Circ-E2F3 promotes cervical cancer progression by inhibiting microRNA-296-5p and increasing STAT3 nuclear translocation.

Circular RNA E2F transcription factor 3 (circ-E2F3) has been demonstrated to be differentially expressed in some diseases and cancers. However, the role of circ-E2F3 in cervical cancer (CC) progression remains unclear. Therefore, we aimed to elucidate the mechanism of circ-E2F3 regulation of CC progression. Circ-E2F3 expression was determined in CC samples, and its correlation with the clinicopathological characteristics of CC patients and cell biological processes was examined. The interaction among circ-E2F3, microRNA-296-5p (miR-296-5p), and signal transducer and activator of transcription 3 (STAT3) was analyzed by dual luciferase reporter gene and fluorescence in situ hybridization assays. Circ-E2F3-depleted CaSki cells were implanted into nude mice to verify the function of circ-E2F3 in vivo. Circ-E2F3 was upregulated in both CC tissues and cell lines, and this correlated with the clinicopathological features and poor prognosis of CC patients. Moreover, circ-E2F3 promoted the proliferation, invasion, and migration of CC cells and tumor growth in vivo. It was also observed that circ-E2F3 promoted the nuclear translocation of STAT3 through inhibition of miR-296-5p, thus affecting the expression of cyclin D1. Taken together, the key findings of our study demonstrate that circ-E2F3 induces inhibition of miR-296-5p, which triggers activation and nuclear translocation of STAT3 that then upregulates cyclin D1 expression.

Silencing long non-coding RNA MIAT ameliorates myocardial dysfunction induced by myocardial infarction via MIAT/miR-10a-5p/EGR2 axis.

Long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) has been widely-demonstrated to function as diagnostic markers for acute myocardial infarction (MI). This study was designed to explore the modulatory role of MIAT and its underlying molecular mechanism in MI. Firstly, MI mouse model was developed via ligation of the descending branch of the left coronary artery, and cell model was established through exposure to hypoxic conditions. Online prediction indicated that MIAT could bind to microRNA-10a-5p (miR-10a-5p), while miR-10a-5p was highlighted to bind to early growth response gene-2 (EGR2). MIAT and EGR2 were subsequently determined to be highly-expressed, whereas miR-10a-5p was found to be poorly-expressed in cardiomyocytes exposed to hypoxia as well as in MI mice using RT-qPCR and Western blot assay. The binding relationships between MIAT and miR-10a-5p, and between miR-10a-5p and EGR2 were further confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. The results of in vitro and in vivo experimentation also suggested that overexpression of miR-10a-5p or silencing of MIAT and EGR2 reduced cardiomyocyte apoptosis and increased ATP content, thus alleviating the impairment of cardiac function following MI. In a word, inhibition of MIAT protects against cardiac dysfunction induced by MI through the crosstalk with miR-10a-5p/EGR2.

Endoplasmic reticulum stress potentiates the autophagy of alveolar macrophage to attenuate acute lung injury and airway inflammation.

Endoplasmic reticulum (ER) stress has been reported to play a role in acute lung injury (ALI), yet the in-depth mechanism remains elusive. This study aims to investigate the effect of ER stress-induced autophagy of alveolar macrophage (AM) on acute lung injury (ALI) and airway inflammation using mouse models. ALI models were induced by intranasal instillation of lipopolysaccharide (LPS). The lung weight/body weight (LW/BW) ratio and excised lung gas volume (ELGV) in each group were measured. Mouse bronchoalveolar lavage fluid (BALF) was collected for cell sorting and protein concentration determination. Expression of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lung tissues and BALF was also detected. Mouse AMs were isolated to observe the autophagy. Expression of GRP78, PERK, LC3I, LC3II and Beclin1 was further determined. The results indicated that tunicamycin (TM) elevated GRP78 and PERK expression of AMs in ALI mice in a dose-dependent manner. Low dosage of TM abated LC3I expression, increased LC3II and Beclin1 expression, triggered ER stress and AM autophagy, and alleviated pathological changes of AMs in ALI mice. Also, in ALI mice, low dosage of TM attenuated goblet cell proliferation of tracheal wall, and declined LW/BW ratio, ELGV, total cells and neutrophils, protein concentrations in BALF, and IL-6 and TNF-α expression in lung tissues and BALF. Collectively, this study suggests that a low dosage of TM-induced ER stress can enhance the autophagy of AM in ALI mice models, thus attenuating the progression of ALI and airway inflammation.

Up-regulation of microRNA-223 inhibits brain injury and hippocampal neuron apoptosis of rats after febrile seizure through the NLRP3-Caspase-1 signaling pathway.

OBJECTIVE: This study is conducted to explore the role of microRNA-223 (miR-223) in brain injury and apoptosis of hippocampal neurons through the NLRP3-Caspase-1 signaling pathway in febrile seizure (FS) rats. METHODS: The models of FS were induced in rats by hot water-bath, which were stereotactically injected with miR-223 mimics and mimics negative control (NC) to perturb the expression of miR-223. A series of experiments was conducted to find out the potential mechanisms of miR-223 on convulsion attack, learning and memory ability, pathological injury of hippocampal neurons, inflammatory injury, apoptosis of hippocampal neurons in FS rats. Besides, the targeting relationship between miR-223 and NLRP3 was also verified. RESULTS: Low expression of miR-223 was found in hippocampus tissues of FS rats. Up-regulation of miR-223 alleviated convulsion attack and improved learning and memory ability, while inhibiting pathological injury of hippocampal neurons and inflammatory injury in FS rats. Up-regulation of miR-223 promoted the survival of hippocampal neurons and inhibited their apoptosis in FS rats. MiR-223 inhibited the activation of NLRP3-Caspase-1 signaling pathway in hippocampus tissues of FS rats by inhibiting NLRP3. CONCLUSION: The inhibited expression of miR-223 after FS may participate in the activation of the NLRP3-Caspase-1 signaling pathway, resulting in brain injury and apoptosis of hippocampal neurons in rat models of FS.

TNF-α-TNFR signal pathway inhibits autophagy and promotes apoptosis of alveolar macrophages in coal worker's pneumoconiosis.

OBJECTIVE: Exposure to coal dust causes the development of coal worker's pneumoconiosis (CWP), which is associated with accumulating macrophages in the lower respiratory tract. This study was performed to investigate the effect of tumor necrosis factor-α (TNF-α)-tumor necrosis factor receptor (TNFR) signal pathway on autophagy and apoptosis of alveolar macrophages (AMs) in CWP. METHODS: AMs from controls exposed to coal dust and CWP patients were collected, in which expressions of TNF-α and TNFR1 were determined. Autophagy was observed by transmission electron microscopy, and apoptosis by light microscope and using terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. AMs in CWP patients were treated with TNF-α or anti-TNF-α antibody. Besides, expressions of autophagy marker proteins, apoptosis-related factors, FAS, caspase-8, and receptor-interacting serine-threonine-protein kinase 3 (RIPK3) were determined by western Blot. Activities of caspase-3 and caspase-8 were determined by a fluorescence kit. Flow cytometry was applied to measure the expression of TNFR1 on the surface of the AM. RESULTS: TNF-α expression and TNFR1 expression on the surface of AM, as well as autophagy and apoptotic index were significantly increased in AMs of CWP patients. In response to the treatment of TNF-α, TNF-α expression and TNFR1 expression on the surface of AM as well as LC3I expression were increased, autophagy was decreased, and LC3, LC3II, Beclin1 and B-cell lymphoma 2 expressions decreased, whereas FAS expression and activity and expression of caspase-3 and caspase-8 increased, and apoptotic index increased. Moreover, the situations were reversed with the treatment of anti-TNF-α antibody. CONCLUSION: TNF-α-TNFR signal pathway was involved in the occurrence and development of CWP by activating FAS-caspase-8 and thus inhibiting autophagy while promoting apoptosis of AM.

TNFR/TNF-α signaling pathway regulates apoptosis of alveolar macrophages in coal workers' pneumoconiosis.

We explored the role of TNFR/TNF-α signalingin apoptosis among alveolar macrophages (AM) and its relevance to the development of coal workers' pneumoconiosis (CWP). Purified alveolar macrophages (AMs) were prepared from bronchoalveolar lavage fluid harvested from 366 CWP patients and 120 healthy subjects enrolled inthe study. The purified AMs were then divided into control, SOD, anti-TNFR, TNFR and NFkB inhibitor groups and analyzed for apoptosis usingflow cytometry (sub-diploid peak) and western blotting (Bcl-2, Caspase-3 and Caspase-8 expression). We found thatAM apoptosis washigher amongCWP patients than thehealthycontrols. Expression ofBcl-2, Caspase-3 and Caspase-8 was higher inAMs from CWP patientsthan in those from the controlsand correlated with increased AM apoptosis. Univariate and multivariate analyses suggested that CWP grade, initial exposure time, exposure time inyears, and CWP onset agewereall associated with altered levels of Bcl-2, Caspase-3 and Caspase-8. Inhibition of TNFR/TNF-α signaling usinganti-TNFR antibody, SOD or NFkB inhibitionreduced AM apoptosisand decreased Bcl-2, Caspase-3 and Caspase-8 expression. These data suggestinhibition of a TNFR/TNF-α signaling pathway is a potentiallyeffective means ofalleviating CWP by inhibiting AM apoptosis.

Correlations of smoking with cumulative total dust exposure and cumulative abnormal rate of pulmonary function in coal-mine workers.

The present study aimed to investigate the correlation of smoking with cumulative total dust exposure (CTE) and cumulative abnormal rate of pulmonary function in coal-mine workers. A total of 376 coal-mine workers were recruited as the observational group, while 179 healthy workers in other industries were selected as the control group. All the workers underwent pulmonary function testing to determine their forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC, in order to compare the abnormal pulmonary function between the two groups. A markedly higher number of smokers was observed in the observational group (200/376, 53.19%) when compared with the control group (72/179, 40.22%). In smokers, the abnormal rate of pulmonary function in the observational group (102/200, 51.00%) was evidently higher compared with that in the control group (19/72, 26.39%), whereas no significant difference was detected between the two groups of non-smokers (P=0.077). In addition, FVC, FEV1 and FEV1/FVC of the observational group were found to be lower compared with those in the control group, in both the smoking and non-smoking subgroups. In the smoking subgroup, FVC and FEV1 in subjects working at the coal mine for different number of years showed significant differences (all P<0.05), whereas comparison of FEV1/FVC in workers with different working durations showed no significant difference (P=0.169). However, in the non-smoking subgroup, the comparison of FVC, FEV1 and FEV1/FVC in different working duration groups also showed no significant difference (all P>0.05). Furthermore, FVC, FEV1 and FEV1/FVC in smoking coal-mine workers were negatively correlated with the dust-exposure working duration (P<0.05). CTE was also positively correlated with cumulative abnormal rate of pulmonary function in the smoking and non-smoking subgroups, while FEV1 was negatively correlated with CTE in the smoking subgroup (P=0.009). In conclusion, smoking is an important risk factor for the damage of pulmonary function in coal-mine workers, and it is positively correlated with dust-exposure time and CTE in these individuals.

Analysis of Hemogram of Radiation Workers in Tangshan, China.

OBJECTIVES: This study aimed to investigate changes in peripheral blood cells of radiation workers and explore the impact of long-term ionizing radiation (IR) on human peripheral hemogram. METHODS: With a cohort method, we selected 1,392 radiation workers (case group) and 1,430 non-health-ray-exposure history persons (control group) to detect and analyze their peripheral hemogram. FAITH3000 automatic biochemical analyzer was used for blood testing. Examination of peripheral hemogram includes the examination of white blood cells (WBCs), platelet (PLTs), red blood cells (RBCs), hemoglobin (Hb), lymphocytes (LYMs), and mononuclear cells (MOs). The data analysis was conducted with software SPSS19.0. RESULTS: All the peripheral hemogram indicators (WBCs, RBCs, Hb, PLTs, LYMs, and MOs) in the case group, in accordance with the order of radiology diagnostic medical group, industrial inspection group, petroleum logging group, and radiotherapy medical group, showed a significant decreasing trend and were lower than those in the control group (all P < 0.05). Besides, with the increase of radiation seniority and accumulative radiation dose, all the peripheral hemogram indicators (WBCs, RBCs, Hb, PLTs, LYMs, and MOs) in the case group dramatically decreased and were lower than those in the control group (all P < 0.05). Seniority was in negative association with the expressions of WBCs, PLTs, RBCs, Hb, LYMs, and MOs and radiation dose with Hb, LYMs, and MOs (all P < 0.05). CONCLUSION: Long-term IR has some effects on the health of radiation workers, thus protective measures should be further strengthened.

Relationship of cumulative dust exposure dose and cumulative abnormal rate of pulmonary function in coal mixture workers.

To investigate the dose-response relationship between cumulative dust exposure (CDE) and cumulative abnormal rate of pulmonary function in coal mixture workers. Three hundred and twenty eight coal mixture workers (exposed group) and 169 nondust-exposed workers (control group) were recruited. Basic information data were collected and pulmonary function tests were performed. Pulmonary function was compared between the two groups after comparing smoking behaviors. Pulmonary function indices [forced vital capacity in 1 second after full inspiration (FVC)%, forced expiratory volume (FEV)1%, and FEV1/FVC%] were compared among groups stratified by service length (exposure duration). The relationship between CDE dose and cumulative abnormal rate of pulmonary function in coal mixture workers was analyzed. Abnormal rate of pulmonary function in the exposed group (35.1%) was significantly higher than the control group (10.1%; p < 0.001); FVC%, FEV1%, and FEV1/FVC% in the exposed group decreased significantly compared with the control group (all p < 0.05). Differences in FVC%, FEV1%, and FEV1/FVC% among coal mixture workers stratified by exposure duration in the exposed group were statistically significant (all p < 0.05). The discernible increase in the cumulative abnormal rate was observed, from ≥ 1000 mg/m(3)·years group to ≥ 1700 mg/m(3)·years group. Correlation analysis revealed a positive correlation between the CDE dose and the cumulative abnormal rate of pulmonary function. Higher abnormal pulmonary function rate was found among coal mixture workers, characterized by decreased pulmonary function indices. Our results suggested a positive relationship between CDE dose and cumulative abnormal pulmonary function rate, and a rapid increase in cumulative abnormal rate within a certain range of CDE dose. A lower limit value of 1000 mg/m(3)·years has reference significance.

Effects of ionising radiation on micronucleus formation and chromosomal aberrations in Chinese radiation workers.

This study is aimed to investigate the effects of ionising radiation (IR) on micronuclei (MN) formation and chromosome aberrations (CAs) in Chinese radiation workers. The study was conducted using peripheral blood lymphocytes from 1392 radiation workers from Public Hospitals of the city of Tangshan (the exposed group), and 143 healthy individuals as the control group. Fluorescence in situ hybridisation (FISH) was used to detect the unstable and stable nuclear CAs on metaphase. The MN assay was performed using the cytochalasin B method for cytokinesis-block. The MN and CA frequencies were significantly higher in the exposed group than in healthy controls (both p < 0.001). Examination of the incidence rates of MN and CA showed an increasing trend among workers in some occupations compared with the others (all p < 0.05). There were also significant differences in MN and CA rates among workers with different exposure times (all p < 0.05). Stable CA rates demonstrated an increased trend among workers with different exposure times (all p < 0.05), while no significance of unstable CA rates was found among workers with different exposure times (all p < 0.05). Importantly, the frequencies of CA and MN increased among different cumulative radiation dose groups (all p < 0.05). Correlation analysis showed that the frequencies of MN and CA were positively associated with the cumulative radiation dose. Long-term exposure to IR may have harmful effects on the health of radiation workers. The data obtained here show an increased risk of genetic instability that correlated with occupation, exposure time and equivalent dose among Chinese radiation workers.

Deep ultraviolet photoluminescence of water-soluble self-passivated graphene quantum dots.

Glucose-derived water-soluble crystalline graphene quantum dots (GQDs) with an average diameter as small as 1.65 nm (∼5 layers) were prepared by a facile microwave-assisted hydrothermal method. The GQDs exhibits deep ultraviolet (DUV) emission of 4.1 eV, which is the shortest emission wavelength among all the solution-based QDs. The GQDs exhibit typical excitation wavelength-dependent properties as expected in carbon-based quantum dots. However, the emission wavelength is independent of the size of the GQDs. The unique optical properties of the GQDs are attributed to the self-passivated layer on the surface of the GQDs as revealed by electron energy loss spectroscopy. The photoluminescence quantum yields of the GQDs were determined to be 7-11%. The GQDs are capable of converting blue light into white light when the GQDs are coated onto a blue light emitting diode.