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BACKGROUND: Gastrointestinal stromal tumors (GISTs) are clinically heterogeneous with various malignant potential in different individuals. It is crucial to explore a reliable method for preoperative risk stratification of gastric GISTs noninvasively. PURPOSE: To establish and evaluate a machine learning model using the combination of computed tomography (CT) morphology, radiomics, and deep learning features to predict the risk stratification of primary gastric GISTs preoperatively. METHODS: The 193 gastric GISTs lesions were randomly divided into training set, validation set, and test set in a ratio of 6:2:2. The qualitative and quantitative CT morphological features were assessed by two radiologists. The tumors were segmented manually, and then radiomic features were extracted using PyRadiomics and the deep learning features were extracted using pre-trained Resnet50 from arterial phase and venous phase CT images, respectively. Pearson correlation analysis and recursive feature elimination were used for feature selection. Support vector machines were employed to build a classifier for predicting the risk stratification of GISTs. This study compared the performance of models using different pre-trained convolutional neural networks (CNNs) to extract deep features for classification, as well as the performance of modeling features from single-phase and dual-phase images. The arterial phase, venous phase and dual-phase machine learning models were built, respectively, and the morphological features were added to the dual-phase machine learning model to construct a combined model. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of each model. The clinical application value of the combined model was determined through the decision curve analysis (DCA) and the net reclassification index (NRI) was analyzed. RESULTS: The area under the curve (AUC) of the dual-phase machine learning model was 0.876, which was higher than that of the arterial phase model or venous phase model (0.813, 0.838, respectively). The combined model had best predictive performance than the above models with an AUC of 0.941 (95% CI: 0.887-0.974) (p = 0.012, Delong test). DCA demonstrated that the combined model had good clinical application value with an NRI of 0.575 (95% CI: 0.357-0.891). CONCLUSION: In this study, we established a combined model that incorporated dual-phase morphology, radiomics, and deep learning characteristics, which can be used to predict the preoperative risk stratification of gastric GISTs.
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BACKGROUND: Glycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay. CASE PRESENTATION: Here, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES). WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother. Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of ß-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive. This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation. After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred. CONCLUSION: The patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.
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Doença de Depósito de Glicogênio Tipo I , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Doença de Depósito de Glicogênio Tipo I/genética , Doença de Depósito de Glicogênio Tipo I/complicações , Doença de Depósito de Glicogênio Tipo I/patologia , Feminino , Adolescente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/complicações , Adenoma/genética , Adenoma/complicações , Adenoma/patologia , Adenoma de Células Hepáticas/genética , Adenoma de Células Hepáticas/complicações , Adenoma de Células Hepáticas/patologia , Inflamação/genética , Inflamação/patologia , Inflamação/complicaçõesRESUMO
Recent studies have indicated that dysregulation of the Hippo/Yes-associated protein (YAP) axis is associated with tumor progression and therapy resistance in various cancer types, including lung adenocarcinoma (LUAD). Understanding the regulation of Hippo signaling in LUAD is of great significance. Elevated levels of TRIB3, a pseudo kinase, have been observed in certain lung malignancies and are associated with an unfavorable prognosis. Our research aims to investigate whether increased TRIB3 levels enhance the malignant characteristics of LUAD cells and tumor progression through its interaction with the Hippo signaling pathway. In this study, we reported a positive correlation between elevated expression of TRIB3 and LUAD progression. Additionally, TRIB3 has the ability to enhance TEAD luciferase function and suppress Hippo pathway activity. Moreover, TRIB3 increases total YAP protein levels and promotes YAP nuclear localization. Mechanistic experiments revealed that TRIB3 directly interacts with large tumor suppressor kinase 1 (LATS1), thereby suppressing Hippo signaling. Moreover, the decrease in METTL3-mediated N6-methyladenosine modification of TRIB3 results in a substantial elevation of its expression levels in LUAD cells. Collectively, our research unveils a novel discovery that TRIB3 enhances the growth and invasion of LUAD cells by interacting with LATS1 and inhibiting the Hippo signaling pathway. TRIB3 may serve as a potential biomarker for an unfavorable prognosis and a target for novel treatments in YAP-driven lung cancer.
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Adenocarcinoma de Pulmão , Proteínas de Ciclo Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Hippo , Neoplasias Pulmonares , Proteínas Serina-Treonina Quinases , Proteínas Repressoras , Animais , Feminino , Humanos , Masculino , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metiltransferases/metabolismo , Metiltransferases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Given the role of chondroitin polymerizing factor (CHPF) in several cancers, we investigated its role in the progression of colorectal cancer (CRC) and its association with NLRP3 inflammasome activation. High expression of CHPF in CRC predicted poor patient prognosis. Using colony formation, EdU staining, wound healing, Transwell invasion, and flow cytometry assays, we revealed that the downregulation of CHPF inhibited the malignant behavior of CRC cells. CHPF promoted NLRP3 inflammasome activation by inducing the MAPK signaling pathway, as evidenced by enhanced expression of Phos-ERK1/2, Phos-MEK1, Phos-MEK2, and NLRP3. Additionally, nuclear factor 1 C-type (NFIC) was revealed as a potential upstream transcription factor of CHPF in the modulation of CRC, and the anti-tumor effects elicited through its knockdown were compromised by CHPF in vitro and in vivo. In summary, we demonstrated that NFIC promoted NLRP3 activation to support CRC development via the CHPF-mediated MAPK signaling.
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Neoplasias Colorretais , Inflamassomos , Humanos , Neoplasias Colorretais/genética , Regulação para Baixo , Sistema de Sinalização das MAP Quinases , Fatores de Transcrição NFI , Proteína 3 que Contém Domínio de Pirina da Família NLR/genéticaRESUMO
Cadmium (Cd) contamination of paddy fields is a global concern, as it can cause the accumulation of Cd in food. To explore the effects of equal application of silicon fertilizers on the bioavailability of cadmium and soil Cd uptake at different growth stages of rice, a field experiment was conducted with five silicon fertilizers under the same silicon dose (225 kg·hm-2). The results revealed that the Cd contents in roots, stems, and leaves increased with the extension of the rice growth stage. The application of silicon fertilizers reduced the Cd contents in roots, stems, and leaves in brown rice by 14.9%, 28.2%, and 12.2%, respectively. Compared with that in the control, the Cd content of brown rice in the SiCaMgFe and SiW treatments was decreased by 21.1% (P<0.05) and 21.2% (P<0.05), respectively. Similarly, Cd content in iron plaque (DCB-Cd) increased with the extension of the rice growth period, which accounted for 15.8%-42.8% of the total Cd content in roots, and the DCB-Cd content was different in each stage of rice. The content of exchangeable Cd (Exc-Cd) in soil at the mature stage of rice decreased by 36.4%, and the other fractions increased by 12.5%-48.2%. The results showed significant negative correlations between the Cd contents and Si in roots, DCB-Cd and soil available Cd and available Si, Exc-Cd and Car-Cd, and soil available Cd and pH value. Cd content in roots was positively correlated with DCB-Cd. With the equal dose of silicon fertilizer, the treatments of SiCaMgFe and SiW could effectively reduce the Cd content in rice. The application of silicon fertilizer promoted the transfer of Exc-Cd to Carb-Cd by increasing the soil pH value and the soil available Si content, meanwhile reducing the soil available Cd, Exc-Cd contents, the adsorption of Cd by the iron film on the root surface, and the adsorption capacity of iron plaque and root, thereby reducing the absorption of Cd by rice.
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Oryza , Poluentes do Solo , Cádmio/análise , Fertilizantes/análise , Solo/química , Silício , Disponibilidade Biológica , Poluentes do Solo/análise , FerroRESUMO
OBJECTIVES: Parenchymal-sparing hepatectomy (PSH) is recommended in patients with colorectal liver metastases (CRLM). Based on the principle of PSH, to investigate the impact of anatomical resection (AR) and non-anatomic resection (NAR) on the outcome of CRLM and to evaluate the potential prognostic impact of three peritumoral imaging features. METHODS: Fifty-six patients who had abdominal gadoxetic acid-enhanced magnetic resonance imaging (MRI) before CRLM surgery were included in this retrospective research. Peritumoral early enhancement, peritumoral hypointensity on hepatobiliary phase (HBP), and biliary dilatation to the CRLM at MRI were evaluated. Survival estimates were calculated using the Kaplan-Meier method, and multivariate analysis was conducted to identify independent predictors of liver recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS). RESULTS: NAR had a lower 3-year LRFS compared with AR (36.6% vs. 78.6%, p = 0.012). No significant differences were found in 3-year RFS (34.1% vs. 41.7%) and OS (61.7% vs. 81.3%) (p > 0.05). In NAR group, peritumoral early enhancement was associated with poor LRFS (p = < 0.001, hazard ratio [HR] = 6.260; 95% confidence interval [CI], 2.322,16.876]) and poor RFS (p = 0.035, HR =2.516; 95% CI, 1.069,5.919). No independent predictors of CRLM were identified in the AR group. CONCLUSIONS: In patients with CRLM, peritumoral early enhancement was a predictor of LRFS and RFS after NAR according to the principle of PSH.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Prognóstico , Hepatectomia/métodos , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologiaRESUMO
OBJECTIVE: Whether preoperative serum carbohydrate antigen 19-9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified. METHODS: Consecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale. RESULTS: A total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5-62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724). CONCLUSIONS: Preoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.
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Antígeno CA-19-9 , Neoplasias Colorretais , Biomarcadores Tumorais , Antígeno Carcinoembrionário , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Traumatic brain injury (TBI) leads to cell and tissue impairment, as well as functional deficits. Stem cells promote structural and functional recovery and thus are considered as a promising therapy for various nerve injuries. Here, we aimed to investigate the role of ectoderm-derived frontal bone mesenchymal stem cells (FbMSCs) in promoting cerebral repair and functional recovery in a murine TBI model. METHODS: A murine TBI model was established by injuring C57BL/6 N mice with moderate-controlled cortical impact to evaluate the extent of brain damage and behavioral deficits. Ectoderm-derived FbMSCs were isolated from the frontal bone and their characteristics were assessed using multiple differentiation assays, flow cytometry and microarray analysis. Brain repairment and functional recovery were analyzed at different days post-injury with or without FbMSC application. Behavioral tests were performed to assess learning and memory improvements. RNA sequencing analysis, immunofluorescence staining, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to examine inflammation reaction and neural regeneration. In vitro co-culture analysis and quantification of glutamate transportation were carried out to explore the possible mechanism of neurogenesis and functional recovery promoted by FbMSCs. RESULTS: Ectoderm-derived FbMSCs showed fibroblast like morphology and osteogenic differentiation capacity. FbMSCs were CD105, CD29 positive and CD45, CD31 negative. Different from mesoderm-derived MSCs, FbMSCs expressed the ectoderm-specific transcription factor Tfap2ß. TBI mice showed impaired learning and memory deficits. Microglia and astrocyte activation, as well as neural damage, were significantly increased post-injury. FbMSC application ameliorated the behavioral deficits of TBI mice and promoted neural regeneration. RNA sequencing analysis showed that signal pathways related to inflammation decreased, whereas those related to neural activation increased. Immunofluorescence staining and qRT-PCR data revealed that microglial activation and astrocyte polarization to the A1 phenotype were suppressed by FbMSC application. In addition, FGF1 secreted from FbMSCs enhanced glutamate transportation by astrocytes and alleviated the cytotoxic effect of excessive glutamate on neurons. CONCLUSIONS: Ectoderm-derived FbMSC application significantly alleviated neuroinflammation, brain injury, and excitatory toxicity to neurons, improved cognition and behavioral deficits in TBI mice. Therefore, ectoderm-derived FbMSCs could be ideal therapeutic candidates for TBI which mostly affect cells from the same embryonic origins as FbMSCs.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Células-Tronco Mesenquimais , Animais , Lesões Encefálicas/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Ectoderma/metabolismo , Fator 1 de Crescimento de Fibroblastos/metabolismo , Fator 1 de Crescimento de Fibroblastos/farmacologia , Fator 1 de Crescimento de Fibroblastos/uso terapêutico , Osso Frontal/metabolismo , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Ácido Glutâmico/uso terapêutico , Inflamação/metabolismo , Inflamação/terapia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Doenças Neuroinflamatórias , OsteogêneseRESUMO
BACKGROUND: The majority of lung cancer(LC) patients are diagnosed at advanced stage with a poor prognosis. However, there is still no ideal diagnostic and prognostic prediction model for lung cancer. METHODS: Data of CEA, CYFRA21-1 and NSE test of patients with LC and benign lung diseases (BLDs) or healthy people from Physical Examination Center was collected. Samples were divided into three data sets as needed. Reassign three kinds of tumor markers (TMs) according to their distribution characteristics in different populations. Diagnostic and prognostic models were thus established, and independent validation was conducted with other data sets. RESULTS: The diagnostic prediction model showed good discrimination ability: the area under the receiver operating characteristic curve (AUC) differentiated LC from healthy people and BLDs (diagnosed within 2 months), being 0.88 and 0.84 respectively. Meanwhile, the prognostic prediction model did great in prediction: AUC in training data set and test data set were 0.85 and 0.8 respectively. CONCLUSION: Reassigned CEA, CYFRA21-1 and NSE can effectively predict the diagnosis and prognosis of LC. Compared with the same TMs that were considered individually, this diagnostic prediction model can identify high-risk population for LC screening more accurately. The prognostic prediction model could be helpful in making more scientific treatment and follow-up plans for patients.
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Antígeno Carcinoembrionário , Neoplasias Pulmonares , Antígenos de Neoplasias , Biomarcadores Tumorais , Humanos , Queratina-19 , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , PrognósticoRESUMO
RATIONALE: Primary biliary non-Hodgkin's lymphoma (PBNHL) is a rare disease with only 41 cases reported since 1982. The incidence of PBNHL in patients with malignant cholangiocarcinoma was 0.6%, and PBNHL accounted for 0.4% of extranodal non-Hodgkin's lymphoma, and only 0.016% of all non-Hodgkin's lymphoma cases. PATIENT CONCERNS: We present a rare case of PBNHL in a 59-year-old female who had jaundice for 3âdays with weight loss and Epstein-Barr virus infection. Initial computed tomography and magnetic resonance imaging showed diffuse thickening wall of bile ducts with corresponding lumen stenosis, blurred fat space around the portal vein, lymphadenopathy, and a normal spleen. These manifestations and images were similar to hilar cholangiocarcinoma. So, the diagnosis of hilar cholangiocarcinoma was initially considered. DIAGNOSES: Postoperative pathology confirmed the final diagnosis was PBNHL. INTERVENTIONS: The patient and her family requested to clarify the histologic diagnosis by laparotomy biopsy. Because the biopsy result could not be defined during operation, then right hemihepatectomy and choledochojejunostomy were performed. She did not receive any antitumor treatment. OUTCOMES: One month after the patient's first examination, both computed tomography and magnetic resonance images showed diminished stenosis of common bile duct and left hepatic duct, but a new mass in segment IV of liver was observed. Unfortunately, the patient died due to disease progression. LESSONS: This case reminds us that although PBNHL is rare, making accurate diagnosis difficult preoperatively, PBNHL should be considered when encountering a case with Epstein-Barr virus infection and those typical imaging findings.
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Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/complicações , Feminino , Humanos , Tumor de Klatskin/patologia , Linfoma não Hodgkin/complicações , Pessoa de Meia-IdadeRESUMO
A field experiment was carried out to investigate the effects of different rice-rape rotation systems on methane and nitrous oxide emissions, which were measured using the static chamber/gas chromatography method, prediction of their global warming potentials (GWP), and greenhouse gas intensity (GHGI) in paddy fields. The results showed that the average cumulative emissions of CH4from a double cropping paddy field, single season rice field (including middle or late), rape field, and leisure land were 135.25, 55.64, 5.05, and 1.89 kg ·hm-2, respectively. The CH4 emission during the rice season accounted for 91.8%-98.5% of the annual CH4 emission in different rotation years, and the contents of dissolved organic carbon in paddy soil exhibited a significantly positive correlation with CH4 emission. The CH4 emission in conventional late rice paddy was 18.7% higher than that of hybrid late rice paddy (P<0.05). The average cumulative emissions of N2O from double cropping paddy field, single season rice field (including middle or late), rape field, and leisure land were 0.94, 0.64, 1.38, and 0.24 kg ·hm-2, respectively. Out of the total annual N2O emission, 57.2% to 70.2% was from the rape field; 17.8% and 30.6% was due to the winter fallow treatments with previous crop type of double corpping rice and single season rice, respectively. There was no significant difference in N2O emission between hybrid rice and conventional rice paddy fields. The GWP of double cropping rice-winter fallow and double cropping rice-rape was higher than that of rice-rape and rice-winter fallow, and the GWP of CH4 in rice season accounted for 71.2% to 90.9% of the annual GWP of rotation. The highest treatment of GHGI was rice-rice-rape, and the treatment of rice-oil and rice-winter slack was lower. According to the comprehensive environmental and economic benefits, the late hybrid rice-rape patterns should be selected to reduce greenhouse gases in multiple cropping rice fields of South China.
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Óxido Nitroso , Oryza , Agricultura , China , Aquecimento Global , Metano/análise , Óxido Nitroso/análise , Rotação , SoloRESUMO
BACKGROUND: Endometrial carcinoma (EC) is the primary cause of death associated with cancer globally. Thus, the possible molecular mechanism of EC needs further exploration. Up-frameshift protein 1 (UPF1) is an ATPase depending on RNA/DNA and RNA helicase depending on ATP. Long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was dysregulated in diverse diseases. METHODS: qRT-PCR and Western blot were applied to detect UPF1 and PVT1 in EC. CCK-8, colony formation, and Transwell assays were used to test the effects of UPF1/PVT1 on cell proliferation and migration. Cells were cultured with actinomycin D to observe mRNA stability, and RNA immunoprecipitation assay was applied to verified the relationship between UPF1 and PVT1. Glucose consumption and lactate generation were measured when cells were transfected with siRNA. RESULTS: Results demonstrated that the expression of UPF1 exhibited a remarkable decrement in EC tissues relative to that in non-tumor tissues. Subsequent functional experiments suggested that UPF1 decrement stimulated EC cells to grow and migrate. Moreover, UPF1 was discovered to be linked to PVT1 and had an inverse correlation with PVT1. Besides, PVT1 expression affected EC growth and migration, and PVT1 decrement alleviated the influence of UPF1 decrement on EC growth and migration and strengthened glycolysis in EC. CONCLUSION: In this study, we found that UPF1 was down-regulated in EC tissues, and UPF1 might exert its role by regulating the expression of PVT1.
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Natural products are becoming increasingly important in chemoprevention and for cancer therapy. Silene viscidula (S. viscidula), a traditional Chinese herb, has long been used as an anti-inflammatory and neuroleptic agent. However, the anticancer activity of S. viscidula has remained unclear. In this study, 16 compounds were extracted from S. viscidula. Among those compounds, sinocrassulosides VI/VII, an inseparable isomer mixture, possess the strongest inhibitory activity on HeLa cells with the IC50 value of 2.37 µM. Mechanism studies found that sinocrassulosides VI/VII downregulated the expression of cyclin D1 and decreased retinoblastoma (Rb) phosphorylation, which arrested HeLa cells in the G1 phase. Also, sinocrassulosides VI/VII could induce senescence via the upregulation of p16 and a significant increase of ß-galactosidase (ß-gal) staining. Our results suggest that sinocrassulosides VI/VII may be a new therapeutic potential agent for cervical cancer. In addition, we explored the structure-activity relationships of three groups of the configurational isomer with similar chemical structure from S. viscidula. We first demonstrated that the length of the ester chains linked to the carboxyl group of the glucuronic acid residue could affect the potent cytotoxicity. This finding will open new avenues for developing effective anticancer compounds by modifying the components derived from plants in nature.
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OBJECTIVE: To research the anti-cancer mechanism of the Traditional Chinese Medicine Fanbaicao (Herba Potentillae Discoloris) oil in the human hepatoma cell line HepG2. METHODS: Gas chromatography was used to analyze the components of Fanbaicao (Herba Potentillae Discoloris). We tested the inhibitory effect of Fanbaicao (Herba Potentillae Discoloris) oil on the human hepatoma cell line HepG2 in vitro using 3-(4, 5-Dimet hylt hiazol-2-yl)-2,5-dip henyltetrazolium bromide assays. Fluorescence activating cell sorter analysis was used to examine the levels of apoptosis, and western blot and immunofluorescence were used to detect the expression of p21, p-p21 and CDK4 proteins. RESULTS: Fanbaicao (Herba Potentillae Discoloris) oil contains 45 ingredients, and L-ascorbic acid 2, 6-bispalmitate was the main component and accounted for 44.96% of total drive-off peak area. Other components included (Z)-14-met hyl-8-exadecenal- acetal (8.56%), phytol (7.74%) and lauric acid (6.31% ). Fanbaicao (Herba Potentillae Discoloris) oil treatment reduced the proliferation of HepG2 cells and the half growth inhibition concentration (IC50) was 2.03 mg/mL. Furthermore, we also observed significantly increased HepG2 cell apoptosis in a dose-dependent manner (P < 0.05). Fanbaicao (Herba Potentillae Discoloris) oil significantly increased the expression of p21 and p-p21 and significantly decreased the expression of CDK4 in HepG2 cells compared with controls (P < 0.01). CONCLUSION: Our results showed that Fanbaicao (Herba Potentillae Discoloris) oil has anti-cancer activities in HepG2 cells, which is probably related to the upregulation of p21 and p-p21 and downregulation of CDK4 expression.
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Quinase 4 Dependente de Ciclina/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Hepáticas/genética , Potentilla/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatologiaRESUMO
Reduction-oxidation-sensitive green fluorescent proteins (roGFPs) have been demonstrated to be valuable tools in sensing cellular redox changes in mammalian cells and model plants, yet have not been applied in crops such as maize. Here we report the characteristics of roGFP1 in transiently transformed maize mesophyll protoplasts in response to environmental stimuli and knocked-down expression of ROS-scavenging genes. We demonstrated that roGFP1 in maize cells ratiometrically responds to cellular redox changes caused by H2O2 and DTT, as it does in mammalian cells and model plants. Moreover, we found that roGFP1 is sensitive enough to cellular redox changes caused by genetic perturbation of single ROS genes, as exemplified by knocked-down expression of individual ZmAPXs, in maize protoplasts under controlled culture conditions and under stress conditions imposed by H2O2 addition. These data provide evidence that roGFP1 functions in maize cells as a biosensor for cellular redox changes triggered by genetic lesion of single ROS genes even under stress conditions, and suggest a potential application of roGFP1 in large-scale screening for maize mutants of ROS signaling involved in development and stress resistance.
Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/metabolismo , Protoplastos/metabolismo , Espécies Reativas de Oxigênio/análise , Zea mays/metabolismo , Ascorbato Peroxidases/antagonistas & inibidores , Ascorbato Peroxidases/genética , Ascorbato Peroxidases/metabolismo , Técnicas Biossensoriais , Ditiotreitol/farmacologia , Glutationa/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Peróxido de Hidrogênio/farmacologia , Oxirredução , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/efeitos dos fármacos , Protoplastos/efeitos dos fármacos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Zea mays/efeitos dos fármacos , Zea mays/genéticaRESUMO
To explore an effective measure to ensure the safety of rice quality in cadmium (Cd)-contaminated farmland, a pot culture experiment was conducted to study the effects of of low Cd content (Cd < 0.2 mg x kg(-1)) phosphorous fertilizers with an application rate of 0.10 or 0.20 g P2O5 x kg(-1) on the phytoavailability of Cd in its contaminated p add y soil, with the related mechanisms discussed. Compared with no phosphorous fertilization, applying 0.10 P2O5 x kg(-1) of calcium magnesium phosphate (CMP) and monopotassium phosphate (MKP) increased soil pH and decreased soil available Cd content significantly, and CMP and calcium superphosphate (CSP) decreased the Cd accumulation in rice significantly. When the application rate was up to 0.20 g P2O5 x kg(-1), calcium hydrogen phosphate (CHP) increased the soil pH and decreased the soil available Cd content significantly, and CMP, MKP, and CHP decreased the DTPA-extractable soil Cd content by 11.8%, 9.8%, and 11.8%, and the NH4 OAc-extractable soil Cd content by 9.5%, 7.1%, and 7.1%, respectively. All test phosphorous fertilizers could significantly decrease the stem and leaf Cd contents, with a decrement of 24.9%-50.8%, and except CHP, the others could significantly decrease the Cd content of brown rice. With the application CMP and CSP, the Cd content of brown rice was close to the National Hygienic Standard for Grains (GB 2715-2005). Among the test phosphorous fertilizers, those can increase soil pH (CMP, MKP, and CHP) could significantly decrease the availability of soil Cd significantly, and those containing calcium (CMP and CSP) were more effective in decreasing the Cd accumulation in rice. The efficiency of the phosphorous fertilizers was mainly determined by their chemical properties. Alkaline calcium-containing phosphorous fertilizers were more effective in decreasing the Cd absorption and accumulation in rice plant in Cd-contaminated farmland.