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Colorectal cancer (CRC) is a common digestive tract tumor with a high incidence and a poor prognosis. Traditional chemotherapy drugs are usually accompanied by unpleasant side effects, highlighting the importance of exploring new adjunctive drugs. In this study, we aimed to explore the role of ursolic acid (UA) in CRC cells. Specifically, HT‐29 cells were treated with UA at different concentrations (10, 20, 30, and 40 μM), and the expression of miR‐140‐5p, tumor growth factor‐β3 (TGF‐β3), β‐catenin, and cyclin D1 was determined by real‐time quantitative PCR. The cell cycle and apoptosis were checked by flow cytometry, and cell proliferation was detected by Cell Counting Kit‐8 assay. The HT‐29 cell model was established through overexpression (miR‐140‐5p mimics) and interference (miR‐140‐5p inhibitor) of miR‐140‐5p. Western blot was used to detect the protein expression of TGF‐β3. We found that UA could inhibit the proliferation of HT‐29 cells, block cells in the G1 phase, and promote cell apoptosis. After UA treatment, the expression of miR‐140‐5p increased and TGF‐β3 decreased. Notably, miR‐140‐5p downregulated the expression of TGF‐β3, while the overexpression of miR‐140‐5p exerted a similar function to UA in HT‐29 cells. Additionally, the messenger RNA expression of TGF‐β3, β‐catenin, and cyclin D1 was decreased in HT‐29 cells after UA treatment. In conclusion, UA inhibited CRC cell proliferation and cell cycle and promoted apoptosis by regulating the miR‐140‐5p/TGF‐β3 axis, which may be related to the inhibition of Wnt/β‐catenin signaling pathway. Highlights: Ursolic acid inhibits cell proliferation and promotes cell apoptosis and cell cycle arrest of colorectal cancer HT‐29 cells.Ursolic acid increased the expression of miR‐140‐5p.miR‐140‐5p exerts a similar function to ursolic acid by downregulating the expression of tumor growth factor‐‐β3 and inhibiting the Wnt/β‐catenin signaling pathway. [ABSTRACT FROM AUTHOR]

DEAH‐box helicase 33 (DHX33) is a potent oncogenic agent on patients with hepatocellular carcinoma and colon cancer. Nevertheless, the prognostic significance of DHX33 in human pan‐cancers remains unclear. Various bioinformatics tools have been used to clarify the oncogenic effects of DHX33 in pan‐cancers. The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were used to evaluate DHX33 at the mRNA and protein levels, respectively. The pan‐cancer prognostic prediction value of DHX33 was evaluated using the Kaplan–Meier plotter. The association between DHX33 levels and clinicopathological features was then determined using the UALCAN database. In addition, gene set enrichment analysis and nomogram prediction models were constructed. The association between DHX33 levels and immune cell infiltration was then assessed using TISIDB. We determined that DHX33 is aberrantly overexpressed in pan‐cancers and related to lung adenocarcinoma (LUAD) clinical stage (p <.001). Moreover, DHX33 overexpression was indicative of poor overall survival, disease‐free survival, and progression‐free interval in patients with LUAD (p <.05). Furthermore, DHX33 levels were associated with age, N stage, T stage, and pathologic stage in patients with LUAD (p <.001). Additionally, multivariate Cox analysis revealed that DHX33 was an independent risk factor for OS in patients with LUAD. A nomogram model between DHX33 levels and characteristic clinical parameters was developed. Additionally, DHX33 levels correlated with immunomodulators and chemokines. Finally, gene set enrichment analysis revealed that the amyloid fiber formation pathway and the WICH complex positively regulates RNA expression pathway, which was the most enriched in LUAD. Our data revealed oncogenic effects of DHX33 in various cancers. We suggest that DHX33 may serve as a biomarker for poor prognosis in LUAD. [ABSTRACT FROM AUTHOR]

Aim: We aimed to explore a new approach and theoretical basis for the diagnosis, treatment and prognosis of pre‐eclampsia. Methods: In total, 103 pre‐eclamptic patients (study group: SG) and 100 healthy pregnant women (control group: CG) were enrolled. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) was used to detect the expression level of serum Hoxb3. Enzyme‐linked immunosorbent assay was used to detect the content of serum sFlt‐1. Pregnancy outcomes in the two groups were recorded, and the correlations of the levels of Hoxb3 and sFlt‐1 with the pregnancy outcomes were analyzed. Results: The relative expression of serum Hoxb3 mRNA in the CG was significantly higher than that in the SG, whereas the content of serum sFlt‐1 in the CG was significantly lower than that in the SG. Compared with the CG, the SG had a significantly lower number of spontaneous deliveries, higher number of cesarean deliveries and significantly higher number of uneventful perinatal births. The incidences of intrauterine growth restriction, intrauterine distress, premature infants and neonatal deaths in perinatal infants in the SG were significantly higher than those in the CG. According to the analysis of receiver operating characteristic curves, the areas under the curves of Hoxb3, sFlt‐1 and their combined detection for diagnosing pre‐eclampsia were 0.799, 0.856 and 0.930, respectively. The areas under the curves for predicting poor perinatal outcomes were 0.724, 0.828 and 0.871, respectively. Conclusion: In conclusion, Hoxb3 and sFlt‐1 have certain reference significance for the risk evaluation of pre‐eclampsia and the adverse pregnancy outcomes of pre‐eclampsia women. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is extremely harmful to human health. In recent years, N6‐methyladenosine (m6A) RNA methylation in eukaryotic mRNA has been increasingly implicated in cancer pathogenesis and prognosis. In this study, we downloaded the expression profile and clinical information of 307 patients from The Cancer Genome Atlas database and 64 patients from the Gene Expression Omnibus (GEO) database, and univariate Cox analysis revealed that METTL14 was a prognostic m6A RNA methylation regulator. For further study on the related genes of METTL14, weighted gene co‐expression network analysis was used to find the relationship between METTL14 and gene expression, and univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) methods were used to identify hub genes that may be associated with HCC prognosis. The results indicated that cysteine sulfinic acid decarboxylase, glutamic‐oxaloacetic transaminase 2, and suppressor of cytokine signaling 2 were key genes affecting the prognosis of HCC patients, and m6A methylation of these mRNAs may be regulated by METTL14. Finally, a nomogram was constructed based on the hub gene expression levels, and its prediction accuracy and discriminative ability were measured by the C‐index and a calibration curve. In conclusion, METTL14, an m6A RNA methylation regulator, may participate in the malignant progression of HCC by adjusting the m6A of cysteine sulfinic acid decarboxylase, glutamic‐oxaloacetic transaminase 2, and suppressor of cytokine signaling 2, and these genes are useful for prognostic stratification and treatment strategy development. [ABSTRACT FROM AUTHOR]

Targeting epigenetic modification of gene expression represents a promising new approach under investigation for the treatment of inflammatory diseases. Accumulating evidence suggests that epigenetic mechanisms, such as histone modification, play a crucial role in a number of inflammatory diseases, including rheumatoid arthritis, asthma, and contact hypersensitivity. Consistent with this role, histone deacetylase (HDAC) inhibitors have shown efficacy in the treatment of inflammatory diseases. In particular, selective inhibitors of HDAC6, a cytoplasmic member of the HDAC family that contains two deacetylase domains, are under investigation as a potential treatment strategy for inflammatory diseases due to their ability to regulate inflammatory cells and cytokines. Here, we review recent findings highlighting the critical roles of HDAC6 in a variety of inflammatory diseases, and discuss the therapeutic potential of HDAC6 inhibitors in these settings. [ABSTRACT FROM AUTHOR]

Accumulating evidence has supported the significance of lncRNAs in tumorigenesis. Recently, some studies indicate the oncogenic role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in hepatocellular carcinoma (HCC). In our present study, we focused on the biological mechanisms through which NEAT1 can regulate HCC development. We found that NEAT1 was greatly upregulated in human HCC cell lines including Huh7, Hep3B, HepG2, Bel-7404, and SK-Hep1 cells compared to the normal human liver cell line LO2. In addition, we observed that miR-485 was significantly downregulated in HCC cells. It was implied that miR-485 was increased by sh-NEAT1 and miR-485 can modulate NEAT1 expression negatively. Meanwhile, NEAT1inhibiton can repress HCC growth, migration, and invasion capacity in HepG2 and Hep3B cells. Through performing bioinformatic analysis, dual-luciferase reporter test, RNA-binding protein immunoprecipitation, and RNA pull-down assay, miR-485 was confirmed as a interacting target of NEAT1. Additionally, STAT3 was recognized as a direct target of miR-485 and miR-485 mimics can inhibit STAT3 expression. It was demonstrated that NEAT1 can increase STAT3 levels while miR-485 mimics can repress STAT3. Moreover, we found that sh-STAT3 was able to restrain HCC cell migration and invasion process. NEAT1 can act as a competing endogenous lncRNA (ceRNA) to regulated STAT3 by sponging miR-485 in HCC. Taken these together, NEAT1 can be used as an important biomarker in HCC diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Environmental stresses are ubiquitous and unavoidable to all living things. Organisms respond and adapt to stresses through defined regulatory mechanisms that drive changes in gene expression, organismal morphology, or physiology. Immune responses illustrate adaptation to bacterial and viral biotic stresses in animals. Dysregulation of the genotoxic stress response system is frequently associated with various types of human cancer. With respect to plants, especially halophytes, complicated systems have been developed to allow for plant growth in high salt environments. In addition, drought, waterlogging, and low temperatures represent other common plant stresses. In this review, we summarize representative examples of organismal response and adaptation to various stresses. We also discuss the molecular mechanisms underlying the above phenomena with a focus on the improvement of organismal tolerance to unfavorable environments. [ABSTRACT FROM AUTHOR]

Objective Increased expression of type I interferon (IFN) and a broad signature of type I IFN-induced gene transcripts are observed in patients with systemic lupus erythematosus (SLE) and other systemic autoimmune diseases. To identify disease-relevant triggers of the type I IFN pathway, this study sought to investigate whether endogenous virus-like genomic repeat elements, normally silent, are expressed in patients with systemic autoimmune disease, and whether these retroelements could activate an innate immune response and induce type I IFN. Methods Expression of type I IFN and long interspersed nuclear element 1 (LINE-1; L1) was studied by polymerase chain reaction, Western blotting, and immunohistochemistry in samples of kidney tissue from patients with lupus nephritis and minor salivary gland (MSG) tissue from patients with primary Sjögren's syndrome (SS). Induction of type I IFN by L1 was investigated by transfection of plasmacytoid dendritic cells (PDCs) or monocytes with an L1-encoding plasmid or L1 RNA. Involvement of innate immune pathways and altered L1 methylation were assessed. Results Levels of L1 messenger RNA transcripts were increased in lupus nephritis kidneys and in MSG tissue from patients with SS. Transcript expression correlated with the expression of type I IFN and L1 DNA demethylation. L1 open-reading frame 1/p40 protein and IFNβ were expressed in MSG ductal epithelial cells and in lupus nephritis kidneys, and IFNα was detected in infiltrating PDCs. Transfection of PDCs or monocytes with L1-encoding DNA or RNA induced type I IFN. Inhibition of Toll-like receptor 7 (TLR-7)/TLR-8 reduced the induction of IFNα by L1 in PDCs, and an inhibitor of IKKε/TANK-binding kinase 1 abrogated the induction of type I IFN by L1 RNA in monocytes. Conclusion L1 genomic repeat elements represent endogenous nucleic acid triggers of the type I IFN pathway in SLE and SS and may contribute to initiation or amplification of autoimmune disease. [ABSTRACT FROM AUTHOR]

Tamoxifen is a widely used anticancer drug with both an estrogen agonist and antagonist effect. This study focused on its endocrine disrupting effect, and overall environmental significance. Zebrafish embryos were exposed to different concentrations (0.5, 5, 50 and 500 µg l-1) of tamoxifen for 96 h. The results showed a complex effect of tamoxifen on zebrafish embryo development. For the 500 µg l-1 exposure group, the heart rate was decreased by 20% and mild defects in caudal fin and skin were observed. Expressions of a series of genes related to endocrine and morphological changes were subsequently tested through quantitative real-time polymerase chain reaction. Bisphenol A as a known estrogen was also tested as an endocrine-related comparison. Among the expression of endocrine-related genes, esr1, ar, cyp19a1b, hsd3b1 and ugt1a1 were all increased by tamoxifen exposure, similar to bisphenol A. The cyp19a1b is a key gene that controls estrogen synthesis. Exposure to 0.5, 5, 50 and 500 µg l-1 of tamoxifen caused upregulation of cyp19a1b expression to 152%, 568%, 953% and 2024% compared to controls, higher than the effects from the same concentrations of bisphenol A treatment, yet vtg1 was suppressed by 24% from exposure to 500 µg l-1 tamoxifen. The expression of metabolic-related genes such as cyp1a, cyp1c2, cyp3a65, gpx1a, gstp1, gsr and genes related to observed morphological changes such as krt17 were also found to be upregulated by high concentrations of tamoxifen. These findings indicated the potential environmental effect of tamoxifen on teleost early development. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]