Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression.

EPB41L3 may play a role as a metastasis suppressor by supporting regular arrangements of actin stress fibres and alleviating the increase in cell motility associated with enhanced metastatic potential. Downregulation of epb41l3 has been observed in many cancers, but the role of this gene in esophageal squamous cell carcinoma (ESCC) remains unclear. Our study aimed to determine the effect of epb41l3 on ESCC cell migration and invasion. We investigated epb41l3 protein expression in tumour and non-tumour tissues by immunohistochemical staining. Expression in the non-neoplastic human esophageal cell line Het-1a and four ESCC cell lines - Kyse150, Kyse510, Kyse450 and Caes17 - was assessed by quantitative Polymerase Chain Reaction (qPCR) and Western blotting. Furthermore, an EPB41L3 overexpression plasmid and EPB41L3-specific small interfering RNA were used to upregulate EPB41L3 expression in Kyse150 cells and to downregulate EPB41L3 expression in Kyse450 cells, respectively. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The expression levels of p-AKT, matrix metalloproteinase (MMP)2 and MMP9 were evaluated. Expression of epb41l3 was significantly lower in tumour tissues than in non-tumour tissues and in ESCC cell lines compared with the Het-1a cell line. Kyse450 and Caes17 cells exhibited higher expression of epb41l3 than Kyse150 and Kyse510 cells. Overexpressing epb41l3 decreased Kyse150 cell migration and invasion, whereas EPB41L3-specific small interfering RNA silencing increased these functions in Kyse450 cells. Furthermore, overexpressing epb41l3 led to downregulation of MMP2 and MMP9 in Kyse150 and Kyse510 cells. Our findings reveal that EPB41L3 suppresses tumour cell invasion and inhibits MMP2 and MMP9 expression in ESCC cells.

E74­like ETS transcription factor 5 facilitates cell proliferation through regulating the expression of adenomatous polyposis coli 2 in non­small cell lung cancer.

E74­like ETS transcription factor 5 (ELF5) is known to regulate the specification and differentiation of epithelial cells in the embryonic lung. However, the pathological function of ELF5 in lung cancer has yet to be fully elucidated. In the present study, the expression of ELF5 was found to be significantly higher in lung adenocarcinoma compared with that in corresponding adjacent normal tissues. Subsequently, cell and animal experiments were performed to investigate the role of ELF5 in lung adenocarcinoma cells. The results indicated that the overexpression of ELF5 increased the proliferation of lung adenocarcinoma cells, whereas, by contrast, a reduction in the expression of ELF5 led to a decrease in their proliferation. Mechanistically, the hypothesis is advanced that ELF5 can promote lung cancer cell proliferation through inhibiting adenomatous polyposis coli 2 and increasing the expression of cyclin D1, which is a critical downstream target of the Wnt pathway. Taken together, these findings support the notion that ELF5 exerts an essential role in the proliferation of lung adenocarcinoma cells and may be a therapeutic target for the treatment of lung adenocarcinoma.

A Ferroptosis-Related lncRNA Model to Enhance the Predicted Value of Cervical Cancer.

BACKGROUND: Cervical cancer (CC) is a common gynecological malignant tumor. Ferroptosis is a new type of programmed cell death, which plays a crucial part in cancer. However, current knowledge regarding ferroptosis-related long noncoding RNAs (lncRNAs) in CC is still limited. Therefore, our aim is to identify ferroptosis-related lncRNAs, build a steady prediction model, and improve the prediction value of CC. METHODS: We obtained RNA expression and ferroptosis-related gene data of female CC patients from TCGA and FerrDb databases, respectively. Then, the ferroptosis-related lncRNAs were obtained by the limma R package and Cytoscape 3.7.1. We constructed the prediction model by Cox regression analysis. Finally, the prediction model was verified by the median risk score, Kaplan-Meier analysis, the time-dependent receiver operating characteristic (ROC) curve, clinical features, and immunoinfiltration analysis. RESULTS: We acquired 1393 ferroptosis-related lncRNAs. The ferroptosis-related lncRNA signature was obtained by multivariate Cox regression analysis, and the patients were divided into a high-risk group and a low-risk group. The prognosis of the high-risk group was worse than that of the low-risk group. We found that the risk score can be used as an independent prognostic index by multivariate Cox regression analysis. The area under the time-dependent ROC curve reached 0.847 at 1 year, 0.906 at 2 years, 0.807 at 3 years, and 0.724 at 5 years in the training cohort. Principal component analysis showed that the diffusion directions of the two groups were different. Gene set enrichment analysis indicated that lncRNAs of two groups may be involved in tumorigenesis. Further analysis showed that high-risk groups were related to immune-related pathways. Ferroptosis-related lncRNAs are related to the proportion of tumor-infiltrating immune cells in CC. CONCLUSION: We have constructed a ferroptosis-related lncRNA prediction model. The prognostic model had important clinical significance, including improving the predictive value and guiding the individualized treatment of CC patients.

Fabrication and characterization of novel edible Pickering emulsion gels stabilized by dihydromyricetin.

The edible Pickering emulsion gels stabilized by dihydromyricetin were fabricated for the first time. To clarify the formation mechanism, dihydromyricetin particles were first characterized. Then, the factors influencingthe gel formation, microstructure and mechanical properties were investigated. Finally, the molecular dynamics simulation was performed to clarify the microscopic behavior of dihydromyricetin in an oil-water system. The results indicated that dihydromyricetin particles occurred as regular rod-shaped crystals with amphiphilicity. They formed a 3D steric network by overlapping with each other, separating oil droplets and stabilizing O/W emulsion gels. The dihydromyricetin concentration and oil-phase weight fraction had a significant influence on the formation and mechanical properties of gels. The alkali and low ionic strength conditions benefited the gel stability. The molecular dynamics showed that dihydromyricetin could spontaneously and quickly transfer to the oil-water interface, reduce the interfacialtension and enhance the interface thickness, which agreed with the experimental results.

Structuring of sunflower oil by stearic acid derivatives: Experimental and molecular modelling studies.

Structuring of vegetable oils has potential application in food, pharmaceutical and cosmetic products. In this study, structuring effects of stearic acid derivatives on sunflower seed oil were systematically investigated by experimental and molecular simulation methods. Stearic acid (SA), 12-hydroxy stearic acid (HSA) and 2-hydroxyethyl stearate (HES) were able to structure sunflower seed oil, among which the structuring ability of HES was reported for the first time. The oleogel formed with HSA exhibited good mechanical properties (such as hardness, fracturability, adhesiveness, chewiness and storage modulus), which coincided with its highest solid fat content and degree of crystallinity. Oleogels containing SA and HES showed similar mechanical properties. Both the molecular dynamics (MD) simulation and independent gradient model (IGM) confirmed that the HSA dimer possessed the strongest interaction during the self-assembly process while the dimers of HES and SA had similar interactions, which could explain their structuring performance.

Interaction mechanism of flavonoids and bovine ß-lactoglobulin: Experimental and molecular modelling studies.

In this study, the quantitative structure-affinity relationship of 28 flavonoids with bovine ß-lactoglobulin (ß-lg) was investigated based on experimental and theoretical methods. The binding constants (Ka) of these flavonoids with ß-lg were systematically compared by spectrofluorimetry, and a multivariate linear model (R2 = 0.8769, Q2 = 0.7963) was established that could explain the effect of the structure parameters of flavonoids on their affinity (lgKa) for ß-lg. Then, the underlying interaction mechanism was further clarified with myricetin and baicalin as representative flavonoids. Thermodynamic analysis showed that hydrogen bonds and van der Waals force played the main roles in maintaining the complexes, which was consistent with the independent gradient model (IGM) and the MM/PBSA binding free energy results. The redshift of the maximum emission peak of tryptophan residues in the synchronous fluorescence was attributed to the interaction of myricetin or baicalin with Trp19 of ß-lg, according to the root mean square fluctuation (RMSF) results.

Preparation and characterization of lutein ester-loaded oleogels developed by monostearin and sunflower oil.

The marigold (Tagetes erecta L.) flower is rich in lutein ester with many health-promoting activities. In this study, the effects of vegetable oil type and extracting the temperature on the extraction efficiency of lutein ester in the marigold flower were evaluated. Then, the structuring of the lutein ester-loaded sunflower oil with the addition of different amounts of monostearin and cooling temperatures (4 and 20°C) was investigated. The XRD analysis suggested that these oleogels were stabilized by the network formed by monostearin crystals in the sunflower oil. The textural properties (firmness, cohesiveness, and hardness) of oleogels were positively related to the monostearin dosage, but negatively related to the cooling temperature. According to the rheological results, the oleogels belonged to the pseudoplastic gel and their gelation temperature (Tg ) was only related to the concentration of monostearin. The light stability of lutein ester in the oleogels was also significantly improved in a monostearin dosage-dependent manner. PRACTICAL APPLICATIONS: The edible lutein ester-loaded oleogel for foods developed by structuring the sunflower oil with monostearin is introduced in this study. Its texture and rheological properties can be adjusted to cater to different requirements in the food industry by changing the monostearin dosage and cooling temperature. This study provides a reference for the development of other liposoluble nutraceuticals.

Interaction Mechanism of Flavonoids and α-Glucosidase: Experimental and Molecular Modelling Studies.

Flavonoids are known to play a role in hypoglycemia by inhibiting α-glucosidase. However, their interaction mechanism with α-glucosidase still needs to be elaborated. In this study, the α-glucosidase inhibitory activities of 15 flavonoids were investigated. Their molecular volume had a negative effect on inhibitory activity, while the number of phenolic hydroxyl groups on the B ring was positively correlated with inhibitory activity. To explain the significant differences in activity, the interaction behaviors of myricetin and dihydromyricetin, which have similar structures, were compared by spectrofluorimetry, molecular docking, and the independent gradient model (IGM). In the fluorescence analysis, myricetin exhibited a higher binding capacity. Based on molecular docking and IGM analysis, their non-covalent interactions with α-glucosidase could be visualized and quantified. It was found that they had different binding modes with the enzymes and that myricetin possessed stronger hydrogen bonding and van der Waals force interactions, which explained the thermodynamic results.

Target Elimination-Denatured and Unstable Proteins, Environmental Toxins, Metabolic Wastes, Immunosuppressive Factors and Chronic Inflammatory Factors of Medical System for Chronic Diseases Prevention and Health Promotion: A Narrative Review.

BACKGROUND: The incidence of chronic diseases, such as cardiovascular disease, diabetes, overweight, obesity, cancer and other diseases has been increasing. It is a huge challenge to public health industry about how to provide risk intervention and preventive medical services and explore advanced technology platform for effective prevention and control of chronic diseases. METHODS: We collaborated domestic and international experts on preventive medicine, and analyzed pathogenesis and risk factors for the major chronic diseases. RESULTS: We established Target Elimination--denatured and unstable proteins, environmental toxins, metabolic wastes, immunosuppressive factors and chronic inflammatory factor (TE-PEMIC) system that offer us the standard and methods to eliminate and intervene pathogenic factors of the chronic diseases. CONCLUSION: It provides new researches and exploring new ideas to prevent and intervene chronic diseases by applying the TE-PEMIC chronic diseases prevention medical technology system.

EPB41L3 is a potential tumor suppressor gene and prognostic indicator in esophageal squamous cell carcinoma.

Although there have been reports about the role of erythrocyte membrane protein band 4.1 like 3 (EPB41L3) in several types of cancer, primarily in non-small-cell lung carcinoma, the molecular function and modulatory mechanisms of EPB41L3 remain unclear. In specific, the functional and clinical significance of EPB41L3 in esophageal squamous cell carcinoma (ESCC) has not been explored to date. In the present study, reduced EPB41L3 expression was demonstrated in ESCC cell lines and tissues, which was due to its high methylation rate. Ectopic expression of EPB41L3 in ESCC cells inhibited cell proliferation in vivo and in vitro. In addition, EPB41L3 overexpression induced apoptosis and G2/M cell cycle arrest by activating Caspase-3/8/9 and Cyclin-dependent kinase 1/Cyclin B1 signaling, respectively. Notably, patients with higher EPB41L3 expression had markedly higher overall survival rates compared with patients with lower EPB41L3 expression. In summary, the present results suggest that EPB41L3 may be a tumor suppressor gene in ESCC development, representing a potential therapeutic target and a prognostic indicator for ESCC.

MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer.

Repeated infection with high-risk HPV is a major cause for the development and metastasis of human cervical cancer, even though the mechanism of the metastasis is still not completely understood. Here, we reported that miR-218 (microRNA-218) was downregulated in cervical cancer tissues, especially in metastatic cancer tissues. We found that miR-218 expression was associated with clinicopathological characteristics of patients with cervical cancer. MiR-218 overexpression inhibited Epithelial-Mesenchymal Transition (EMT), migration and invasiveness of cervical cancer cells in vitro. Moreover, miR-218 repressed the expression of SFMFBT1 (Scm-like with four MBT domains 1) and DCUN1D1 (defective in cullin neddylation 1, domain containing 1) by direct binding to the 3'UTRs of the mRNAs. The overexpression of SFMBT1 induced EMT and increased the migration and invasiveness of cervical cancer cells, while the overexpression of DCUN1D1 increased the migration and invasiveness of these cells, but did not induce EMT. An inverse correlation was observed between the expression of miR-218 and DCUN1D1 protein in cervical cancer tissues. Importantly, HPV16 E6 downregulated the expression of miR-218 in cervical cancer, while miR-218 rescued the promotion effect of HPV16 E6 on the expression of SFMBT1 and DCUN1D1. Taken together, our results revealed that HPV16 E6 promoted EMT and invasion in cervical cancer via the repression of miR-218, while miR-218 inhibited EMT and invasion in cervical cancer by targeting SFMBT1 and DCUN1D1.

Serum microRNA-218 is a potential biomarker for esophageal cancer.

BACKGROUND: Several studies demonstrated that microRNAs are stably detectable in plasma/serum and are potential biomarkers for some diseases. The expression of microRNA-218 (miR-218) is downregulated in esophageal cancer as reported in previous research. OBJECTIVE: The purpose of this study is to investigate whether miR-218 can be served as a serum biomarker for esophageal cancer. METHODS: We tested the expression level of miR-218 in serum of 106 patients with esophageal cancer and 60 healthy volunteers by RT-PCR and analyzed the relationship between serum miR-218 expression and the clinical characteristics. RESULTS: The serum expression of miR-218 was significantly lower in patients with esophageal cancer than that in healthy individuals. The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.833. Furthermore, the ROC curves to detect early esophageal cancer with Tis-T1 or Stage 0-I showed AUCs of 0.825 and 0.829, respectively. In the esophageal cancer group, the serum expression of miR-218 was found to be lower in esophageal cancer patients with poorer differentiation, later stage, and lymph node metastasis, highlighting that low serum expression of miR-218 may be related to tumor development and progression in esophageal cancer. CONCLUSIONS: The serum expression of miR-218 is downregulated in esophageal cancer patients and is correlated with tumor differentiation, stage, and lymph node metastasis. Serum miR-218 may be a potential biomarker for early detection and clinical evaluation in patient with esophageal cancer.