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1.
Exp Cell Res ; 431(1): 113696, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37423512

RESUMO

Epigenetic alterations have essential roles during colon adenocarcinoma (COAD) progression. As the coactivator of Wnt/b-catenin signaling, Pygopus 2 (Pygo2) binds H3K4me2/3 and participate in chromatin remodeling in multiple cancers. However, It remains unclear whether the Pygo2-H3K4me2/3 association has significance in COAD. We aimed to elucidate the roles of Pygo2 in COAD. Functionally, Pygo2 inhibition attenuated cell proliferation, self-renewal capacities in vitro. Pygo2 overexpression enhanced in vivo tumor growth. Besides, Pygo2 overexpression could also enhance cell migration ability and in vivo distal metastasis. Mechanistically, Pygo2 correlates positively with BRPF1 expressions, one epigenetic reader of histone acetylation. The luciferase reporter assay and Chromatin Immunoprecipitation (ChIP)-qPCR assay were used to find that Pygo2 coordinated with H3K4me2/3 modifications to activate BRPF1 transcriptions via binding to the promoter. Both Pygo2 and BRPF1 expressed highly in tumors and Pygo2 relied on BRPF1 to accelerate COAD progression, including cell proliferation rate, migration abilities, stemness features and in vivo tumor growth. Targeting BPRF1 (GSK5959) is effective to suppress in vitro growth of Pygo2high cell lines, and has mild effect on Pygo2low cells. The subcutaneous tumor model further demonstrated that GSK5959 could effectively suppress the in vivo growth of Pygo2high COAD, but not the Pygo2low subtype. Collectively, our study represented Pygo2/BRPF1 as an epigenetic vulnerability for COAD treatment with predictive significance.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/genética , Regulação da Expressão Gênica , Linhagem Celular , Via de Sinalização Wnt , Proteínas de Ligação a DNA , Proteínas Adaptadoras de Transdução de Sinal
2.
Neoplasma ; 71(3): 266-278, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38958711

RESUMO

Neural invasion underlies the local spread of gastric cancer and is associated with poor prognosis. This process has been receiving increasing attention in recent years. However, the relationship between neural invasion and the malignant phenotypes of gastric cancer cells, as well as the molecular mechanism involved in this process, remain unclear. In this study, bioinformatics analysis was performed using a dataset obtained from The Cancer Genome Atlas-Stomach Adenocarcinoma. The results revealed that high expression of GDNF family receptor alpha 3 (GFRA3) was associated with a poor prognosis of patients with gastric cancer. GFRA3 is a receptor for artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF). This association was indicated by short overall/disease-free survival, as well as the presence of high-stage and high-grade disease. Gene set enrichment analysis showed that two cancer-associated pathways, namely KRAS signaling and epithelial-mesenchymal transition (EMT), were activated when GFRA3 was highly expressed in gastric cancer. Further studies confirmed that GFRA3 activated KRAS downstream signaling phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) or extracellular signal-regulated kinase (ERK) and induced EMT markers, as well as promoted the migration and invasion of gastric cancer cells. As a ligand of GFRA3, ARTN induced the EMT, migration, and invasion of gastric cancer cells via GFRA3. Notably, the effects of the ARTN-GFRA3 axis were attenuated by treatment with a KRAS inhibitor. The present findings indicated that, during the neural invasion of gastric cancer, ARTN-mediated activation of GFRA3 induces EMT phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.


Assuntos
Movimento Celular , Transição Epitelial-Mesenquimal , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial , Invasividade Neoplásica , Proteínas do Tecido Nervoso , Proteínas Proto-Oncogênicas p21(ras) , Transdução de Sinais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Linhagem Celular Tumoral , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Fenótipo , Prognóstico , Fosfatidilinositol 3-Quinases/metabolismo , Regulação Neoplásica da Expressão Gênica
3.
BMC Gastroenterol ; 23(1): 2, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600208

RESUMO

BACKGROUND: Emerging evidence has shown the crucial roles of pleomorphic adenoma gene (PLAG) family genes in multiple cancers. However, their functions and mechanisms in pancreatic adenocarcinoma (PAAD) remain poorly understood. METHODS: We analyzed the expression levels of PLAG family genes in both The Cancer Genome Atlas (TCGA) database and a Gene Expression Omnibus (GEO) database, and confirmed the results in our three independent cohorts of 382 PAAD tissues and 362 adjacent nontumor pancreatic tissues. Integrated analyses were carried out to explore the function, mechanism and prognostic value of the selected PLAG family gene in PAAD patients. RESULTS: By analyzing the TCGA and GEO databases, PLAGL1 was identified to be downregulated in PAAD tissues, and its decreasing levels of both mRNA and protein were verified in our three independent PAAD cohorts. PLAGL1 expression was inversely correlated with clinicopathological factors including the Ki67+ cell rate and pathologic stage. Further GSEA of the TCGA-PAAD cohort demonstrated that multiple signaling pathways implicated in cell proliferation were enriched in the lower PLAGL1 expressing PAAD group. Moreover, we demonstrated that PLAGL1 expression was obviously negatively associated with patients' overall survival outcome in both the TCGA-PAAD cohort and our verification cohorts. Additionally, through MTS and BrdU assays, we further demonstrated in vitro that PLAGL1 had the impact of preventing the proliferation of pancreatic cancer cells. CONCLUSIONS: Our present study suggested that downregulated PLAGL1 might act as a biomarker in predicts poor prognosis and one of important factors in increasing cell proliferation in PAAD. This study provides us with a novel prognostic marker and therapeutic strategy for PAAD, which deserves further study.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Fatores de Transcrição , Proteínas Supressoras de Tumor , Humanos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias Pancreáticas
4.
Environ Geochem Health ; 45(7): 4127-4163, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36906650

RESUMO

The remediation of soil contaminated by heavy metals has long been a concern of academics. This is due to the fact that heavy metals discharged into the environment as a result of natural and anthropogenic activities may have detrimental consequences for human health, the ecological environment, the economy, and society. Metal stabilization has received considerable attention and has shown to be a promising soil remediation option among the several techniques for the remediation of heavy metal-contaminated soils. This review discusses various stabilizing materials, including inorganic materials like clay minerals, phosphorus-containing materials, calcium silicon materials, metals, and metal oxides, as well as organic materials like manure, municipal solid waste, and biochar, for the remediation of heavy metal-contaminated soils. Through diverse remediation processes such as adsorption, complexation, precipitation, and redox reactions, these additives efficiently limit the biological effectiveness of heavy metals in soils. It should also be emphasized that the effectiveness of metal stabilization is influenced by soil pH, organic matter content, amendment type and dosage, heavy metal species and contamination level, and plant variety. Furthermore, a comprehensive overview of the methods for evaluating the effectiveness of heavy metal stabilization based on soil physicochemical properties, heavy metal morphology, and bioactivity has also been provided. At the same time, it is critical to assess the stability and timeliness of the heavy metals' long-term remedial effect. Finally, the priority should be on developing novel, efficient, environmentally friendly, and economically feasible stabilizing agents, as well as establishing a systematic assessment method and criteria for analyzing their long-term effects.


Assuntos
Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Humanos , Poluentes do Solo/análise , Poluição Ambiental , Metais Pesados/análise , Solo/química
5.
Environ Geochem Health ; 45(12): 9599-9619, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37776470

RESUMO

Groundwater pollution caused by lead ions has become a widespread issue worldwide due to the ever-increasing development of industrial activities. Such pollution poses significant threats to both humans and the environment. Oyster shell powder-peanut shell biochar mixture (OSP-PSB mixture) was used for lead-contaminated groundwater treatment by permeable reactive barrier (PRB) technology. Basic characteristics of materials proved that OSP-PSB mixture has good adsorption properties; OSP with particle sizes ranging from 0.85 to 1.18 mm was used in this research; according to engineering and adsorption characteristics, OSP-PSB mixture (5:1) showed excellent permeability (4.35 × 10-4 cm/s) and lead adsorption capacity(27 mg/g); long-term permeability of the OSP-PSB mixture slightly decreased over time and met the permeability requirements for PRB; the removal mechanisms of lead ions by OSP-PSB mixture include precipitation, surface complexation, ion exchange, and physical adsorption. The experiment results showed that the OSP-PSB mixture fulfills the actual project requirements of PRB.


Assuntos
Água Subterrânea , Ostreidae , Poluentes Químicos da Água , Humanos , Animais , Arachis , Poluentes Químicos da Água/análise , Pós , Adsorção , Íons
6.
Cell Biol Int ; 46(7): 1074-1088, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35347804

RESUMO

TOX high mobility group box family member 3 (TOX3) can function as tumor suppressor or oncogene in different tumors, while ras homolog family member B (RhoB) is a well-known tumor suppressor. The expression and role of TOX3 in colorectal cancer (CRC) are unknown. This study aimed to investigate the expression of TOX3 in CRC and the role of TOX3/mitogen-activated protein kinase (MAPK)/RhoB signaling in the proliferation and apoptosis of CRC cells. We showed that TOX3 messenger RNA (mRNA) and protein expression levels were significantly upregulated in CRC tissues and cell lines. High TOX3 expression was associated with high T stage, nodal invasion, and advanced tumor stage. Disease-free survival (DFS) was shortened for CRC patients with high expression of TOX3, while overall survival showed no significant difference. TOX3 promoted proliferation, inhibited apoptosis, and decreased the sensitivity to oxaliplatin of CRC cells. In addition, the inhibition of TOX3 led to the upregulation of RhoB, and RhoB overexpression suppressed the proliferation and promoted apoptosis of CRC cells. Moreover, TOX3 overexpression upregulated MAPK signaling, while MAPK signaling inhibitor U0126 induced CRC cell proliferation arrest or apoptosis, and attenuated the inhibition of RhoB in TOX3 overexpression cells. In addition, the overexpression of TOX3 increased tumor volume in nude mice. In conclusion, TOX3 may be an oncogene in CRC and can predict DFS in CRC patients. TOX3/MAPK/RhoB signaling plays an important role in the modulation of proliferation and apoptosis of CRC cells.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Colorretais , Proteínas Quinases Ativadas por Mitógeno , Transativadores/metabolismo , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína rhoB de Ligação ao GTP/genética , Proteína rhoB de Ligação ao GTP/metabolismo
7.
Sensors (Basel) ; 20(17)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32854189

RESUMO

Hydromechanical and structural properties of compacted loess have a significant impact on the stability and reliability of subbase and subgrade, which needs to be quickly determined in the field and laboratory. Hence, an electrical resistivity method was used to characterize the hydromechanical and structural properties of compacted loess during constant rate of strain compression. In the present work, compacted loess samples with a dry density of 1.7 g/cm3, a diameter of 64 mm, a height of 10 mm and different water content ranging from 5-25% were prepared. The constant rate of strain (CRS) tests were conducted by a developed oedometer cell equipped with a pair of horizontal circular electrodes (diameter of 20 mm) and vertical rectangular electrodes (width of 3.5 mm) to determine the electrical resistivity of compacted loess. The results showed that as average water content increases, plastic compression indices increase from 0.220 to 0.350 and the elastic compression indices increase from 0.0152 to 0.030, but they decrease to 0.167 and 0.010 and yield stress decreases from 381.28 kPa to 72.35 kPa. Moreover, as vertical strain increases, the variation trend of average formation factor and average shape factor for the lower water content decreases but increases for the maximum water content, and the anisotropy index first decrease and then tend to increase slightly, which indicates that the structural properties of unsaturated and saturated samples during compression exhibits different trend and the anisotropy of samples tend to be stable as vertical strain increases. As the water content increases, the average formation factor and average shape factor decrease, but the anisotropy index first decreases then increases, suggesting that water content has a significant impact on these electrical indices. More important, The coefficients of average formation factor decrease from 33.830 to -1.698 and the coefficients of average shape factor decrease from 8.339 to -0.398 as water content increases, whereas there is less variation for the coefficient of anisotropic index with a value of 2.190. An equation correlating average formation factor and water content and vertical strain is regressed to characterize the hydromechanical properties of compacted loess by measuring its impedance, which can be used to evaluate the stability of compacted loessic ground and subgrade.

8.
J Viral Hepat ; 25(11): 1363-1371, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29969176

RESUMO

Previously, we identified UBE2L3 as a susceptibility gene for chronic hepatitis B virus (HBV) infection through genome-wide association study. Here, we analysed the association between genetic variants of UBE2L3 and the susceptibility to HBV-related hepatocellular carcinoma (HCC) and further explored its role in HCC. This case-control study included 1344 subjects who cleared HBV, 1560 HBV carriers and 1057 HBV-related HCC patients. Two single nucleotide polymorphisms (SNPs) were genotyped, including rs2266959 and rs4821116. Logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI). We further analysed the expression of UBE2L3 and its association with pathological features based on The Cancer Genome Atlas (TCGA) data and our tissue microarray. Proliferation and migration assays were performed in hepatoma cell lines with or without UBE2L3 knockdown. Further RNA-seq analysis was performed to explore the underlying oncogenic mechanism. The variant genotypes of rs4821116 in UBE2L3 were associated with decreased risk for HCC and chronic HBV infection. Moreover, based on both TCGA and our tissue microarray data, higher levels of UBE2L3 expression were correlated with higher tumour grade, advanced tumour stage and poor survival. In vitro analysis revealed that UBE2L3 may promote hepatocyte proliferation and migration. RNA-seq analysis showed that UBE2L3 was inversely correlated with CDKN2B, a negative regulator of cell cycle, and CLDN1, loss of which may promote cancer metastasis. In conclusion, UBE2L3 may also be a susceptibility gene in HBV-related HCC, and it may promote HCC proliferation and migration by negatively regulating CDKN2B and CLDN1.


Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Hepatite B Crônica/complicações , Neoplasias Hepáticas/genética , Enzimas de Conjugação de Ubiquitina/genética , Animais , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , China/epidemiologia , Progressão da Doença , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Camundongos , Camundongos Transgênicos , Polimorfismo de Nucleotídeo Único , Regulação para Cima/genética
9.
Int J Cancer ; 141(10): 2103-2111, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28734015

RESUMO

MiR-21, the only microRNA (miRNA) found to be overexpressed in any type of solid tumor, its guide stand, miR-21-5p, has been studied a lot in colorectal cancer (CRC); however, few researchers focused on its passenger strand, miR-21-3p. In our study, based on The Cancer Genome Atlas (TCGA) data, we found that there were more varieties and quantities of miR-21-3p isoforms in microsatellite instability (MSI)-type CRC. We further examined the role of miR-21-3p by in vitro and in vivo studies. MiR-21-3p may be an oncogene in CRC by promoting cellular mobility through epithelial-mesenchymal transition. However, different isoforms, especially miR-21-3p 0 | 2, may be a favorable prognostic marker for CRC survival, probably due to increased complementary effect of miR-21-5p and/or target genes. Further study investigating the underlying mechanism of miRNA isoforms is needed.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Animais , Apoptose , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estadiamento de Neoplasias , Prognóstico , Isoformas de Proteínas , Proteína Smad7/genética , Proteína Smad7/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Materials (Basel) ; 17(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38730857

RESUMO

This study investigates the adsorption of cadmium (Cd) by red mud-loess mixed materials and assesses the influence of quartz sand content on permeability. Shear tests are conducted using various pore solutions to analyze shear strength parameters. The research validates solidification methods for cadmium-contaminated soils and utilizes SEM-EDS, FTIR, and XRD analysis to elucidate remediation mechanisms. The findings suggest that the quartz sand content crucially affects the permeability of fine-grained red mud-loess mixtures. The optimal proportion of quartz sand is over 80%, significantly enhancing permeability, reaching a coefficient of 6.7 × 10-4 cm/s. Insufficient quartz sand content of less than 80% fails to meet the barrier permeability standards, leading to a reduced service life of the engineered barrier. Adsorption tests were conducted using various pore solutions, including distilled water, acidic solutions, and solutions containing Cd, to evaluate the adsorption capacity and shear characteristics of the red mud-loess mixture. Additionally, the study examines the behavior of Cd-loaded red mud-loess mixtures in various pore solutions, revealing strain-hardening trends and alterations in cohesiveness and internal friction angle with increasing Cd concentrations. The analysis of cement-red mud-loess-solidified soil demonstrates enhancements in soil structure and strength over time, attributed to the formation of crystalline structures and mineral formations induced by the curing agent. These findings provide valuable insights into the remediation of cadmium-contaminated soils.

11.
Waste Manag ; 174: 340-350, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38091658

RESUMO

The complex seabed conditions and ocean environment pose significant challenges to the material selection and construction of bottom liners for offshore final disposal sites. To overcome the challenges, this study proposed a novel isolation particle layer for offshore final disposal sites. The isolation particle was composed by salt-resistant bentonite coating material and cement core material (D10 was 10 mm in core diameter and 2 mm in coating thickness; D20 was 20 mm and 4 mm). Upon immersion in artificial seawater, the isolation particles underwent expansion, leading to the formation of the novel isolation particle layers with low hydraulic conductivity less than 1 × 10-7 cm/s and adsorption of heavy metals in bentonite interlayers. Large column tests showed that both D10 and D20 isolation particle layers exhibited remarkable swelling capacity and low hydraulic conductivity (4.3 × 10-9 cm/s and 2.6 × 10-8 cm/s) under 3 m seawater pressure. During one year of observation, water tank test demonstrated that both isolation particle layers displayed remarkable stability and low hydraulic conductivity of 2.73 × 10-10 cm/s and 8.36 × 10-10 cm/s with load. The maximum adsorption capacities of salt-resistant bentonite were 123.55 mg/g for Pb2+, 60.29 mg/g for Cd2+ and 54.22 mg/g for Cu2+. Both isolation particle layers exhibited a high removal rate of over 95 % for heavy metals in water tank tests. The large-scale laboratory tests indicated the significant potential of the novel isolation particle layer for offshore final disposal sites. Subsequently, a testing ocean site will be selected to further investigate its practical engineering performance.


Assuntos
Bentonita , Metais Pesados , Água , Água do Mar , Adsorção
12.
Environ Sci Pollut Res Int ; 31(2): 2745-2758, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38066274

RESUMO

The prolonged stacking of substantial volumes of industrial waste red mud (RM) can have significantly hazardous effects on the environment. In order to address this critical problem, this study proposes the synergistic preparation of geopolymers utilizing RM in conjunction with another industrial waste, rice husk ash (RHA). Geopolymers with varying incorporation of RHA were prepared using sodium hydroxide and sodium silicate composite alkaline activator. The mechanical properties, microstructure, and environmental characteristics of geopolymers were investigated. The incorporation of RHA significantly enhanced the strength of RM-based geopolymers, with the highest strength of 25.40 MPa achieved at 40% incorporation. According to XRD patterns and FTIR spectra, C-(A)-S-H and N-(A)-S-H were generated during the geopolymerization, thereby enhancing the strength of geopolymers. From SEM micrographs of geopolymers, it was evident that the geopolymer matrix was constituted by the encapsulation of unreacted inert particles of RM and residual fragments of RHA with C-(A)-S-H and N-(A)-S-H. The leaching levels of trace elements and heavy metals in geopolymers are both below the regulatory thresholds, thereby effectively mitigating the presence of hazardous substances in raw materials. These findings proved that the reuse of RM and RHA for the synergistic preparation of environmentally friendly geopolymers is a promising approach to address the issue of substantial RM stacking.


Assuntos
Metais Pesados , Oryza , Resíduos Industriais , Cinza de Carvão/química , Polímeros/química , Metais Pesados/análise
13.
Front Oncol ; 14: 1337219, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380369

RESUMO

Background: Laparoscopic total mesorectal excision (LaTME) is standard surgical methods for rectal cancer, and LaTME operation is a challenging procedure. This study is intended to use machine learning to develop and validate prediction models for surgical difficulty of LaTME in patients with rectal cancer and compare these models' performance. Methods: We retrospectively collected the preoperative clinical and MRI pelvimetry parameter of rectal cancer patients who underwent laparoscopic total mesorectal resection from 2017 to 2022. The difficulty of LaTME was defined according to the scoring criteria reported by Escal. Patients were randomly divided into training group (80%) and test group (20%). We selected independent influencing features using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression method. Adopt synthetic minority oversampling technique (SMOTE) to alleviate the class imbalance problem. Six machine learning model were developed: light gradient boosting machine (LGBM); categorical boosting (CatBoost); extreme gradient boost (XGBoost), logistic regression (LR); random forests (RF); multilayer perceptron (MLP). The area under receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity and F1 score were used to evaluate the performance of the model. The Shapley Additive Explanations (SHAP) analysis provided interpretation for the best machine learning model. Further decision curve analysis (DCA) was used to evaluate the clinical manifestations of the model. Results: A total of 626 patients were included. LASSO regression analysis shows that tumor height, prognostic nutrition index (PNI), pelvic inlet, pelvic outlet, sacrococcygeal distance, mesorectal fat area and angle 5 (the angle between the apex of the sacral angle and the lower edge of the pubic bone) are the predictor variables of the machine learning model. In addition, the correlation heatmap shows that there is no significant correlation between these seven variables. When predicting the difficulty of LaTME surgery, the XGBoost model performed best among the six machine learning models (AUROC=0.855). Based on the decision curve analysis (DCA) results, the XGBoost model is also superior, and feature importance analysis shows that tumor height is the most important variable among the seven factors. Conclusions: This study developed an XGBoost model to predict the difficulty of LaTME surgery. This model can help clinicians quickly and accurately predict the difficulty of surgery and adopt individualized surgical methods.

14.
Cancer Med ; 12(2): 1572-1587, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35778964

RESUMO

BACKGROUND: The intensive interplay between aberrant epigenetic events and metabolic remodeling represents one of the hallmarks of tumors, including colon cancer. The functions of Bromodomain Containing Protein BRD-9 in colon cancer remains indefinite. We aimed to identify the biological roles and clinical significance of BRD9 in colon cancer. METHODS: The univariate- and multi-variate Cox regression models were used to screen risk epigenetic regulators. Kaplan-Meier analysis and Pearson correlation analysis were used to assess clinical significance of BRD9. CCK-8 assays, colony formation assay, Transwell, and soft-agar assay were performed to determine the in vitro roles of BRD9. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of colon cancer cells were evaluated by a Seahorse XF Extracellular Flux Analyzer. In vivo models and RT-qPCR, western blotting, and Chromatin Immunoprecipitation (ChIP) assay were conducted to explore the functional roles of BRD9 in COAD. RESULTS: In the study, we detected the expressions of 662 epigenetic regulators in COAD and identified a series of 42 hazard epigenetic factors with p < 0.05. Low-throughput MTT assays highlighted that BRD9 is an essential target, and targeting BRD9 could reduce significant decreases of cell growth. BRD9 overexpression could notably elevate proliferation and migration potentialities, whereas, BRD9 ablation abolished these effects. Mechanistically, functional enrichment analysis indicated the potential associations between BRD9 and glycolysis metabolism. In addition, BRD9 epigenetically coordinates the H3K27ac modifications on the promoter regions of ENO2 and ALDOC, inducing enhanced glycolysis activity. Lastly, I-BRD9 could significantly suppress the growth of colon cancer cells in vitro and in vivo. CONCLUSIONS: Together, our study revealed previously unidentified roles of BRD9 in colon cancer metabolism and tumor progression, indicating that BRD9 could be a valuable therapeutic target for COAD patients.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Adenocarcinoma/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Epigênese Genética , Glicólise
15.
Front Nutr ; 10: 1107551, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969821

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is a leading cause of cirrhosis and hepatocellular carcinoma. Due to its complex pathophysiology, there is currently no approved therapy. Polysaccharide, a kind of natural product, possesses a wide range of pharmacological activities. Numerous preclinical studies have confirmed that polysaccharides could interfere with the occurrence and development of NAFLD at multiple interrelated levels, such as improvement of glucose and lipid metabolism, antioxidation, anti-inflammation, and regulation of gut-liver axis, thus showing great potential as novel anti-NAFLD drugs. In this paper, we reviewed the polysaccharides with anti-NAFLD effect in recent years, and also systematically analyzed their possible pharmacological mechanisms.

16.
Heliyon ; 9(9): e19805, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809464

RESUMO

Objective: This research was aimed to preliminarily explore the clinical roles and potential molecular mechanisms of MIR99AHG and its significant transcripts in breast cancer (BRCA). Methods: Public databases were utilized to analyze the expression and prognostic roles of MIR99AHG and its transcripts. Relationships between MIR99AHG expression and immune cells infiltration were analyzed in Xiantao platform. In addition, co-expressed genes and interacting proteins of MIR99AHG were predicted. CancerSEA analyzed its relationship with functional states. Next, CNV status, DNA methylation, interacting transcription factors (TFs) and ceRNA network were analyzed to explore its possible mechanisms. Then, RNA ISH and FISH assays were used to detect its expression and location in BRCA tissues and cell lines, respectively. Finally, qRT-PCR was utilized to investigate MIR99AHG expression in cell lines. Results: Compared with the corresponding normal tissues, MIR99AHG expression levels were lower in all BRCA subtypes, and luminal B's was the lowest one. And MIR99AHG expression was negatively related to the tumor stage. In addition, 4 transcripts (ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5) of MIR99AHG showed significant differences in the expression. Databases also suggested that the high MIR99AHG expression levels indicated good prognosis, especially in patients without lymph node metastasis. Xiantao found that MIR99AHG was positively related to 17 immune cells and negatively linked with 2 immune cells. CancerSEA analysis showed no relationships between MIR99AHG and functional states. From GEPIA and BCIP databases, 19 co-expressed genes were highly related to these four significant transcripts of MIR99AHG. StarBase, RNAct and HDOCK showed that several tumor-associated proteins, including U2AF65, hnRNPC, AEBP2, CHIC1 and so on, might interact with MIR99AHG. Genetically, BRCA had a higher proportion of MIR99AHG CNV loss than CNV gain, and the high level of DNA methylation indicated a good prognosis. Furthermore, 19 TFs were predicted to combine with the promoter of MIR99AHG. Then, we screened out 10 miRNAs potentially interacting with the significant transcripts of MIR99AHG, and five were significantly increased in breast tumors compared to normal tissues, including miR-194-5p, miR-320 b and so on, which could combine 14 mRNAs. Through ISH and FISH assays, we verified that MIR99AHG was down-regulated in BRCA samples and cell lines in comparison to non-tumor tissues and mammary epithelial cell line (MCF10A), and MIR99AHG was located both in cytoplasm and nucleus. qRT-PCR assay also showed the lower expression of MIR99AHG in breast cancer cells than that in MCF10A. Conclusion: These results indicate that MIR99AHG can be a favorable prognostic indicator for BRCA. ENST00000619222.4, ENST00000418813.6, ENST00000602901.5 and ENST00000453910.5 are significant transcripts and their down-regulation may play crucial roles in the progression of BRCA.

17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(11): 2976-80, 2012 Nov.
Artigo em Zh | MEDLINE | ID: mdl-23387161

RESUMO

To non-dispersive infrared gas analysis, it was the most difficult challenge to maintain very low zero and temperature drift over long periods. Electronic and detector response drifts irremediably required some form of manual zeroing procedure. To solve zero and temperature drift, a multi-parameters model was developed, by which zero and temperature drifts were automatically corrected. These parameters include zero gas intensity, reference channels intensity, standard temperature, environment temperature, temperature drift coefficients etc. Trial results and in-situ applications showed that the monitoring precisions of the instrument were lesser than 5% F. S in different temperatures and for a long time. The average precision of monitoring carbon monoxide concentration increased respectively from 9.26 to 1.23%, and monitoring hydrocarbon concentration from 10.61% to 0.70% before and after compensated. The instrument required essentially no periodic calibration and have very low maintenance cost.

18.
Comput Methods Programs Biomed ; 207: 106173, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34058630

RESUMO

BACKGROUND AND OBJECTIVE: Thrombus simulation plays an important role in many specialist areas in the field of medicine such as surgical education and training, clinical diagnosis and prediction, treatment planning, etc. Although a considerable number of methods have been developed to simulate various kinds of fluid flows, it remains a non-trivial task to effectively simulate thrombus because of its unique physiological properties in contrast to other types of fluids. To tackle this issue, this study introduces a novel method to model the formation mechanism of thrombus and its interaction with blood flow. METHODS: The proposed method for thrombus formation simulation mainly consists of three steps. First, we formulate the formation of thrombus as a particle-based model and obtain the fibrin concentration of the particles with a discretized form of the convection-diffusion-reaction equation; then, we calculate the velocity decay factor using the obtained fibrin concentration. Finally, the formation of thrombus can be simulated by applying the velocity decay factor on particles. RESULTS: We carried out extensive experiments under different settings to verify the efficacy of the proposed method. The experimental results demonstrate that our method can yield more realistic simulation of thrombus and is superior to peer method in terms of computational efficiency, maintaining the stability of the dynamic particle motion, and preventing particle penetration at the boundary. CONCLUSION: The proposed method can simulate the formation mechanism of thrombus and the interaction between blood flow and thrombus both efficiently and effectively.


Assuntos
Hidrodinâmica , Trombose , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Hemodinâmica , Humanos
19.
Materials (Basel) ; 14(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34501065

RESUMO

Desiccation cracking frequently occurs in mud, clay, and pavement. Understanding the evolution of desiccation cracking may facilitate the development of techniques to mitigate cracking and even prevent it from developing altogether. In this study, experimental investigations were performed focusing on the effects of fibers on the evolution of desiccation cracking in soil-cement. Varied types of fibers (i.e., jute fiber and polyvinyl alcohol fiber (PVA)) and fiber contents (i.e., 0%, 0.25%, 0.5%, and 1%) were involved. The digital image correlation (DIC) method was employed to capture the evolution and propagation of cracks in the soil-cement specimens when subjected to desiccation. The results show that the presence of fibers imposes significant effects on the crack propagation pattern as well as the area and length of the cracks in the soil-cement during shrinkage. The addition of fibers, however, insignificantly affects the evaporation rate of the specimens. The crack area and crack length of the specimens decreased significantly when more fibers were included. There were no macroscopic cracks observed in the specimens where the fiber content was 1%. The DIC method effectively helped to determine the evolution of displacement and strain field on the specimens' surface during the drying process. The DIC method is therefore useful for crack monitoring.

20.
Materials (Basel) ; 14(22)2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34832385

RESUMO

The durability against wet-dry (w-d) cycles is an important parameter for the service life design of solidified permeable reactive barrier (PRB) waste. This study introduces the potential use of cement, fly ash, and carbide slag (CFC) for the stabilization/solidification (S/S) of PRB waste. In this study, solidified PRB waste was subjected to different w-d cycles ranging in times from 0 to 10. By analyzing the mass loss, the unconfined compressive strength (UCS), initial resistivity (IR), and the Mn2+ leaching concentration under different durability conditions, the results demonstrate that these variables increased and then tended to decrease with the number of w-d cycles. The UCS of contaminated soil is significantly correlated with IR. Moreover, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD) analyses indicate that the hydration products calcium silicate hydrate (C-S-H) and ettringite (AFt) are the main reasons for the enhancement of the UCS. However, the increase in Mn2+ concentration leads to a decrease in hydration products and the compactness of solidified soil, which has negative effects for the UCS and the leaching ion concentration. In general, the durability exhibited by the PRB waste treated with S/S in this paper was satisfactory. This study can provide theoretical guidance for practical engineering applications.

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