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1.
J Cancer ; 15(13): 4360-4373, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947375

RESUMO

Background: Pancreatic cancer continues to pose a significant threat due to its high mortality rate. While MYB family genes have been identified as oncogenes in certain cancer types, their role in pancreatic cancer remains largely unexplored. Methods: The mRNA and protein expression of MYB family genes in pancreatic cancer samples was analyzed using TNMplot, HPA, and TISBID online bioinformatics tools, sourced from the TCGA and GETx databases. The relationship between MYB family gene expression and survival time was assessed through Kaplan-Meier analysis, while the prognostic impact of MYB family gene expression was evaluated using the Cox proportional hazards model. Additionally, Spearman's correlation analysis was employed to investigate the correlation between MYB family genes and TMB/MSI. Results: The integration of data from various databases demonstrated that all MYB family genes exhibited dysregulated expression in pancreatic cancer. However, only the expression of the MYBL2 gene displayed a notable association with the grade and stage of pancreatic cancer. Furthermore, the MYBL2 gene exhibited significant variations in both univariate and multivariate factor analyses.Subsequent functional analyses revealed a significant correlation between MYBL2 expression in pancreatic cancers and various biological processes, such as DNA replication, tumor proliferation, G2M checkpoint regulation, pyrimidine metabolism, and the P53 pathway. Additionally, a notable positive association was observed between MYBL2 expression and tumor mutational burden (TMB), a predictive indicator for response to PD1 antibody treatment. Conclusion: MYBL2 may be a double marker for independent diagnosis and PD1 antibody response prediction of pancreatic cancer patients.

2.
J Cardiothorac Surg ; 19(1): 332, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877547

RESUMO

BACKGROUND: Pneumothorax is the most frequent complication after CT-guided percutaneous transthoracic lung biopsy (CT-PTLB). Many studies reported that injection of autologous blood patch (ABP) during biopsy needle withdrawal could reduce the pneumothorax and chest tube insertion rate after CT-PTLB, but the result is debatable. The aim of this systematic review and meta-analysis is to synthesize evidence regarding the efficacy of ABP procedure in patients receiving CT-PTLB. METHODS: Eligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between ABP and the pneumothorax and/or chest tube insertion rate after CT-PTLB. Subgroup analyses according to study type, emphysema status and ABP technique applied were also conducted. Odds ratio (OR) with 95% confidence interval (CI) were calculated to examine the risk association. RESULTS: A total of 10 studies including 3874 patients were qualified for analysis. Our analysis suggested that ABP reduced the pneumothorax (incidence: 20.0% vs. 27.9%, OR = 0.67, 95% CI = 0.48-0.66, P < 0.001) and chest tube insertion rate (incidence: 4.0% vs. 8.0%, OR = 0.47, 95% CI = 0.34-0.65, P < 0.001) after CT-PTLB. Subgroup analysis according to study type (RCT or retrospective study), emphysema status (with or without emphysema), and ABP technique applied (clotted or non-clotted ABP) were also performed and we found ABP reduced the pneumothorax and chest tube insertion rate in all subgroups. CONCLUSIONS: Our study indicated that the use of ABP was effective technique in reducing the pneumothorax and chest tube insertion rate after CT-PTLB.


Assuntos
Biópsia Guiada por Imagem , Pulmão , Pneumotórax , Tomografia Computadorizada por Raios X , Pneumotórax/etiologia , Pneumotórax/prevenção & controle , Humanos , Tomografia Computadorizada por Raios X/métodos , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/efeitos adversos , Pulmão/patologia , Transfusão de Sangue Autóloga/métodos , Tubos Torácicos
3.
Front Surg ; 11: 1329771, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655210

RESUMO

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement. Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection. Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe.

4.
Sci Total Environ ; 926: 171923, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38522523

RESUMO

The detrimental effects of heavy metal accumulation on both ecosystems and public health have raised widespread concern. Source-specific risk assessment is crucial for developing effective strategies to prevent and control heavy metal contamination in surface water. This study aims to investigate the contamination characteristics of heavy metals in the Yangtze River Basin, identifying the pollution sources, assessing the risk levels, and further evaluating the health risks to humans. The results indicated that the average concentrations of heavy metals were ranked as follows: zinc (Zn) > arsenic (As) > copper (Cu) > chromium (Cr) > cadmium (Cd) > nickel (Ni) > lead (Pb), with average concentrations of 38.02 µg/L, 4.34 µg/L, 2.53 µg/L, 2.10 µg/L, 1.17 µg/L, 0.84 µg/L, and 0.32 µg/L, respectively, all below the WHO 2017 standards for safe drinking water. The distribution trend indicates higher concentrations in the upper and lower reaches and lower concentrations in the mid-reaches of the river. By integrating the Absolute Principal Component Scores-Multiple Linear Regression (APCS-MLR) receptor model and Positive Matrix Factorization (PMF) model, the main sources of heavy metals were identified as industrial activities (APCS-MLR: 41.3 %; PMF: 42.1 %), agricultural activities (APCS-MLR: 30.1 %; PMF: 27.4 %), and unknown mix sources (APCS-MLR: 29.1 %; PMF: 30.4 %). The calculation of the hazard index (HI) for both children and adults was <1, indicating no non-carcinogenic or carcinogenic risks. Based on the source-specific risk assessment, agricultural activities contribute the most to non-carcinogenic risks, while industrial activities pose the greatest contribution to carcinogenic risks. This study offers a reference for monitoring heavy metals and controlling health risks to residents, and provides crucial evidence for the utilization and protection of surface water in the Yangtze River Basin.


Assuntos
Água Potável , Metais Pesados , Adulto , Criança , Humanos , Rios , Ecossistema , Monitoramento Ambiental , Metais Pesados/análise , Cádmio , Medição de Risco , China
5.
Cancer Cell Int ; 24(1): 15, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184562

RESUMO

Metabolic reprogramming, which is recognized as a hallmark of cancer, refers to the phenomenon by which cancer cells change their metabolism to support their increased biosynthetic demands. Tumor cells undergo substantial alterations in metabolic pathways, such as glycolysis, oxidative phosphorylation, pentose phosphate pathway, tricarboxylic acid cycle, fatty acid metabolism, and amino acid metabolism. Latest studies have revealed that long non-coding RNAs (lncRNAs), a group of non-coding RNAs over 200 nucleotides long, mediate metabolic reprogramming in tumor cells by regulating the transcription, translation and post-translational modification of metabolic-related signaling pathways and metabolism-related enzymes through transcriptional, translational, and post-translational modifications of genes. In addition, lncRNAs are closely related to the tumor microenvironment, and they directly or indirectly affect the proliferation and migration of tumor cells, drug resistance and other processes. Here, we review the mechanisms of lncRNA-mediated regulation of glucose, lipid, amino acid metabolism and tumor immunity in gastrointestinal tumors, aiming to provide more information on effective therapeutic targets and drug molecules for gastrointestinal tumors.

6.
Clin Med Insights Oncol ; 18: 11795549231219239, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38187458

RESUMO

Background: Copper chaperone for superoxide dismutase (CCS) is an essential component of the oxidation-reduction system. In breast cancer cells, CCS expression is highly up-regulated, which contributes to cellular proliferation and migration. Breast cancer is a multifaceted disease with different tumor prognoses and responses to clinical treatments, which may be associated with multiple molecular subtypes of CCS. Methods: The CCS expression patterns in breast cancer were investigated by TNMplot, cBioPortal, and HPA network database. The correlation of CCS expression with clinicopathological parameters was analyzed using the UALCAN database. The Cancer Genome Atlas (TCGA) data set was used to analyze the Clinical characteristics of CCS in luminal B patients. The bc-GenExMiner database was used to analyze the effects of BReast-CAncer susceptibility gene (BRCA)1/2, TP53 mutation status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER) expression on CCS expression. The survival curves and prognostic value of CCS in luminal B breast cancer were performed through Kaplan-Meier curves, univariate and multivariate Cox regression using the PrognoScan, bc-GenExMiner, and Clinical bioinformatics analysis platform. Results: We found that CCS expression was associated with patient age, race, ER, and PR status. We also discovered that BRCA1/2 mutations had an effect on CCS expression. The luminal B subtype had the highest CCS expression, which was linked to poor survival compared with other subtypes. In addition, Kaplan-Meier curve analysis showed that luminal B patients with high CCS mRNA expression showed a poor survival and the CCS gene is an independent predictor of outcome in patients with luminal B breast cancer by univariate and multivariate Cox regression. Conclusions: Our findings emphasize the significant expression of CCS in luminal B breast cancer and its potential as an autonomous prognostic determinant for this specific molecular subtype. These findings suggest that CCS holds promise as a prospective marker for the treatment of luminal B breast cancer.

7.
Int J Surg ; 110(3): 1620-1626, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38052020

RESUMO

BACKGROUND: Data on new onset postoperative atrial fibrillation (POAF) after Stanford type A dissection (STAAD) surgery was limited. This study aimed to detect the risk factors for developing POAF after STAAD procedures and the association between POAF and in-hospital mortality. METHODS: A total of 1354 patients who underwent surgical treatment for STAAD in Beijing Anzhen hospital were enrolled in this single-center retrospective study from January 2015 to October 2020. POAF were defined as atrial fibrillation/flutter requiring treatment after surgery procedure. Logistic model was conducted to detect the predictors of POAF, and inverse probability of treatment weighting (IPTW) and subgroup analysis were used to compare the mortality of POAF and non-POAF groups. RESULTS: There were 176 patients (13.0%) diagnosed with POAF according to the definition. Multivariate logistics analyses revealed that advanced age [odds ratio (OR), 1.07; 95% CI: 1.05-1.08; P <0.001)], creatinine (OR, 1.00; 95% CI: 1.00-1.01; P =0.001) and cross-clamp time (OR, 1.00; 95% CI: 1.00-1.01; P =0.021) were independent risk factors of developing POAF in STAAD patients. POAF patients were associated with significantly higher in-hospital mortality compared with non-POAF patients (6.5 vs. 19.9%, OR, 3.60; 95% CI: 2.30-5.54; P <0.001), IPTW and subgroup analysis had reached consistent conclusions. CONCLUSIONS: The incidence of POAF was 13.0% after STAAD surgery, advanced age, creatinine, and cross-clamp time were independent risk factors of developing POAF in STAAD patients. POAF is associated with increased mortality after STAAD procedures.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Estudos Retrospectivos , Creatinina , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
8.
Sci Total Environ ; 912: 169077, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38056672

RESUMO

The aim of this study is to propose a desulfurized rubber powder / styrene butadiene styrene (DRP/SBS) composite modified asphalt technology by combining the advantages of DRP and SBS. This reduces the production cost of modified asphalt and improves the performance of asphalt. In this paper, orthogonal tests were used to optimize preparation process parameters of DRP/SBS composite modified asphalt. And the physicochemical properties, modification mechanism of composite modified asphalt had been thoroughly studied. Subsequently, the results showed that the optimum content of DRP and SBS modifiers are 25 % and 2 %, respectively. The suitable preparation process is to add SBS first, then DRP, while shearing at 5000 r/min for 50 min. In addition, DRP/SBS composite modified asphalt has better high-temperature performance, viscosity-temperature characteristics, aging resistance, and storage stability. Meanwhile, the storage stability of the composite modified asphalt was verified by fluorescence microscopy test. Through the Fourier transform infrared spectroscopy test, it was observed that the composite modified asphalt modification process is a compatible and stable modification of physical and chemical coexistence. Overall, the composite modification method achieves recycling of waste tires while improving pavement performance, thus promoting the sustainability of pavement.

9.
J Chem Inf Model ; 64(7): 2889-2900, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37733290

RESUMO

MicroRNAs (miRNAs) are an essential type of small molecule RNAs that play significant regulatory roles in organisms. Recent studies have demonstrated that small open reading frames (sORFs) harbored in primary miRNAs (pri-miRNAs) can encode small peptides, known as miPEPs. Plant miPEPs can increase the abundance and activity of cognate miRNAs by promoting the transcription of their corresponding pri-miRNAs, thereby modulating plant traits. Biological experiments are the most effective way to accurately identify miPEPs; however, they are time-consuming and expensive. Hence, an efficient computational method for the identification of miPEPs on a large scale is highly desirable. Up to now, there have been no specialized computational tools for identifying miPEPs. In this work, a novel predictor named miPEPPred-FRL based on an adaptive feature representation learning framework that consists of the feature transformation module and the cascade architecture has been proposed. The feature transformation module integrating a newly designed feature selection method and classifier selection rule is developed to convert sequence-based features into primary class and probabilistic features, which are then fed into the improved cascade architecture to obtain more stable and discriminative augmented features. Finally, the augmented features are utilized to construct the final predictor. Cross-validation experiments illustrate that the novel feature selection method and classifier selection rule contribute to boosting the feature representation ability of the framework. Furthermore, the high accuracy of miPEPPred-FRL on independent testing data suggests that it is a trustworthy and valuable tool for the identification of miPEPs.


Assuntos
MicroRNAs , MicroRNAs/química , Plantas , Peptídeos , Biologia Computacional/métodos
10.
Front Mol Biosci ; 10: 1269478, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074089

RESUMO

Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI. Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting. Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells. Conclusion: NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI.

11.
Sensors (Basel) ; 23(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37765745

RESUMO

(1) Objective: To explore the neurobiological effects of terahertz (THz) radiation on zebrafish larvae using calcium (Ca2+) imaging technology. (2) Methods: Zebrafish larvae at 7 days post fertilization (dpf) were exposed to THz radiation for 10 or 20 min; the frequency was 2.52 THz and the amplitude 50 mW/cm2. The behavioral experiments, neural Ca2+ imaging, and quantitative polymerase chain reaction (qPCR) of the dopamine-related genes were conducted following the irradiation. (3) Results: Compared with the control group, the behavioral experiments demonstrated that THz radiation significantly increased the distance travelled and speed of zebrafish larvae. In addition, the maximum acceleration and motion frequency were elevated in the 20 min radiation group. The neural Ca2+ imaging results indicated a substantial increase in zebrafish neuronal activity. qPCR experiments revealed a significant upregulation of dopamine-related genes, such as drd2b, drd4a, slc6a3 and th. (4) Conclusion: THz radiation (2.52 THz, 50 mW/cm2, 20 min) upregulated dopamine-related genes and significantly enhanced neuronal excitability, and the neurobiological effect of THz radiation can be visualized using neural Ca2+ imaging in vivo.


Assuntos
Cálcio , Peixe-Zebra , Animais , Radiação Terahertz , Larva , Dopamina
12.
Front Cell Dev Biol ; 11: 1208566, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547477

RESUMO

Background: The role of the cellular level in kidney transplant rejection is unclear, and single-cell RNA sequencing (scRNA-seq) can reveal the single-cell landscape behind rejection of human kidney allografts at the single-cell level. Methods: High-quality transcriptomes were generated from scRNA-seq data from five human kidney transplantation biopsy cores. Cluster analysis was performed on the scRNA-seq data by known cell marker genes in order to identify different cell types. In addition, pathways, pseudotime developmental trajectories and transcriptional regulatory networks involved in different cell subpopulations were explored. Next, we systematically analyzed the scoring of gene sets regarding single-cell expression profiles based on biological processes associated with oxidative stress. Results: We obtained 81,139 single cells by scRNA-seq from kidney transplant tissue biopsies of three antibody-mediated rejection (ABMR) patients and two acute kidney injury (AKI) patients with non-rejection causes and identified 11 cell types, including immune cells, renal cells and several stromal cells. Immune cells such as macrophages showed inflammatory activation and antigen presentation and complement signaling, especially in rejection where some subpopulations of cells specifically expressed in rejection showed specific pro-inflammatory responses. In addition, patients with rejection are characterized by an increased number of fibroblasts, and further analysis of subpopulations of fibroblasts revealed their involvement in inflammatory and fibrosis-related pathways leading to increased renal rejection and fibrosis. Notably, the gene set score for response to oxidative stress was higher in patients with rejection. Conclusion: Insight into histological differences in kidney transplant patients with or without rejection was gained by assessing differences in cellular levels at single-cell resolution. In conclusion, we applied scRNA-seq to rejection after renal transplantation to deconstruct its heterogeneity and identify new targets for personalized therapeutic approaches.

13.
Environ Sci Pollut Res Int ; 30(37): 87433-87448, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37422565

RESUMO

Due to the high viscosity, rubber asphalt displays poor construction workability, which ultimately compromises the comfort and safety of pavement. In this study, specified control variates were used to study the effect of the waste engine oil (WEO) addition sequence on the properties of rubber asphalt while ensuring the consistency of other preparation parameters. Initially, in order to evaluate their compatibility, the storage stability and aging properties of the three groups of samples were determined. The variation of asphalt viscosity was then analyzed using a low-field nuclear magnetic resonance (LF-NMR) test, by predicting the fluidity of each sample. Subsequently, the results showed that the rubber asphalt prepared by premixing WEO and crumb rubber (CR) had the best properties of low temperature, compatibility, and fluidity. On this basis, the effects of WEO content, shear rate, shear temperature, and shear time on the properties of low viscosity rubber asphalt were investigated separately through response surface methodology (RSM). Quantitative data from the basic performance experiment were used to fit the high precision regression equation, thereby correlating a more precise level of factors with experimental results. The response surface model prediction analysis showed that the optimal preparation parameters of the low viscosity rubber asphalt were 60 min shear time, 180 °C shear temperature, and 5000 r/min shear rate. Simultaneously, the addition of 3.5% of WEO showed great potential as an asphalt viscosity reducer. Ultimately, this study provides an accurate method for determining the optimum preparation parameters of asphalt.


Assuntos
Temperatura Baixa , Borracha , Viscosidade
14.
Environ Sci Pollut Res Int ; 30(38): 89910-89926, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37460879

RESUMO

The typical treatment of waste plastics has become a global environmental problem. In light of recent developments, waste plastics used as asphalt modifiers offer an efficient approach to solve this problem. This paper studied the effects of three kinds of waste plastic-modified asphalts (WPMA), with polypropylene (PP), polyethylene (PE) and ethylene-vinyl acetate copolymer (EVA) as their respective modifiers, on the conventional asphalt performance. Furthermore, an orthogonal experimental design (OED) was used to determine the preparation parameters of WPMA. Thereafter, thermogravimetric-differential scanning calorimetry (TG-DSC) and Fourier transform infrared spectroscopy (FTIR) were employed to expound the mechanism of WPMA. It was then subsequently ascertained that the optimum preparation parameters of PP-modified asphalt (PPMA) and PE-modified asphalt (PEMA) were 170 °C, 3000 rpm, and 30 min, while the optimum preparation parameters of EVA-modified asphalt (EVAMA) were 180 °C, 3000 rpm, and 30 min. In addition, WPMA displayed better high-temperature performance and are inherently more suitable for pavement in high-temperature regions. Ultimately, this study will effectively solve the disposal of waste plastic and promote the research and application of WPMA in the future.


Assuntos
Hidrocarbonetos , Plásticos , Plásticos/química , Polipropilenos , Polietileno
15.
Am J Cancer Res ; 13(5): 2030-2040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37293174

RESUMO

Therapeutic resistance to androgen-deprivation therapy is a major challenge for prostate cancer therapy. The present study aims to explore the effects of poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and STL127705 on castration-resistant prostate cancer. Cell lines including PC-3 and enzalutamide-resistant LNCaP (erLNCaP) cells were treated with enzalutamide, enzalutamide plus olaparib, enzalutamide plus STL127705, or the combination of olaparib, STL127705, and enzalutamide. Cell viabilities and cell apoptosis were determined using the sulforhodamine B (SRB) assay and Annexin V/propidium iodide staining, respectively. Flow cytometry assay was applied to determine γH2AX intensity and the percentage of homologous recombination and non-homologous end-joining. Besides, a tumor-bearing animal model was established and treated with drugs as for cell lines. STL127705 and olaparib enhanced cytotoxicity of enzalutamide on erLNCaP and PC-3 cells. Furthermore, STL127705 and olaparib promoted enzalutamide-induced cell apoptosis and enhanced γH2AX intensity. In vitro study also showed that the combination of STL127705, olaparib, and enzalutamide inhibited homologous recombination and non-homologous end-joining repair systems in PC-3 cells. In vivo study demonstrated that the combination of STL127705, olaparib, and enzalutamide exhibited a significant anti-tumor effect. STL127705 combined with olaparib have a potential therapeutic effect on castration-resistant prostate cancer through inhibiting homologous recombination and non-homologous end-joining repair.

16.
Environ Monit Assess ; 195(6): 660, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37169981

RESUMO

Nanyi Lake is a tributary in the lower reaches of the Yangtze River and the largest freshwater lake in southern Anhui. Anthropogenic activities have significantly affected the lake with the rapid development of the surrounding economy in recent years. This study collected a total of 39 × 2 water samples of surface water and overlying water, detected the heavy metal concentrations (As, Cr, Cu, Mn, Ni, Pb, Sb, Zn, Fe, Cd), and analyzed the spectral characteristics of the dissolved organic matter (DOM). The results demonstrated that the concentrations of heavy metals (As, Cr, Cu, Mn, Ni, Pb, Sb, Zn, Fe, Cd) in the surface water were 1.00-7.78, 0.40-5.59, 0.20-4.52, 20.00-269.50, 0.40-5.56, 0.20-5.06, 1.00-7.64, 20.00-252.50, 60.00-590.00, and 0.04-0.60, respectively (unit: µg L-1). The risk assessment showed that the carcinogenic risks of heavy metals (As, Cr, Cd) through drinking water were ranged from 10-7 to 10-4a-1 in Nanyi Lake, and Cr was the main carcinogen which should be the focus of environmental health risk management. The average personal non-carcinogenic risks of heavy metals (Cu, Mn, Ni, Pb, Sb, Zn, Fe) were ranged from 10-9 to 10-13a-1, and considered to be acceptable risk level. The contour map of spatial distribution demonstrated different degrees of heavy metals (except Zn) enrichment near the Langchuan River in the East Lake District. Parallel factor analysis showed that the main components of DOM in Nanyi Lake were tryptophan like, fulvic acid like, and tyrosine like, and the dissolved organic matter was primarily derived from autogenous endogenous sources. The heavy metals Cr, Ni, Pb, Fe, Cd, and HIX in the surface water of West Lake were significantly positively correlated, among which Ni, Fe and C2 were significantly negatively correlated (P < 0.05), Mn and BIX demonstrated extremely significant positive correlations (P < 0.01), while no significant correlation was observed between heavy metals and the DOM indexes in the surface water of the East Lake. The principal component and correlation analysis showed that the heavy metals in Nanyi Lake were primarily derived from the production wastewater discharged by the surrounding industrial and mining enterprises through the rivers input, followed by the non-point source runoff input of the surrounding agricultural production and lake aquaculture.


Assuntos
Água Potável , Metais Pesados , Poluentes Químicos da Água , Lagos/análise , Matéria Orgânica Dissolvida , Monitoramento Ambiental/métodos , Cádmio/análise , Chumbo/análise , Metais Pesados/análise , Água Potável/análise , Medição de Risco , China , Poluentes Químicos da Água/análise , Sedimentos Geológicos
17.
Environ Sci Pollut Res Int ; 30(15): 44251-44265, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36683109

RESUMO

Traditional asphalt rubber (AR) has a high viscosity and poor fluidity, which makes its construction very difficult. Reducing viscosity has been identified as one of the effective way of solving these problems. Meanwhile, the mass production and improper discharge of waste engine oil (WEO) have a serious impact on the ecological environment, and its rational reuse needs to be addressed. In this paper, molecular models of AR and WEO-modified asphalt rubber (WEOMAR) was established by molecular dynamics (MD) simulations. The influence of WEO on asphalt component's behavior was studied by radial distribution function (RDF) and diffusion coefficient (D). Then, the microscopic mechanism of viscosity reduction was evaluated. Furthermore, the viscosity reduction behavior of WEO in AR was analyzed and verified by basic properties and low field nuclear magnetic resonance (LF-NMR) laboratory tests. The results showed that the RDF peak value of rubber molecules in WEOMAR is 14.07 higher than that of AR, at r = 2.16 Å. The D of saturated and aromatic components in WEOMAR obviously increased by 140% and 67.9%, respectively. The light component molecules increased after adding WEO into AR. The rubber molecule reduces the contact with asphaltene and resin, and the viscosity of AR is significantly reduced, which is confirmed by the macro tests.


Assuntos
Simulação de Dinâmica Molecular , Borracha , Viscosidade , Hidrocarbonetos
18.
Neuro Oncol ; 25(4): 635-647, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-36215227

RESUMO

BACKGROUND: Alterations in transcriptional regulators of glycolytic metabolism have been implicated in brain tumor growth, but the underlying molecular mechanisms remain poorly understood. METHODS: Knockdown and overexpression cells were used to explore the functional roles of HOXA3 in cell proliferation, tumor formation, and aerobic glycolysis. Chromatin immunoprecipitation, luciferase assays, and western blotting were performed to verify the regulation of HK2 and PKM2 by HOXA3. PLA, Immunoprecipitation, and GST-pull-down assays were used to examine the interaction of HOXA3 and KDM6A. RESULTS: We report that transcription factor homeobox A3 (HOXA3), which is aberrantly highly expressed in glioblastoma (GBM) patients and predicts poor prognosis, transcriptionally activates aerobic glycolysis, leading to a significant acceleration in cell proliferation and tumor growth. Mechanically, we identified KDM6A, a lysine-specific demethylase, as an important cooperator of HOXA3 in regulating aerobic glycolysis. HOXA3 activates KDM6A transcription and recruits KDM6A to genomic binding sites of glycolytic genes, targeting glycolytic genes for transcriptional activation by removing the suppressive histone modification H3K27 trimethylation. Further evidence demonstrates that HOXA3 requires KDM6A for transcriptional activation of aerobic glycolysis and brain tumor growth. CONCLUSIONS: Our findings provide a novel molecular mechanism linking HOXA3-mediated transactivation and KDM6A-coupled H3K27 demethylation in regulating glucose metabolism and GBM progression.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Genes Homeobox , Glioblastoma/genética , Fatores de Transcrição/genética , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Glicólise , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
19.
Environ Toxicol ; 38(2): 460-471, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36305172

RESUMO

Silicosis is an occupational lung disease that results from long-term inhalation of free silica dust, the expression is sustained inflammation response, fibroblast hyperplasia, and excessive collagen deposit, bringing about pulmonary interstitial fibrosis. Wnt signaling pathway exists in various kinds of eukaryotic cells, is a highly conservative signaling pathway in biological evolution, and participates in cell proliferation, differentiation, migration, and polarity of physiological activity, such as in embryonic development, organ morphology, and tumor. In addition, it plays an important role in the progress of fibrosis disease. At present, studies related to silicosis are increasing, but the pathogenesis of silicosis still is not clear. In recent years, more and more studies have suggested that the Wnt signaling pathway could participate in the pathogenesis of silicosis fibrosis. In the study, we explored the mechanism of the Wnt signaling pathway in the pathogenesis of silicosis fibrosis and evaluated the effect of XAV-939 treatment epithelial-mesenchymal transformation (EMT) induced by silica. In addition, the results showed that EMT and activation of the Wnt signaling pathway would occur after stimulation of silica or TGF-ß1. However, after treatment with the Wnt signaling pathway inhibitor XAV-939, EMT was reversed and the expression of the ß-catenin decreased. These results suggested that the Wnt signaling pathway is associated with EMT induced by silica and it could be a potential target for the treatment of silicosis.


Assuntos
Transição Epitelial-Mesenquimal , Fibrose Pulmonar , Silicose , Humanos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose , Fibrose Pulmonar/induzido quimicamente , Dióxido de Silício/toxicidade , Silicose/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
20.
Polymers (Basel) ; 14(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36297928

RESUMO

The sustainable reuse of waste plastic as an alternative construction material has numerous environmental and economic advantages. New opportunities to recycle waste plastic in asphalt for road construction would mitigate landfill issues and significantly reduce global carbon emissions. With a clear aim to contribute to a more efficient reuse of waste plastic, this paper reutilized two types of waste plastic (polypropylene (PP) and polyethylene (PE)) as asphalt modifiers to improve the performance of asphalt pavement as well as to achieve the purpose of sustainable recycling waste plastic. Therefore, the optimal preparation parameters of plastic-modified asphalt were recommended by the orthogonal test. Then, the dispersion and modification mechanisms of plastic particles in plastic-modified asphalt were further studied by Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Differential Scanning Calorimetry (TG-DSC). The results show that the asphalt containing PP and PE shows better overall performance at high temperatures compared with the base asphalt. Furthermore, PE-modified asphalt and PP-modified asphalt exhibited optimal properties when prepared at 3000 rpm for 30 min at 170 °C. Moreover, the results of the expansion mechanism show that the main reaction process of plastic asphalt is a physical change. Finally, PP-modified asphalt and PE-modified asphalt generally perform well and are suitable for high-temperature areas. Consequentially, the results of this research promote the recycling of waste plastic, ultimately advocating the recycling of waste materials and environmental protection of pavement construction.

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