β‐catenin regulates IRF3‐mediated innate immune signalling in colorectal cancer

Objective

β‐catenin is one of the most critical oncogenes associated with many kinds of human cancers, especially in the human CRC. Innate immunity recognizes tumour derived damage‐associated molecular patterns (DAMPs) and primes the anti‐tumour adaptive responses. While the function of β‐catenin in CRC tumourigenesis is well established, its impact on innate immune evasion is largely unknown. The aim of this study is to characterize the role of β‐catenin in inhibiting RIG‐I‐like receptor (RLR)‐mediated IFN‐β signalling in colorectal cancer.

Materials and Methods

Immunohistochemical staining and western blotting were conducted to study the expression of β‐catenin, IRF3 and phospho‐IRF3 (p‐IRF3) in CRC samples and cell lines. Plaque assay determining virus replication was performed to assess the regulation of β‐catenin on IFN‐β signalling. The inhibition of β‐catenin on RLR‐mediated IFN‐β signalling was further studied by real‐time analyses and reporter assays in the context of lentiviral‐mediated β‐catenin stably knocking down. Lastly, co‐immunoprecipitation and nuclear fractionation assay were conducted to monitor the interaction between β‐catenin and IRF3.

Results

We found that high expression of β‐catenin positively correlated with the expression of IRF3 in CRC cells. Overexpression of β‐catenin increased the viral replication. Conversely knocking down of β‐catenin inhibited viral replication. Furthermore, our data demonstrated that β‐catenin could inhibit the expression of IFN‐β and interferon‐stimulated gene 56 (ISG56). Mechanistically, we found that β‐catenin interacted with IRF3 and blocked its nuclear translocation.

Conclusion

Our study reveals an unprecedented role of β‐catenin in enabling innate immune evasion in CRC.

     

Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA‐4295 that activates CDKN1A

Objectives

Ginsenoside Rh2 (GRh2) has demonstrative therapeutic effects on a variety of diseases, including some tumours. However, the effects of GRh2 on prostate cancer (PC) cell growth remain unknown, and were, thus, addressed in the present study.

Materials and methods

PC3 and DU145 PC cell lines were exposed to GRh2. Cell proliferation was assessed in an MTT assay and by BrdU incorporation. Apoptosis of the cells were assessed by TUNEL staining. Total RNA was assessed by RT‐qPCR. Protein levels were assessed by Western blotting. Bioinformatics and dual luciferase reporter assay were applied to determine the functional binding of miRNA to mRNA of target gene.

Results

GRh2 dose‐dependently decreased PC cell proliferation, but did not alter cell apoptosis. Mechanistically, GRh2 dose‐dependently increased the protein, but not mRNA of a cell‐cycle suppressor CDKN1A in PC cells, suggesting the presence of microRNA (miRNA)‐mediated protein translation control of CDKN1A by GRh2. In all candidate miRNAs that bind to 3′‐UTR of CDKN1A, miR‐4295 was specifically found to be suppressed dose‐dependently by GRh2 in PC cells. Moreover, miR‐4295 bound CDKN1A to suppress its protein translation. Furthermore, cell proliferation in PC cells that overexpressed miR‐4295 did not alter in response to GRh2.

Conclusions

GRh2 may inhibit PC cell growth through suppression of microRNA‐4295 that activates CDKN1A.

     

LncRNA-135528 inhibits tumor progression by up-regulating CXCL10 through the JAK/STAT pathway

Spontaneous tumor regression can be observed in many tumors, however, studies related to the altered expression of lncRNA in spontaneous glioma regression are limited, and the potential contributions of lncRNAs to spontaneous glioma regression remain unknown. To investigate the biological roles of lncRNA-135528 in spontaneous glioma regression. The cDNA fragment of lncRNA-135528 was obtained by rapid-amplification of cDNA ends (RACE) technology and cloned into the plvx-mcmv-zsgreen-puro vector. Additionally, we stably silenced or overexpressed lncRNA-135528 in G422 cells by transfecting with siRNA against lncRNA-135528 or lncRNA-135528 overexpression plasmid. Then, we examined lncRNA-135528 overexpressing and lncRNA-135528 silencing on glioma cells and its effects on CXCL10 and JAK/STAT pathways. The main findings indicated that lncRNA-135528 promoted glioma cell apoptosis, inhibited cell proliferation and arrested cell cycle progression; the up-regulation of lncRNA135528 led to significantly increased CXCL10 levels and the differential expression of mRNA associated with JAK/STAT pathway in glioma cells. lncRNA-135528 can inhibit tumor progression by up-regulating CXCL10 through the JAK/STAT pathway.     

Distinct Mechanisms of Nuclease-Directed DNA-Structure-Induced Genetic Instability in Cancer Genomes

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A novel real-time driving fatigue detection system based on wireless dry EEG

Development of techniques for detection of mental fatigue has varied applications in areas where sustaining attention is of critical importance like security and transportation. The objective of this study is to develop a novel real-time driving fatigue detection methodology based on dry Electroencephalographic (EEG) signals. The study has employed two methods in the online detection of mental fatigue: power spectrum density (PSD) and sample entropy (SE). The wavelet packets transform (WPT) method was utilized to obtain the \(\theta \) (4–7 Hz), \(\alpha \) (8–12 Hz) and \(\beta \) (13–30 Hz) bands frequency components for calculating corresponding PSD of the selected channels. In order to improve the fatigue detection performance, the system was individually calibrated for each subject in terms of fatigue-sensitive channels selection. Two fatigue-related indexes: (\(\theta +\alpha \))/\(\beta \) and \(\theta \)/\(\beta \) were computed and then fused into an integrated metric to predict the degree of driving fatigue. In the case of SE extraction, the mean of SE averaged across two EEG channels (‘O1h’ and ‘O2h’) was used for fatigue detection. Ten healthy subjects participated in our study and each of them performed two sessions of simulated driving. In each session, subjects were required to drive simulated car for 90 min without any break. The results demonstrate that our proposed methods are effective for fatigue detection. The prediction of fatigue is consistent with the observation of reaction time that was recorded during simulated driving, which is considered as an objective behavioral measure.     

The phenylpropanoid pathway affects apple fruit resistance to Botrytis cinerea

Apple fruits are rich in phenolic compounds that may enhance resistance to grey mould disease caused by Botrytis cinerea. Using Malus domestica Borkh. cultivars Fuji and Qinguan, we analysed the contents of total phenols, total flavonoids, eight individual phenolic compounds, H₂O₂ and O₂^.? as well as the activities of key enzymes in the phenylpropanoid pathway in the flesh of control and B. cinerea‐inoculated fruits. Chlorogenic acid contents increased for a short period in the less susceptible cultivar Qinguan fruits, but decreased in the disease‐susceptible Fuji fruits. Additionally, ferulic acid production was induced in both cultivars in response to B. cinerea. Furthermore, the activities of phenylalanine ammonia lyase, cinnamate 4‐hydroxylase, 4‐coumarate:coenzyme A ligase and cinnamyl alcohol dehydrogenase were differentially induced between the two apple cultivars. Remarkably, the contents of H₂O₂ and O₂^.? as well as the activities of enzymes in phenolic metabolism tested in this study were always higher in Qinguan fruits than in Fuji fruits. Our data imply that phenylpropanoid metabolism is closely associated with apple fruit resistance to grey mould disease. These findings may be useful for characterizing the mechanism(s) underlying plant resistance to B. cinerea, with potential implications for the screening of grey mould disease‐resistant apple varieties in breeding programmes.     

Effect of Cys,GSH, and pH on Mercury Release from Tibetan Medicine Zuotai, β-HgS,and α-HgS in Artificial Gastrointestinal Juices

Biological Trace Element Research - Zuotai, also named as “gTso thal”, a known Tibetan medicinal mixture containing insoluble cubic crystal mercuric sulfide (β-HgS), has been used...     

Effects of 1-Methylcyclopropene on Rice Growth Characteristics and Superior and Inferior Spikelet Development Under Salt Stress

Journal of Plant Growth Regulation - Salinity stress hampers rice growth and development due to its osmotic, ionic, and hormonal (ethylene) stresses. High ethylene production affects inferior and...     

Biology and life history of Dabry's sturgeon, Acipenser dabryanus, in the Yangtze River

Dabry's sturgeon, Acipenser dabryanus, is a relatively small (130 cm, 16 kg) and now rare sturgeon restricted to the Yangtze River Basin. It behaves as a resident freshwater fish, does not undertake long distance migrations (except for spawning), and lives in a variety of habitats. It historically spawned in the upper Yangtze River, but the spawning sites are unknown. Acipenser dabryanus reaches maturity earlier than do other Chinese sturgeons, which gives the species aquaculture potential, and artificial spawning has been carried out. However, the native population in the Yangtze has sharply declined in the last two decades due to overfishing, pollution and habitat alteration and destruction, especially since the construction of the Gezhouba Dam, which was built in 1981 across the Yangtze River at Yichang, Hubei Province. Since 1981, Dabry's sturgeon rarely occurs below the Gezhouba Dam because downstream movements are blocked. Clearly, conservation of Dabry's sturgeon must be emphasized. Conservation methods may include protecting habitats, controlling capture and stock replenishment.     

Motor Adaptive Remodeling Speeds Up Bacterial Chemotactic Adaptation

Bacterial chemotaxis is a canonical system for the study of signal transduction. One of the hallmarks of this system is its robust adaptive behavior. However, how fast the system adapts remains controversial. The adaptation time measured at the level of the kinase activity was tens of seconds, whereas that measured at the level of the flagellar motor was <10 s. The flagellar motor was recently shown to exhibit adaptive remodeling, its main physiological function being to provide a robust match between the chemoreceptor output and the motor input, whereas its adaptation timescale was thought to be too slow to contribute much to the overall adaptation timescale of the chemotaxis system. Here, through theoretical modeling of the motor adaptive remodeling and experimental tests, we show that this motor adaptation contributes significantly to speeding up the overall chemotactic adaptation, thereby resolving the previous inconsistency.