Bystander effects can be induced through cellular communication between irradiated cells and non-irradiated cells. The signals that mediate this cellular communication, such as cytokines, reactive oxygen species, nitric oxide and even microRNAs, can be transferred between cells via gap junctions or extracellular medium. We have previously reported that miR-21, a well described DDR (DNA damage response) microRNA, is involved in radiation-induced bystander effects through a medium-mediated way. However, the mechanisms of the microRNA transfer have not been elucidated in details. In the present study, it was found that exosomes isolated from irradiated conditioned medium could induce bystander effects. Furthermore, we demonstrated plenty of evidences that miR-21, which is up-regulated as a result of mimic transfection or irradiation, can be transferred from donor or irradiated cells into extracellular medium and subsequently get access to the recipient or bystander cells through exosomes to induce bystander effects. Inhibiting the miR-21 expression in advance can offset the bystander effects to some extent. From all of these results, it can be concluded that the exosome-mediated microRNA transfer plays an important role in the radiation-induced bystander effects. These findings provide new insights into the functions of microRNAs and the cellular communication between the directly irradiated cells and the non-irradiated cells.

Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was −0.21% (95% CI: −0.34% to −0.08%), and the ER for 1 mm increase in rainfall was −0.23% (95% CI: −0.37% to −0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations.

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Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication.

The mechanisms of radiation-induced bystander effects (RIBE) have been investigated intensively over the past two decades. Although quite a few reports demonstrated that cytokines such as TGF-b1 are induced within the directly irradiated cells and play critical roles in mediating the bystander effects, little is known about the signaling pathways that occur in bystander cells. The crucial question as to why RIBE signals cannot be infinitely transmitted, therefore, remains unclear. In the present study, we showed that miR-663, a radiosensitive microRNA, participates in the regulation of biological effects in both directly irradiated and bystander cells via its targeting of TGF-b1. MiR-663 was downregulated, while TGFB1 was upregulated in directly irradiated cells. The regulation profile of miR-663 and TGFB1, on the other hand, was reversed in bystander cells, in which an elevated miR-663 expression was exhibited and led to downregulation of TGF-b1. Further studies revealed that miR-663 interacts with TGFB1 directly and that through its binding to the core regulation sequence, miR-663 suppresses the expression of TGFB1. Based on the results, we propose that miR-663 inhibits the propagation of RIBE in a feedback mode, in which the induction of TGF-b1 by reduced miR-663 in directly irradiated cells leads to increased level of miR-663 in bystander cells. The upregulation of miR-663 in turn suppresses the expression of TGF-b1 and limits further transmission of the bystander signals.

BackgroundSeveral meta-analyses have indicated that periodontal disease (PD) are related to cardiovascular diseases (CVDs). However, the association between PD and myocardial infarction (MI) remains controversial. Here we aimed to assess the association between PD and MI by meta-analysis of observational studies.MethodsPubMed, EMBASE and the Cochrane Library were searched through July, 2016. Observational studies including cohort, cross-sectional and case–control studies reporting odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CIs) were included in the analysis. Either fixed or random-effects model were applied to evaluate the pooled risk estimates. Sensitivity and subgroup analyses were also carried out to identify the sources of heterogeneity. Publication bias was assessed by the Begg’s, Egger’s test and funnel plot.ResultsWe included 22 observational studies with 4 cohort, 6 cross-sectional and 12 case–control studies, including 129,630 participants. Patients with PD have increased risk of MI (OR 2.02; 95% CI 1.59-2.57). Substantial heterogeneity in risk estimates was revealed. Subgroup analyses showed that the higher risk of MI in PD patients exists in both cross-sectional studies (OR 1.71; 95% CI 1.07-2.73) and case–control studies (OR 2.93; 95% CI 1.95-4.39), and marginally in cohort studies (OR 1.18; 95% CI 0.98-1.42). Further, subgroup meta-analyses by location, PD exposure, participant number, and study quality showed that PD was significantly associated with elevated risk of MI.ConclusionOur meta-analysis suggested that PD is associated with increased risk of future MI. However, the causative relation between PD and MI remains not established based on the pooled estimates from observational studies and more studies are warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-017-0480-y) contains supplementary material, which is available to authorized users.

Previous studies examining the weather-bacillary dysentery association were of a large time scale (monthly or weekly) and examined the linear relationship without checking the linearity assumption. We examined this association in Beijing at a daily scale based on the exposure-response curves using generalized additive models. Our analyses suggested that there were thresholds for effects of temperature and relative humidity, with an approximately linear effect for temperature >12·5 °C [excess risk (ER) for 1 °C increase: 1·06%, 95% confidence interval (CI) 0·63-1·49 on lag day 3] and for relative humidity >40% (ER for 1% increase: 0·18%, 95% CI 0·12-0·24 at lag day 4); and there were linear effects of rainfall (ER for 1-mm increase: 0·22%, 95% CI 0·12-0·32), negative effects for wind speed (ER: -2·91%, 95% CI -4·28 to -1·52 at lag day 3) and sunshine duration (ER: -0·25% 95% CI -0·43 to -0·07 at lag day 4). This study suggests that there are thresholds for the effects of temperature and relative humidity on bacillary dysentery, and these findings should be considered in its prevention and control programmes.

Genetic alteration involving N6-methyladenosine (m6A) regulatory genes is a frequent characteristic of multiple tumors. Nevertheless, little is known regarding their genetic alteration signatures and prognostic values in head and neck squamous cell carcinoma (HNSCC). In this study, RNA sequence profiles and copy number variation (CNV) data of 506 HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Correlation analysis involving alteration of m6A regulatory genes, clinicopathological characteristics, and patient survival was performed using R language. The results suggest that alteration of m6A regulatory genes was correlated with clinical staging. Patients with high expression of ALKBH5, FTO, METTL14, WTAP, YTHDC1, YTHDF1, and YTHDF2 had poor overall survival (OS) than those with low expression. Univariate and multivariate Cox regression analyses showed that ALKBH5 and YTHDC2 were independent risk factors for OS. However, patients with high YTHDC2 expression had better OS. Moreover, according to machine learning results, YTHDC2 was found to be the most important gene among the 10 m6A regulators. Additionally, high expression of YTHDC2 was correlated with activation of apoptosis and ubiquitin-mediated proteolysis. Here, we identified alterations to m6A regulatory genes in HNSCC for the first time and found that seven m6A regulators were associated with poor prognosis, especially ALKBH5, whereas YTHDC2 was associated with better prognosis. These m6A-related regulators could act as novel prognostic biomarkers for HNSCC. Our findings provide clues for understanding RNA epigenetic modifications in HNSCC.