (n = 7) signal intensity and heterogeneous mixed isointense and hypointense signal intensity (n = 6) on T1-weighted images, whereas most tumors were predominantly isointense (n = 13) and hypointense (n = 4) to the cortex on T2-weighted images; on postcontrast CT and MR images, enhancement was marked homogeneous (n = 10) or heterogeneous (n = 12). Fourteen tumors had thickening of the meninges adjacent to the tumor. CONCLUSIONS: Although SFT is a rare neoplasm in the CNS, it should be considered in the differential diagnosis. The most affected area is the cerebellopontine angle zone. Solitary fibrous tumor tends to have some imaging features, such as high attenuation on CT, isointense to hypointense signal intensity on MR images, and marked enhancement.


Assuntos
Neoplasias Encefálicas/diagnóstico , Imageamento por Ressonância Magnética/métodos , Tumores Fibrosos Solitários/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
17.
Childs Nerv Syst ; 28(1): 129-36, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21947034

RESUMO

OBJECT: The purpose of this retrospective study is to determine the clinical characteristics and the prognosis of the spinal meningioma in childhood (under 18 years of age) based on the treatment at our institution. METHODS: Ten spinal meningioma cases in children were treated during the last 9 years. The clinical data was retrospectively analyzed and the results were compared with those in the literature. RESULTS: The series included eight males and two females and the mean age was 13.2 years. The most common initial symptoms were pain (6/10) and the common signs were limb weakness (4/10) and gait disturbance (2/10) and distal paresthesia (1/10) and bladder disturbance (1/10). Four patients had other clinical signs of neurofibromatosis type II (NF-2) such as tumors elsewhere. All the tumors were located in cervical and thoracic vertebrae. Resection according to Simpson Grade I (6/10), II (2/10), III (1/10), and IV (1/10) were performed. Grade II meningiomas accounted for 3/10 in this series. All patients were followed up with mean follow-up period of 43 months. Seven patients had recurrence of the tumor in that period and one had died. CONCLUSIONS: Spinal meningioma is an uncommon pediatric neoplasm and has a poor prognosis. It has a male predominance and is inclined to be associated with NF-2, and those that are associated with higher pathologic subtypes and NF-2 have more unfavorable outcome. Every effort should be made to achieve total removal which may decrease the incidence of recurrence.


Assuntos
Neoplasias Meníngeas/patologia , Meningioma/patologia , Neoplasias da Medula Espinal/patologia , Adolescente , Criança , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Gradação de Tumores , Procedimentos Neurocirúrgicos , Prognóstico , Estudos Retrospectivos , Neoplasias da Medula Espinal/cirurgia
18.
Toxicol In Vitro ; 26(1): 74-80, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22056766

RESUMO

Quercetin, one of the most widely distributed flavonoids in plants, possesses strong free radical scavenging ability and potent hepatoprotective effects. However, the protective effect and mechanism of quercetin on ethanol-induced oxidative damage in hepatocytes remain unclear. In this study, primary rat hepatocytes were incubated with ethanol and quercetin in the presence or absence of ZnPP 9, an antagonist of HO-1 induction. The ethanol-induced hepatotoxicity was found to be greatly diminished by pre-treatment of quercetin and this hepatoprotective effect could be partly blocked by ZnPP 9. This study also showed that quercetin significantly stimulated HO-1 expression at both mRNA and protein levels, then subsequently induced HO-1 activity. To further study the signaling pathways underlying quercetin-induced HO-1 up-regulation, HO-1 expression and activity in cytosolic microsomal fractions and Nrf2 expression in nuclear fractions were analyzed following quercetin or/and MAPK inhibitor(s) as well as PI3K inhibitor incubation for primary rat hepatocytes. These results indicated that ERK was required to induce HO-1 expression in rat hepatocytes. In summary, these data suggested that quercetin attenuates ethanol-induced oxidative stress through a pathway which involves ERK activation and HO-1 upregulation.


Assuntos
Antioxidantes/farmacologia , Etanol/toxicidade , Heme Oxigenase-1/metabolismo , Hepatócitos/efeitos dos fármacos , Quercetina/farmacologia , Animais , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Células Cultivadas , Glutationa/metabolismo , Hepatócitos/metabolismo , L-Lactato Desidrogenase/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
19.
J Comput Assist Tomogr ; 35(6): 667-73, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22082533

RESUMO

OBJECTIVE: To investigate the features of pathologically confirmed gliosarcomas using computed tomography (CT) and magnetic resonance (MR) imaging. METHODS: We retrospectively reviewed the cross-sectional CT and MR images of 54 patients (37 males and 17 females; mean age, 44.5 years; range, 13-74 years) with gliosarcomas confirmed by histopathology. RESULTS: Across all patients, there were 59 lesions. On nonenhanced CT and MR images, tumors were predominantly inhomogeneous. On the postcontrast CT and MR images, 50 (84.7%) irregular lesions had thick walls with a strong rim- and ringlike enhancement, whereas the remaining 9 (15.3%) round or oval lesions had even thin walls with an enhanced peripheral ring. Magnetic resonance spectroscopy showed increased choline and lactate values, along with decreased N-acetylaspartate and creatine values. On diffusion-weighted imaging, the tumor was slightly or markedly hyperintense compared with the white matter. CONCLUSION: A well-demarcated mass located peripherally, with rimlike or ring enhancement, is a common presentation of gliosarcoma on CT and MR images. In addition, magnetic resonance spectroscopy and diffusion-weighted imaging can be used to make a differential diagnosis.


Assuntos
Neoplasias Encefálicas/diagnóstico , Gliossarcoma/diagnóstico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Colina/metabolismo , Meios de Contraste , Creatina/metabolismo , Imagem de Difusão por Ressonância Magnética , Feminino , Gadolínio DTPA , Gliossarcoma/diagnóstico por imagem , Gliossarcoma/metabolismo , Humanos , Iohexol , Lactatos/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Int J Gynaecol Obstet ; 108(2): 135-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19897189

RESUMO

OBJECTIVE: To determine risk factors for recurrent spontaneous abortion (RSA) in women from southern China. METHOD: We looked for associations between RSA and body mass index (BMI), family history of spontaneous abortion, smoking, exposure to environmental tobacco smoke (ETS [also known as passive smoking]), and alcohol and coffee consumption using an unconditional logistic regression model involving 326 patients with RSA and 400 controls. RESULTS: Whereas smoking, alcohol consumption, and coffee consumption were not associated with increased risk of RSA, both short (<1 hour/day) and long (> or =1 hour/day) periods of ETS were associated (adjusted odds ratio [OR], 2.30; 95% confidence interval [CI], 1.50-3.52 and adjusted OR, 4.75; 95% CI, 3.23-6.99, respectively). The increased risk of RSA was significant for participants with a BMI of 24.0 or greater (adjusted OR, 1.54; 95% CI, 1.12-2.14) and those with a family history of miscarriage (adjusted OR, 2.12; 95% CI, 1.28-3.49). CONCLUSION: We found ETS, a higher BMI, and a family history of RSA to be independent risk factors for RSA in our population.


Assuntos
Aborto Habitual/epidemiologia , Aborto Habitual/etiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Cafeína/efeitos adversos , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Fatores de Risco , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto Jovem
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