DSGAT: predicting frequencies of drug side effects by graph attention networks.

A critical issue of drug risk-benefit evaluation is to determine the frequencies of drug side effects. Randomized controlled trail is the conventional method for obtaining the frequencies of side effects, while it is laborious and slow. Therefore, it is necessary to guide the trail by computational methods. Existing methods for predicting the frequencies of drug side effects focus on modeling drug-side effect interaction graph. The inherent disadvantage of these approaches is that their performance is closely linked to the density of interactions but which is highly sparse. More importantly, for a cold start drug that does not appear in the training data, such methods cannot learn the preference embedding of the drug because there is no link to the drug in the interaction graph. In this work, we propose a new method for predicting the frequencies of drug side effects, DSGAT, by using the drug molecular graph instead of the commonly used interaction graph. This leads to the ability to learn embeddings for cold start drugs with graph attention networks. The proposed novel loss function, i.e. weighted $\varepsilon$-insensitive loss function, could alleviate the sparsity problem. Experimental results on one benchmark dataset demonstrate that DSGAT yields significant improvement for cold start drugs and outperforms the state-of-the-art performance in the warm start scenario. Source code and datasets are available at https://github.com/xxy45/DSGAT.

The enhancing antibiofilm activity of curcumin on Streptococcus mutans strains from severe early childhood caries.

BACKGROUND: Streptococcus mutans (S. mutans) is one of the main cariogenic bacteria for caries. It was found that the clinical strains of S. mutans isolated from caries active population have stronger cariogenic ability than the isolates from caries-free (CF) people. Previous studies have found that curcumin can inhibit biofilm formation of S. mutans UA159. The objective of this study is to explore the antibiofilm effect of curcumin on the clinical isolates of S. mutans from severe early childhood caries(SECC). RESULTS: The isolates from SECC group had more biomass than CF group (t = 4.296, P < 0.001). The acidogenicity and aciduricity of the strains from two groups showed no significant difference. After treatment with curcumin, the viability of biofilm was reduced to 61.865% ± 7.108% in SECC and to 84.059% ± 10.227% in CF group at 24 h (P < 0.05). The net reduction of live bacteria and total bacteria in the SECC group was significantly higher than that of the CF group (live bacteria t = 3.305, P = 0.016; total bacteria t = 2.378, P = 0.045) at 5 min. For 24 h, the net reduction of live bacteria and total bacteria in the SECC group was significantly higher than that of the CF group (live bacteria t = 3.305, P = 0.016; total bacteria t = 2.378, P = 0.045). The reduction of biofilm thickness reduced significantly in 5 min (t = 4.110, P = 0.015) and in 24 h (t = 3.453, P = 0.014). Long-term (24 h) curcumin treatment inhibited the amount of EPS in SECC group from (25.980 ± 1.156) µm3/µm2 to (20.136 ± 1.042) µm3/µm2, the difference was statistically significant (t = 7.510, P < 0.001). The gene of gtfC, gtfD, ftf, gbpB, fruA and srtA in the CF group and the gtfB, gtfC, gtfD, ftf, gbpB, srtA in SECC group were respectively reduced after 5 min curcumin treatment. After 24 h treatment, the gtfB, gtfC, gtfD, ftf, gbpB, fruA and srtA in both two groups were downregulation, all the differences were statistically significant. CONCLUSIONS: Curcumin has antibiofilm activity on clinical strains of S. mutans, especially for those isolated from SECC.

Assessing the impact of curcumin on dual-species biofilms formed by Streptococcus mutans and Candida albicans.

Streptococcus mutans and Candida albicans are often isolated from plaques associated with early childhood caries. However, there are limited studies examining how these microorganisms interact with one another and how best to manage them. Recent studies have shown that curcumin (CUR), a natural compound, has the potential to independently control both of these microorganisms. The purpose of this study was to investigate how S. mutans and C. albicans respond in mono- and dual-species biofilms challenged with CUR. Quantitative biofilm biomass and viability were first evaluated and supported by live-dead PCR to assess biofilm composition. Confocal laser scanning microscopy (CLSM) was used to evaluate the exopolysaccharide (EPS) content and thickness of the biofilms, and the structure of the biofilms and morphology of the cells were observed by scanning electron microscopy (SEM). Quantitative real-time PCR (qRT-PCR) was applied to assess relative gene expression. The 50% minimum biofilm eradication concentration (MBEC50 ) of CUR against S. mutans and C. albicans was 0.5 mM. The biomass and viability decreased after treatment with CUR both in dual-species biofilms and in mono-species biofilm. CUR inhibited S. mutans and C. albicans in both mono- and dual-species biofilms. Streptococcus mutans was more sensitive to CUR in dual-species biofilm than in mono-species biofilms, whereas C. albicans was less sensitive in dual-species biofilms. EPS production was decreased by CUR in both mono- and dual-species biofilms, which coincided with the downregulation of glucosyltransferase and quorum sensing-related gene expression of S. mutans. In C. albicans, the agglutinin-like sequence family of C. albicans was also downregulated in dual-species biofilms. Collectively, these data show the potential benefit of using a natural antimicrobial, CUR, to control caries-related dual-species plaque biofilms.

ΜicroRNA­889 plays a suppressive role in cell proliferation and invasion by directly targeting TAB1 in non­small cell lung cancer.

MicroRNAs (miRNAs) are frequently reported to be aberrantly expressed in non­small cell lung cancer (NSCLC) and are closely associated with aggressive tumor phenotypes. Hence, identification of cancer­related miRNAs in NSCLC may be helpful for improving the cure rate of NSCLC treatments. miR­889 has been demonstrated to be a novel cancer­associated miRNA that is aberrantly expressed and plays an important role in esophageal squamous cell carcinoma and hepatocellular carcinoma. However, the exact functions and precise molecular mechanisms through which miR­889 affects NSCLC progression are still unknown. In the present study, we report for the first time that miR­889 expression is low in NSCLC tissues and cell lines. Clinically, low miR­889 expression was found to be correlated with the TNM stage and distant metastasis in NSCLC patients. Functionally, miR­889 overexpression suppressed the proliferation and invasiveness of NSCLC cells in vitro and decreased NSCLC xenograft tumor growth in mice. Furthermore, TGF­ß­activated kinase 1­binding protein 1 (TAB1) was confirmed as a direct target gene of miR­889 in NSCLC cells. TAB1 was revealed to be overexpressed in NSCLC tissue samples and was inversely correlated with miR­889 levels. Moreover, a TAB1 knockdown had effects similar to that of miR­889 overexpression, whereas restoration of TAB1 expression counteracted the actions of miR­889 in NSCLC cells. Overall, the present results indicated that miR­889 inhibits the aggressive behaviors of NSCLC by directly targeting TAB1 mRNA, thus highlighting the importance of the miR­889/TAB1 pathway in the malignant progression of NSCLC.

Curcumin as a Promising Antibacterial Agent: Effects on Metabolism and Biofilm Formation in S. mutans.

Streptococcus mutans (S. mutans) has been proved to be the main aetiological factor in dental caries. Curcumin, a natural product, has been shown to exhibit therapeutic antibacterial activity, suggesting that curcumin may be of clinical interest. The objective of this study is to evaluate the inhibitory effects of curcumin on metabolism and biofilm formation in S. mutans using a vitro biofilm model in an artificial oral environment. S. mutans biofilms were treated with varying concentrations of curcumin. The biofilm metabolism and biofilm biomass were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and the crystal violet assay. Confocal laser scanning microscopy was used to analyse the composition and extracellular polysaccharide content of S. mutans biofilm after curcumin treatment. The biofilm structure was evaluated using a scanning electron microscope. The gene expression of virulence-related factors was assessed by real-time PCR. The antibiofilm effect of curcumin was compared with that of chlorhexidine. The sessile minimum inhibitory concentration (SMIC50%) of curcumin against S. mutans biofilm was 500 µM. Curcumin reduced the biofilm metabolism from 5 min to 24 h. Curcumin inhibited the quantity of live bacteria and total bacteria in both the short term (5 min) and the long term. Moreover, curcumin decreased the production of extracellular polysaccharide in the short term. The expression of genes related to extracellular polysaccharide synthesis, carbohydrate metabolism, adherence, and the two-component transduction system decreased after curcumin treatment. The chlorhexidine-treated group showed similar results. We speculate that curcumin has the capacity to be developed as an alternative agent with the potential to reduce the pathogenic traits of S. mutans biofilm.